Siriraj Medical Journal
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SMJ
Volume 74, Number 10, October 2022
MONTHLY
Indexed by
THAILAND SECTION
1954
ORIGINAL ARTICLE
REVIEW ARTICLE
By I Putu Eka Widyadharma, et al.
Siriraj Medical Journal SMJ
Volume 74, Number 10, October 2022
ORIGINAL ARTICLE
618 Paradigm Shift from Open Surgery to Minimally Invasive Surgery in Three Approaches for
Radical Prostatectomy: Comparing outcomes and learning curves
Sittiporn Srinualnad, et al.
627 Risk Factor of Proximal Lag Screw Cut-Out After Cephalomedullary Nail Fixation in
Trochanteric Femoral Fractures: A Retrospective Analytic Study
Chantas Mahaisavariya, et al.
634 Comparative Study Regarding Autonomy of Final-Year Surgical Residents: A Case Study of
Perception among Surgical Residents, Surgical Staff, Administrators, and Patients at
Siriraj University Hospital
Ravit Ruangtrakool, et al.
650 Text Size Affects Eye Movement during Reading among Young Adults and Adults with
Presbyopia
Noor Halilah Buari, et al.
658 Predicting the Need for Continuation of N-acetylcysteine Treatment among Acute
Paracetamol Overdose Patients with Psi Parameter
Pattaraporn Mekavuthikul, et al.
666 Determinants of Modern Contraceptive Usage among Married Women: A Mixed-Methods
Study in a Rural Community of India
Trina Sengupta, et al.
675 Simulated Surgical Model Design for Myringotomy and Tympanostomy Tube Insertion in
Children using Medical Image Processing and 3D-Printing Technologies
Kawin Pratumaneechai, et al.
684 Survival Analysis of and Prognostic Factors for Metastatic Epidural Spinal Cord
Compression Compared between Preoperative Known and Unknown Primary Tumors
Nitiwut Saenmanot, et al.
693 Types and Levels of Colostomy in Children with Anorectal Malformation
Ravit Ruangtrakool, et al.
699 Lidocaine Reducing Pain from Benzathine Penicillin Injection: A Controlled Trial
Sukhum Jiamton, et al.
REVIEW ARTICLE
705 An Overview on Postoperative Cognitive Dysfunction; Pathophysiology, Risk Factors,
Prevention and Treatment
Thanathip Suenghataiphorn, et al.
714 Serum Neurofilament Light Chain: A Potential Biomarker for Peripheral Neuropathy
I Putu Eka Widyadharma, et al.
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SMJ
Volume 74, No.10: 2022 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index
618
Sittiporn Srinualnad, M.D.*, Thitipat Hansomwong, M.D.*, Pubordee Aussavavirojekul, M.D.*,
Pat Saksirisampant, M.D.**
*Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Division of Urology,
Department of Surgery, Somdech Phra Pinklao Hospital, Naval Medical Department, Royal ai Navy, Bangkok, ailand.
Paradigm Shift from Open Surgery to Minimally
Invasive Surgery in Three Approaches for Radical
Prostatectomy: Comparing Outcomes and Learning
Curves
ABSTRACT
Objective: Radical prostatectomy (RP) can be performed by several approaches, such as open retropubic radical
prostatectomy (RRP), laparoscopic radical prostatectomy (LRP), and robotic-assisted laparoscopic prostatectomy
(RALP). is study investigated and shared the dierences in the surgical techniques, learning curves, and outcomes
of each approach of RP.
Materials and Methods: e data of patients who received RP given by one of the authors between January 2002
to June 2016 were retrospectively reviewed. We compared perioperative and postoperative outcomes among
approaches, searched for predictors of a positive surgical margin (PSM), and assess the learning curves of the two
minimally invasive approaches.
Results: 527 patients underwent RP during January 2002 to June 2016 including 42 RRP, 198 LRP, and 327 RALP.
RALP had the highest negative surgical margin (68.8%) and lowest multifocal positive surgical margin (10.7%).
PSM predictors were the Gleason score and pathological T staging. e learning curve showed that RALP needed
one-hundred-cases experience to achieve the lowest PSM rate and 200 cases to master bleeding control. In the rst
100 cases in each group, the PSM rate in LRP was lower than in RALP.
Conclusion: Minimally invasive approach in radical prostatectomy showed signicant improvements over RRP,
especially the RALP approach. RALP would take a surgeon 100 and 200 cases to reach the plateau on the learning
curve for achieving the desired oncologic and perioperative outcome eciencies, respectively. However, LRP and
RRP are still feasible in a service setting and for training purposes.
Keywords: Radical prostatectomy; Laparoscopic; Robotic; Localized prostate cancer; Learning curve (Siriraj Med
J 2022; 74: 618-626)
Corresponding author: Sittiporn Srinualnad
E-mail: sitsrinualnad@gmail.com
Received 6 September 2021 Revised 28 January 2022 Accepted 31 January 2022
ORCID ID: http://orcid.org/0000-0002-5118-7675
http://dx.doi.org/10.33192/Smj.2022.73
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
Srinualnad et al.
INTRODUCTION
Prostate cancer is one of the most commonly diagnosed
cancers in male populations worldwide.1 Back in the
day, ai patients usually developed lower urinary tract
symptoms such as frequency, intermittent voiding, and a
sense of residual urine as the tumor progressed extensively
before their rst visit to the hospital.2 erefore, initial
radical prostatectomy (RP) had signicant morbidity and
mortality due to the late detection of cancer and poor
understanding of the procedure. Aer early detection
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Original Article SMJ
with PSA screening was adopted, it provided a window
of opportunity to eradicate cancer while the patient
was still in a curable state and encouraged surgeons to
improve both their surgical technique and the operative
outcome.3
Currently, RP is a standard treatment for localized
prostate cancer. e procedure can proceed via several
approaches: open retropubic radical prostatectomy (RRP),
laparoscopic radical prostatectomy (LRP), and robotic-
assisted laparoscopic prostatectomy (RALP).3-9 Minimally
invasive approaches (LRP and RALP) provide several
benets to both the patient and surgeon by helping minimize
blood loss, shortening the hospital stay, and improving
the oncological outcome in patients.10,11 From the point
of view of the surgeon, minimally invasive approaches
allow a better-magnied vision, 3D perception, more
comfortable ergonomic posture during operation, and
intracorporal wrist rotation in RALP.12,13
e present study aimed to investigate and share the
dierences in the surgical technique, surgeon learning
curve for RALP, and oncological outcome of each approach
for RP.
MATERIALS AND METHODS
We retrospectively reviewed the RP cases from
January 2002 to June 2016 performed by one of the
authors (Sittiporn Srinualnad) since he was a novice in
the eld. In total, 567 cases were eligible for inclusion
in the study, comprising 42 RRP cases, 198 LRP cases,
and 327 RALP cases. e surgeon started to perform a
high number of cases of RRP, LRP, and RALP in 2002,
2006, and 2007, respectively.
All patients were placed in low lithotomy with
Trendelenburg position and were under general anesthesia.
In RRP setting, the surgeon made a lower midline incision,
while in LRP and RALP, the surgeon had laparoscopic
ports set in position with one 12 mm camera port, three
8 mm working ports, a 12 mm assistant port, and a
5 mm assistant port. In RALP, the Intuitive da Vinci
robotic surgical system (model S, Si, or Xi) was docked
into position and its robotic arms were installed to all
8 mm working ports. For visualization, LRP was the
only approach performed without depth perception as
only 2D monitors were used. On the contrary, RALP
had the consoles which provide 3D footage and RRP
exposed the surgeon directly to the surgical eld. Aer
the initialization had been done, the retropubic radical
prostatectomy was similarly commenced. Notably, in
the dorsal venous complex (DVC) controlling step,
the surgeon used barbed suture ligation to secure the
vascular structures.
Preoperative, perioperative, and postoperative data
consisting of the patient’s demographics, stage of the
disease, operative choice decision, operation details,
pathological report of the excised gland, and follow-up
information were reviewed and analyzed. e positive
surgical margin (PSM), operative time, complication
rate, perioperative blood loss, and blood transfusion
rate were measured and compared among the groups.
The primary objective was defined to compare
perioperative and postoperative outcomes of three
dierent surgical approaches of radical prostatectomy.
e secondary objectives were the identication of factors
associated with PSM and the learning curves of two
minimally invasive approaches.
Shapiro-Wilk test, D’Agostino K2 test, and Anderson-
Darling test to evaluate the distribution of continuous
data. Normally distributed data with mean and standard
deviation were assessed using the Student’s t-test. Non-
normally distributed continuous data with the median
and the interquartile range (IQR) were assessed using
the Kruskal–Wallis test among groups. Categorical data
are reported as the frequency and percentage and were
assessed using the chi-square test. Each type of PSM,
such as multifocal positive surgical margin (MPSM) and
single focal positive surgical margin (SPSM), and the site
of the PSM (i.e., apex, anterior, posterior, bladder neck)
are reported as the frequency in each group and were
assessed using the chi-square test. We also constructed
univariate and multivariate analyses to nd the predictors
responsible for PSM.
Statistical analysis was performed using the Python
statistical packages: SciPy version 1.5.2, lifelines version
0.25.10, and Matplotlib version 3.3.2. Univariate and
multivariate analyses were performed using linear regression
and multiple linear regression via the package statsmodels
version 0.12.0. A p-value less than 0.05 was considered
signicant.
RESULTS
Demographics of the patients’ group by surgical approach
Between January 2002 to June 2016, the author
performed RP on 527 patients, of whom 42 (7.9%) were
assigned to the RRP group, 198 (37.6%) to the LRP
group, and 327 (62.0%) to the RALP group. e median
ages of the patients in each group were 69.5 years old
(IQR 63.3, 73.8), 68 years old (IQR 63.3, 73.0), and 66.4
years old (IQR 60.0, 73.0) for the RRP, LRP, and RALP
groups. e median preoperative serum prostate-specic
antigen levels (PSA) were 15 ng/ml (IQR 5.9, 33.6), 8.5
ng/ml (IQR 5.6, 18.8), and 8.9 ng/ml (IQR 5.9, 16.0),
respectively, for the RRP, LRP, and RALP groups. e
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620
median prostate weights in each group were 46.0 g (32.0,
55.0), 38.8 g (31.0, 53.5), and 39.2 g (30.4, 49.6), respectively,
for the RRP, LRP, and RALP groups. We found no
signicant dierences in age, preoperative PSA, or prostate
weight among the three groups of surgical approaches
(Table 1).
Perioperative blood loss, as one of the evaluation
indexes, was signicantly dierent among the three
groups with a p-value less than 0.01. e median blood
loss in the RRP group was 1200 ml (900, 2000), which
was the worst loss compared to its minimally invasive
surgery (MIS) counterpart. Between the MIS approaches,
LRP had a median blood loss of 800 ml (500, 1300) and
RALP had a loss of 300 ml (200, 550) (Table 1).
The operative times were remarkably different
with a p-value less than 0.01. e most time-consuming
operation was LRP with a median duration of 265 minutes
(215, 310). RALP had a median operative time of 180
minutes (155,220), while RRP still involved the lowest
operative time of 165 minutes (145, 200) (Table 1).
Nerve-sparing attempts were signicantly performed
more frequently in RALP (26.6%) than RRP and LRP (7.1%
and 9.6%, respectively) with a p-value < 0.01. We found
that RRP had a signicantly higher postoperative persistent
PSA rate of 14.3% compared to the other approaches at
6.6% and 4.3% for LRP and RALP, respectively. Patients
with seminal vesicle invasion proportionally underwent the
RRP approach more frequently than any other approach
with a p-value of 0.02, but this proportion between the
two minimally invasive approaches was not signicantly
dierent (Table 2).
Adjuvant therapy was given proportionally the
most frequently in the RRP group (42.9%) compared to
LRP (17.2%) and RALP (28.8%), to cover any residual
tumor at the PSM. Androgen deprivation therapy (ADT),
which comprises bilateral orchidectomy or intramuscular
injection of GnRH agonist, was the most popular selection,
with 42.9%, 16.7%, and 27.8% of patients from the RRP,
LRP, and RALP groups receiving ADT as either a single
treatment or as a part of combination treatment as their
adjuvant therapy. Novel androgen receptor inhibitors
(AR) were rarely given aer RRP (4.8%) and LRP (5.1%)
but were given in 11.9% of patients aer RALP. Radiation
therapy was only given in combination treatment with
ADT and/or AR, which happened in 0.5% and 7.7% of
patients aer LRP and RALP, respectively (Table 2).
TABLE 1. Characteristics of chronic low back pain patients.
RRP (n = 42) LRP (n = 198) RALP (n = 327) P-value
Median IQR Median IQR Median IQR
Age (years old) 69.5 63.3 - 73.8 68 63.3 - 73.0 67 60.0 - 73.0 0.16
PSA (ng/mL) 15 5.9 - 33.6 8.5 5.6 - 18.8 8.9 5.9 - 16.0 0.21
post-op PSA (ng/mL) 0.01 0.00 - 0.06 0 0.00 - 0.03 0 0.00 - 0.01 0.08
Op-time (min) 165 145.0 - 200.0 265 215.0 - 310.0 180 155.0 - 220.0 < 0.01
Hospital stays after 8 7.0 - 10.0 8 7.0 - 9.0 7 7.0 - 8.0 < 0.01
surgery (days)
Highest PSA after 0.1 0.00 - 0.90 0.1 0.01 - 0.56 0.03 0.00 - 0.40 0.39
surgery (ng/mL)
Prostate (g) 46 32.0 - 55.0 38.8 31.0 - 53.5 39.2 30.4 - 49.6 0.33
F/u time (years) 6.8 1.3 - 12.2 6.9 2.6 - 9.3 5.49 2.3 - 8.2 0.01
Blood loss (ml) 1200 900.0 - 2000.0 800 500.0 - 1300.0 300 200.0 - 550.0 < 0.01
node gain 4.5 3.0 - 7.0 7 4.0 - 10.0 6 4.0 - 8.0 0.06
positive node 0 0.0 - 0.0 0 0.0 - 0.0 0 0.0 - 0.0 0.52
Srinualnad et al.
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Original Article SMJ
TABLE 2. Categorical data of patients categorized by the three surgical approaches.
RRP (n = 42) LRP (n = 198) RALP (n = 327) P-value
n % n % n %
NVB sparing
None 39 92.9% 179 90.4% 240 73.4% <0.01
Unilateral 2 4.8% 4 2.0% 31 9.5%
Bilateral 1 2.4% 15 7.6% 56 17.1%
Pathological T stage
0 0 0.0% 10 5.1% 4 1.2% 0.12
2 24 57.1% 103 52.0% 200 61.2%
3a 5 11.9% 55 27.8% 76 23.2%
3b 13 31.0% 30 15.2% 47 14.4%
Pathological N stage
pN0 39 92.9% 190 96.0% 315 96.3% 0.56
pN1 3 7.1% 8 4.0% 12 3.7%
Seminal vesical invasion 13 31.0% 30 15.2% 46 14.1% 0.02
Extra prostatic extension 17 40.5% 81 40.9% 112 34.3% 0.28
Perineural invasion 25 59.5% 134 67.7% 243 74.3% 0.06
Persistent PSA 6 14.3% 13 6.6% 14 4.3% 0.03
Adjuvant therapy
None 24 57.1% 164 82.8% 233 71.3% <0.01
ADT 16 38.1% 23 11.6% 30 9.2%
AR 0 0.0% 1 0.5% 2 0.6%
ADT AR 2 4.8% 9 4.6% 37 11.3%
ADT RT 0 0.0% 0 0.0% 7 2.1%
AR RT 0 0.0% 0 0.0% 1 0.3%
ADT AR RT 0 0.0% 1 0.5% 17 5.2%
Immediate complication
Surgical site infection 2 4.76% 0 0.0% 0 0.0% 0.22
Bowel injury 0 0.00% 1 0.5% 1 0.3%
Ureter injury 0 0.00% 1 0.5% 0 0.0%
Hematoma 0 0.00% 1 0.5% 1 0.3%
Other 0 0.00% 0 0.0% 2 0.6%
Delay complication
inguinal hernia 5 11.9% 8 4.0% 27 8.3% 0.05
urethral stricture 3 7.1% 5 2.5% 4 1.2%
incontinence 1 2.4% 5 2.5% 15 4.6%
Gleason score from surgery
6 9 21.4% 47 24.0% 86 27.5% 0.94
3+4 8 19.1% 68 34.7% 116 37.1%
4+3 8 19.1% 34 17.4% 55 17.6%
8 6 14.3% 22 11.2% 23 7.4%
9 11 26.2% 24 12.2% 33 10.5%
10 0 0.0% 1 0.5% 0 0.0%
Abbreviations: ADT; Androgen deprivation therapy: including bilateral orchidectomy and GnRH-agonist injection,
AR; Novel anti-androgen receptor therapy, RT; Radiation therapy.
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Factors responsible for a positive surgical margin rate
According to Table 3, only the negative surgical
margin rate (NSM) and MPSM rate were signicantly
dierent among the surgical approaches, with a p-value
less than 0.05. RALP had the highest NSM rate (68.8%)
and the lowest MSPM rate (10.7%), while RRP remained
on the worst side with a 50.0% NSM and 28.6% MPSM.
Having categorized SPSM into specic sites where
the PSM resides, we found that the statistical analysis
did not nd a signicant dierence for the PSM sites
among the three approaches, and the most common site
of SPSM was at the apex of the prostate for all approaches
(11.9% in RRP, 20.2% in LRP, 20.2% in RALP).
While the frequency of patients with each pathological
T staging (pT) was not signicantly dierent among
the three approaches (Table 2), the PSM rates were.
We detected signicantly higher odds ratios of PSM in
the pT3a and pT3b stages compared to the pT2 stage
in both the univariate and multivariate models, with a
p-value less than 0.001 (Table 4).
e nerve-sparing technique was attempted signicantly
more frequently in RALP than in the other surgical
approaches, with a p-value less than 0.01 (Table 2). e
data on the univariate analysis showed that the bilateral
nerve-sparing technique might lower the PSM rate, with
an odd ratio of 0.40, 95% condence interval -1.53 to
-0.30, and p-value of less than 0.01, but the multivariate
analysis proved otherwise (Table 4).
Learning curve
e split method was used to analyze the learning curves
of the surgeon for all approaches of RP, as presented in
Table 5. e 567 patients in total were split into two groups
chronologically. Perioperative blood loss, transfusion rate,
and NSM all improved over time. Delay complications
were the only group that did not seem to be related to
the surgeon experience. According to Table 2, the most
common delay complication encountered was an inguinal
hernia, which is common in 50–69-year-old men.14
Furthermore, subgroup learning curve analysis was
performed, especially for the minimally invasive surgery
platform, as shown in Fig 1. e factors focused on were
perioperative blood loss, number of cases that received
blood transfusion, surgical margin status, hospital stay
aer surgery, and number of dissected lymph nodes.
In Fig 1, it can be seen that both the perioperative
blood loss and transfusion rates showed a relative decrease
with the increasing experience of the surgeon in the
RALP approach, whereas the LRP approach group still
had relatively high perioperative blood loss and needed
transfusions more oen than for RALP. By the time the
surgeon’s RALP experience had reached the 90th case,
the transfusion rate was almost reduced in half. LRP
still needed experience from over 100 cases to show a
reduced transfusion rate.
For the positive surgical margin, the RALP learning
curve suggested it would take around 90-120 cases to
achieve a plateau, which was faster than for LRP. However,
LRP was able to achieve a lower PSM rate than RALP in
the rst 100 cases (Fig 1).
In terms of the operative time, the learning curve
had already taken place at 30–60 cases of RALP and
continued to reduce to a plateau at the 200th case. LRP
also could reduce the operative time within the rst 100
cases, but it could not match RALP’s slope, as shown in
Fig 1.
TABLE 3. Frequency of PSM among the three surgical approaches.
RRP (n = 42) LRP (n = 198) RALP (n = 327) P-value
n % n % n %
Negative SM 21 50.0% 127 64.1% 225 68.8% 0.04
SPSM 10 23.8% 67 33.8% 129 39.5% 0.09
Apical 5 11.9% 40 20.2% 66 20.2% 0.43
Posterior 3 7.1% 10 5.1% 31 9.5% 0.18
Posterolateral 0 0.0% 1 0.5% 2 0.6% 0.87
Anterior 0 0.0% 1 0.5% 7 2.1% 0.22
Bladder neck 1 2.4% 15 7.6% 23 7.0% 0.47
Vas Deferens + Seminal Vesicle 1 2.4% 0 0.0% 0 0.0%
MPSM 12 28.6% 29 14.7% 35 10.7% < 0.01
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TABLE 4. Univariate and multivariate analyses of the risk factors for PSM.
Univariate analysis Multivariate analysis
Crude OR (95% CI) P-value Adjusted OR (95% CI) P-value
Surgical approach
RRP 1(ref) 1(ref)
LRP 0.6(-1.3, 0.1) 0.089 0.7(-1.1, 0.5) 0.399
RALP 0.5(-1.4, -0.1) 0.017 0.7(-1.2, 0.4) 0.343
Gleason score
6 1(ref) 1(ref)
3+4 3.8(0.7, 1.9) <0.001 2.3(0.2, 1.5) 0.012
4+3 3.9(0.7, 2.0) <0.001 2.2(0.04, 1.5) 0.037
8 11.3(1.7, 3.2) <0.001 5.9(0.9, 2.6) <0.001
9 20.3(2.3, 3.8) <0.001 6.9(1.1, 2.8) <0.001
NVB sparing
None 1(ref) 1(ref)
Unilateral 0.5(-1.6, 0.03) 0.058 0.5(-1.6, 0.4) 0.211
Bilateral 0.4(-1.5, -0.3) 0.004 0.6(-1.2, 0.2) 0.148
Pathological T
pT2 1(ref) 1(ref)
pT3a 4.4(1.1, 1.9) <0.001 3.1(0.6, 1.6) <0.001
pT3b 8.8(1.7, 2.7) <0.001 3.6(0.6, 1.9) <0.001
PSA (ng/ml)
<10 1(ref) 1(ref)
10 to 20 1.3(-0.2, 0.7) 0.280 0.9(-0.6, 0.5) 0.791
>=20 3.8(0.9, 1.8) <0.001 1.3(-0.3, 0.8) 0.356
Prostate volume (g)
<25 1(ref)
25 to 50 0.9(-0.8, 0.5) 0.638
50 to 75 0.6(-1.3, 0.2) 0.150
>=75 0.8(-1.1, 0.6) 0.602
TABLE 5. Split method analysis of the learning curves
Outcome First half (n = 284) Later half (n = 283) P-value
NSM (n, %) 157 55.5% 216 76.1% <0.05
SPSM (n, %) 109 38.5% 97 34.2% 0.31
MSPM (n, %) 43 15.2% 33 11.6% 0.22
Immediate complication (n, %) 5 1.8% 4 1.4% 0.74
Delay complication (n, %) 25 8.8% 49 17.3% <0.05
Blood transfusion (n, %) 104 36.8% 25 8.8% <0.05
Blood loss (median, IQR) 700 400-1200 350 200-600 <0.05
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Fig 1. Learning curve analyses using perioperative parameters and a subgrouping of every 30 cases
DISCUSSION
Originally when RP was rst developed, patients
were usually diagnosed as having prostate cancer with a
higher clinical and pathological stage due to the lack of
screening serum PSA level. e outcome of the procedure
was described as very poor and played very little part in
the management. Aer the serum PSA level was widely
used as a screening tool, patients could have prostate
cancer diagnosed 7–9 years earlier than previously was
possible, which meant it was more likely to be found in
a curable stage of the disease. Later, Patrick Walsh made
dramatic contributions to the RP eld by sharing a better
understanding of the anatomy of the prostate, which he
described by a cavernous nerve-sparing technique, and
he proposed DVC ligation for early bleeding control.3,15
e procedure then achieved improvements in both safety
and functional outcome. Aer that, the laparoscopic
approach came into play for pelvic lymph node dissection
early on. en, LRP was rst described in 2000.3,16. e
procedure could clearly improve patient recovery but
still could not achieve a comparable functional outcome,
i.e., continence. In the 21st century, RALP was introduced
to the eld. e procedure drove another revolution in
outcome expectations by reducing the transfusion rate
to near zero while requiring only 24 hours hospital stay,
and achieving better functional outcomes in terms of
both continence and sexual function.3
Although the average blood loss of RALP is similar
to the previous publication with a mean of 300 and
IQR of 200-500 mL, LRP is more complicated.10 For
LRP, the step that is majorly responsible for bleeding is
controlling DVC, which could be done in two manners:
suture ligation or endoscopic stapler. In this study,
the surgeon favors the suture ligation technique with
barbed suture material over another technique. Even
though the two techniques shouldn’t make dierence
in estimate blood loss17, two potential reasons might
entitle for more blood loss in LRP group. Firstly, as the
surgeon aimed for preserving urethral length to secure
long-term functional outcomes of the patients, he made
fewer ligations on DVC. With the cruder movement of
LRP, sometimes the suture was slipped and led to more
bleeding. e second explanation associate with tumor
location as apical tumor did increase the diculty of
the dissection step and needed wider excision around
DVC, which directly related to more bleeding.
Regarding Saksirisampant et al, although PSM status
could be inuenced by several preoperative factors, which
were serum PSA level, small prostate, percentage of tumor
volume, pathological T stage, and ISUP Gleason grade
group, it is one of the outcomes that directly demonstrate
one’s surgical skills.18 e surgeon’s always responsible for
the decision making whether to perform wider excision
on which border to compensate for the aggressiveness of
the tumor. Having prostate MRI preoperatively might
help specify tumor’s locations and boundaries, which
aware the surgeon of those areas and eventually reduce
PSM.
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While the oncological outcome result showed
little to no dierence among the three approaches of
RP10,11, outcomes in the perioperative and immediate
postoperative periods, such as blood loss, transfusion
rate, and postoperative hospital stay, were improved
signicantly in RALP. Recent research in the eld suggests
that a single night’s stay or same-day discharge might be
possible for selected patients regarding safety.19,20 Compared
to our study, RALP did show a lower transfusion rate
and minimized the immediate complications, while
our data did not show an extremely shortened hospital
stay due to various reasons, such as institute policy and
the patients’ request. Implementing enhanced recovery
aer surgery (ERAS) protocols might be one solution
that could contribute toward this outcome.21-23
Between the two minimally invasive approaches,
there are many dierences in the way the operations
are performed. LRP uses surgical instruments that need
holding and control directly by the surgeon’s hand in the
surgical eld themselves, whereas RALP has a surgical
robot to hold and move the instruments, which the
surgeon operates from a console in a sitting posture. e
time required to initialize for each operation is obviously
longer in RALP, including the cleaning and docking
time, but the RALP console time could be reduced lower
than in LRP with a more experienced surgeon. While
RALP may lack haptic feedback from the operating
eld, the platform allows the surgeon to operate with
steady tool movement, at ease and in a relaxed manner.
erefore, RALP helps reduce fatigue and minimize
the surgeon’s stress. With a good magnifying view and
precise movement, robotic-assisted surgery eliminates
the need for excellent human eye vision and perfectly
steady human hand movement. erefore, it could extend
the surgeon’s retirement age in terms of overcoming the
physical limitations due to their increasing age.
According to our study, RALP would take around
100 cases to master full PSM control and another 100 cases
to achieve minimal blood loss and operative time, which
was similar to in Song et al. and Kongchareonsombat’s
studies that marked 230 operations experience as needed
for the best bleeding control performance in RALP.24,25
Compared to LRP in the same evaluating matrix, LRP
would take a much longer time to improve the outcome
and would achieve even less. According to Secin et al.,
it would take 200 to 250 cases to nd the plateau for
the PSM rate in the learning curve of LRP.26 Due to
the limitations of our dataset, which consisted of only
198 cases of LRP, our ndings on this issue remain
inconclusive in our study.
Interestingly, the oncological outcome (i.e., PSM)
was poorer in RALP at the beginning of the surgeon’s
expertise. However, aer 100 cases of experience were
gained, the surgeon’s performance in RALP eventually
surpassed LRP with a very surprising steep slope for the
PSM rate. e surgeon’s familiarity with the platform
may play an important role in this nding, because the
loss of tactile sensation, hand-eye coordination process,
and tools handling may not play along with the surgeon’s
expectations in the early phase of their learning experience.
However, aer the surgeon has become more familiar
with the robotic platform and can handle it well, then
the PSM rate is improved.
With the advancement of technology and surgical
options, there might be some questions regarding
whether RRP should be performed in the modern-day.
Despite the improvement in outcomes that RALP may
give, we believe that there is still some role for RRP to
play. For example, barriers to nancial aordability and
accessibility to a minimally invasive surgery platform
should allow RRP to continue thriving in this century. In
some countries where surgical fees may also increase by
the time under anesthesia, a shorter operative time might
have a considerable benecial impact for patients with
nancial problems. erefore, many surgeons still see
benets in the RRP approach and will continue to rene
their skills in this area. Recently, they can even match
some of RRP’s benecial outcomes to the MIS platform,
such as sexual function and continence function.27-29
ere are limitations in learning curve interpretation
including a possible confounder as the author started
performing these three approaches of RP at dierent
times in his career. We believe some surgical experience
could be used as cross-platform knowledge, whereby the
outcome of learning a later proposed surgical approach,
such as RALP, could be confounded by prior experience of
RRP and LRP.30 erefore, the number of cases required
for a surgeon who is a complete novice in minimally
invasive surgery to learn RALP could not be determined
by this study and needs further research.
CONCLUSION
Nowadays, urologists in academic centers have a
high interest in the MIS approach of RP and prefer RALP
most of the time. RALP has clear advantages in disease
control and hospital resource utilization. Here, learning
curve analysis determined that 100 cases of RALP were
the minimal requirement for a surgeon to master the
procedure. However, not all patients can aord such
an operation and cost is a major concern. erefore,
LRP and RRP still play important roles in both service
hospital settings and academic training centers.
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626
ACKNOWLEDGEMENTS
e authors would like to thank Ms. Jitsiri Chaiyatho,
Ms. Julaporn Pooliam, and all the coordinators at Siriraj
Hospital for their important contributions to this study.
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13. Haga N, Takinami R, Tanji R, Onagi A, Matsuoka K, Koguchi T,
et al. Comprehensive approach for post-prostatectomy incontinence
in the era of robot-assisted radical prostatectomy. Fukushima
J Med Sci. 2017;63(2):46-56.
14. Kark AE, Kurzer M. Groin hernias in women. Hernia. 2008;
12(3):267-70.
15. Walsh PC, Donker PJ. Impotence Following Radical Prostatectomy:
Insight Into Etiology and Prevention. J Urol. 1982;128(3):492-7.
16. Ballantyne GH, Moll F. e da Vinci telerobotic surgical system:
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North Am. 2003;83(6):1293-304.
17. Feng T, Heulitt G, Lee JJ, Liao M, Li HF, Porter JR. Randomised
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complex during robot-assisted laparoscopic radical prostatectomy.
BJU Int. 2020;126(5):586-94.
18. Saksirisampant P, Nualyong C, Srinualnad S, Leewansangtong
S, Taweemonkongsap T, Jitpraphai S, et al. Positive surgical
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in ai prostate cancer patients. J Med Assoc ai. 2020;103(5):
68-74.
19. Kotamarti S, Williams T, Silver M, Silver DA, Schulman AA.
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23. Zhao Y, Zhang S, Liu B, Li J, Hong H. Clinical ecacy of enhanced
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24. Song W, Lee SW, Chung JH, Kang M, Sung HH, Jeon HG, et al.
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and retropubic radical prostatectomy in the learning curve of
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25. Kongchareonsombat W. Perioperative Outcomes and the Learning
Curve for Robotic-Assisted Laparoscopic Radical Prostatectomy
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26. Secin FP, Savage C, Abbou C, de La Taille A, Salomon L,
Rassweiler J, et al. e Learning Curve for Laparoscopic Radical
Prostatectomy: An International Multicenter Study. J Urol.
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27. Coughlin GD, Yaxley JW, Chambers SK, Occhipinti S, Samaratunga
H, Zajdlewicz L, et al. Robot-assisted laparoscopic prostatectomy
versus open radical retropubic prostatectomy: 24-month
outcomes from a randomised controlled study. Lancet Oncol.
2018;19(8):1051-60.
28. Pereira R, Joshi A, Roberts M, Yaxley J, Vela I. Open retropubic
radical prostatectomy. Transl Androl Urol. 2020;9(6):3025-35.
29. Yaxley JW, Coughlin GD, Chambers SK, Occhipinti S,
Samaratunga H, Zajdlewicz L, et al. Robot-assisted laparoscopic
prostatectomy versus open radical retropubic prostatectomy:
early outcomes from a randomised controlled phase 3 study.
Lancet. 2016;388(10049):1057-66.
30. Tobias-Machado M, Mitre AI, Rubinstein M, Costa EF,
Hidaka AK. Robotic-assisted radical prostatectomy learning
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Srinualnad et al.
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Original Article SMJ
Chantas Mahaisavariya, M.D.*, Nomina Pradhan, M.D.**, Kongkhet Riansuwan, M.D.**, eerawoot armviboonsri,
M.D.**, Likit Rugpolmuang, M.D.**, Banchong Mahaisavariya, M.D.**, Direk Tantigate, M.D.**
*Golden Jubilee Medical Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Department of Orthopedic Surgery,
Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand.
Risk Factor of Proximal Lag Screw Cut-Out After
Cephalomedullary Nail Fixation in Trochanteric
Femoral Fractures: A Retrospective Analytic Study
ABSTRACT
Objective: A cephalomedullary nail is the treatment of choice for trochanteric fractures; however, a lag screw cut-
out is one of the most devastating complications. e lag screw cut-out rate was reported to be around 2.5%–8.3%.
is study aimed to evaluate the prevalence of lag screw cut-outs and identify the associated risk factors.
Materials and Methods: A retrospective review of 267 trochanteric fracture patients treated with cephalomedullary
nail xation from January 2007 to December 2017 was conducted. e demographic variables were documented,
comprising age, gender, fracture pattern, and AO/OTA classication. Immediate postoperative radiographs were
assessed for quality of reduction and implant position. Lag screw cut-outs or radiographic union were determined
using the nal follow-up radiograph. Prognostic factors associated with lag screw cut-out were determined using
univariate and multivariate logistic regression analyses.
Results: Of the 175 patients, 154 were successfully treated, and 21 had a lag screw cut-out. ere were no signicant
dierences in mean ages or genders of the union and cut-out groups. No lag screw cut-outs were observed in patients
with AO/OTA 31-A1. Patients with AO/OTA 31-B2.1 had a higher rate of screw cut-out (OR 10.5, [3.22, 34.25]
p < .001). e disintegration of basicervical fragments was signicantly associated with lag screw cut-out (OR 5.51,
[2.01, 15.12] p = .001). e highest cut-out rate was found in the superoanterior and superoposterior positions of
the lag screw. However, the screw position did not reach the signicance level in a multivariate analysis (p = .094).
Conclusion: e prevalence of lag screw cut-out aer cephalomedullary nail xation for trochanteric fractures
was 12%. A simple, two-part, basicervical trochanteric fracture hads a signicantly higher risk of lag screw cut-out.
Keywords: Trochanteric fracture; pertrochanteric fracture; hip fracture; cut-out; cephalomedullary nail (Siriraj
Med J 2022; 74: 627-633)
Corresponding author: Direk Tantigate
E-mail: dtantigate@gmail.com
Received 22 June 2021 Revised 29 June 2022 Accepted 4 July 2022
ORCID ID: http://orcid.org/0000-0002-3502-8252
http://dx.doi.org/10.33192/Smj.2022.74
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Hip fracture is one of the common osteoporotic
fractures in the geriatric population. Surgical treatment
can reduce mortality and improve patients’ quality of
life.1-5 A cephalomedullary nail is the treatment of choice
for trochanteric fractures, oering superior biomechanical
stability to a sliding hip screw.2,6 However, a lag screw
cut-out is one of the most devastating complications,
causing diculties for reoperations or hip replacements.7,8
e risk factors associated with lag screw cut-outs
have been reported in recent studies. As well as patient
factors-age, bone mineral density (BMD) and fracture
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conguration-the xation technique strongly inuences
the outcomes.7,9-11 e tip-apex distance (TAD) is the most
commonly used parameter to determine the prognosis
of a lag screw cut-out.12
Even though implant development has tended
to match the conguration of a proximal femur, the
reported lag screw cut-out rate is still around 2.5% - 8.3%,
according to the previous study.2 is study aimed to
evaluate the prevalence of lag screw cut-outs and identify
the associated risk factors.
MATERIALS AND METHODS
A retrospective review was conducted of all patients
admitted with a trochanteric fracture between January
2007 and December 2017. Only those patients treated
with a short cephalomedullary nail (Natural Nail system
cephalomedullary nails, Zimmer) with no additional
xation were enrolled. e exclusion criteria were: (1)
a patient was treated with other implants; (2) a patient
had a pathologic fracture; (3) the pre-or postoperative
radiograph was not present in a patient’s medical records;
(4) a patient was lost to follow-up before the fracture
union or screw cut-out; and (5) a patient had a peri-
implant fracture.
e demographic data recorded were age, gender,
and fracture classification. Based on the AO/OTA
classication system13, the patients were grouped into
31-A1, 31-A2, 31-A3, and 31-B2.1. e preoperative
radiographs were reviewed by two investigators (MC
and PN), who recorded the following data: (1) lateral
buttress fragment-anatomically dened as the lateral
femoral cortex distal to the vastus ridge in the trochanteric
region10; (2) posteromedial fragment-represented by the
calcar femorale. e integrity of the lesser trochanter was
used as evidence of the presence or absence of the calcar
femorale14; and (3) basicervical fragment-the fracture line
separating the proximal fragment at the intertrochanteric
line, corresponding with AO/OTA classication 31-B2.1
(Fig 1). Data from both investigators were compared for
inter-observer reliability. Disagreements regarding the
result of the measurements were resolved by a third-
person review.
e following parameters were measured in the
immediate postoperative radiographs: (1) TAD in the
anteroposterior (AP) and lateral view; (2) the medial gap
aer reduction; (3) the postoperative neck-sha angle;
(4) the position of the lag screw in the AP view-dened
as inferior, centered and superior; (5) the position of
the lag screw in the lateral view-dened as posterior,
centered and anterior; (6) the number of distal locking
screws; and (7) the mode of distal locking. e TAD
measurement was obtained using the Baumgaertner
method.1 In this, an imaginary line was drawn parallel
to the femur neck, dividing it into superior and inferior
portions. e position of the lag screw was recorded
using this line as a reference. If the line bisected the
screw, the position was recorded as centered.1 e lateral
radiograph used the same method but labeled the positions
as posterior, centered, and anterior.
e radiograph with a minimum of 3 months follow-
up was measured again when the patient met the endpoint
of xation-union or cut-out. e fracture was labeled as
“union” if the bone bridge was present in both the AP
and lateral views. If the last follow-up lm did not have
a lateral view, the presence of both the medial and lateral
bone bridges in the AP view was labeled as a union.4,5,7,15
Alag screw cut-outwas dened as a protrusion of the
screw past the subchondral bone on either the AP or
lateral projection (Fig 2).8,16 Medial migration of the
screw past the subchondral bone-recently called “axial
migration”-was also labeled as a cut-out.8
Statistical analysis
e sample size calculation was based on a report on
lag screw cut-outs, which indicated that they represented
about 10% of the overall population.7 A minimum of
139 patients was needed to demonstrate a 10% lag screw
cut-out prevalence with a 95% condence interval and
5% allowable error. Statistical analyses were performed
Fig 1. Integrity of specic fragment: Lateral buttress fragment (L),
Posteromedial fragment (PM), Basicervical fragment (B)
Mahaisavariya et al.
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Original Article SMJ
Fig 2. Le e radiograph of the aected hip in AP view shows proximal screw cut-out. e proximal screw cut through superolateral aspect
of the femoral neck. Right e radiograph of the aected hip in the Lateral cross-table view shows proximal screw protrusion past the anterior
aspect of the subchondral bone of the femoral head.
using IBM SPSS Statistics for Windows, version 20
(IBM Corp., Armonk, N.Y., USA). e chi-square and
independent t-test were used for univariate analyses of
the categorical and continuous parameters, respectively,
with the signicance level (p)< .05. A multivariate analysis
was performed for all parameters withp< .2.
e inter-observer reliability was calculated for the
parameters identied as signicant in the univariate analysis.
A two-way random-eects model with a 95% condence
interval was used to determine the measurements’ intra-
class correlation coecient (ICC). e ICC interpretation
scale used was poor to fair (< 0.4), moderate (0.41 to
0.60), excellent (0.61 to 0.80) and almost perfect (0.81 to
1). For categorical data, the κ coecients were calculated
using the same interpretation scale as for the ICC.
RESULTS
Between January 2007 and December 2017, 267
patients diagnosed with a trochanteric fracture treated at
Siriraj Hospital, Bangkok, ailand, with cephalomedullary
nails were enrolled. Of those, 92 were excluded: the
preoperative radiograph was missing for 7 patients; 6
had a pathologic fracture; the endpoint was unable to be
determined for 10 patients due to incomplete radiographs,
and 69 were lost to follow-up aer discharge from the
hospital. e total number of patients included in this
study was 175; 154 were successfully treated with a
radiographic union of the trochanteric fracture, while
21 (12%) had a lag screw cut-out.
e demographic data are summarized in Table 1.
ere were no signicant dierences in the mean ages or
the gender proportions of the union and cut-out groups.
However, the fracture classications of the groups were
signicantly dierent, with all patients with AO/OTA 31-
A1 having been successfully treated without a lag screw
cut-out, whereas one-third of the patients with AO/OTA
31-B2.1 experienced a lag screw cut-out. e T-scores
of BMD were only available for 40 patients due to the
surgeons’ judgment to forego a further investigation.
Concerned that a large amount of missing data would
reduce the study’s statistical power, the authors excluded
this factor from the multivariate analysis, notwithstanding
that it reached a statistically signicant level (p= .048).
All recorded parameters were evaluated in univariate
analysis for an association with lag screw cut-out; the
results are in Table 2. e integrities of the basicervical
fragment fractures of the union and cut-out groups were
statistically signicantly dierent (p= <.001). However,
the lateral buttress and posteromedial fragment fractures
of the two groups showed no significant difference
(p= 1.0 and .064, respectively).
e postoperative lag screw positions were evaluated
in the AP and lateral projections. e screw placement
was divided into nine zones (Fig 3). e screws were
most frequently placed in the inferoposterior zone. e
lowest rate of cut-outs occurred in the center-inferior
zone, while the highest cut-out rate was found in the
peripheral area, in the superoanterior and superoposterior
positions. However, aer comparing the cut-out rate
of each zone, no statistical significance was found
(p = .053).
An inter-observer reliability test was performed on
the factors withp< .2 before a multivariate analysis was
carried out; all factors demonstrated good inter-observer
reliability (Table 3). e results of the multivariate regression
analysis are in Table 4. e integrity of the basicervical
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TABLE 1. Summary of demographic data.
TABLE 2. Summary of associated factors evaluated in univariate analysis.
Factor All (n=175) Union (n=154) Cut-out (n=21) P-value
Age 80.45 ± 10.17 80.21 ± 10.01 82.24 ± 11.35 .39
Gender .62
Male 31.4% (55) 32.5% (50) 23.8% (5)
Female 68.6% (120) 67.5% (104) 76.2% (16)
Fracture classication <.0001
31-A1 8.6% (15) 9.7% (15) 0%
31-A2 75.4% (132) 77.3% (119) 61.9% (13)
31-A3 8% (14) 8.4% (13) 4.8% (1)
31-B2.1 8% (14) 4.5% (7) 33.3% (7)
Total T-score of hip BMD* -2.6 ± 1.0 -2.4 + 1 -3.3 + 0.7 .048
*Data were available for only 40 out of the total of 175 patients.
Factor All (n=175) Union (n=154) Cut-out (n=21) P-value
Lateral buttress fracture 18.3% (32) 18.2% (28) 19% (4) 1.0
Posteromedial fragment fracture 80% (140) 81.8% (126) 66.7% (14) .142
Basicervical fragment fracture 20% (35) 15.6% (24) 52.4% (11) <.001
TAD* 19.62±5.53 19.53±5.48 20.3±5.97 .56
Neck-shaft angle 137.25±7 137.15±6.75 137.95±8.79 .62
Medial gap 2.07±2.4 2.04±2.35 2.27±2.71 .68
Distal locking screw .62
Single screw 93.7% (164) 94.2% (145) 90.5% (19)
Two screws 6.3% (11) 5.8% (9) 9.5% (2)
Distal locking mode .49
Static 54.3% (95) 53.2% (82) 61.9% (13)
Dynamic 45.7% (80) 46.8% (72) 38.1% (8)
*Post-operative lateral lms were retrieved for 143 patients. e missing data were not included in the analysis.
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Fig 3. Summary of screw position: e total number of
screws in each position was represented by the denominator,
and the number of the screw(s) cut-out was represented
by the numerator. Post-operative lateral lms were retrieved
for 143 patients. e missing data were not included in
the analysis.
TABLE 3. Summary of inter-observer reliability tests.
TABLE 4. Summary of multivariate analyses by odds ratio.
Factor Measure of agreement (κ)
Fracture classication 0.932
Posteromedial fragment fracture 0.888
Basicervical fragment fracture 0.982
Screw position 0.867
Factor P-value Odds ratio 95% condence interval
for odds ratio
Fracture classication <.001 10.5 [3.22, 34.25]
Posteromedial fragment fracture .62
Basicervical fragment fracture .001 5.51 [2.01, 15.12]
Screw position .094
fragment fractures and the fracture classication reached
a signicant level. ose patients with AO/OTA 31-B2.1
had a signicantly high rate of lag screw cut-out (OR
10.5, [3.22, 34.25]p< .001). e disintegration of the
basicervical fragments was associated with lag screw
cut-out (OR 5.51, [2.01, 15.12] p = .001), whereas neither
posteromedial fragments nor the lag screw position
showed a signicant association.
DISCUSSION
e xation of choice for trochanteric fractures has
shown a paradigm shi toward cephalomedullary nails
(CMNs) from sliding hip screws (SHSs).8 e advantages
of CMNs include; more biomechanical stability, less
invasive, and safer for early weight-bearing ambulation
than SHSs.2 Another factor encouraging using CMNs
instead of SHSs is the fracture conguration.2,4 To date,
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the fragments associated with xation failure in SHS are
posteromedial and lateral buttress fragments.10 With the
size of the geriatric population steadily growing, patients
with trochanteric fractures increasingly present with
osteoporotic bones and comminuted congurations.
With such complex fracture congurations, xation
with an SHS has a higher failure rate than with a CMN.
Although the design of CMNs has improved over
several generations, the xation failure rate remains
nearly the same. Our study showed a cut-out rate of
12%, which was similar to that reported by another
study. Aside from the patient factors, surgical technique
plays an important role in predicting the outcomes. e
tip-apex distance (TAD) has been proposed to predict
a failed SHS or CMN xation.1,4,9 With this concerning
factor of TAD, careful placement of lag screw during
surgery was attempted in all cases of this series; patients
in both groups treated in our institute had a mean TAD
value of 20 mm. us, our study revealed no signicant
association between the TAD and lag screw cut-outs.
Reduction quality also plays a vital role in achieving bone
union. Varus mal-reduction or wide posteromedial gap
resulted in unstable xation and increased the cut-out
rate. is study’s overall reduction quality was good to
excellent, with minimal medial gap and slightly valgus
neck-sha angle. From this result, the authors conclude
that the surgical technique was appropriate in both the
union and cut-out groups, with an insignicant dierence
in the reduction quality.
Proximal screw position also has been reported to
have an association with lag screw cut-outs. e most
common direction of the cut-outs in the anterosuperior
portion of the femoral head17,18; although placing the
screw in this position might increase the risk of lag screw
cut-outs, the results of the multivariate analysis in this
study did not reach the signicant level.
Most hip fragility fractures tend to be comminuted,
classied as AO/OTA 31-A2. About half of the patients
with a lag screw cut-out fall into this classification.
eoretically, a complex fracture conguration tends
to give poor results aer xation.4,7,8 Interestingly, when
the proportions of unions to cut-outs are compared,
simple basicervical trochanteric fractures-classied as
31-B2.1-have a 50% cut-out rate, while comminuted
fractures have only a 9.8% cut-out rate. In our study,
simple trochanteric fractures-AO/OTA 31-A1-showed
promising results with cephalomedullary nails, with zero
cut-outs. Aer analyzing specic fragment integrity,
the authors found an association between basicervical
fragment fractures and ve times the odds of a lag screw
cut-out. Based on this result, the authors believe that a
specic fragment has more inuence on the results than
the comminution of fracture.
Bone mineral density has been reported as a factor
associated with lag screw cut-outs.2 Osteoporosis decreases
the density of the cancellous bone in the femoral head
and decreases the pull-out strength aer xation, which
results in xation failure. e current study showed a
signicant association with BMD; nevertheless, due to the
large amount of missing data that would have resulted
in an underpowered analysis, the authors cannot draw
any conclusions about the eects of BMD on lag screw
cut-outs.
e dilemma in choosing a xation implant probably
stems from the intraoperative additional fragment fracture.
Because lateral buttress disintegration can cause a xation
failure if SHS is chosen, an intraoperative lateral wall
fracture in the osteoporotic bone can be a signicant
drawback, inuencing surgeons to choose CMN xation.
e most suitable treatment for basicervical fractures
is a contentious issue. Because the fracture line stays
between the femoral neck and the intertrochanteric
region, the treatment can be either for a femoral neck
or a trochanteric fracture. A previous study described
this area as an “extracapsular area,” which should be
considered for treatment as a trochanteric fracture.19 Still,
as the conguration is comprised mainly of the femoral
neck, the motion of the basicervical fragment aer xation
behaves as a femoral neck fracture with high rotational
instability. Massoud19 reported an excellent result with
no cut-out of the lag screw using SHS combined with a
derotation screw as the xation of choice for this type of
fracture as it provides an interfragmentary compression
eect along with rotational stability via the additional
screw. e results of the present study support this
concept since the CMN did not provide a lag eect, and
there was no room for an additional screw to improve the
rotational stability, resulting in a higher rate of lag screw
cut-out aer xation for simple basicervical fractures.
e rate of screw cut-out for basicervical fractures was
also higher than those for other types of trochanteric
fractures in a large case series of trochanteric fracture
xations using a gamma nail, reported by Bojan et al.7
Recently, Yoo et al. and Yoon et al. have also reported
that the basicervical fracture is the most important risk
factor for the cut-out problem of cephalomedullary nail
xation in treating the trochanteric fracture in their case
series.20,21 Our ndings also support the awareness of
using cephalomedullary nails in basicervical fractures. We
believe such a gray-zone fracture should be considered
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dierently from the typical neck or trochanteric fracture.
Further investigation for an appropriate xation device
or design should be considered.
e limitations of this study are its retrospective
design, the sizeable proportion of excluded patients, and
the small number of patients with lag screw cut-outs.
e overall trochanteric fracture patient admitted to
Siriraj Hospital was about 100 cases per year. Due to
the strict criteria, only the patient who received surgical
treatment with short CMN were included, resulting in
only about 26 cases per year. ose patients who were
lost to follow-up possibly moved to another province
or may have been inconvenient to visit the hospital.
CONCLUSION
The prevalence of lag screw cut-outs after
cephalomedullary nail xation for trochanteric fractures
was 12%-a simple, two-part, basicervical trochanteric
fracture has a signicantly higher risk of a lag screw
cut-out. Using a CMN xation for basicervical fractures
should be avoided.
Disclosure
No benets in any form related directly or indirectly
to the subject of this article have been received or will
be received from a commercial party
REFERENCES
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e value of the tip-apex distance in predicting failure of
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2. Lorich DG, Geller DS, Nielson JH. Osteoporotic pertrochanteric
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5. Lobo-Escolar A, Joven E, Iglesias D, Herrera A. Predictive
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6. Riansuwan K, Jivasomboonkul S, Phimolsarnti R,
Chandhanayingyong C, Asavamongkolkul A. Outcomes of
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7. Bojan AJ, Beimel C, Taglang G, Collin D, Ekholm C, Jönsson A.
Critical factors in cut-out complication aer Gamma Nail
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8. Stern LC, Gorczyca JT, Kates S, Ketz J, Soles G, Humphrey
CA. Radiographic Review of Helical Blade Versus Lag Screw
Fixation for Cephalomedullary Nailing of Low-Energy
Peritrochanteric Femur Fractures: ere is a Dierence in
Cutout. J Orthop Trauma. 2017;31(6):305-10.
9. Kashigar A, Vincent A, Gunton MJ, Backstein D, Sar O, Kuzyk
PR. Predictors of failure for cephalomedullary nailing of
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10. Palm H, Jacobsen S, Sonne-Holm S, Gebuhr P. Integrity of the
lateral femoral wall in intertrochanteric hip fractures: an important
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11. Kane P, Vopat B, Heard W, akur N, Paller D, Koruprolu S,
et al. Is tip apex distance as important as we think? A biomechanical
study examining optimal lag screw placement. Clin Orthop
Relat Res. 2014;472(8):2492-8.
12. Davis TR, Sher JL, Horsman A, Simpson M, Porter BB, Checketts
RG. Intertrochanteric femoral fractures. Mechanical failure
aer internal xation. J Bone Joint Surg Br. 1990;72(1):26-31.
13. Marsh JL, Slongo TF, Agel J, Broderick JS, Creevey W, DeCoster
TA, et al. Fracture and dislocation classication compendium
- 2007: Orthopaedic Trauma Association classication, database
and outcomes committee. J Orthop Trauma. 2007;21(10 Suppl):
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14. Wroblewski BM, Siney PD, Fleming PA, Bobak P. e calcar
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15. De Bruijn K, den Hartog D, Tuinebreijer W, Roukema G.
Reliability of predictors for screw cutout in intertrochanteric
hip fractures. J Bone Joint Surg Am. 2012;94(14):1266-72.
16. Ciufo DJ, Zaruta DA, Lipof JS, Judd KT, Gorczyca JT, Ketz
JP. Risk Factors Associated With Cephalomedullary Nail
Cutout in the Treatment of Trochanteric Hip Fractures. J
Orthop Trauma. 2017;31(11):583-8.
17. Ehmke LW, Fitzpatrick DC, Krieg JC, Madey SM, Bottlang M.
Lag screws for hip fracture xation: Evaluation of migration
resistance under simulated walking. J Orthop Res. 2005;23(6):1329-
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Orthop. 2010;34(4):577-82.
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21. Yoon JY, Park S, Kim T, Im GI. Cut-out risk factor analysis aer
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634
Ravit Ruangtrakool, M.D.*, Oranuch Pruetipibultham**
*Department of Surgery, Faculty of Medicine Siriraj University Hospital, Mahidol University, Bangkok, ailand, **Graduate School of Human
Resource Development, National Institute of Development Administration (NIDA), Bangkok, ailand.
Comparative Study Regarding Autonomy of
Final-Year Surgical Residents: A Case Study of
Perception among Surgical Residents, Surgical Staff,
Administrators, and Patients at Siriraj University
Hospital
ABSTRACT
Objective: To identify barriers towards resident autonomy as perceived through four groups; surgical residents,
surgical sta, administrators, and patients.
Materials and Methods: Anonymous surveys were distributed to these four groups. Data were thematically analyzed.
Results: 401 responses were collected including 231 patients. e response rate of residents, surgical sta, and
administrators was 62.2% (119), 44.8% (26), and 43.1% (25) respectively. Patients had more favorable views of
resident participation than administrators and surgical sta. Administrators and surgical sta indicated that
residents have a positive eect on overall quality of care provided and so do the patients, however, administrators
and surgical sta believed that too much autonomy for a resident deceased patient safety. When resident autonomy
increased, increased cost of patient care was considered. Residents and patients have the same opinion that patients
should receive a discount on medical expenses, which is opposite to administrators’ and surgical sta’s opinion.
e presence of surgical sta in the operation room had a major impact on resident autonomy and a big inuence
on patient acceptance of operative complications. Even in complicated operations, most patients felt comfortable
having a resident perform on with surgical sta controlling the operation. Surgical sta provided too much direction
in either patient care or operation and did not take residents’ input as seriously as expected and seldom explained
the reasons before changing treatment regimens.
Conclusion: Surgical residents, surgical sta, and patients had discordant perceptions of resident autonomy in many
aspects. Self-determination theory should be applied. Scaolding strategy, mentoring program would be the solutions.
Keywords: Autonomy; independence; resident; surgery (Siriraj Med J 2022; 74: 634-649)
Corresponding author: Oranuch Pruetipibultham
E-mail: oranuch.p@nida.ac.th
Received 9 May 2022 Revised 8 September 2022 Accepted 9 September 2022
ORCID ID:http://orcid.org/0000-0003-1037-5730
http://dx.doi.org/10.33192/Smj.2022.75
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Currently, the problem of a lack of surgical skills,
including pre- and post-operative care is being studied.
is could possibly be the result of the fact that surgical
residents have little opportunity to care for patients
requiring surgery from the time they are a medical
student.1 More importantly, during the period in which
surgical residents practice in provincial hospitals aer
completing their MD, they do not have the opportunity
to practice surgical skills.2 Another factor to consider is
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that the Department of Surgery, the Faculty of Medicine
at Siriraj Hospital oers various training opportunities
in various sub-disciplines following the completion of
the Diplomate of the ai Board of Surgery. ese sub-
disciplines take another one to two years to complete.
is means surgical residents who have not completed
the Diplomate of the ai Board of Surgery before, lose
the opportunity to develop surgical skills and techniques
required in pre and post-operative care. Such problems
do not occur only in ailand, but also in the United
States as well.3
e ability of surgical residents to have autonomy
from surgical sta plays a very important role in the
skills needed to train capable surgeons. Once surgical
residents have autonomy, they are more willing to take
on responsibility and work hard to become capable
surgeons. Any competent and skilled surgical resident
to care for surgical patients will be accepted by surgical
sta and then this surgical resident would be given the
autonomy to make treatment decisions and operate on
patients. However, surgical residents who do not take
care of patients or do not have the required surgical
skills as expected of a sta member, will not be given
autonomy, which can lead to an inability to develop
skills in caring for patients and surgical techniques.
Without the trust of surgical sta, a resident will not
be allowed to operate by himself or herself. Hence, the
skills of a surgical resident to care for a patient cannot be
developed. Sterkenburg et al4 reported that when surgical
residents are given greater autonomy than they expected
to make treatment decisions, they are more condent
in learning, maintaining, and practicing which leads
to increased competency. A review by Kempenich JW5
stated that 47% of surgical residents and 38% of surgical
sta commented that surgical residents did not have
sucient independence to make treatment decisions.
Factors aecting the lack of autonomy and/or lack
of surgical residents’ independence in decision making
were reviewed.
1. Perspectives of surgical sta who teach and train6
1.1 Surgical treatment. If a surgical resident is
capable and has good surgical skills, he/she is given
the autonomy to operate on a patient. However, this
depends not only his/her surgical skill, but also on the
diculty of the procedure.5,7 On the other hand, surgical
residents who don’t have the skills to perform a dicult
operation should not be given the autonomy to perform
operations on their own.
1.2 Pre and post-operative care. Any surgical
resident who doesn’t have the skill to handle pre and
post-operative care of patients, is not given autonomy by
surgical sta, making it impossible to develop the skills
needed to care for patients. e more trust surgical sta
have in a resident, the greater the likelihood of surgical
residents developing adequate skills.6,8
2. Administrator’s perspective
Administrators were more likely to prevent the
degree of autonomy surgical residents expected.5 It may
be related to the following factors:
2.1. Finance and reimbursement. e administrator
has to limit payments of surgical treatments. ere are
many sources of reimbursement, such as the ailand
National Health Services, Social Security Fund, or other
measures. If surgical residents have too much autonomy,
it will increase cost of treatment, either due to prolonged
operative time and costs incurred because of an increase
in complications caused by surgical residents. On the
contrary, the administrator has the duty to strike a balance
between autonomy of surgical residents as well as costs
incurred by them. Financial issues are another factor in the
regulation of autonomy aorded to surgical residents.9,10
2.2. Legal prosecution. If a surgical resident was
granted too much autonomy without adequate supervision,
a decision-making error or mistake in surgical technique
can lead to a civil or criminal case. erefore, legal
prosecution is another factor to consider when regulating
the autonomy of surgical residents.11
2.3. Regulation of resident training standards.
Regulatory systems aim to manipulate the ability of
surgical residents during training such as those established
by the Royal College of Surgeons of ailand, Advanced
Hospital Accreditation or other standards like the World
Federation for Medical Education (WFME). ese factors
relate to the autonomy of surgical residents and dene
what they can and cannot do during any operation.12
Some regulations of resident training standards
also encourage surgical sta to remain in the operating
room at all times while the resident is performing the
operation on his/her own, which further leads to reduced
autonomy of surgical residents.9,12
3. Patient and relatives’ point of view
3.1. Safety was considered by patients and their
relatives. e patient and their relatives view the presence
of a surgical resident to have an eect on safety.13 According
to the Kempenich JW5 study, 95% of patients felt good to
have a surgical resident taking part in the care process.
3.2. Complexity of the procedure. e complexity
and diculty of the operation was a major consideration.
Patients become worried if surgical residents are allowed
to perform complex operations.5 Kim HN, et al14 reported
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636
on patients who received a hysterectomy by a team of
obstetrics and gynecologists. e study revealed that up to
80% of patients wanted to know to what extent gynecologist
residents would be involved in the operation and how the
gynecologist sta selected this extent. Moreover, 61% of
patients wanted to know which part of the gynecology
operation was performed by gynecologist residents.14
Different points of view between patients and
surgical residents were realized. Although 80.6% of
patients stated that surgical residents should be able to
perform surgeries on their own before graduating from
resident training, only 73.1% agreed to allow nal year
residents to perform a surgery on them even if it was a
basic operation.5
e question of independence mostly focuses on
decision-making and to what extent should surgical
residents be given freedom during surgery. erefore,
the focus of this research is to compare the viewpoints of
surgical decision-making among relevant stakeholders,
namely surgical residents, surgical sta, administrators,
and patients and relatives. e results of the study look
at factors aecting the autonomy of surgical residents
and could be used as academic information to formulate
a policy for the surgical resident training program at the
Faculty of Medicine, Siriraj Hospital, Mahidol University.
MATERIALS AND METHODS
Siriraj Institutional Review Board Approval (Si
812/2021) was obtained before commencement of the
study. For this study, four questionnaires were created
to determine how much autonomy and independence in
regards to decision-making should surgical residents be
given during an operation to compare the perceptions of
relevant stakeholders, namely surgical residents, surgical
sta, administrators, and patients and relatives. e
questionnaire was created by modifying the questionnaire
in Kempenich JW5 and Biondi EA6 but the researcher also
added more questions in this survey (see appendix). Each
survey was specic to the appropriate group, but the
questions were similar to those given to other groups for
comparison purposes. A ve-point Likert scale was used
for all questions except two which asked the participants
to rate the degree of appropriate independence on a scale
from 0 to 10 for a second-year resident and a nal year
resident in the process of completing the Diplomate of
the ai Board of Surgery.
e surgical resident and sta surveys contained 23
questions, while the administrator survey had 14 questions
and patient and relative survey had 16 questions. Each
survey was piloted and feedback was solicited from
representative individuals in each group. Responses
from the surgical resident group were collected using
a Google form, while responses from the surgical sta
and administrator groups were collected by mail. Last
but not least, responses from patients and their relatives
were collected directly in person at surgical OPD, and
no personally identiable information was collected.
All responses of all groups were collected anonymously.
ere was no compensation or reward for participation.
Inclusion criteria
1. Surgical resident refers to full-time residents
training in all disciplines at the Department of Surgery,
Faculty of Medicine Siriraj Hospital (190 persons).
2. Surgical sta refers to sta and Clinical Educators
in the Department of Surgery, Faculty of Medicine Siriraj
Hospital who presently teach and train surgical residents
(58 persons). Surgical sta who are members of the
Postgraduate Education Committee of the Department
of Surgery were counted as administrators.
3. e administrator refers to positions that control,
supervise, train surgical residents and regulate patient
safety standards. e administrators include: Head of
Department of Surgery, Head of all divisions of the
Department of Surgery, all members of the Postgraduate
Education Committee of the Department of Surgery,
Associate Dean for Postgraduate Studies, Assistant Dean
for Postgraduate Studies, Director of Siriraj Hospital,
Deputy Director of Siriraj Hospital, Deputy Dean for
Quality Development, Deputy Dean for Human Resources,
Head of Surgical and Orthopedic Nursing, Head of
Operating room Nursing, Head of Disciplinary and
Legal Aairs Unit. e total number of administrators
was 58.
4. e patient refers to the sample of patients and
relatives (over 18), and nonmedical persons receiving
care at the Department of Surgery, Faculty of Medicine,
Siriraj Hospital.
ree experts checked the validity of the content of
questionnaires of surgical residents, surgical sta form,
administrators’ form. e Content Validity Index (CVI)
of these questionnaires was 0.80.
For the reliability of questionnaires, the Cronbach’s
alpha coecient (a) was used, with the researcher setting
an acceptable coecient of 0.70 or higher (H0: α=0.70). e
reliability of questionnaires using the Cronbach’s alpha
coecient (α) was determined in the surgical resident
and surgical sta group, who had a Cronbach’s alpha
coecient of 0.87 and 0.8, respectively. e reliability of
patient and relatives questionnaire was not tested due
to ethical problems.
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Statistical analysis
In regards to descriptive statistics, qualitative data,
including number and percentage was used. A comparison
of scores of relevant questions among surgical residents,
surgical sta, administrators and patients and relatives
was conducted. e responses were compiled for each
survey group, and the median response for each question
calculated. Subsequently, the Kruskal-Wallis test was
used to analyze the distribution of responses between the
survey groups. In cases where a signicant dierence was
identied via the Kruskal-Wallis test, a Dunn Bonferroni’s
post-hoc pairwise comparison test was used to compare
variables among groups.
In certain cases, in which the questions compared two
separate questionnaires, especially from the perception
of surgical resident and surgical sta, the Mann-Whitney
U test was used.
If some questions in the questionnaire regarding
patients and relatives were not comparable to other groups,
the researcher used descriptive statistics to present this
information.
Analysis was done using SPSS Inc or PASW Statistics
for Windows, Version 22.0, released in 2009. All data
was analyzed and determined as statistically signicant
when the p-value was < 0.05.
RESULTS
A total of 401 responses were collected; 119 from surgical
residents, 26 from surgical sta, 25 from administrators,
and 231 from patients and relatives. e response rate
for surgical residents, surgical sta, and administrators
was 62.2%, 44.8%, and 43.1%, respectively. e number
of years of experience working at Siriraj Hospital among
administrators, surgical sta, and surgical residents is
displayed in Table 1. Patients and their relative’s ages
are shown in Table 2.
A. Perception of resident participation on quality of
patient care
1) How welcome resident participation was in the
healthcare process is show in Table 3.
Patients and relatives were more welcoming of
resident participation than administrators, surgical sta
and surgical residents. e Kruskal-Wallis test showed
that there was a statistically signicant dierence in
perception of having surgical residents participate in
patient care among the dierent populations (p < 0.000).
Pairwise comparisons using the Dunn Bonferroni test
revealed that patients and relatives had a signicantly
higher rating for patient involvement than administrators
(p = 0.031), surgical sta (p = 0.020), and surgical residents
(p < 0.000). is indicated that patients and relatives
have more favorable views of resident participation
in patient care than administrators and surgical sta.
Surgical residents do not realize how welcoming patients
and relatives are of their participation during treatment.
e eect on overall quality of care when a surgical
resident was involved in the patient care process in the
hospital either in OPD, IPD, or in the operating room
is shown in Table 4.
When patients and relatives were asked whether
quality of care was better with residents involved, 80.9%
agreed or strongly agreed and only 3.6% strongly disagreed
or disagreed.
2) A comparison of perception amongst administrators,
surgical sta, and surgical residents was done to understand
the eect of resident participation on quality of care
provided. It was divided into two aspects, OPD/IPD
and operation room.
In both the OPD/IPD and operating room comparison,
the Kruskal-Wallis test showed a statistically signicant
difference in quality-of-care perception among the
dierent populations (administrators, surgical sta,
and surgical residents) with a p-value of <0.000. In OPD/
IPD, pairwise comparisons using the Dunn Bonferroni
test revealed administrators and surgical sta reported
signicantly higher eects on overall quality of care
provided in hospitals than surgical residents (p = 0.006 and
p < 0.000 respectively). In the operating room, pairwise
comparisons using the Dunn Bonferroni test revealed
administrators and surgical sta rated a signicantly
higher effect in the hospital than surgical residents
(p < 0.000 and p < 0.000), respectively.
is information indicates that surgical residents
have a positive eect on the overall quality of care in
patient care. is valuable eect on overall quality of
care was realized and admired by all stakeholders, with
the exception of surgical residents themselves.
3) Increasing resident autonomy has impacts on
patient safety.
Whether increasing resident autonomy has an
impact on patient safety is demonstrated in Table 5.
The Kruskal-Wallis test showed a statistically
signicant dierence in perception in whether increasing
resident autonomy would impact on patient safety among
dierent populations (administrators, surgical sta,
and surgical residents) with a p-value = 0.001. A Dunn
Bonferroni’s post-hoc pairwise comparison test was
performed (administrator – surgical resident, pairwise
comparison p = 0.021, surgical sta – surgical resident,
pairwise comparison p = 0.027). is information indicated
that surgical residents believed the more autonomy they
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638
TABLE 1. Years of experience at Siriraj Hospital of administrators, surgical stas, and surgical residents.
TABLE 2. Patient and relatives’ ages.
TABLE 3. How welcoming patients and relatives were of resident participation in their healthcare.
Experience in years at Siriraj Hospital
Administrator Surgical staff Surgical resident
As an administrator As a surgical staff
who regulates who trains and teaches As a surgical resident
training surgical residents
N % N % Resident years N %
0-5 4 16.0 6 23.1 1 29 24.4
6-10 8 32.0 2 7.7 2 33 27.7
11-15 6 24.0 6 23.1 3 18 15.1
16-20 2 8.0 5 19.2 4 27 22.7
> 20 5 20.0 7 26.9 5 12 10.1
Total 25 100.0 26 100 Total 119 100
Patient and relatives’ ages
Patient and relatives’ ages N %
18-30 26 11.9
31-40 51 23.4
41-50 38 17.4
51-60 42 19.3
> 60 61 28
Total 218 100
Receptiveness of patients and relatives towards resident participation in their healthcare
Median* Mean Rank** n
Administrator 4 (3,5) 174.28 25
Surgical staff 4 (2,5) 172.44 26
Surgical resident 4 (2,5) 144.22 119
Patient and relative 4 (1,5) 235.64 230
Median (range) p < 0.000**
*A ve-point Likert scale
**e Kruskal-Wallis test
Dunn Bonferroni's pairwise comparison (administrator – patient, pairwise comparison p = 0.031), (surgical sta – patient, pairwise
comparison p = 0.020), (surgical resident – patient, pairwise comparison p < 0.000)
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TABLE 4. Eect of surgical residents’ involvement in patient care on the overall quality of care provided in the
hospital.
TABLE 5. Increasing resident autonomy has an impact
on patient safety.
Patient’s perception n Strongly Disagree Neutral Agree Strongly
disagree Agree
My overall hospital and 225 2 (0.9%) 6 (2.7%) 35 (15.6%) 120 (53.3%) 62 (27.6%)
surgical care is of better
quality with residents involved
Perception of administrators, surgical stas, and surgical residents were queried regarding the eect of resident participation in patient care
and the eect on quality of care provided.
in OPD and IPD
Median* Mean Rank** n
Administrator 5 (4,5) 106.86 25
Surgical staff 5 (4,5) 116.42 26
Surgical resident 4 (3,5) 74.26 119
Median (range) p < 0.000**
in the operating room
Median* Mean Rank** n
Administrator 5 (3,5) 112.42 24
Surgical staff 5 (4,5) 116.35 26
Surgical resident 4 (1,5) 72.62 119
Median (range) p < 0.000**
*A ve-point Likert scale
**e Kruskal-Wallis test
Dunn Bonferroni’s pairwise comparison
(administrator – resident, pairwise comparison p = 0.006)
(surgical sta – resident, pairwise comparison p < 0.000)
*A ve-point Likert scale
**e Kruskal-Wallis test
Dunn Bonferroni's pairwise comparison
(administrator – resident, pairwise comparison p < 0.000)
(Surgical sta – resident, pairwise comparison p < 0.000)
Median* Mean Rank** n
Administrator 3 (2,5) 64.50 25
Surgical staff 3 (1,5) 65.85 26
Surgical resident 4 (2,5) 94.21 119
Median (range) p = 0.001**
*A ve-point Likert scale
**e Kruskal-Wallis test
Dunn Bonferroni's post-hoc pairwise comparison
(administrator – resident, pairwise comparison p = 0.021),
(surgical sta – resident, pairwise comparison p = 0.027)
had, the more safe care patients received. is perception
was dierent from administrators and surgical sta who
believed that too much autonomy for a surgical resident
would decrease patient safety.
B. Administrator, surgical sta, and patient and relatives
views of autonomy of residents in training
e question whether a surgical resident should
perform procedures independently prior to completing
residency and entering independent practice is shown
in Table 6.
The Kruskal-Wallis test showed a statistically
signicant dierence in perception of whether a surgical
resident should perform procedures independently
prior to graduating residency and entering independent
practice among certain groups, with a p-value = 0.016.
A Dunn Bonferroni’s post-hoc pairwise comparison
found a dierence in perception only between surgical
residents and patients and relatives (pairwise comparison
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640
TABLE 6. A surgical resident should perform procedures
independently prior to graduating residency and entering
independent practice.
TABLE 7. Resident independence or autonomy is required
for their development into a competent surgeon.
Median* Mean Rank** n
Administrator 4 (2,5) 215.38 25
Surgical staff 4 (1,5) 173.92 26
Surgical resident 4 (2,5) 224.75 119
Patient and relative 4 (1,5) 189.34 230
Medan (range) p = 0.016**
Median* Mean Rank** n
Administrator 4 (2,5) 103.28 25
Surgical staff 4 (2,5) 78.42 26
Surgical resident 4 (2,5) 83.31 119
Median (range) p = 0.081**
*A ve-point Likert scale
**e Kruskal-Wallis test
Kruskal-Wallis test followed by Dunn Bonferroni's post-hoc pairwise
comparison
(surgical resident – patient, pairwise comparison p = 0.024)
p = 0.024). It means surgical sta and administrators
agree with patients and relatives regarding the goal of
surgical resident training. e perception of whether a
surgical resident should perform procedures independently
prior to graduating residency and entering independent
practice was in agreement among administrators, surgical
sta, and patients and relatives.
e questions about if “resident independence”
or autonomy is required to ensure a resident becomes
a competent surgeon” are shown in Table 7. It reveals
that administrators, surgical sta, surgical residents, all
agreed that residents require autonomy during training
to become a competent surgeon.
Calibrating the autonomy of surgical residents was
attempted by asking stakeholders to rate on a scale of 0
to 10 (0 being no independence and 10 the most) aer
various years of training. e researcher chose second-
year residents because this was the rst step of a resident
having to adhere to his or her surgical sub-specialty and
nal year residents about to graduate and receive the
Diplomate of the ai Board of Surgery the following
year. Administrators, surgical sta and each surgical
resident were asked to rate on a scale of 0 to 10 (0 being
no independence and 10 the most) the appropriate degree
of autonomy for a second-year resident and a nal year
resident. e results are shown in Table 8.
e median scale of autonomy of nal year residents
rated by surgical residents was 7, whereas administrators
and surgical sta rated the median scale of autonomy of
a nal year resident to be 8. e Kruskal-Wallis test was
performed to evaluate the distribution of responses and
there was no signicant dierence among these three
groups. e surgical residents rated the median scale
of autonomy of second-year residents as 5, whereas
administrators and surgical sta rated the median scale
of autonomy of the second-year residents as 5 and 3,
respectively. e autonomy of surgical residents increased
when surgical residents passed each year of training.
Finally, all groups rated an appropriate level of autonomy
for nal year residents, without any statistic signicant
dierences.
C. Administrators’ role. Perception of the eect of
regulation on reimbursement and liability concerns
for the hospital and surgical resident autonomy
Administrators, surgical sta, and surgical residents
were asked if they felt regulations regarding reimbursement
were responsible for decreased autonomy. Perceptions of
the eect of regulations on reimbursement on resident
autonomy were investigated. e question if an increase
in resident autonomy led to an increase in patient cost
care is shown in Table 9. is information indicated that
all three groups agreed that when resident autonomy
increased, it was likely to increase cost of patient care.
Responses to the more serious question “if patients
should get a discount on medical expenses when a surgical
resident does an operation?” are shown in Table 10.
Surgical residents, and patients and relatives had the same
opinion that patients should get a discount on medical
expenses, which was the complete opposite response
provided by administrators and surgical sta. e Kruskal-
Wallis test was performed to evaluate this opinion and
the distribution of responses were signicantly dierent
(p < 0.000). Pairwise comparisons using the Dunn Bonferroni
*A ve-point Likert scale
**e Kruskal-Wallis test
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Original Article SMJ
TABLE 8. Appropriate level of independence for nal year surgical residents and a second-year surgical resident
on a scale of 0-10.
(No independence -> Fully independent (0-10))
Final Year Final Year Second Year Second Year
Resident Resident n Resident Resident n
Median* Mean Rank** Median* Mean Rank**
Administrator 8 (3,10) 99.58 25 5 (1,7) 75.50 25
Surgical staff 8 (4,9) 86.38 26 3 (0,8) 57.17 26
Surgical resident 7(3,10) 82.35 119 5 (1,9) 93.79 119
Median (range) p = 0.254** Median (range) p = 0.001***
*A scale from 0 to 10
**e Kruskal-Wallis test
***Kruskal-Wallis test followed by Dunn Bonferroni's post-hoc pairwise comparison was used to compare continuous variables among
second-year residents. (surgical sta - surgical resident, pairwise comparison p = 0.003)
TABLE 9. e question whether increasing resident
autonomy would lead to increased cost of patient care.
TABLE 10. Perception of question: “Should patients
receive a discount on medical expenses when a surgical
resident performs an operation?”
TABLE 11. Whether an increase in resident autonomy
caused liability concerns for the hospital.
Median* Mean Rank** n
Administrator 3 (1,5) 80.86 25
Surgical staff 3 (1,4) 70.38 26
Surgical resident 3 (1,5) 89.78 119
Median (range) p = 0.138**
Median* Mean Rank** n
Administrator 2 (1,4) 107.70 25
Surgical staff 2 (1,5) 104.83 26
Surgical resident 3 (1,5) 197.24 119
Patient and relative 4 (1,5) 216.84 222
Median (range) p < 0.000**
Median* Mean Rank** n
Administrator 3 (1,5) 73.29 24
Surgical staff 3 (1,5) 84.69 26
Surgical resident 3 (1,5) 87.43 119
Medan (range) p = 0.396**
*A ve-point Likert scale
**e Kruskal-Wallis test
*A ve-point Likert scale
**e Kruskal-Wallis test
Kruskal-Wallis test followed by Dunn Bonferroni's post-hoc pairwise
comparison
(administrator – patient, pairwise comparison p < 0.000)
(administrator – resident, pairwise comparison p = 0.001)
(surgical sta – patient, pairwise comparison p < 0.000)
(surgical sta – surgical resident, pairwise comparison p = 0.001)
(surgical resident – patient, pairwise comparison p = 0.684)
test revealed that surgical sta and administrators have
the same opinion that medical expenses should not be
reduced while surgical residents and patients (surgical
resident - patient, pairwise comparison p = 0.684) both
agreed that the cost should be reduced.
e question of whether increased resident autonomy
caused liability concerns for the hospital is shown in
Table 11. is table indicated that all three groups agreed
that legal liability was not a concern when resident
autonomy increased (p = 0.396)
D. Patient and relatives’ views on resident participation
in the health care process
is section will demonstrate patients’ perception
regarding all aspects of surgical residency, quality of
care provided by surgical residents, informed consent
of patients’ ability to choose a “true” surgeon, and if
surgical sta should be present in the operating room
even in basic and uncomplicated operations as well
*A ve-point Likert scale
**e Kruskal-Wallis test
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642
as acceptance of complications incurred by surgical
residents. Patients and relatives opinions are shown in
Table 12.
As long as surgical outcomes are the same or better
with resident participation, 86.7% of patients agreed or
strongly agreed to have residents involved in surgical
care.
However, who the operating surgeon was and his/her
experiences were still the main consideration. If patients
have an operation performed by a surgical resident,
80.9 % of patients agreed or strongly agreed to wanting
to know how many times the resident had done this
operation. Another 72.5% of patients agreed or strongly
agreed to wanting to choose the surgeon who operated
on them.
Patients and relatives felt comfortable to allow
surgical residents to perform only basic and uncomplicated
operations without the need for surgical sta in the
operating room, however, in complicated operations,
74.4% of patients strongly disagreed or disagreed with
allowing a surgical resident to perform the operation
by himself or herself without the presence of surgical
sta in the operating room. In operations of increasing
complexity, there was less willingness to allow resident
involvement in surgical procedures.
e presence of surgical sta in operations had a
major impact on resident autonomy. Even in complicated
operations, 79.5% of patients agreed or strongly agreed
to allow residents to carry out a complicated operation
with surgical sta controlling the operating room.
Attention in the operation by surgical sta had a big
inuence on acceptance by patients of incurred operative
complications. e majority of patients or 81.8%, (44.1%
strongly disagreed or 37.7% disagreed) were unwilling
to accept serious complications following an operation
by a surgical resident without the presence of surgical
sta in the operating room. Even for mild complications,
25.5% of patients could accept operations carried out
by surgical residents alone.
E. Comparison of perception in improving surgical
residents’ autonomy in surgical staff and surgical
residents
Table 13 summarizes the comparison of perception
in increasing surgical residents’s autonomy between
surgical sta and surgical residents.
Most of the surgical sta and surgical residents
opinions were compared in two questionnaires, one
looking at the perception of surgical sta and the other at
the perception of surgical residents. Dierences in surgical
sta and surgical residents were statistically signicant
for 5 of the 9 parallel items. Surgical sta provided too
much direction in either patient care activities (p = 0.004)
or operative procedures (p < 0.000).
Surgical sta tend to follow the plan of residents
even if they prefer an alternative plan (p = 0.432), but
when it comes to making important medical decisions,
surgical sta did not take the input of surgical residents
as seriously as expected (p = 0.022). When the surgical
sta changed a surgical resident’s method of treatment,
a reason was seldom given to the resident to explain
the change in treatment regimen (p = 0.001). Surgical
sta gave too little feedback to surgical residents that
could help motivate them to improve their performance
(p = 0.001).
DISCUSSION
Individuals who receive support when given autonomy
(e.g., sensitivity to their perspectives, acknowledgment
of their feelings, provision of choices, minimization of
controls) from important authority gures, are more
motivated to pursue their goals, more satised with their
work and life, and ultimately become high achievers
compared to individuals who are forced or persuaded
to pursue the goals of others.15,16 Self-determination
theory states that humans have a natural tendency for
autonomous behavior, and those who are able to act
autonomously learn and perform better.6,15,17
e preparedness of surgeons graduate for independent
practice was concerned, owing to a lack of autonomy in
their training.18 is may be due to the fact that surgical
residents had fewer opportunities to care for patients
since their time as a medical student.1 More importantly,
during the time they practiced in provincial hospitals
aer nishing their MD, these surgical residents did
not have the opportunity to practice surgical skills.2 In
addition, the number of residents seeking fellowship
training or subspecialist training aer residency has
increased, which contributes to the major problem of
lack of autonomy in residency.3
e issue of resident autonomy or independence
becomes even more complicated when there is a discussion
of how much autonomy should be aorded to a resident.
e aim of this study was to evaluate perceptions regarding
resident autonomy from hospital administrators, surgical
sta, surgical residents, and patients and relatives.
e rst part looked at the eect of resident participation
on quality of patient care, and contained three questions:
1.1. How welcome resident participation was by
patients and relatives.
In this study, patients and relatives welcomed
resident participation in their health care process.
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TABLE 12. Patient and relatives’ opinions.
Patient and relative’s n Strongly Disagree Neutral Agree Strongly
opinions disagree Agree
As long as surgical outcomes 227 2 (0.9%) 7 (3.1%) 21 (9.3%) 144 (63.4%) 53 (23.3%)
are the same or better with
resident participation, I agree
with having residents involved
in my surgical care.
If I have an operation done by 225 4 (1.8%) 9 (4.0%) 30 (13.3%) 105 (46.7%) 77 (34.2%)
a surgical resident, I want to
know how many similar previous
cases he/she has handled before.
You want to choose the surgeon 225 2 (0.9%) 14 (6.2%) 46 (20.4%) 83 (36.9%) 80 (35.6%)
who operates on you.
If I had to have a basic and
uncomplicated surgery, I would
consent to a resident performing
the operation,
A. without the need for surgical 229 22(9.6%) 95 (41.5%) 36 (15.7%) 61 (26.6%) 15 (6.6%)
staff to be in the operating room
while the surgical resident is
operating.
B. with surgical staff controlling 229 3 (1.3%) 18 (7.9%) 23 (10.0%) 123 (53.7%) 62 (27.1%)
the operating room.
If I had to have a complicated
surgery, I would consent to
a resident performing the
operation
A. without the need for surgical 230 89 (38.7%) 82 (35.7%) 21 (9.1%) 26 (11.3%) 12 (5.2%)
staff to be in the operating room
while surgical resident is operating.
B. with surgical staff controlling 205 8 (3.9%) 25 (12.2%) 9 (4.4%) 91 (44.4%) 72 (35.1%)
the operating room.
I could accept mild complications 204 30 (14.7%) 89 (43.6%) 33 (16.2%) 43 (21.1%) 9 (4.4%)
following an operation by a surgical
resident without any surgical staff
in the operating room.
I could accept serious complications 204 90 (44.1%) 77 (37.7%) 6 (2.9%) 24 (11.8%) 7 (3.4%)
following an operation by a surgical
resident without any surgical staff
in the operating room.
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644
TABLE 13. Comparison of perceptions in improving surgical residents’ autonomy between surgical stas and
surgical residents.
Surgical staff Surgical resident
Surgical Surgical Surgical Surgical Mann-
staff staff n resident resident n Whitney
(Median (Mean (Median (Mean test
(Range))* Rank)** (Range))* Rank)**
Residents’ self-condence 4 (3,5) 65.92 26 4 (2,5) 74.55 119 p = 0.283
increases when attending
staff allows more autonomy.
Decreasing resident autonomy 4 (1,5) 68.02 26 4 (1,5) 74.09 119 p = 0.471
leads to a decreased sense
of patient ownership.
Surgical staff gives too much 2 (1,5) 52.27 26 3 (1,5) 77.53 119 p = 0.004
direction to a surgical resident
regarding patient- care activities.
Surgical staff gives too much 2 (1,5) 47.92 26 3 (1,5) 78.48 119 p < 0.000
direction to a surgical resident
regarding operative procedures.
Surgical staff encourages surgical 4 (2,4) 77.90 26 4 (2,5) 71.93 119 p = 0.478
residents to develop an
independent thought process.
Surgical resident's input is taken 3 (1,4) 56.98 26 4 (1,5) 76.50 119 p = 0.022
seriously by the surgical staff
when making important medical
decisions.
Surgical staff allows the surgical 3 (1,5) 67.52 26 3 (1,5) 74.20 119 p = 0.432
resident to plan even if surgical
staff prefers an alternative plan.
When the surgical staff change 4 (1,5) 94.88 26 4 (1,5) 68.22 119 p = 0.001
the surgical resident’s method of
treatment, staff always explains
the reasons before changing
the treatment regimen.
Surgical staff give feedback to 4 (3,5) 96.65 26 4 (1,5) 67.83 119 p = 0.001
surgical residents that helps them
feel motivated to improve their
performance.
*A ve-point Likert scale
** Mann-Whitney test
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Surprisingly, it was higher than the welcome aorded
by administrators, surgical sta, and surgical residents.
Pairwise comparisons using the Dunn Bonferroni test
revealed that patients and relatives had a signicantly higher
acceptance rate of resident involvement than administrators
(p = 0.031), surgical sta (p = 0.020) and surgical residents
(p < 0.000). is indicated that patients and relatives had
more favorable views of resident participation in patient
care than administrators and surgical sta. Surgical
residents do not realize how much patients and their
relatives welcome their participation in treatment.
1.2. e eect on overall quality of care when a
surgical resident was involved in patient care, either in
OPD, IPD, or in the operating room. In our study, 80.9%
of patients and relatives agreed or strongly agreed that the
quality of care was better when surgical residents were
involved. Our study also compared the perceptions of
the administrator, surgical sta, and surgical residents
regarding the eect of resident participation on quality
of care provided in OPD/IPD and the operating room.
In the OPD/IPD and operating room, pairwise
comparisons using the Dunn Bonferroni test revealed
that administrators and surgical sta reported statistically
signicant higher scores on overall quality of care than
surgical residents did. is information indicates that
surgical residents have a positive eect on overall quality
of care provided in either OPD/IPD or the operating
room. In the study by Kempenich JW5, the team found that
only 3% of the general public had responses indicating
that residents had a negative eect on quality of care.
is eect on overall quality of care was realized and
admired by all groups of stakeholders except the surgical
resident.
1.3. Increased resident autonomy has an impact
on patient safety.
e prevalence of complications due to resident
involvement was completely dierent to the perception of
relevant stakeholders, including administrators, surgical
sta, surgical residents, and patients.
Regarding the prevalence of complications due
to resident involvement, Castleberry et al19 found that
although there was increased morbidity with residents
involved, the 30-day mortality rate decreased and there
was a lower “failure-to-rescue”. Other studies found no
increase in complications or morbidity with residents
involved.11,20
In our study, Dunn Bonferroni’s post-hoc pairwise
comparison tests were performed and they conrmed
that surgical residents believed that the higher the level of
autonomy, the better the safety prole was for patients.
is perception was dierent from administrators and
surgical sta continue to believe that too much autonomy
for a surgical resident will decease patient safety. e
ones who have the duty to control autonomy of surgical
residents believe that too much freedom will lead to less
safety for patients.
e second part looked at the views of administrators,
surgical sta, surgical residents, and the views of patients
and relatives in training. is step focused on perceptions
such as essential autonomy required to become a competent
surgeon, proper level of surgical resident autonomy,
level of autonomy currently present, and development of
autonomy. is second step composed of three questions:
2.1. e reasons why a surgical resident should
perform procedures independently prior to graduating
residency and starting independent practice are shown in
Table 6. e Kruskal-Wallis test found that administrators
and surgical sta also agreed with patients and relatives
about the goals of surgical training. e perceptions of if a
surgical resident should perform procedures independently
prior to graduating residency and entering independent
practice were in agreement between administrators,
surgical sta and patients and relatives.
2.2. The question “resident independence or
autonomy is required for development of a resident
into a competent surgeon” was explored in Table 7. It
revealed that administrators, surgical sta, and surgical
residents, all agreed that residents require autonomy
during training to develop into a surgeon.
Surgical residents who were surveyed felt most
strongly about the importance of performing procedures
independently before graduation as important.9 Kempenich
JW5 reported that although most of the teaching faculty,
administrators, and the general public felt that residents
should perform procedures independently before
graduation, their responses were less enthusiastic than
those of residents. Among the general public, 80.6%
agreed or strongly agreed that residents need to perform
procedures independently before graduation. When
asked “should the surgical resident be able to perform
the surgery on his/her own condently before graduating
resident training”, 96% of surgical residents’ were in total
agreement or agreement, however, from the point of
view of surgical sta, that was not as important. When
patients were asked if they would consent to a nal year
resident performing a routine procedure independently,
less of them agreed (73.1%; p = 0.05).5
2.3. Appropriate level of independence for nal year
surgical residents and second-year surgical resident on
a scale of 0-10. In our study, the autonomy of surgical
residents could be calibrated by asking them to rate on
a scale of 0 to 10 (0 being no independence and 10 the
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646
most) dierent years of resident training. e median
scale of autonomy of nal year residents was rated by an
administrator, surgical sta, and surgical resident. e
Kruskal-Wallis test was done to evaluate the distribution
of responses and there was no signicant dierence among
the three groups. e surgical residents rated median
scale of autonomy of second-year residents as 5, whereas
administrators and surgical sta rated the autonomy
of second-year residents as 5 and 3, respectively. e
autonomy of surgical residents increased when surgical
residents completed each year of training.4 Finally, all
groups rated the appropriate level of autonomy for
nal year residents without any statistically signicant
dierences.
e results of how much autonomy should be given
to a resident, in our study, were dierent from results
observed by Sterkenburg et al.4 In our study, the nal
year resident rated autonomy as same as surgical sta
whereas Sterkenburg et at4 revealed that surgical sta
consistently rated the appropriate level of independence
as lower than residents. ey went on to suggest that: “…
it may be necessary for residents to overestimate their
ability to stimulate learning.”
e third part looked at the role of the administrator.
Perceptions of the eect of regulations on reimbursement
and liability concerns for the hospital on surgical resident’s
autonomy were questioned.
When surgical residents perform any operation,
the operating time is denitely prolonged. Improper or
inadequate treatment decisions, whether in the ward or
in the operating room, will increase the cost for patients.
If any complications following the operation occur, it will
increase medical expenses. In our study, administrators,
surgical sta, and surgical residents were asked if they felt
regulations regarding reimbursement were responsible
for decreased resident autonomy. Our results indicate
that all three groups agreed when resident autonomy
increased, it was likely to lead to increased cost of patient
care.
e question “should patients receive a discount
on medical expenses when a surgical resident performs
an operation for a patient?” was explored in Table 10.
Surgical residents, patients and relatives have the same
opinion that patients should receive a discount on
medical expenses, which is opposite to the opinion of
administrators and surgical sta. Pairwise comparisons
using the Dunn Bonferroni test revealed that surgical
sta and administrators have the same opinion that
medical expenses should not be reduced while surgical
residents and patients both agreed that the cost should
be reduced. is disagreement is statistically signicant.
An ethical consideration would be raised if some patients
were operated on exclusively by surgical sta, (with the
exclusion of any residents, if these patients paid more).
Furthermore, how to compensate for higher medical
expenses of a patient and relatives should be considered.
Most likely, the patient and relatives should not pay extra
because of unnecessary medical expenses incurred by
surgical residents.
Although Arriaga AF et al11 reported there were
liability concerns over complications incurred by surgical
residents, it was not clear if it is obstacle for the autonomy
of a surgical resident. Our study indicated that all three
groups (administrators, surgical sta, surgical residents)
agreed that legal liability was not much of a concern as
resident autonomy increased (p = 0.396).
e fourth part investigated the views of patients
and relatives on resident participation.
Patient and relatives’ opinions are shown in Table 12.
As long as surgical outcomes are the same or better
with resident participation, 86.7% of patients agreed or
strongly agreed to have residents involved in surgical
care. If guarantees could be provided to patients that
outcomes would be the same or better with resident
participation, then the general public would be more
receptive to their involvement in procedures.
Who the operating surgeon is and how much
experience he/she has is still the main consideration. If
patients had an operation done by a surgical resident,
80.9% of patients agreed or strongly agreed to wanting to
know how many cases the resident had handled before.
A total of 72.5% of patients agreed or strongly agreed to
wanting to choose the surgeon who operated on them.
In a survey of patients who underwent hysterectomy14
(where 100% of patients had a resident involved in their
care), 80% wanted to know what a resident would do
during their operation and how they would be supervised.
Reichgott and Schwartz21 found that most negative
responses to resident participation were due to patients
not being aware of what part of the process the resident
would be involved in their care. Patients oen had anxiety
and did not want surgical residents to have too much
autonomy in an operation. is might be due to the
fact that patients did not know the true role of surgical
residents at the time of admission. e surgical sta
should ensure patients know the role of surgical residents.
Attention to this issue could allow the teaching faculty
to assuage patient fears.5,21
Patients and relatives felt comfortable to let surgical
residents perform only basic and uncomplicated operations
without the presence of surgical sta in the operating
room, but in complicated operations, 74.4% of patients
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strongly disagreed or disagreed to let the surgical resident
perform the operation alone without the presence of
surgical sta in the operating room. Regarding resident
involvement in surgical procedures with increasing
complexity, the general public was less willing. Kempenich
JW5 asked the general public if they would welcome
resident participation if they did a routine vs complex
surgical procedure, and there was statistically signicant
negative stance for complex surgical procedures.
In our study, the presence of surgical sta in the
operation room had a major impact on resident autonomy.
Even in complicated operations, 79.5% of patients agreed
or strongly agreed to have a resident perform complicated
operations with surgical sta controlling the operating
room.
e attention of the surgical sta in the operation
room had a big influence on patient acceptance of
operative complications. e majority of patients, or
81.8% (44.1% strongly disagreed or 37.7% disagreed)
could not accept serious complications following an
operation by a surgical resident without surgical sta
supervision in the operating room. Even in cases of mild
complications, only 25.5% of patients could accept the
absence of surgical sta.
e h part investigated dierences in perception
between surgical sta and residents in improving the
autonomy of a surgical resident.
Surgical sta and surgical residents both endorsed
autonomy as important for the development of residents.
Surgical sta provided too much direction in either
activities related to patient care (p = 0.004) or operative
procedures (p < 0.000). Over direction by surgical sta
may make residents more passive, and this may stimulate
faculty to exert even more control. Any regulations have
made it necessary to increase the presence of attending
surgeons in the OR, and this may cause decreased resident
autonomy as the OR sta and residents naturally defer to
the attending surgeon. Chalabian and Bremne9 performed
a survey of surgical residents in the late 1990s which
revealed that 71% of residents felt that “…mandatory
presence of surgeons in the OR was bad.”
When making important medical decisions, surgical
sta did not take the input of surgical residents as seriously
as expected (p = 0.022). When surgical sta changed the
surgical resident’s method of treatment, the sta seldom
explained the reasons to the resident before changing the
treatment regimen (p = 0.001). Hence, surgical residents
may express their frustration about sta restriction on
opportunities to make decisions and about unexplained
changes in patient care plans. Lack of mutual trust is
a serious threat to learning and in-patient care teams.
Moreover, problems around communication still persist.
Surgical sta do not provide enough feedback to surgical
residents to help motivate them to improve performance.
(p = 0.001)
e consistent dierence between surgical sta and
surgical residents’ perceptions of autonomy suggests that
a common underlying factor or set of related factors
may drive observed dierences. Hence, the researcher
explored three possible underlying causes.6
1. Challenges to self-determination
Scholars have studied trust in leaders and stated
having trust in their team leaders was a key driver for
employee commitment and eectiveness.22-24 Being able
to build trust between junior and senior team members
fosters organizational eectiveness, positive work attitude,
goal acceptance, and better performance.25,26
Trust is developed between a resident and surgical sta
when a competent resident executes a task appropriately.8
Not challenging residents with appropriate responsibility
and independence can lead to stunted learning and
development.3,4,9 Without trust, it is dicult for surgical
sta to extend sucient autonomy to residents.8 Lack of
mutual trust is a serious threat. In in-patient care teams,
a major concern is that when surgical sta restrict the
independence of “passive” residents whose competence
is questioned, they get fewer opportunities for active
learning.
Scaolding strategy6 is likely to encourage development
of competence and enhance their relationships with team
members and supervisors. Residents who are reluctant
to act autonomously may benet from more scaolding
in their education, so that they can gradually gain the
condence they need to assume a more independent
role in patient care. Biondi EA, et al6 encourages surgical
sta to scaold the learning of residents they view as
passive including novices who are reluctant to take
on independent roles by giving them decision-making
responsibilities in increasingly complex situations aer
they prove themselves in less challenging settings.
To enhance the scaolding scheme, the researcher
recommends a series of “mentoring program” to address
the communication and trust issues between surgical sta
(mentors) and surgical residents (mentees). In medicine,
mentoring refers to a dynamic and context-dependent
process between experience clinicians and junior clinicians
to advance the development of the mentees as well as
create relationships with mutual benet between the
two parties.27 In mentoring, goal setting and elaborating
expectation at the beginning of the relationship are
essential. Research studies regarding mentoring program
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648
in medical school28-30 suggested that the key success
factors are to provide a choice of mentors who share
similar clinical and specialties interest (regardless of
dierences in generation), uses of questionnaire, prole
matching, mentor’s professional orientation, work-life
priorities and share values and interest between mentor
and mentee. Mentoring program not only addresses the
trust issue but also handles enhance communication
through reective and honest feedback.
In this study, the researcher recommends that
surgical sta (mentors) should be trained to be able to
assess surgical residents (mentees)’ needs, competencies,
experiences, personalities, values, beliefs and goals to
create the mentoring environment that personalizes
and increases their autonomy.
2. Generational dierences
Descriptions of generation Y (individuals born
aer 1982) showed some of the attitudes expressed by
surgical residents.31,32 For example, surgical residents
indicated they would like surgical sta to provide more
specic expectations, more support, better explanations
when residents’ treatment plans were changed, and
frequent feedback. Most responding residents belong to
Generation Y, but the surgical stas were a composite
of generations.
3. Inaccurate self-assessments on the part of both
surgical sta and surgical residents33,34
e resident and surgical sta groups sometimes
rated themselves higher than other groups and there
was a lack of insight into how their own behaviors could
drive behaviors of the other group. For example, over
direction by surgical sta might make surgical residents
more passive, and this may stimulate surgical sta to
exert more control.
Our study did have some limitations.
First, the response rate of surgical residents, surgical
sta, and administrators was 62.2%, 44.8%, and 43.1%,
respectively, however, this does not represent real results
due to non-responder bias. e sample size calculation
was not available for this study.
Second, generalizability may be restricted. e
study was conducted within one residency program
where autonomy issues may have elicited dierences
between residents and faculty that would not be evident
elsewhere.
ird, the reliability of questionnaires, using the
Cronbach’s alpha coecient (α), of the patients and
relatives’ questionnaire was not tested due to ethical
concerns.
Despite these limitations, the strength of our study
are that: 1. It characterizes views of resident autonomy
from the perspective of four major groups who have
a stake in surgical resident training. 2. is study is a
multidisciplinary integration of knowledge between
social science and medical education discipline.
ACKNOWLEDGEMENTS
e researcher would like to thank Dr. Sasima
Tongsai from the Division of Clinical Epidemiology,
Department of Research and Development, Faculty of
Medicine Siriraj Hospital, Mahidol University for her
continuous help with data processing and statistical
analysis, Mrs. Sirirat Khawsaard and Mrs. Angkana
Seetasang, from the Department of Surgery, Faculty of
Medicine Siriraj Hospital, Mahidol University for their
continuous help with data collection.
Finally, the researcher would like to thank the Faculty
of Medicine Siriraj Hospital, Mahidol Univeristy for
granting me the full scholarship for enrolling M.S. Program
in Human Resource and Organization Development,
National Institute of Development Administration,
which delivers professional knowledge in social science
to conduct this study.
Conicts of interest: e authors have no conicts of
interest to declare.
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12. Babbott S. Commentary: watching closely at a distance-: key
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13. Phitayakorn R, Williams RG, Yudkowsky R, Harris IB, Hauge LS,
Widmann WD, et al. Patient-care-related telephone communication
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Am Coll Surg. 2008;206(4):742-50.
14. Kim HN, Gates E, Lo B. What hysterectomy patients want to
know about the roles of residents and medical students in their
care. Acad Med. 1998;73(3):339-41.
15. Ryan RM, Deci EL. Self-determination theory and the facilitation
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16. Williams GC, Deci EL. e importance of supporting autonomy
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17. Kusurkar R, Cate OT. AM last page: education is not lling a
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18. Greene FL. Transition to practice: a bold move. General Surgery
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19. Castleberry AW, Clary BM, Migaly J, Worni M, Ferranti JM,
Pappas TN, et al. Resident education in the era of patient safety:
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and Organization Development Journal. 2018;10(1):2-33.
25. Dirks KT. Trust in leadership and team performance: evidence
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26. Fulmer CA, Gelfand MJ. At what level (and in whom) we trust:
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27. Wu JT, Wahab MT, Ikbal MF, Loo TWW, Kanesvaran R,
Radha Krishna LK. Toward an interprofessional mentoring
program in palliative care - a review of undergraduate and
postgraduate mentoring in medicine, nursing, surgery and
social work. J Palliat Care Med. 2016;6:292.
28. Ramanan RA, Taylor WC, Davis RB, Phillips RS. Mentoring
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residency training. J Gen Intern Med. 2006;21:340-5.
29. Dimitriadis K, Borch PVD, Störmann S, Meinel FG, Moder S,
Reincke M, et al. Characteristics of mentoring relationships formed
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30. Yehia BR, Cronholm PF, Wilson N, Palmer SC, Sisson SD,
Guilliames CE, et al. Mentorship and pursuit of academic
medicine careers: a mixed methods study of residents from
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31. Eckleberry-Hunt J, Tucciarone J. e challenges and opportunities
of teaching “Generation Y”. J Grad Med Educ. 2011;3:458-61.
32. Shangraw RE, Whitten CW. Managing intergenerational
dierences in academic anesthesiology. Curr Opin Anaesthesiol.
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34. Davis DA, Mazmanian PE, Fordis M, Van Harrison R, orpe
KE, Perrier L. Accuracy of physician self-assessment compared
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Noor Halilah Buari, M.H.Sc (Optom)*, Siti Nurnazihah Hamka, B.Optom*, Anis Nur Fazlyana Md-Isa, B.Optom*,
Shauqiah Jufri, M.HSc (Optom)**
*Centre of Optometry Studies, Faculty of Health Sciences, Universiti Teknologi MARA Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam,
Selangor, Malaysia, **Topvision Eye Specialist Center, 55, Jalan Peninsula Utama 1, Peninsula Park, Pasir Penambang, 45000 Kuala Selangor,
Selangor, Malaysia.
Text Size Affects Eye Movement during Reading
among Young Adults and Adults with Presbyopia
ABSTRACT
Objective: Reading is an activity that indirectly informs a person’s visual capacity to distinguish letters and words.
Reading begins with eye movements, then substantial cognitive processing and synthesis, before becoming voice
reading. erefore, text is a factor that could impact reading quality through its control of eye movements. is
study examined the eye movements of young adults and adults with presbyopia using texts of dierent sizes.
Materials and Methods: Twenty-ve young adults and twenty-two adults with presbyopia and good vision were
included in this study. Six text sizes of a passage were chosen as the reading stimuli. e eye movement of participants
in saccades and xation were captured, tracked, and analyzed using the Dikablis eye tracker glasses.
Results: Eye movement of young adults diered signicantly (p<0.05) when reading texts of dierent sizes. e eyes
moved more and had a wider saccadic angle as the font size increased. An increase in xations or stopping of the
eyes were observed with larger texts. Adults with presbyopia had signicantly dierent eye movement patterns than
young adults (p<0.05), whereby these participants stopped more frequently at longer periods and had a narrower
saccadic angle.
Conclusion: Eye movements changed when reading texts of varied sizes and the movements diered between younger
and older adults. ese translate to altered visual searching and attention strategies with varied text readability,
indicating that the oculomotor system adapts to the pattern, shape, and size of the presented reading material. is
behavior could imply that cognitive processes have been altered to facilitate comprehension.
Keywords: Reading; xations; saccadic; presbyopia; readers (Siriraj Med J 2022; 74: 650-657)
Corresponding author: Noor Halilah Buari
E-mail: noorhalilah@uitm.edu.my
Received 7 April 2022 Revised 16 August 2022 Accepted 16 August 2022
ORCID ID:http://orcid.org/0000-0002-7058-1176
http://dx.doi.org/10.33192/Smj.2022.76
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Reading is more than just looking at a bunch of
words, rather a process of transferring and processing
knowledge from a presented reading material. Reading is
a process of deciphering the meaning of written symbols
and letters. To read, a person must be able to (i) recognize
the words they see (word recognition), (ii) comprehend
what the words mean (comprehension), and (iii) connect
word and meaning so that reading becomes automatic
and accurate (uency).1,2
Reading materials come in a variety of sizes and
formats. Books are the most common type of reading
material. Newspapers, magazines, food labels, brochures,
emails, reports, and a variety of other available reading
materials that are used by children and adults in their
daily reading activities. Given the wide range of reading
Buari et al.
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Original Article SMJ
materials available, they are presented in dierent ways.
Reading materials come in varying font styles, text sizes,
color, and layout, which may inuence the outcome of
reading. Font size, in particular, has been signicantly
shown to impact reading performance.3-5 Readers with
normal vision increased their reading speed as the font
size increased.5 while individuals with a blurred vision
also have a similar aect in reading speed.3
e size of text also possibly inuences eye movement
during reading.2,6-8 Eye movement is a microprocess of
reading that causes changes in eye movement parameters
such as xations and saccades. Increased text size has resulted
in altered saccadic eye movements.7,8 Schoolchildren who
read 25pt and 30pt sized texts, had increased amplitude
of saccade movement.8 Additionally, as the text size
increased, the number of xations increased, and the
duration of xations decreased.
When text was displayed on an LCD screen, the
visual angle measured by saccade length, changed as
the text size increased.7 Here, saccadic eye movement
remained consistent at smaller print sizes of up to 32pt
text size. When eight dierent text sizes were compared,
readers had the most prolonged xation duration with a
text size of 20pt.7 Beymer et al.6 studied online reading
and discovered that participants read faster with larger
fonts. When reading an online text, smaller text (10pt)
retained the reader’s attention for a more extended
time than larger text (12pt).6 Fixation also occurs more
frequently with larger print sizes (32 pixels) than with
smaller print sizes (24 pixels).9
Normal aging in late adulthood was likely associated
with ocular and neural changes resulting in subtle
deterioration of visual functions.10,11 Changing optical
features that occurs in older adults signicantly reduces
sensitivity towards contrast. Due to pupillary miosis,
illuminance of the retina in aged eyes is diminished. e
aging eye also has increased intraocular light dispersion and
optical aberrations, impairing the contrasting appearance
of an image.12 ese physiological changes indirectly
aect vision performance, such as reading. Characters
that are either too small or too huge impede reading
speed in the aged population.13 As a result, adults with
reduced contrast sensitivity in low and high spatial
frequency have diculty reading and thus, additional
lens with increased dioptric power are required to view
standard size prints.14 Healthy older adults with decreased
visual processing speed on the other hand, have decits
in visual attention, associative learning, and executive
function.10,15,16 us, it was established that a generalized
slowdown of information processing is likely caused by
many aging-related cognitive impairments.
ere is also a substantial change of the reading
process in dierent age groups.13,17-19 In preschoolers
and elementary school children, reading speed improved
with age.19 Reading speed was fairly constant between
teenagers and young adults, indicating that the reading
skills had fully developed.17,18 As people aged, their reading
speed slowed. Adults read at approximately 9% slower
than teenagers.17,18 Slower reading could be due to some
vision decits in the healthy but aging eyes. Aer the age
of 45, signicant vision losses occur, and most notably
in the middle and high spatial frequencies.17
Studies had established that changes in the size of texts
caused eye movements to change as well. To investigate
the cognitive processes of reading, the movement of the
eyes were extensively investigated. However, studies in
the past were conducted with a limited range of font size
or reading materials were from electronic devices, such as
online reading or reading from a digital screen (tablets,
smartphones and laptops). Moreover, discrepancies exist
regarding eye movements and there is limited research
which compared reading using various font size on
printed materials or among varied age groups. Data on
these parameters are key as reading also occurs with
printed or hard copy reading materials such as books,
newspapers, food labels, brochures and medication labels
on a daily basis, apart from reading through electronic
displays. Given the age-related variation in reading ability,
it is worthwhile to investigate eye movement patterns
among young adults and adults with presbyopia. In this
current study, the eect of text size and age on reading
eye movement was examined between these two groups
of readers.
MATERIALS AND METHODS
Participants
e eye movement behavior in reading dierent text
sizes was conducted using a cross-sectional experiment
of young adults (mean age: 22.28±1.46 years) and adults
with presbyopia (mean age: age 49±6.65 years). e
sample size was estimated using the formula n=(Zσ/Δ)2
computed using the G-power sample size soware. e
precision (σ) was set at 1. e standard deviation (Δ)
was 2.3, and the Z for the 95 percent condence interval
was 1.96. As a result, each group needed a total of 25
participants.
is study included twenty-ve young adults and
twenty-two adults with presbyopia. Corruption of data led
to, three (3) participants with presbyopia to be eliminated.
e inclusion criteria were short-sightedness and long-
sightedness with a low to moderate habitual refractive
error (sphere correction between +2.00DS and -3.00DS;
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652
astigmatism up to -2.00DC; and addition for near up to
+3.00DS). e best-corrected distance and near visual
acuity were 6/9 and N6 or better. Participants with any
form of binocular vision impairments and ocular illnesses
and eye diseases were excluded.
Reading stimuli
Reading passages in the Malay language from the
Shauqiah-Ai Hong-Halilah Reading Passage Compendium
(SAHRPC) were used as a reading stimuli.20 e SAHRPC
consisted of 42 passages divided into three sets of 13 each.
Each set had 13 dierent Arial font text sizes, ranging
from 1.2logMAR to 0.0logMAR. The passages were
organized on a 0.1-step logarithmic scale in decreasing
order. Each set of eight-page ip designs contained
13 printed passages in landscape format on a matte
type A3 sized paper. A paragraph of four to ve lines
consisting of 50 words were arranged in each passage.
Passages were taken from the Malaysian Ministry of
Education’s Malay language textbook, which is used in
primary schools. is study used six Malay excerpts from
the SAHRPC. e text sizes were 5pt, 8pt, 14pt, 20pt,
30pt, and 52pt, which were equivalent to 0.2logMAR,
0.4logMAR, 0.6logMAR, 0.8logMAR, 1.0logMAR, and
1.2logMAR text legibility, respectively. e six text sizes
were chosen to resemble actual reading materials, with
the text size of 52pt representing conventional newspaper
headlines. Text of 30pt is similar to newspaper sub-
headlines and children’s books, 20pt is the same size as
books for children aged seven to eight years old, 14pt is
the equivalent to grade one to three children’s textbooks,
8pt is the same size as tiny column newsprints, and 5pt
is comparable to the small print found in e Bible or
footnotes.
Eye Tracker
e Dikablis Eye Tracking Glasses Professional
(Ergoneer, Germany) is a wireless, head-based eye-
tracking device that ts as a glasses-like frame. It includes
two small cameras in front of the eyes that record and
detect eye movement. e camera captures a 384 ×
288-pixel black-and-white video of the eye. e scene
camera, positioned on the nose portion of the spectacles,
is another small camera. e scene camera records the
participant’s viewing scene at a resolution of 1,920 ×
1,080 pixels during data recording. e scene camera
can be tilted up to 12 degrees upward and 81 degrees
downward. e eye cameras may be adjusted to meet the
wearer’s interpupillary distance. e head unit can also
be easily adjusted to t the size of the head using the cord
stopper on the drawstring. e head unit can be worn
over polarized glasses or spectacles. e D-Lab soware
version 3.0, installed on a computer, was used to send
and analyze the collected data. e Dikablis Eye Tracking
Glasses Professional has various data visualization tools,
including an eye tracker, heat maps, and a glance ow
diagram.
Experimental procedures
e experiment was conducted in a room with
ambient lighting and installed with a light booth and
the reading stimuli. All participants provided a written
informed consent before the experiment was commenced.
e study was approved by the university’s research ethics
committee, in accordance with the Helsinki Declaration
(Approval No: REC/426/17). e participants sat facing
the reading stimuli (e Malay passage) placed on a
reading stand at a working distance of 40 cm aer passing
the screening procedures. e passages were covered
to prevent the participant from reading ahead of time.
Along with their spectacle (if any), the participant wore
the Dikablis eye tracker. e eye tracker was calibrated
and the participant was asked to read aloud at a regular
reading speed. e Dikablis eye tracker recorded the eye
movement simultaneously during the reading process.
e experiment was carried out individually for each
text size.
Statistical analysis
Eye movement data consisting of frequency of
saccades, saccade angles, number of xations, and xation
durations were recorded and sent to the D-Lab program.
e SPSS version 21.0 soware was used for statistical
analysis. The median, quartile, mean, and standard
deviation were derived as descriptive data from the eye
movements. e Kolmogorov-Smirnov test showed that
young adults’ eye movement data were normally distributed
(p>0.05). Hence, eye movements with dierent text sizes
among the participants were compared using the One-
way ANOVA test. Schee post-hoc test was selected for
further analysis. A comparison of eye movement behavior
between young adults and adults with presbyopia was
conducted using an independent t-test. e statistical
signicance was set at p<0.05.
RESULTS
is study compares the eye movement among
young adults for texts in dierent font sizes. e number
of saccades was found to be signicantly increased (F (5,
144) = 96.6, P<0.001) when reading dierent text sizes.
More saccadic movements were made when the text size
increased, starting from 0.8logMAR to 1.2logMAR. Fig 1
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Fig 1. e saccadic eye movement behavior for dierent text sizes is shown in box plots. (a) Number of saccadic and (b) saccadic angles are
shown above. e median is the horizontal line at the center of the box, and ‘X’ represents the mean value.
depicts the trend of the number saccadic movement.
e saccadic angle became wider and more substantial
as the text size increased, F (5, 144) = 7.03, p<0.001.
When young adults read 1.2logMAR text size, which
was comparable to 52pt, there were substantial changes
in the saccadic angle data.
Fig 2 shows the frequency of xations and xation
time. When font size increased, young adults made more
stops during reading, F (5,144) =95.6, p<0.001. e
number of xations gradually rose with increasing text
size, while xation changed at text sizes 1.0logMAR and
1.2logMAR in young adults. e time the eye takes to stop
during reading is called xation duration. Fig 2 shows
the xation duration for dierent text sizes. Fixation
duration was signicantly longer for smaller text sizes, F
(5,144)=7.04, p<0.001. At 0.2logMAR, 0.4logMAR, and
0.8logMAR, the eyes made more prolonged duration of
stopping during reading.
Fig 3 shows the comparison of the number of
saccadic movements and saccadic angles between adults
with presbyopia and young adults. It was found that
the number of saccadic movements were signicantly
dierent for dierent text sizes at 0.2logMAR (t(45)=-
2.43, p=0.019), 0.6logMAR (t(45)=-2.77, p=0.008) and
0.8logMAR (t(45)=-2.32, p=0.025). Presbyopia readers
made more saccadic movements compared to young
adults.
The saccadic angle was significantly different
at 0.2logMAR (t(45)=2.5, p=0.016) and 0.6logMAR
(t(45)=2.5, p=0.015) between both groups of adults.
Adults with presbyopia produced smaller and narrow
saccadic angles when they moved from one xation to
another, especially with smaller text sizes.
Fig 4 shows the comparison of the number of
xation and xation duration between young adults
and adults with presbyopia. Adults with presbyopia made
signicantly (p<0.05) more pauses during a reading at
all text sizes than young adults except at 1.2logMAR.
Both adults with presbyopia and young adults had more
xation at larger text size than smaller text size. e
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Fig 2. e xation eye movement
behavior for dierent text sizes is
charted in box plots. e median
value represents a middle horizontal
line in the box, and the mean value
is represented by the ‘X’ symbol
within the box.
Fig 3. Comparison of saccadic
eye movement for dierent text
sizes between adults with presbyopia
and young adults. (a) Number of
saccadic and (b) saccadic angles
is shown above.
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current data also demonstrates that xation duration
in adults with presbyopia was signicantly slower at
0.2logMAR (mean:1523±254ms, t(45)=-3.83, p<0.001)
and at 0.4logMAR (mean:1003±115ms, t(45)=-2.23,
p=0.025) compared to the young adults readers. Fixation
duration was longer at smaller text sizes than larger text
sizes.
DISCUSSION
Two elements of eye movement behaviours investigated
in this study were saccadic movement and xation.
Reading at a size of 20pt displayed a signicant change
in eye movement behaviour. e ndings revealed that
saccadic angle became broader as the text size increased,
which was also demonstrated in a previous study.7,8 e
amplitude of the saccade movement was also increased
in 7- to 12-year-old children as they read 25pt and 30pt
texts.8
Investigation of the shape and size of text on an
LCD screen discovered that saccade lengths in degrees
of visual angle widened with large texts.7 e ndings
Fig 4. Comparison of xation eye
movement for dierent text sizes between
adults with presbyopia and young adults.
(a) Number of xation and (b) xation
duration is shown above.
of Franken et al.7 mirrored the current study that also
showed saccade movement changed at a larger text.
Other studies however, found no signicant dierences
in saccadic movement, both length and the number of
saccades between dierent print sizes.6,9 Considering the
major dierence, Baymer et al.6 used reading stimuli with
texts with the font sizes of 10pt, 12pt, and 14pt, while this
study used a wider range of size. In the current study,
saccades and saccadic lengths were similar at smaller text
size, but, increased with increasing text size due to more
jumping eye movements between the lines of the whole
passage, which were laid out to t the page layout. e
participant’s shiing visual searching strategies could
account for the dierent outcome gained in this study
compared to the literature from the past.
As text size increased, the number of fixations
increased and xation duration reduced. For example,
a 30-point text size had a signicant increase in xation,
whereby, smaller text size led to less frequent stops but
more time processing visual information. Studies have
revealed a similar pattern whereby the eye made fewer
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656
and longer xations with smaller text sizes.6-9 Decreasing
text size (10-pt or 24 pixels) resulted in signicantly
longer xation durations.6-9 At a text size of 2-pt, the
xation duration changed substantially.7
Atypical xation behaviour was also revealed with
reading materials of various text sizes. For smaller texts,
the eye may spend more time xating due to the crowding
eect,8,21 as longer stops were necessary for the eye to
focus and extract visual information. Another possibility
for longer stops is that letters or words printed closer
to each other may interfere with the visual extraction
process. Reading texts presented with larger spaces
between the words did not seem to promote enhanced
concentration.22 However, readers found it dicult to
read the smaller texts, which could explain how xation
behaviour diminishes with smaller texts. Changes in
xation behaviour also suggested that the eye employs
visual attentional strategies to adapt to changes in dierent
reading stimuli.
Compared to young adults, adults with presbyopia
made more saccadic movements across dierent text sizes
when eye movement data was analyzed. In terms of the
size of the saccadic movement, adults with presbyopia
made smaller and narrower angles between one xation
to another, especially with smaller text size. Furthermore,
as the age increased, more stopping or pauses were made
during reading for all text sizes. Fixations were also
longer with smaller texts among adults with presbyopia
compared to young adults.
Apart from a few other plausible explanations,
this nding relates to reading performance, which has
been shown to gradually decrease with age, even among
individuals with good vision.13,23 Contrast sensitivity
have been demonstrated to decrease with age.12,24-26
Physiological changes in the crystalline lens causes
increment in light dispersion and aberration of sensitivity
that reduces contrast.12 Reduced contrast sensitivity also
inuenced visual-based cognitive abilities and visual
speed processing.12,26 Longer latencies in low contrast
text aect information processing speed.24 Previous
research found that older adults have slower cognitive
visual processing than younger adults.10,27
Decreased speed in reading could also be caused by
deterioration in the transient system in an older adult.10,27
e reduced spatial frequency may directly aect reading
speed and change eye movements. Cognitive decits
in the elderly, such as visual attention and associative
learning have been linked to changes in oculomotor
function.16,26,27 Age-related decline in motor function and
ocular disease also aect eye movement.27-30 Furthermore,
older adults make more pronounced eye movement
transitions compared to younger adults.29 Young adults
also had the quickest saccadic reaction compared to the
aged participants. ese ndings demonstrate extremely
strong age-related eects, corresponding to the various
stages of normal nervous system development and
degeneration.31
CONCLUSION
In conclusion, eye movement changes when young
adults and presbyopia readers read passages with varying
text sizes. Changes in saccade eye movements proposed
that visual searching strategy had shied and changes in
xation behavior suggested a shi in visual attentional
strategy. Age also aects eye movement behavior during
reading, as adults with presbyopia demonstrated signicantly
dierent saccadic eye movements and xation compared
to young adults. ese changes, however, reveal that
the eye movement behavior is adaptable to changes in
the pattern, shape, and size of the reading materials.
Trend of these eye movement parameters may provide
some insight that cognitive and brain processing during
reading are altered to facilitate understanding a variety
of reading materials.
ACKNOWLEDGMENTS
e authors would like to thank all participants
who participated in this study.
Conict of interest: e authors have no conict of
interest to declare.
REFERENCES
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11. Owsley C. Vision and Aging. Ann Rev Vis Sci. 2016;2(1):255-
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12. Artal P, Guirao A, Berrio E, Piers P, Norrby S. Optical Aberrations
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13. Akutsu H, Legge GE, Ross JA, Schuebel KJ. Psychophysics of
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14. Gupta N, Wolsohn JS, Naroo SA. Comparison of near visual
acuity and reading metrics in presbyopia correction. J Cataract
Refract Surg. 2009;35(8):1401-9.
15. Rubin GS, Ng ESW, Bandeen-Roche K, Keyl PM, Freeman EE,
West SK, et al. A Prospective, Population-Based Study of the
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19. Virgili G, Cordaro C, Bigoni A, Crovato S, Cecchini P, Menchini U.
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27. Chan CYH, Chan AB, Lee TMC, Hsiao JH. Eye-movement
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Pattaraporn Mekavuthikul, M.D.*, Sunsern Cheamanunkul, Ph.D.**, Pinsumon Chomchai,***, Jariya
Phuditshinnapatra, M.D.*
*Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ailand, **Division of Science,
Mahidol University International College, Mahidol University, Nakhon Pathom, ailand, ***Shrewsbury International School Bangkok Riverside,
ailand.
Predicting the Need for Continuation of
N-acetylcysteine Treatment among Acute Paracetamol
Overdose Patients with Psi Parameter
ABSTRACT
Objective: AcetaCalc was used to evaluate Psi’s accuracy in predicting cases that required prolonged N-acetylcysteine
(NAC) therapy, as well as Psi’s optimal cut-o.
Materials and Methods: is is a retrospective study of patients with acute paracetamol overdose who were
treated with NAC at Siriraj Hospital between 2007 and 2016. e Psi parameter was calculated using the Acetacalc
aer entering paracetamol concentrations, blood sampling times, and NAC onset times. Indications for NAC
continuation is in accordance with the guidelines, which recommended that NAC treatment be continued if the
follow-up aminotransferase reached 50 U/L or higher.
Results: We enrolled 403 patients, the proportion of NAC prolongation was 50.4 %. Psi was shown to be a signicant
predictor of NAC prolongation (p < 0.001) with area under the receiver operational characteristics curve 0.766 (95%
condence interval (CI) 0.719-0.813). e Psi cuto with highest Youden index was 1.757 mM-hour. e sensitivities
and specicities of the cuto were 0.517 (95% CI 0.449-0.585) and 0.940 (95% CI 0.898-0.965), respectively.
Conclusion: Psi parameter calculated through AcetaCalc is a useful tool for the prediction of cases where extension
of NAC therapy beyond the standard regimen is indicated.
Keywords: Paracetamol; acute liver injury; N-acetylcysteine; prognosis; psi (Siriraj Med J 2022; 74: 658-665)
Corresponding author: Jariya Phuditshinnapatra
E-mail: jariya.ohu@mahidol.ac.th
Received 11 July 2022 Revised 14 August 2022 Accepted 20 August 2022
ORCID ID:http://orcid.org/0000-0002-6474-5613
http://dx.doi.org/10.33192/Smj.2022.77
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Hepatotoxicity from paracetamol overdose remains a
signicant healthcare burden in ailand and worldwide.1
e most denitive treatment for the overdose is the
timely and sucient use of N-acetylcysteine (NAC),
administered as a 300 mg/kg intravenous infusion over
21 hours.1 When NAC therapy is started early, usually
within 8 hours aer the overdose, hepatotoxicity can
eectively be minimized. Factors that can contribute to the
development of hepatotoxicity secondary to paracetamol
overdose are a high initial serum paracetamol concentration
and a delay in the initiation of NAC treatment. Studies
have shown that the risks of hepatotoxicity (dened by
aminotransferase concentration ≥ 1,000 U/L) when NAC
is initiated before 8 hours aer ingestion can range from
3.5-7.7%. at risk increases progressively to 10.3-22.2
% when NAC is given at 10-16 hours post ingestion.
Subsequently, it can be as high as 12.9-45.1% when NAC
is given later than 16 hours aer ingestion.1,2
Mekavuthikul et al.
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In addition, even in instances where paracetamol-induced
hepatitis has already occurred, NAC therapy beyond the
initial 21-hour period has been shown to reduce the severity
of hepatotoxicity, as well as the rate of complications and
mortality.3,4 e indication for prolonging NAC therapy is
an aminotransferase concentration of 50 U/L or higher.5
It is recommended that the infusion be maintained until
aspartate aminotransferase concentration has decreased
to half of the peak level or lower.6 On the other hand, the
assessment of hepatotoxicity risks has many interacting
clinical parameters such as the time of ingestion, the dose
of ingestion, the time to treatment initiation with NAC,
and the initial paracetamol level.1,2 ese parameters
make up a risk prole which, with the right tool namely
the Psi parameter, can be individualized and extended
to predict the need for prolonged NAC treatment in
specic patients.1,7 e Psi (Greek letter Ψ) parameter
is a composite calculation that accounts for both timed
serum paracetamol concentration and the time aer
ingestion until N-acetylcysteine therapy is initiated.
It was developed based on a toxicokinetic model as a
quasi-trapezoidal area-under–the-curve of paracetamol
concentration and the duration of hepatic glutathione
deciency.8,9 (Fig 1) Its purpose is to individualize each
patient’s hepatotoxicity risk which can help clinicians
determine the disease prognosis with reasonable accuracy.
Overall, the Psi parameter reects exposure to N-acetyl-p-
benzoquinone imine (NAPQI), paracetamol’s hepatotoxic
metabolite, prior to starting NAC. Higher paracetamol
concentration and longer delay in NAC treatment results
in a higher calculated Psi parameter.10,11 e details
about mathematical derivation of Psi can be found in
previously published works.8,9 Consequently, the utility
and accuracy of the Psi parameter in predicting individual
risk of hepatotoxicity have been substantiated in various
publications.9-12 In the ai population, high Psi (≥ 5.0
mM-hour) predicts hepatotoxicity with sensitivity of 96.9%
(95% condence interval (CI) 84.3-99.4) and specicity of
91.5% (95% CI 87.1-94.5).10 However, despite such excellent
clinical data, its complex calculations severely limit its
usefulness in busy clinical settings.9 In 2021, AcetaCalc,
a web-based application developed jointly by the Faculty
of Medicine Siriraj Hospital, Mahidol University and
Mahidol University International College, has made this
task much simpler. Users can simply input paracetamol
concentration, time aer ingestion when paracetamol
level was obtained, and the time to NAC initiation and
the application can calculate Psi parameter, as well as
other predictors of hepatotoxicity. is application can
be accessed at https://sunsern.github.io/aceta-calc/#/
tabs/info. In the present study, we evaluate the use of
Psi parameter, which is derived with AcetaCalc, as a
predictor of the need for prolonging NAC treatment
among patients with acute paracetamol overdose.
MATERIALS AND METHODS
is was a retrospective review of patients who
presented at Siriraj Hospital, Bangkok, ailand from
January 1, 2007 to December 31, 2016 with paracetamol
overdose. Inclusion criteria included age 12 years or older
and treatment with N-acetylcysteine. Patients were excluded
if they t one of the following criteria: mixed ingestion,
staggered ingestion (overdose process longer than 1 hour)
and abnormal initial aminotransferase concentrations.
A standard case record form was used to extract the
information from the medical records, including age,
gender, type and dose of the overdose, initial paracetamol
concentration, blood chemistry results, treatment, follow-
up blood chemistry results and clinical outcomes. e
study protocol was approved by the Siriraj Human
Research Protection Unit (MU-MOU CoA 472/2021).
e Psi parameter was calculated using the AcetaCalc
Application. Input data for Psi calculation included time of
blood sampling (hours aer overdose), measured paracetamol
Fig 1. Calculation of Psi parameter
Shaded area represents Psi parameter, tGD
= time of glutathione depletion (6 hours is
used as a default), tF = time of N-acetylcysteine
initiation, threshold = threshold paracetamol
concentration (45 mg/L is used)
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concentration (mg/L) and lag time from overdose to
NAC initiation (hours). Patients fullled the primary
outcome of the study if the follow-up aminotransferase
concentration was 50 U/L or higher, indicating the need
for prolonged NAC therapy. Hepatotoxicity was dened
as an aminotransferase concentration of 1,000 U/L or
above. For the purpose of comparison, extrapolated
paracetamol concentration at 4 hours post ingestion
([APAP]4hour) was calculated using the formula [APAP]4hour
= Ct/2e>-(0.693/4)t where Ct represents measured paracetamol
concentrations and t indicated the time interval (hours)
from ingestion to blood sampling.
During the study period, intravenous NAC was
the mainstay treatment for acute paracetamol overdose.
e standard regimen for NAC administration was 150
mg/kg in one hour, 50 mg/kg in four hours and 100 mg/
kg in 16 hours, consecutively. Oral administration was
used only when the patients had a contraindication to
IV NAC or could not tolerate the intravenous regimen.
NAC prolongation was carried out by the administration
of 150 mg/kg/24 hours of NAC intravenously. In actual
clinical settings, the decision to start and then discontinue
the prolonged NAC therapy was based on each clinician’s
perception of whether a signicant elevation and subsequent
decline of aminotransferase had occurred.
Statistical analysis
Descriptive data were displayed as frequencies with
percentages and means with 95% condence intervals
(CI). However, medians with interquartile ranges (IQR)
were used for variables with non-normal distributions.
Dierences were tested with Student’s t-test or Mann-
Whitney U test. Proportions were tested with a chi-
squared test or Fisher’s exact test. Factors or co-variates
with p ≥ 0.05 were further tested with multiple logistic
regression in order to predict cases that required NAC
prolongation. Multiple logistic models were assessed using
backward stepwise multiple logistic regression. Receiver
operating characteristics (ROC) curve and area under
the curve (AUC) with 95% CI were used to assess the
accuracy of Psi in predicting the outcome. e optimal
cuto was selected using the highest Youden index.13
Validities of the predictions were evaluated by sensitivity,
specicity, positive likelihood ratio (LR+) and negative
likelihood ratio (LR-) with 95% CIs. Statistical analyses
were performed using PASW 18 (Release version18.0.0)
statistical program.
e sample size estimation for this study was performed
based on the “rule of 10 for logistic regression”.14 Since we
expected no more than four factors or co-variates in the
predicting model, the minimal number of events in this
study was estimated to be 40. erefore, we required at least
40 cases that fulll the indication for NAC prolongation
to achieve a desirable statistical power.
RESULTS
During the study period, 1,286 patients presented to
Siriraj Hospital due to paracetamol overdose. Among these,
883 cases were excluded. erefore, we enrolled 403 into
the analyses. (Fig 2) e subjects consisted of 332 females
(82.4%) with a median age of 23 years (IQR 20 28, range
13-62). Compared with the group receiving standard NAC
duration, the NAC prolongation group had signicantly
higher extrapolated four-hour paracetamol concentrations,
Fig 2. Subject enrollment ow
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Psi values, peak aminotransferase concentrations and
proportion of hepatotoxicity and longer time-to-NAC-
therapy, while having a signicantly lower proportion of
patients who received decontamination with activated
charcoal. (Table 1) None of the patients experienced
liver failure and no mortality occurred in this study.
Both the Psi parameter and the decontamination
with activated charcoal were entered into the multiple
logistic regression analysis. However, activated charcoal
yielded no statistical signicance (p-value 0.401) in the
multiple logistic regression model (Model 1). Activated
charcoal was removed since the resultant Nagelkerke R2
of Model 2 with Psi parameter alone was higher than
Model 1 (a higher score meant better t of the model).
(Table 2) When using the equation Logit P = -0.918
+ (0.824 * Psi), Psi was a signicant predictor of the
need to prolong NAC treatment (p-value <0.001). Fig 3
demonstrates the scatter plots of [APAP]4hour and onset
of NAC therapy, as classied by cases with and without
the need for NAC prolongation. ere is a clear pattern
of the need for NAC prolongation in cases with high
[APAP]4hour or delayed NAC onset.
e ROC curve for Psi in predicting NAC prolongation
has an AUC of 0.766 (95%CI 0.721-0.806) and is shown
in Fig 4. e highest Youden index was found at the Psi
concentration of 1.757 mM-hour. e 1.757 mM-hour
cuto yielded a sensitivity 51.7% and a specicity 94.0%.
When the cuto was increased to 2.948 mM-hour, the
specicity achieved a maximal value of 99.5%. (Table 3)
TABLE 1. Demographic and clinical characteristics of the overall subjects, groups with and without N-acetylcysteine
(NAC) prolongation.
Characteristics Overall NAC prolongation No NAC prolongation P-value
(403 case) (203 cases) (200 cases)
Female (frequency (%) 332 (82.4) 167 (82.3) 165 (82.5) 0.951
Age (median (IQR) (years) 23 (20-28) 24 (21-27) 23 (19-31) 0.387
Paracetamol 281.7 294.1 256.4 0.250
dose (mg/kg) (200.0-400.0) (202.0-408.2) (200.0-378.8)
[APAP]4hour 237.3 356.0 195.5 <0.001
(mg/L) (181.4-355.5) (289.3-474.1) (170.6-222.8)
NAC onset (hours) 7 (5-9) 8 (6-10) 5 (4-7) <0.001
Psi (mM-hour) 0.476 1.873 0.001 <0.001
(0.001-2.250) (0.001-4.995) (0.001-0.639)
Initial AST (U/L) 13 (10-18) 16 (11-31) 14 (10-30) 0.742
Initial ALT (U/L) 11 (8-17) 15 (8-31) 14 (9-30) 0.861
Peak AST (U/L) 37 (22-79) 76 (54-457) 24 (19-30) <0.001
Peak ALT (U/L) 41 (19-86) 86 (60-572) 26 (15-37) <0.001
Peak INR 1.1 (1.0-1.2) 1.1 (1.0-1.2) 1.1 (1.0-1.2) 0.048
Activated Charcoal 87 (21.6) 22 (10.8) 64 (32.5) <0.001
Hepatotoxicity 45 (11.2) 45 (22.2) 0 (0) <0.001
Abbreviations: NAC, N-acetylcysteine; IQR, interquartile range; [APAP]4hour, Extrapolated 4-hour paracetamol
concentration; AST, aspartate aminotransferase; ALT, alanine aminotransferase
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TABLE 2. Logistic regression models of Psi and activated charcoal administration as predictors of N-acetylcysteine
prolongation.
Models Factors or co-variates Regression coefcients P-value -2 log likelihood Nagelkerke R2
1 Psi 0.786 <0.001 423.678 0.285
Activated charcoal -0.253 0.401
2 Psi 0.824 <0.001 424.394 0.378
Fig 3. Scatter plots of extrapolated paracetamol
concentration at 4 hours and onset of
N-acetylcysteine (NAC) treatment (cases are
classied as cases with (1) and without (0)
NAC prolongation)
Fig 4. Receiver operating characteristics curve
of Psi for predicting prolongation of
N-acetylcysteine therapy
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TABLE 3. Diagnostic validities of Psi for predicting N-acetylcysteine prolongation at various cuto concentrations
(* remarks cuto psi concentration with highest Youden index).
Psi cutoff Sensitivity Specicity LR+ LR-
(mM-hour) (95% CI) (95% CI) (95% CI) (95% CI)
2.948 39.9 (33.4-46.8) 99.5 (97.2-99.9) 79.80 0.60
(11.22-567.87) (0.54-0.68)
1.757* 51.7 (44.9-58.5) 94.0 (89.8-96.5) 8.62 0.51
(4.90-15.16) (0.44-0.60)
0.257 70.9 (64.3-76.7) 67.0 (60.2-73.1) 2.15 0.43
(1.73-2.67) (0.34-0.55)
0.001 100.0 (98.1-100.0) 0.0 (0.0-0.019) 100.0 (100.0-100.0) -
Abbreviations: CI, condence interval; LR+, positive likelihood ratio; LR-, negative likelihood ratio
DISCUSSION
NAC therapy for paracetamol overdose is one of
the most studied antidotal treatments, as apparent by
the numerous guidelines for its administration. When
given early, its ecacy in preventing hepatotoxicity is
well-established. Currently, it is most oen given in
either a two-bag (200 mg in four hours and 100 mg in
16 hours) or a three-bag (150 mg/kg in one hour, 50 mg
in 4 hours and 100 mg/kg in 16 hours) regimen over a
period of 21 hours.1,2 Serum paracetamol concentration
and time-to-NAC therapy are two regularly assessed
clinical parameters for clinicians when prognosticating the
outcome of patients with paracetamol overdose.2,8,10 e
availability of these information makes the derivation of
Psi parameter possible. Because the treatment regimens are
so well adopted by clinicians, the associated demands for
healthcare resources such as the frequency of laboratory
monitoring eorts, the amount of antidote needed, as
well as the patient’s length of stay can oen be reasonably
predicted. However, in a subset of patients, paracetamol-
induced hepatotoxicity can occur despite the completion
of a standard NAC administration. In these cases, the
continuation of NAC has been shown to signicantly
reduce mortality and complications. Postulated mechanisms
of the action include NAC acting as an inammatory
modulator, increasing oxygen delivery and utilization
and improving blood ow in the microvasculature.1,3,4
According to the current guideline on the treatment
of acute paracetamol poisoning, NAC continuation is
recommended when the aminotransferase is elevated, as
determined by AST or ALT of 50 U/L or higher.1,5 Despite
the seemingly low value, we believe that this cuto oers
maximal safety for patients with paracetamol induced
hepatotoxicity. erefore, we used this value to select
cases for the primary outcome of this research. NAC
continuation means intravenous infusion of NAC at the
rate 150 mg/kg/24hours aer completing the standard
21-hours NAC regimen.
In this study, the Psi parameter is shown to be an
accurate predictor of NAC prolongation. e ROC’s AUC
of 0.766 implies that Psi has an acceptable accuracy in
discriminating cases with and without the need for NAC
prolongation. Although decontamination with activated
charcoal is also signicantly associated with the need
for NAC prolongation, we postulate the mechanism to
be the reduction of serum paracetamol due to activated
charcoal’s eects which, in turn, aects the calculation
of the Psi value. Subsequently, when activated charcoal
is eliminated from the logistic regression model, the Psi
parameter remains as a sole and adequate predictor of
the need for NAC prolongation. Our study illustrates the
tendency for increasing need of prolonging NAC therapy
as a function of higher paracetamol concentration and
greater delay in NAC administration (Fig 3). Similarly,
Cairney et al, reported a phenomenon whereby incidences
of acute liver injury, as dened by aminotransferase
> 150 U/L, gradually increased as a function of paracetamol
nomogram groups. e incidence was 6% in the 0-100
mg/L nomogram group and progressed to as high as 27%
in the > 500 mg/L nomogram group. e rates of acute
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liver injury were lower in patients who were treated with
NAC within 8 hours.15 Of note, the term ‘nomogram group’
in this study is similar to the [APAP]4hour concentration
groups in our study.
We proposed that the Psi cuto of 1.757 mM-hour
be used as the criterion to predict the need for NAC
prolongation, since it yielded good specicity, although
the sensitivity was mediocre. (Table 3) On the other hand,
the 2.948 mM-hour cuto had very high specicity, but
the sensitivity became unacceptably low. e cuto of
0.257 is shown in Table 3 because it is the second lowest
concentration cuto, next to 0.001 mM-hour. e cuto
value of 0.001 mM-hour is also signicant because it has
100% sensitivity for the need for NAC prolongation, in
concordance with previous ndings that Psi of 0.001
mM-hour has a very high sensitivity for hepatotoxicity
(aminotransferase > 1,000 U/L).12
e ndings in our study have relevant clinical
implications. Firstly, when Psi is calculated at the onset of
treatment, physicians can expect to have to continue NAC
therapy beyond the standard regimen if its value is 1.757
mM-hours or higher. is has signicant ramication on
the expected length of stay in the hospital and suggests
that, in these cases, the reimbursement scheme may
need to be adjusted. Secondly, when Psi is at its lowest
possible value of 0.001 mM hour the probability of
requiring NAC beyond the routine protocol should be
very low since the value signies early NAC treatment
and low paracetamol concentration. Furthermore, the
omission of a follow-up aminotransferase level aer
completion of the standard NAC therapy can also be
justied based on such reasoning. irdly, our study
shows that decontamination with activated charcoal
can signicantly reduce the need for NAC continuation
beyond the routine protocol. is recapitulates the ndings
of previous studies and reiterates the importance of
adequate gastric decontamination.16-18
e limitations of this study are in its retrospective
nature. e data in medical records are intended for clinical
services, and some errors in information obtained from
the medical records may exist. e most important piece
of information that can aect the result of this study is
the time of paracetamol overdose, since it is a reference
point from which the time of blood sampling and NAC
initiation are calculated. In this study, a large number of
subjects were excluded because they did not fulll the
requirement for Psi application. However, we do not
expect them to result in any distortion of the results.
For the future, we suggest that the study question is
re-evaluated in a prospective observational study.
CONCLUSION
Psi parameter, a composite value of paracetamol
concentration, time of blood sampling and onset of
N-acetylcysteine treatment, is a useful tool to help clinicians
predict the need for the continuation of NAC treatment
beyond the standard regimen. e Psi parameter can
be derived conveniently with the use of a computer
application.
REFERENCES
1. Chiew AL, Buckley NA. Acetaminophen Poisoning. Crit Care
Clin. 2021;37(3):543-61.
2. Rumack BH. Acetaminophen hepatotoxicity: the rst 35 years.
J Toxicol Clin Toxicol. 2002;40(1):3-20.
3. Harrison PM, Keays R, Bray GP, Alexander GJ, Williams R.
Improved outcome of paracetamol-induced fulminant hepatic
failure by late administration of acetylcysteine. Lancet. 1990;
335(8705):1572-3.
4. Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander
GJ, et al. Intravenous acetylcysteine in paracetamol induced
fulminant hepatic failure: a prospective controlled trial. Bmj.
1991;303(6809):1026-9.
5. Chiew AL, Reith D, Pomerleau A, Wong A, Isoardi KZ,
Soderstrom J, et al. Updated guidelines for the management of
paracetamol poisoning in Australia and New Zealand. Med J
Aust. 2020;212(4):175-83.
6. Curtis RM, Sivilotti ML. A descriptive analysis of aspartate and
alanine aminotransferase rise and fall following acetaminophen
overdose. Clin Toxicol (Phila). 2015;53(9):849-55.
7. Wong A, Graudins A. Risk prediction of hepatotoxicity in
paracetamol poisoning. Clin Toxicol (Phila). 2017;55(8):879-
92.
8. Chomchai S, Chomchai C, Anusornsuwan T. Acetaminophen
psi parameter: a useful tool to quantify hepatotoxicity risk in
acute acetaminophen overdose. Clin Toxicol (Phila). 2011;49(7):
664-7.
9. Sivilotti ML, Good AM, Yarema MC, Juurlink DN, Johnson DW.
A new predictor of toxicity following acetaminophen overdose
based on pretreatment exposure. Clin Toxicol (Phila). 2005;
43(4):229-34.
10. Chomchai S, Lawattanatrakul N, Chomchai C. Acetaminophen
Psi Nomogram: a sensitive and specic clinical tool to predict
hepatotoxicity secondary to acute acetaminophen overdose.
J Med Assoc ai. 2014;97(2):165-72.
11. Sivilotti ML, Yarema MC, Juurlink DN, Good AM, Johnson
DW. A risk quantication instrument for acute acetaminophen
overdose patients treated with N-acetylcysteine. Ann Emerg
Med. 2005;46(3):263-71.
12. Chomchai S, Chomchai C. Predicting acute acetaminophen
hepatotoxicity with acetaminophen-aminotransferase multiplication
product and the Psi parameter. Clin Toxicol (Phila). 2014;52(5):
506-11.
13. Akobeng AK. Understanding diagnostic tests 3: Receiver
operating characteristic curves. Acta Paediatr. 2007;96(5):
644-7.
14. Peduzzi P, Concato J, Kemper E, Holford TR, Feinstein AR.
A simulation study of the number of events per variable in
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logistic regression analysis. J Clin Epidemiol. 1996;49(12):
1373-9.
15. Cairney DG, Beckwith HK, Al-Hourani K, Eddleston M,
Bateman DN, Dear JW. Plasma paracetamol concentration at
hospital presentation has a dose-dependent relationship with
liver injury despite prompt treatment with intravenous
acetylcysteine. Clin Toxicol (Phila). 2016;54(5):405-10.
16. Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for
paracetamol (acetaminophen) overdose. Cochrane Database
Syst Rev. 2018;2(2):Cd003328.
17. Chomchai S, Mekavuthikul P, Phuditshinnapatra J, Chomchai
C. Sensitivity of dose-estimations for acute acetaminophen
overdose in predicting hepatotoxicity risk using the Rumack-
Matthew Nomogram. Pharmacol Res Perspect. 2022;10(1):e00920.
18. Hoegberg LCG, Shepherd G, Wood DM, Johnson J, Homan
RS, Caravati EM, et al. Systematic review on the use of activated
charcoal for gastrointestinal decontamination following acute
oral overdose. Clin Toxicol (Phila). 2021;59(12):1196-227.
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Trina Sengupta, MBBS*, Bobby Paul, DCH, M.D.(PSM)**, Lina Bandyopadhyay, M.D. (PSM)***, Ranjan Das,
M.D.(PSM)****, Ankush Banerjee, MBBS, M.D.******
*Department of Preventive & Social Medicine, All India Institute of Hygiene & Public Health, Kolkata, India, **Department of Occupational Health,
All India Institute of Hygiene & Public Health, Kolkata, India, ***Department of Preventive & Social Medicine, All India Institute of Hygiene &
Public Health Kolkata, India, ****Department of Preventive and Social Medicine, All India Institute of Hygiene & Public Health Kolkata, India,
*****Department of Preventive & Social Medicine, All India Institute of Hygiene & Public Health Kolkata, India.
Determinants of Modern Contraceptive Usage
among Married Women: A Mixed-Methods Study
in a Rural Community of India
ABSTRACT
Objective: A woman’s multifaceted feelings, knowledge, and perceptions of their intimate relations greatly inuence
their contraceptive behavior. In addition, women empowerment has been increasingly recognized as a key factor
in family planning and reproductive health outcomes. is study aimed to assess modern contraceptive usage and
its determinants among currently married women of reproductive-age (WRA) in rural Bengal.
Materials and Methods: is mixed-method study was conducted in a rural area of Hooghly District, West Bengal
from April to September 2021. e quantitative strand of the study was conducted by interviewing 210 currently
married WRA. e qualitative strand was conducted via focussed group discussions among husbands/mothers-
in-law and in-depth interviews with healthcare workers. SPSS soware was utilized for quantitative data analysis
and factors associated with contraceptive usage were analyzed using logistic regression models. Qualitative data
were analyzed thematically.
Result: Currently 114 (54.8%) study participants were using modern contraceptive methods. Education (aOR=7.65,
95% CI=1.85-31.67), empowerment through freedom from family domination (aOR=5.56, 95% CI=1.30-23.66),
attitude on contraception (aOR=4.67, 95% CI=1.26-17.19), and family planning counselling (aOR=4.41, 95%
CI=1.12-17.33) were found to be signicantly associated with modern contraceptive usage. Lack of couple counselling,
family support, and knowledge gap was identied as the major barriers to contraceptive usage.
Conclusion: Since a woman’s decision-making ability signicantly aects their sexual and reproductive health
outcomes, eective measures should be undertaken to empower them by creating awareness regarding their rights
and freedom to make strategic life choices. Couple counselling should be prioritized to enhance male involvement
and eliminate perceived barriers.
Keywords: Contraceptive; empowerment; family support; India; mixed-methods (Siriraj Med J 2022; 74: 666-674)
Corresponding author: Ankush Banerjee
E-mail: ankush.banerjee20@gmail.com
Received 3 August 2022 Revised 24 August 2022 Accepted 7 September 2022
ORCID ID:http://orcid.org/0000-0003-2762-123X
http://dx.doi.org/10.33192/Smj.2022.78
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Family Planning (FP) is a cost-eective investment,
the timely intervention of which can help in reducing
the impact of high population growth in any country.
India became the pioneer country in the world to launch
a National Family Planning Programme in 1952. e
current slogan of this program: “Jodi Zimmeder Jo Plan
Kare Parivar” (Responsible couples are those who plan
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their family) reflects the broader holistic aspects of
family planning rather than just mere achievement of
replacement level of fertility.1 Modern contraceptive
services which are available under this program are
broadly of two types- spacing methods (condoms, oral
contraceptive pills, intrauterine devices), and permanent
methods (sterilization techniques). e present aim of
this program in India is to emphasize the need for a
reduction in the number of unintended pregnancies,
proper birth spacing, and attainment of the ideal age
of rst pregnancy.
is current initiative has helped the country to
traverse a long way in achieving its goal of slowing the
population growth as recent data as per the National
Family Health Survey (NFHS-5) statistics have shown that
India’s TFR (Total Fertility Rate) has come down to the
replacement level of 2. Despite this nationwide laudable
achievement, some states in India (Madhya Pradesh,
Rajasthan, Uttar Pradesh, Jharkhand) are still lagging
behind their desired fertility rates. Moreover, India still
houses approximately 9.4% of eligible couples with an
unmet need for FP, reecting a signicant gap between
their reproductive intentions and contraceptive behavior.2
Family planning plays a central role in women’s health
by reducing the mortality rate of unsafe abortions and
undesired pregnancies.3 Previous studies have shown
that approximately 15.6 million abortions have been
performed in India in the year 2015, which was associated
with a high rate of unintended pregnancy (70.1 per 1000
women aged 15-49 years).4 NFHS-5 also showed that
the state of West Bengal deserves special mention as the
proportion of total unmet needs is particularly high in
rural areas (7.8%) as compared to urban areas(5.2%).
Lower rates of contraceptive usage in India; especially
in rural areas are largely driven by gender inequality
and lack of female autonomy over family planning
choices. A study by Shakya et al done in rural India
had shown that women empowerment was higher in
those couples who received increasing communication
regarding contraception.5 Women empowerment which
has been dened as ‘the expansion of people’s ability to
make strategic life choices in a context where this ability
was previously denied to them’ has increasingly been
recognized as a key factor aecting FP and reproductive
health outcomes among women.6,7 In developing nations
like India where gender discrimination is very prominent
(particularly in rural areas), a complete understanding
of how gender-based power inuences the ability to
access and use contraceptives is the need of the hour.
Moreover, the inuence of family-level stakeholders on a
woman’s choice of contraceptives as well as deciencies
at the health sector level needs further exploration, thus
mandating the necessity of mixed-method research. With
this backdrop, the present study aimed to assess the
contraceptive usage patterns and their major determinants
(through quantitative strand) among the currently married
women of the reproductive age group (WRA). Again the
perspective about using modern contraceptives among
family-level stakeholders (husbands and mothers-in-
law in the case of this particular study) and also the felt
barriers of healthcare workers with regards to providing
family planning services to the rural community were
explored through the qualitative strand of the study.
MATERIALS AND METHODS
is cross-sectional study with a mixed-methods
approach (convergent parallel design) was conducted
from April to September 2021in the rural service area of
the Rural Health Unit and Training Centre (RHUTC),
Singur, Hooghly District, West Bengal. Two primary
health centres and 12 sub-centers are situated in the
study area from where family planning services are
provided to the community comprising of 64 villages. e
quantitative strand of this study was conducted among the
currently married WRA (15 to 49 years of age), residing
in the study area for at least ve years. ose who did
not give written informed consent were critically ill or
had undergone hysterectomy or oophorectomy were
excluded. For the qualitative strand, family members
comprising of husbands and mothers-in-law of study
participants, as well as healthcare workers working in
the study area for at least 1 year, were selected.
Sampling:
According to the National Family Health Survey 5
(NFHS 5), the prevalence of modern contraceptive usage
among currently married women in West Bengal was
found to be 60.6%.2 Considering P=0.606, an absolute
error of precision (L)=10%, design eect=2 (for cluster
sampling in the rst stage), and non-response rate=5%
(for simple random sampling done in the second stage)
the sample size estimated using standard Cochran’s
formula was 201.8 Since a two-stage cluster sampling
technique was applied comprising 15 clusters, the nal
sample size came to be 210.
A list of all 64 villages (along with the population of
each village) situated in the rural service area of RHUTC,
Singur was taken. From that list, 15 villages were selected
through a probability proportional to size (PPS) method.
From each of those 15 villages, 16 currently married
WRA, residing at those villages were selected by Simple
Random Sampling. ese selected participants were
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668
approached at their residences with help of eld-level
healthcare workers. For the qualitative strand, participants
were selected purposively and data was collected till the
point of data saturation.
Data Collection, Study Tools, and Parameters used:
e quantitative part of the study was conducted
through face-to-face interviews among the currently
married WRA. A predesigned, pretested structured
questionnaire was prepared [translated into the local
language of Bengali] which was face and content validated
by a team of public health experts. It consisted of the
following domains-
a) Socio-demographic characteristics which included age,
religion, educational status, occupation, socio-
economic status, type of family, and number of
children.
b) Knowledge regarding contraceptives and attitude
towards their usage: e knowledge-based section
consisted of 12 items where the participants had to
respond as “True, False, or Don’t Know” (Cronbach’s
alpha=0.73). The correct response was given a
score of ‘1’ while the wrong response or “Don’t know”
fetched a score of ‘0’. Total scores ranged from 0 to
12 while the cut-o for having satisfactory knowledge
was taken to be the 75th percentile of the total attained
score (=8). Attitude toward using contraceptives
consisted of a 10-items questionnaire, distributed
across three domains: Attitude towards perceived
benets of contraception, perceived barriers from
family-level stakeholders, and perceived self-barriers
to contraceptive use (Cronbach’s alpha= 0.67). Each
item had three options (Disagree, Neutral, and
Agree) with scores ranging from -1 to 1. e total
(ranging from -10 to 10) was calculated by adding
scores of each domain. Cut-o for having a favorable
attitude was taken to be the 75th percentile of the
total attained score (=5).
c) Women’s Empowerment Scale adopted from
Compendium of Gender Scale by C-change (previously
applied in a similar demographic setting in Bangladesh):
It consisted of 18 items, distributed across three
sub-scales: i) women’s mobility (8 items) in which
each respondent was given a score of ‘1’ for each
place she had visited and an additional score of ‘1’
if she had ever gone there alone. us, the scores
ranged from 0 to 8 [Cut-o for being empowered
was taken as 75th percentile of the attained total score
(=5)] ii) Freedom from Family Domination (4 items);
the responses were scored as 1 for ‘Yes’ and 0 for
‘No’ response. A woman was classied as “empowered”
if she said that none of the mentioned items ever
happened to her or as “not empowered” if any of
these items had happened to her, iii) Economic
Security (4 items): A score of ‘1’ was assigned for
each of the following items: if a woman owned her
house or land; owned any productive asset; had her
cash savings or her savings were ever used for
business or money-lending. A woman with a score
of ≥2 was classied as being empowered. Levels
of women empowerment were measured separately
for each sub-scale.9
d) e current usage of modern contraceptives by the
study participants was the outcome variable of this
study. Participants were asked whether they have
used any of the modern contraceptive methods
(oral contraceptive pills, IUDs, condoms, injectables,
tubectomy) in the past 6 months. Any participant
who had utilized at least one of the mentioned
methods was considered a modern contraceptive
user.
For the qualitative strand of the study, two focus
group discussions (FGDs) were conducted among family-
level stakeholders of the study participants. One FGD
was conducted among six husbands (median age= 30
years) and the other among six mothers-in-law (median
age=67 years) to explore their diverse view-point about
family planning. Each FGD took place for about 45
minutes and was conducted with the help of an FGD
guide. In addition, in-depth interviews of health workers
[one public health nurse (56 years), one multipurpose
worker female (42 years), and three accredited social
health activists (median age=35 years)] were carried
out to explore their perceived barriers to providing
contraceptive services to the community. ey were
interviewed with a pre-tested, semi-structured interviewer
guide. All FGDs and IDIs were audio-recorded with the
prior consent of the study participants.
Data analysis
Quantitative data were analyzed by Microso Excel
(2016) & SPSS soware (IBM Corp. Chicago. USA.
version 16). Appropriate descriptive statistics were
utilized for denoting the outcome variables as well as the
independent variables. Aer excluding multicollinearity
(variance ination factor > 5), factors associated with
the current usage of modern contraceptives among the
study participants were analyzed by a test of signicance
(p-value <.05) via univariate logistic regression analysis
separately. All the biologically plausible signicant variables
in the respective univariate analysis were included in the
nal multivariable models. e data obtained through
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FGDs and IDIs were simultaneously processed using a
manual thematic analysis approach. e records were
listened to and transcribed verbatim in Microso Word
Version 2016. e transcripts were read thoroughly, the
important sentences were underlined and the main ideas
derived from them were labeled as codes. Appropriate
codes were then placed under appropriate themes.
RESULTS
Background characteristics of the study participants
Among 210 study participants, the median age was
found to be 28 years (IQR=23-32 years). e majority
(82.4%) were in the age group of 20-34 years. 58 (27.6%)
participants had an education level of primary or below
while only 6.2% of participants were involved in some
other occupation and the rest were home-maker. 84 (40%)
belonged to socio-economic class III and 79 (37.6%)
belonged to class IV according to Modied B.G. Prasad’s
Scale 2020.10 (Table 1)
Contraceptive usage patterns among the study participants
Currently, 114 (54.8%) study participants were using
any of the modern methods of contraceptives. Among all
participants, ligation was used by 21.4% while condom
was utilized by 19% of the participants. (Fig 1)
TABLE 1. Descriptive characteristics of the study participants (N=210).
Parameters Categories Number (Percentage)
Age (in completed years) 15-19 2 (1.0)
20-34 173 (82.4)
35-49 35 (16.6)
Religion Hindu 190 (90.4)
Muslim 20 (9.6)
Respondent’s education¥ Illiterate 19 (9.0)
Primary or below 58 (27.6)
Middle 54 (25.7)
Secondary 43 (20.5)
Higher Secondary 21 (10.0)
Graduate or above 15 (7.2)
Husband’s education Illiterate 15 (7.2)
Primary or below 66 (31.4)
Middle 51 (24.3)
Secondary 29 (13.8)
Higher Secondary 27 (12.9)
Graduate or above 22 (10.4)
Occupational status of the respondents Home-maker 197 (93.8)
Other professionals 13 (6.2)
Type of family Joint 81 (38.6)
Nuclear 129 (61.4)
Socio-economic status£ Class I (upper class) 3 (1.4)
Class II (upper middle class) 39 (18.6)
Class III (middle class) 84 (40.0)
Class IV (lower middle class) 79 (37.6)
Class V (lower class) 5 (2.4)
No of children ≤2 143 (68.1)
>2 67 (31.9)
¥ below primary= below 5th standard, primary=passed 5th standard, middle= passed 8th standard, secondary= passed 10th standard, higher
secondary= passed 12th standard
£ according to modied B.G Prasad’s scale 2020
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670
Fig 1. Pie-Diagram showing the current pattern of contraceptive usage among the study participants (n=210).
Knowledge regarding contraceptives and Attitudes
toward their usage among the study participants
51.9% (n=109) of the participants had satisfactory
knowledge about contraceptives (median score=7, IQR=
6-8) while only 29.5% (n=61) had a favorable attitude
towards their usage (median score=3, IQR=1-5).
Women’s Empowerment among the study participants
58.6% of women were found to be empowered
through the ‘Women’s Mobility’ scale whereas 56.2% were
empowered on the ‘Freedom from Family Domination’
scale. Only 20% of the participants were found to be
empowered through the ‘Economic Security’ sub-scale.
It was detected that women who were using any of the
modern contraceptive methods were more empowered
in all the three sub-scales compared to those not using
any. (Fig 2)
Factors associated with the current usage of modern
contraceptives by the study participants
Signicant factors of modern contraceptives use
among study participants were educational status of
middle school and above [aOR=7.65, 95% CI = 1.85-
31.67], favourable attitude towards modern contraceptive
usage [aOR=4.67, 95% CI = 1.26-17.19], empowerment
through freedom from family domination [aOR = 5.56,
95% CI = 1.30-23.66], recipients of family planning
counselling [aOR = 4.41, 95% CI = 1.12-17.33]. e
Fig 2. Radar diagram showing the association of usage and non-usage of modern contraceptive methods with woman empowerment.
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multivariable regression model deduced was of good
t (non-signicant Hosmer-Lemeshow test, P-value
>.05) while 42% to 63% of the variance of the outcome
variable could be explained by this model. (Table 2)
Qualitative exploratory ndings
Qualitative exploration from the two FGDs among
family-level stakeholders and 5 IDIs among healthcare
workers revealed two major themes: a) Perspective about
TABLE 2. Factors associated with modern contraceptive usage among the study participants: Logistic Regression
Analysis (N=210)
Total No. Usage of Modern Unadjusted ORƪ Adjusted OR
Parameters Contraceptives (95% CI) (95% CI)
n (%)
Education
Below middle school 77 20 (25.9) 1 (Ref) 1 (Ref)
Middle school and above 133 94 (70.6) 6.89 (3.04-15.62) 7.65 (1.85-31.67)
Husband’s Education
Below middle school 81 22 (27.1) 1 (Ref) 1 (Ref)
Middle school and above 129 92 (71.3) 6.73 (3-15.07) 3.21 (0.87-11.7)
Type of Family
Joint Family 81 28 (34.5) 1 (Ref) 1 (Ref)
Nuclear Family 129 89 (66.7) 3.57 (1.67-7.62) 3.31 (0.96-11.44)
Socio-economicƚ Status
Below middle class 84 25 (29.7) 1 (Ref) 1 (Ref)
Middle class and above 126 86 (70.6) 5.62 (2.56-12.29) 1.44 (0.37-5.61)
No. of Children
≤2 143 65 (45.4) 3.11 (1.37-7.02) 3.24 (0.86-12.24)
>2 67 49 (73.1) 1 (Ref) 1 (Ref)
Knowledge regarding modern contraceptives
Satisfactory 109 77 (70.6) 4.18 (1.97-8.84) 2.10 (0.58-7.55)
Unsatisfactory 101 37 (36.6) 1 (Ref) 1 (Ref)
Attitude towards usage of contraceptives
Favorable 81 77 (70.6) 5.95 (2.58-13.70) 4.67 (1.26-17.19)
Unfavorable 129 37 (36.6) 1 (Ref) 1 (Ref)
Women’s mobility
Empowered 123 82 (66.7) 3.54 (1.68-7.48) 1.10 (0.26-4.68)
Non-empowered 87 32 (36.8) 1 (Ref) 1 (Ref)
Freedom from family Domination
Empowered 118 89 (75.4) 8.31 (3.71-18.62) 5.56 (1.30-23.66)
Non-empowered 92 25 (27.1) 1 (Ref) 1 (Ref)
Economic Security
Empowered 94 67 (71.2) 3.66 (1.72-7.77) 2.86 (0.69-11.81)
Non-empowered 116 47 (40.5) 1 (Ref) 1 (Ref)
Received FP Counselling
Yes 136 101 (74.2) 3.66 (1.72-7.77) 4.41 (1.12-17.33)
No 74 13 (17.5) 1 (Ref) 1 (Ref)
ƪ OR- Odds Ratio, CI- Condence Interval
ƚ according to B.G Prasad Scale 2020
Hosmer-Lemeshow test statistic=0.61, Cox and Snell’s R2=0.42 & Nagelkerke’s R2=0.63
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modern methods of contraceptives and b) Barriers to
adopting modern family planning methods. Communication
gap, woman’s authority in choice of contraception, and
lack of couple counselling were the major codes under
the theme ‘Barriers to adopting modern family planning
methods’. Lack of knowledge and experience emerged as
the most important code under the theme of ‘Perspective
about modern methods of contraception. (Table 3).
TABLE 3. Juxtaposed Findings of both Qualitative and Quantitative Inquiry on Modern Contraceptive Usage
among study participants.
Associated Quantitative Qualitative Components Qualitative
Survey Themes Components with Quotable quotes Codes
Barriers to
adopting modern
family planning
methods
Perspective about
Modern methods
of Family
Planning
Communication
Gap
Women’s Authority
in Contraceptive
Choices
Knowledge Gap
Lack of Couple
Counselling
Lack of knowledge
and experience
“One can feel
embarrassed in discussing
contraceptives with
spouse”-46.7%
responded “YES”
“Husband’s objection to
contraceptive methods can
prevent a woman
from using it”- 52.3%
responded ‘YES’
“Does your partner know
about newer contraceptive
methods like Antara”-87.4%
responded “NO”
“Have you received
a couple counseling”-
98% replied “NO”
“Change in Mother-in-
law’s attitude may improve
contraceptive use”- 46.2%
replied “YES”
Less interaction about sexual and
reproductive life with spouses.
Husband’s domination in decision-making.
Decient knowledge of husbands about
various contraceptive choices.
“In our time there was no one to teach us
about reproductive health. It is important to
teach sex education in schools”- a 35 years
old male quoted.
Men do not feel enough empowered for
choosing contraceptives due to a lack of
couple counseling.
“ASHA didi told my wife to use contraceptives,
but it would have been better if both of us were
counselled in private. We could share more
things then”- a 28-year-old husband remarked.
“When we visit house to house we only get the
women at home, their husbands are at work
then. And especially we target the women who
come for ANC or PNC clinics at health-centres,
for FP counseling”- a 38-year-old ASHA told.
Preformed notions about harmful side-effects
of modern-day methods of contraception
and lack of experience.
“These modern-day girls don’t discuss their
lives with us, the elderly. They won’t take our
advice too. So I don’t talk about this with my
daughter-in-law and I personally never used
any contraceptives in our times”- a 68-year-old
mother-in-law remarked.
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DISCUSSION
e present study tried to address holistically all
the aspects of FP and elicited some major determinants
of practicing modern FP methods among currently
married women of reproductive age group in a rural area
of Bengal. A study by Ahirwar RK et al, done in central
India showed that 88.5% of study participants had never
used any contraceptive methods while the current study
found a considerable proportion of reproductive-aged
married women using any of the modern contraceptive
methods (54.8%).11 Another research work done in
rural Maharashtra, India by Dixit A et al found this
percentage to be only 38.3% (more than one-third of
the study sample).12 e current study detected that
tubal ligation was the most commonly used method of
contraception which was found concordant with a study
conducted at the national level in India by Ewerling F et al,
where it was found that the majority of the reproductive-
aged married women were using modern methods of
contraceptives mostly in the form of sterilization. Condom
and oral contraceptives were the second and third most
commonly used contraceptive methods.13 Another study
done by Talungchit et al in ailand showed that the most
commonly used method of contraception among teenage
multigravida and primigravida was oral contraceptive
pills, while only 5% among primis and 25% among
multigravidas were using contraceptives.14 A retrospective
cohort study conducted at a medical college clinic in
ailand showed that approximately 15% of women
had never used any contraceptive methods.3 A research
work conducted by Chopra S et al demonstrated that
acceptance of a permanent method of contraception
among a tribal population in northern India was only
5%.15
Although the status of women in India has improved
over time, across dierent dimensions, gender discrimination
and patriarchal social norms still remain a burning
issue in this nation, especially in rural areas. Only 20%
of participants in the present study were found to be
empowered by means of economic security. Moreover,
this study found that women who are free from any kind
of family domination were more likely to use modern
contraceptives. Another study of rural Maharashtra,
India by Reed E et al elicited that there was a signicant
association between woman’s access to money and the
usage of condoms or other methods of contraceptives.
Other signicant determinants detected in that research
work were women’s control over reproductive health
decision-making and freedom of movement to seek
health care.16 A study conducted in Egypt by Samari G
et al found that determinants of women empowerment
like household decision-making, non-acceptance towards
intimate partner violence, and joint decision-making power
are signicantly associated with modern contraceptive
usage.17
is mixed-methods study is a strength in itself as the
qualitative exploration led to an in-depth understanding
of the perspectives of modern contraceptive usage and its
important barriers among the family-level stakeholders
and healthcare providers. Previous studies in India and
abroad had explored some of the major barriers to modern
contraceptive usage such as a woman’s fear of side eects or
other health concerns and the absent cafeteria approach.18-20
A scoping review on determinants of unmet need of
family planning in low and middle income countries
by Wulan et al showed that the reasons behind the
non-usage of contraceptives among women were mostly
opposition from husbands, their fear of indelity and
fear of side eects.21 From the health workers’ point of
view, the barriers that had been explored by prior studies
are low prioritization of contraceptive training, disputes
over funding, and an overburdened health system.22,23
In addition to these above ndings, the current study
found some new emerging barriers like lack of couple
counselling, misinformation from peer groups, generalized
fear, and misconception about modern contraceptive
methods among the elder generation. Hence appropriate
and suitable interventions are necessary so that they can
gradually adjust to and overcome these pre-existing as
well as emerging barriers to modern family planning
use.
Limitations
As the study participants came from a unique
population, the generalizability of the present study had
been compromised. Since this study was of cross-sectional
nature, a causal relationship between the variables and
contraceptive usage could not be established. Moreover,
as some information obtained was recall-based, bias
might be possible.
CONCLUSION
Investing in family planning is the most intelligent
step that developing nations like India can undertake to
improve their socio-economic and maternal-child health
scenario. us, in order to improve the overall family
planning practice, certain measures like awareness generation,
education, extending help for self-empowerment, and
most importantly economic independence among women
need to be prioritized. Support from healthcare facilities
like couple counseling is needed to overcome barriers
like the lack of involvement of family-level stakeholders,
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674
especially the husbands in process of making a decision
on contraception. Ensuring the availability of all kinds
of modern contraceptives in remote and rural health
centres should also be done sustainably.
ACKNOWLEDGMENTS
e authors were grateful to the ocer-in-charge
and sta of RHUTC, Singur, for their constant support
and co-operation during this dicult pandemic phase
throughout our study. We extend our heartfelt gratitude
to all the participants who participated in this study.
Declaration of Conicting Interests: e authors declared
no potential conicts of interest concerning the research,
authorship, and/or publication of this article.
Funding: e authors received no nancial support for
the research, authorship, and/or publication of this article.
Ethical Issues: is study was conducted aer ethical
clearance from the Institutional Ethics Committee of All
India Institute of Hygiene and Public Health, Kolkata.
Appropriate written informed consent was taken from
the participants before conducting the study. ey were
assured of the condentiality of the data provided by
them. All other ethical principles as per the Declaration
of Helsinki were strictly adhered to.
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Donta B, et al. Spousal discordance on reports of contraceptive
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10. Dalvi TM, Khairnar MR, Kalghatgi SR. An update of BG
Prasad and Kuppuswamy socio-economic status classication
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12. Dixit A, Johns NE, Ghule M, Battala M, Begum S, Yore J, et al.
Male–female concordance in reported involvement of women
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India. Reprod Health. 2021;18(1):139.
13. Ewerling F, McDougal L, Raj A, Ferreira LZ, Blumenberg C,
Parmar D, et al. Modern contraceptive use among women
in need of family planning in India: an analysis of the inequalities
related to the mix of methods used. Reprod Health. 2021;18(1):173.
14. Talungchit P, Lertbunnaphong T, Russameecharoen K. Prevalence
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women. Siriraj Med J. 2017;69(6):363-9.
15. Chopra S, Dhaliwal L. Knowledge, attitude and practices of
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16. Reed E, Donta B, Dasgupta A, Ghule M, Battala M, Nair S, et al.
Access to money and relation to women’s use of family planning
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Child Health J. 2016;20(6):1203-10.
17. Samari G. Women’s empowerment and short-and long-acting
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458-73.
18. Jain M, Caplan Y, Ramesh BM, Isac S, Anand P, Engl E, et al.
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19. McClendon KA, McDougal L, Ayyaluru S, Belayneh Y, Sinha
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Sengupta et al.
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Original Article SMJ
Kawin Pratumaneechai, M.A.*, Archwin Tanphaichitr, M.D.**, anongchai Siriapisith, M.D.***, Vannipa
Vathanophas, M.D.**, Kitirat Ungkanont, M.D.**, Puttinun Patpituck, Ph.D.*
*Vejnitatphattana School, Medical Educational Technology Program, **Department of Otorhinolaryngology, ***Department of Radiology, Faculty of
Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.
Simulated Surgical Model Design for Myringotomy
and Tympanostomy Tube Insertion in Children
using Medical Image Processing and 3D-Printing
Technologies
ABSTRACT
Objective: Researchers aimed to design surgical simulation models using medical image processing and 3D-printing
technologies to train otolaryngologie residents with correct surgical techniques and study their skills improvement.
Materials and Methods: e models were produced for three age ranges (group A: 8-12 years old, group B: 3-7 years
old, and group C: 10 months - 2 years old). Eleven residents were practiced from older to younger child models.
Overall surgical time and results were evaluated to determine improvement. Both residents and specialists assessed
satisfaction surveys aer training.
Results: e median operational time was signicantly reduced by 64.57% in model A and 50.24% in model B
(p < 0.05). Operating time and surgical skills improved in order from models A, B, and C. Model C showed the most
improvement with correct operational techniques in myringotomy incision (66.7%, p = 0.003) and tympanostomy
tube insertion (48.5%, p = 0.011). Residents’ and specialists’ satisfaction assessments exhibited prominent satisfaction
results with surgical simulation model training.
Conclusion: Surgical simulation models training enhanced residencies’ condence and improved correct surgical
techniques. Residencies can gradually practice skills from fundamental to more complicated techniques in younger
child model where symptom occurs.
Keywords: Myringotomy; tympanostomy tube insertion; medical image processing; 3D-print; surgical simulation
(Siriraj Med J 2022; 74: 675-683)
Corresponding author: Puttinun Patpituck
E-mail: puttinun.pat@mahidol.ac.th
Received 25 April 2022 Revised 11 September 2022 Accepted 19 September 2022
ORCID ID:http://orcid.org/0000-0002-2669-7999
http://dx.doi.org/10.33192/Smj.2022.79
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Otitis media with eusion (OME) is accumulation
of uid in middle ear that causes inammation and uid
build-up behind eardrum. 90% occurred in children
between six months and four years.1,2 Build-up of uid
in middle ear aects tympanic membrane and middle
ear functions, leading to conductive hearing loss and
occasional pain from pressure changes while also aecting
speech, cognition, behavioral problems, and language
development. Ear tube insertion is a procedure whereby
doctor inserts a tympanostomy tube into eardrum to
ameliorate ear infections and allow drainage of excess uid
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676
from middle ear. e myringotomy and tympanostomy
tube insertion require precise surgical skills under a
microscope.3-5
Medical practitioners should improve their knowledge
of operational procedures and practice performing with
correct surgical techniques to reduce surgical risks. e
major problem is the procedures are dicult to learn
and practice. Anatomical structures of children are
signicantly dierent from adults concerning anatomy and
physiological dierences in bone growth and development.
e research study by Ungkanont et al., also found
that 70% of the children with cle palate had their rst
myringotomy before they were 3 years old, while 62.5%
of normal children had their rst ventilation tubes within
their rst 5 years. e mean age at rst myringotomy
in children with cle palate was 1.3 years old, which
required precision surgical techniques for operation.6
e complication from myringotomy and tympanostomy
tube insertion can also develop to granular myringitis in
the patient with a history of other ear diseases. Having
the ability to better operations can reduce the risk factors
for the development of complications aer surgery.7
Many simulation models are designed for practicing
myringotomy and tympanostomy tube insertion. But
use easily found materials, such as boxes and syringes
to simulate the ear holes,8-10 which model appearance
is unrealistic.11-13 Also the medical models are designed
as adult, and have not been designed as a child, where
the symptom most occurs.14 Hence researchers aimed
to design and build more realistic simulation models of
the children in various age ranges that allow unlimited
practice with the operating microscope and surgical
instruments used during the actual operation, which can
be a benecial teaching tool for medical practitioners.
The designed simulation models were continued to
be benecially used for training the otolaryngology
residents at the Department of Otorhinolaryngology,
Siriraj Hospital, Mahidol University, until the present.
In addition, the researchers suggested that the study
subjects should be conducted with a larger population
in future studies
Medical imaging data conversion to surgical simulation
models
Image data were collected from CT scans of healthy
children’s heads and related organs. Patients’ age ranges
were categorized into three groups; group A: 8 to 12 years
old, group B: 3 to 7 years old, and group C: 10 months
to 2 years old. Two-dimensional image data from CT
scans were transferred to Materialize Mimics soware
by uploading DICOM les and selecting the particular
tissues.15,16 Anatomical positions of tympanic membrane,
ossicular ligaments, and oval window were captured to
ensure that ear canal, tympanic cavity, and middle ear
were accurate. 2D image data processing in Mimics
soware makes it possible to generate three-dimensional
models in stereolithography (.stl) le format that can be
designed on a computer-aided design soware (Pixologic
ZBrush).15-17 Connective parts between ears and head were
designed, and model head circumference was adjusted
to match average data from World Health Organization
(WHO). Standard ratios of model perimeters as follows;
group A: 52 – 54 cm, group B: 49 – 51 cm and group C:
45 – 48 cm. (Fig 1)
e designed 3D models were imported to Ultimaker
Cura 4.2.1 soware to convert to G-code (gcode) that
commands path and instructs 3D printing machine
(Anet A8 Plus).18,19 e selected thermoplastic material
was Polylactic-acid plastic (PLA). Injector temperature
was set at 220 °C, with build plate temperature at 70 °C
and layer detail as ‘Normal’ (0.15 mm). Solid 3D printed
models appeared horizontal lines of plastic laments.
Hence surfaces of the models were polished to remove
lines from silicone casting molds. Yellow polyester putty
was used as a primer before workpieces were polished
using No. 800 and No. 1000 sandpapers. Clean water
was applied to surface before spraying with a gray primer
(Leyland Polypropylene Primer) to detect any rough
areas on 3D printed models. Primer provided a smooth
surface that was easy to separate from mold. Various types
of silicone rubber are used for casting medical models,
depending on underlying objectives and level of realism
required by application. 1300 silicone rubber was chosen
Fig 1. Surgical simulation models designs
for three age ranges
(Model A, Model B and Model C)
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to create ear models, with RTV-357 silicone rubber to
create head models. A food-grade plastic bag with 15-18
microns thickness was selected by specialists in pediatric
otolaryngology for articial eardrum. When viewed from
a microscope, the material is slightly opaque with a glossy
surface, and surface tension is similar to eardrum. e
articial eardrum was attached by applying a thin layer
of latex glue over cylindrical end of ear model, using an
O-ring (No. 113) to tighten. Aer straightening plastic
sheet, a skin-color marker was used to draw the line to
refer to malleus bone location.
MATERIALS AND METHODS
Ethical consideration
e research was approved by the Institutional
Review Board of the Faculty of Medicine Siriraj Hospital,
Mahidol University (SIRB) (Si 251/2020). e study has
requested permission to use CT scan image data of healthy
children’s heads and related organs from the Department
of Radiology, Siriraj Hospital, Mahidol University. ere
are three groups of patients categorized by the age range:
the age of 10 months to 2 years old, 3 to 7 years old, and
8 to 12 years old, with three patients in each group, for a
total of 9 patients. e names are concealed, and the data
only indicates their ages and genders. e subjects of the
study are rst-year otolaryngology residents who had not
previously experienced myringotomy and tympanostomy
tube insertion. e researchers announced participants
who volunteered by posting an invitation poster at the
Department of Otorhinolaryngology, Siriraj Hospital,
Mahidol University inviting residencies to participate in
the practice session. If any participants did not want to
join this research project, their study and grades would
not be aected. e clarication participant information
sheet was distributed to the participants who voluntarily
registered before joining the research project, which
informed the study’s objectives, methods, data collection,
and expected benets. e participants’ data were kept
in condence, and the research ndings will be reported
in the overall results.
Recruitment and instruction
Residencies who volunteered to participate in the
study were advised the myringotomy and tympanostomy
tube insertion procedures before training. Instruction
included lectures and a demonstration of operational
techniques using surgical simulation models. e list of
equipment used for training includes; 1) microscope, 2)
ear speculum, 3) alligator forceps, 4) myringotomy knife,
5) straight pick, 6) tympanostomy tube or grommet;
polyethylene tube no.90, 7) simulated surgical models,
and 8) adjustable table
Data collection
Two videos recorded otolaryngologie residents’
training using a microscope (OPMI Pico) to view
tympanic membrane, DSLR camera (Canon 7D) captured
hand movements and the use of equipment. (Picture
2) Participant information was encoded by a number
instead of student’s name and ID, with faces and voices
concealed. Participants performed in order from model
A, B, and C, the older to younger child model. e second
training session was repeated in the same setting aer
one week. e videos were arranged side-by-side to show
time duration of operation.
Fig 2. Myringotomy and tympanostomy tube insertion training.
Case record form and surveys
1. e residencies’ operation times were recorded from
the beginning to the last procedure. e three specialists
in pediatric otolaryngology watched videos and assessed
residencies’ prociencies in each procedure in the case
record form. By the scoring criteria, 10 (completed), 5 (not
completed), and 0 (not performed) in the corresponding
score box.
2. e satisfaction survey was used to assess the
residencies’ satisfaction in surgical simulation model
training. e residencies rated their level of agreement as
strongly agreed, agreed, disagree, and strongly disagree
regarding knowledge, understanding, and condence in
operation. e comments section is open for residencies
to suggest improvement ideas for the surgical simulation
model training.
3. e specialists in pediatric otolaryngology also
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678
completed a satisfaction survey to assess the eectiveness
of the training with simulated surgical models compared
with their regular teaching experiences, rated by the level
of satisfaction as very satised, satised, neutral, and not
satised. e comments section is open for specialists in
pediatric otolaryngology to suggest improvement ideas
for the surgical simulation model training.
Statistical analysis
1) e residencies’ operation time were compared,
ranked, and calculated statistically by Wilcoxon’s Signed
Ranks Test. PASW Statistics (SPSS) version 18.0 (SPSS Inc.,
Chicago, IL., USA) was used for the statistical analysis. If
the p-value less than 0.05, the result is concluded that the
operation time was reduced with statistical signicance.
And would be concluded that the medical models could
enhance faster operation time.
2)e analysis of the residencies’ operation skill
results; McNemar Bowker Test was used in each procedure
to test the signicance of the score comparison in Test
1 and Test 2, and calculated the testing results with the
statistical SPSS Program. When the p-value less than 0.05,
it is concluded that the residencies’ skill was developed
in the particular operative procedure with statistical
signicance.
3) Satisfaction survey analysis; the competencies of
the medical models were rated by level of agreement as
strongly agreed, agreed, disagree, and strongly disagree
regarding knowledge, understanding, and condence in
operation. e researchers summarized the statistical
scoring results in the table with frequency distribution
and conversed them into percentages.
RESULTS
Improvements in operational time
e otolaryngologie residents spent a shorter time
performing model A and B, with statistically signicant
results. e median operational time was 64.57% faster in
model A, while model B was 50.24% faster. e Wilcoxon
signed-rank test’s statistical analysis showed a two-
tailed signicance (p < 0.05) in model A (p = 0.007) and
model B (p = 0.003). Results in model C gave uctuating
operational time (p = 0.147) Overall operational time
were reduced from model A, B, and C in order, indicating
that residencies have gained familiarity by frequent
repetition practices. (Table 1)
TABLE 1. Operational time using the simulated surgical models.
Time (sec)
n Median IQR Minimum Maximum
Model A Test 1 11 587 325 197 1195
Model A Test 2 11 208 263 125 515
Test 1 – Test 2 11 379 363
Percentage 64.57%
P-valuea 0.007*
Time (sec)
n Median IQR Minimum Maximum
Model B Test 1 11 613 205 156 759
Model B Test 2 11 305 280 157 483
Test 1 – Test 2 11 308 159
Percentage 50.24%
P-valuea 0.003*
Time (sec)
n Median IQR Minimum Maximum
Model C Test 1 11 382 263 104 1044
Model C Test 2 11 204 267 88 527
Test 1 – Test 2 11 178 270
Percentage 46.6%
P-valuea 0.147
aWilcoxon signed rank test
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Operational skill results
e operational skill results also indicated that
residencies improved their correct surgical techniques in
order from model A, B, and C. e number of prociencies
that showed statistical signicance evaluated by the
McNemar-Bowker test was increased from older to younger
child model (p < 0.05). (Table 2) For instance, model A
showed one prociency improvement 54.4% in checking
the tympanostomy tube position on completion (p =
0.004). Model B showed three prociencies improvement
as 42.4% in correction of holding the myringotomy
knife in the right direction (p = 0.039). Correction of
incision size showed 54.6% improvement (p = 0.021),
and 47.7% improvement in checking the tympanostomy
tube position on completion (p = 0.057). While model
C showed four prociencies improvement as 42.4% in
microscope camera adjustment (p = 0.046). e correction
of incision size showed 66.7% improvement (p = 0.003).
e correction of tympanostomy tube insertion showed
48.5% improvement (p = 0.011), and 42.4% improvement
in checking the tympanostomy tube position on completion
(p = 0.039).
Additional results in model A also occurred that
some residencies had diculty making an incision in
the correct position. e incision should be made on the
anterosuperior quadrant or anteroinferior quadrant of
tympanic membrane. Some residencies could not estimate
the incision size during rst performance. e incision
is too wide and causes to dropped the tympanostomy
tube into middle ear, which is unacceptable in actual
operation. Results in model B also showed that some
residencies used straight pick to push the tympanostomy
tube through the myringotomy incision using the outer
ange instead of inner ange. Model C results also showed
that some residencies encountered diculties pushing
tympanostomy tube into the incision in narrower ear
canal and oen accidentally touched the malleus, which
is also unacceptable in actual operation.
TABLE 2. Operational skills using the simulated surgical models.
P-valueb
(Percentage of Improvement)
Item Prociency Model A Model B Model C
1 Adjust the microscope 18.2% 6% 42.4%
camera to clearly see the eardrum (0.613) (0.816) (0.046*)
2 Select the correct ear speculum 66.6% 18.1% 12.2%
(0.388) (0.312) (0.5)
3 Hold the myringotomy knife 24.2% 42.4% 36.4%
in the right direction (0.065) (0.039*) (0.109)
4 Correct incision position 30.4% 48.4% 36.4%
(0.168) (0.076) (0.2144)
5 Correct incision size 30.2% 54.6% 66.7%
(0.5287) (0.021*) (0.003*)
6 Use the knife without touching the ear canal 12% 12.2% 24.2%
or causing the eardrum to tear apart (0.5313) (0.774) (0.359)
7 Handle the tympanostomy tube properly 48.5% 6.1% 36.4%
using alligator forceps (0.078) (1) (0.302)
8 Insert the tympanostomy tube in the correct direction 24.2% -12.1% 48.5%
at the myringotomy incision (0.348) (0.847) (0.011*)
9 Use the straight pick to push the tympanostomy tube 12.1% 60.6% -15.2%
or alligator forceps to insert the tympanostomy tube (1) (0.15) (0.668)
through the myringotomy incision
10 Check the tympanostomy tube positionon completion 54.4% 47.7% 42.4%
(0.004*) (0.057*) (0.039*)
b McNemar-Bowker test
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680
Recidencies satisfaction with the training
e satisfaction assessment showed strongly agreed
results in all competencies. (Table 3) e major inuencing
competencies indicated that the simulated surgical
models eectively increased residencies’ operational
skills (x = 3.91), and the models should be expanded to
encompass dierent medical practices. (x = 3.91). e minor
inuencing competencies showed that the simulated surgical
models increased residencies’ condence when operating
(x = 3.82). e simulated surgical models were eective
and easy to understand learning techniques (x = 3.82)
and had a level of diculty in practicing skills suitable for
residencies year (x = 3.82). Additional comments from
residencies also noted that using the same tympanostomy
tube repeatedly during training caused the outer ange
to deteriorate. e residencies suggested changing the
tympanostomy tube aer repeating the training, while the
material used for the tympanic membrane was too elastic,
making it dicult to attach to the tympanostomy tube.
Satisfaction of the specialists in pediatric otolaryngology
with simulated surgical models training
e simulated surgical models can simulate complicated
hands-on surgical procedures to supplement observation
before operating on patients. e major inuence on
specialists’ satisfaction indicated that simulated surgical
models improved residencies’ understanding in operational
processes (x = 3.67). e residencies gained condence
through practicing the operational techniques (x = 3.67)
and were consistent with the learning objectives according
to the training content (x = 3.67). e simulated surgical
models were easy to use, durable, and easy to maintain
for repetitive training (x = 3.67) and should be further
developed to simulate other operational techniques in
the future (x = 3.67). (Table 4) Additional comments
from the specialists in pediatric otolaryngology also
suggested that the position of the malleus was uncertain.
is issue caused some residencies to accidentally touch
the malleus. In some cases, the tympanic membrane was
not tight and less realistic, while the O-ring should not
be too tight because this caused narrowing of the ear
canal and presented diculties for some residencies.
DISCUSSION
e results showed that the residencies have gained
more condence and enhanced surgery fundamentals
through repetitive training with surgical simulation models.
Residencies can understand operational procedures with
TABLE 3. Training satisfaction using the simulated surgical models.
Item Competency Mean (x
) SD Result
1 Simulated surgical models improved knowledge and 3.73 0.47 strongly agreed
understanding of the operational processes
2 Simulated surgical models increased operational skills 3.91 0.30 strongly agreed
3 Simulated surgical models increased condence 3.82 0.40 strongly agreed
when performing the operation
4 Simulated surgical models were practical and 3.82 0.40 strongly agreed
easy-to-understand learning techniques
5 Simulated surgical models were easy to use, 3.55 0.52 strongly agreed
durable and simple to maintain
6 Simulated surgical models were effective tools 3.73 0.47 strongly agreed
that increased their roles as practitioners
7 Simulated surgical models had a level of difculty in 3.82 0.40 strongly agreed
practicing skills suitable forresidence’s year
8 Simulated surgical models should be developed 3.91 0.30 strongly agreed
to practice skills in other clinical areas
* Four-points scale: 1 = strongly disagree; 4 = strongly agreed
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TABLE 4. Satisfaction of the specialists in pediatric otolaryngology with simulated surgical models training.
* Four-points scale: 1 = not satised; 4 = very satised
Item Competency Mean (x
) SD Result
1 Simulated surgical models improved
residencies’ operational processes 3.67 0.58 very satised
2 Simulated surgical models increased 3.33 0.58 satised
residencies’ operational skills
3 Simulated surgical models increased 3.67 0.58 very satised
residencies’ operational condence
4 Simulated surgical models were consistent with 3.67 0.58 very satised
the learning objectives according to the training content
5 Simulated surgical models had a level of difculty 3.33 0.58 satised
in practicing skills appropriate for the residencies’ year
6 Simulated surgical models increased interaction 3.33 0.58 satised
between the instructor and residencies
7 Simulated surgical models were cost-effective 3.33 0.58 satised
and suitable for the number of trainees
8 Simulated surgical models were easy to use, 3.67 0.58 very satised
durable and easy to maintain
9 Simulated surgical models should be further developed 3.67 0.58 very satised
for other operational simulations
an improvement of operation times in Model A (64.57%,
p = 0.007) and Model B (50.24%, p = 0.003) and develop
better skills in correct incision size in Model B (54.6%,
p = 0.021) and Model C (66.7%, p = 0.003), and inserting
the tympanostomy tube in the correct direction in Model
C (48.5%, p = 0.011), which these skills are essential to
reduce surgical complications. e major inuence on
residents’ satisfaction showed that the surgical simulation
models eectively increased residencies’ operational skills
(x = 3.91). Residencies can encounter problems or unforeseen
circumstances and help improve skills for practitioners
who lack the experience to reduce the risks of surgery
with real patients. To date, residencies can only learn by
observing medical lecturers or seniors. Hence, the second
major inuence on residents’ satisfaction showed that
the models should be expanded to encompass dierent
medical practices. (x = 3.91) e specialists’ satisfaction
assessment also showed prominent satisfaction results
with surgical simulation model training. e major
inuence on specialists’ satisfaction showed that simulated
surgical models improved residencies’ understanding
in operational processes (x = 3.67), gained condence
through practicing the operational techniques (x = 3.67),
and were consistent with the learning objectives according
to the training content (x = 3.67). e models were
easy to use, durable, and easy to maintain for repetitive
training (x = 3.67) and should be further developed
to simulate other operational techniques in the future
(x = 3.67). e specialists’ satisfaction was evaluated
with the normal teaching experiences and found that the
simulation-trained residencies were notably outperformed.
Simulators can provide a safe and standardized method
for surgery training without risks. ey allow trainees to
practice their surgical skills, contribute detailed feedback
by performance assessment, and enable better patient
safety and standards of care. e evidence exhibits that
surgical skills are acquired through simulation training,
and specialists are positively considered to transfer
simulation training to the clinical teaching setting and
improve operative outcomes.
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From the study, the surgical simulation models
can be further developed to become more realistic. e
following areas of improvement were discussed. 1) e
ear canal in Model C is narrower than Model A and B.
Some residencies encountered diculties during operation
in model C that were more complicated than Model A
and B. 2) Scanned le of the ear canal is too narrow,
which may cause problems for residencies in operating
procedures. CT scans were captured with the head of
the patient (temporal area) lying on a pillow, which
caused uncertainties in ear canal size. Future simulation
models need to adjust the ear canal width to be suitable
for production and training purposes. 3) e material
used to imitate the tympanic membrane had a muscular
and bouncing surface tension, which caused diculties
when placing the tympanostomy tube in the incision.
A more appropriate material should be used. Whereas,
the appearance of the studied material when looking
through a microscope camera was already similar to real
tympanic membrane. 4) A skin color marker pen used to
imitate the malleus was uncertain. Marking the position
of the malleus should have a standard setting. 5) Some
residencies pressed down on the outer-ear during training,
which compressed the gap inside the middle ear part and
made it dicult to insert the tympanostomy tube in the
incision. e gap between the tympanic membrane and
the middle ear should be increased. With more realistic
simulation model design, medical practitioners can
practice with the microscope and surgical instruments as
the actual operation. Real-time myringotomy simulations
using virtual reality (VR) are benecial, with savings on
manufacturing costs.20-22 However, the tangible surgical
simulation models lack response to feedback from the
practitioners as other simulations. With current technology,
surgical simulation models can incorporate capacitive
sensing technology to track equipment placement and
quantitatively measure operator prociency in live surgical
procedures.23 Researchers suggest combining medical
models with innovative features such as sensors and
intelligent tracking systems that can enhance realistic
experiences for medical practitioners. Researchers believe
that more research studies will need to develop and
transfer the benets of surgical simulation training to
clinical teaching and aim to create surgical simulation
models for other symptoms in the future.
e limitation in this study was due to a small
number of sample subjects, which aected the study’s
statistical results. Hence, the researchers recommended
that future research should be conducted with more
sample subjects in the study.
CONCLUSION
e myringotomy procedure and tympanostomy tube
insertion require specialized training with the microscope.
Using surgical simulation models as a learning tool
increased condence and improved the expertise of
the residencies to reduce surgical risks and improve
their knowledge of operational procedures. Training
with various model age ranges also allows residencies
to frequent repetition practices from fundamental to
experiment with more complicated techniques in the
younger child model where the symptom most occurs.
ACKNOWLEDGEMENTS
The authors extend their deepest gratitude
to the Veinitatphattana School, Department of
Otorhinolaryngology, and Department of Radiology,
Faculty of Medicine Siriraj Hospital, Mahidol University
for their support and contributions to the design and
development of the simulator, and for providing the
location for testing and clinical advice.
Conict of interest: e authors declare they have no
potential conicts of interest with respect to the research,
authorship, and/or publication of this article.
Funding: e authors received no nancial support for
the research, authorship, and/or publication of this article.
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Nitiwut Saenmanot, M.D.*, Monchai Ruangchainikom, M.D.*, anase Ariyawatkul, M.D.*, Ekkapoj Korwutthikulrangsri,
M.D.*, Soraya Saenmanot, Ph.D.**, Panya Luksanapruksa, M.D.*, Werasak Sutipornpalangkul, M.D.*, Sirichai
Wilartratsami, M.D.*, Chatupon Chotigavanichaya, M.D.*
*Department of Orthopedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand, **Faculty of Public Health,
Mahidol University Amnatcharoen Campus, Amnatcharoen, ailand.
Survival Analysis of and Prognostic Factors for
Metastatic Epidural Spinal Cord Compression
Compared between Preoperative Known and
Unknown Primary Tumors
ABSTRACT
Objective: To analyze the median survival time of and prognostic factors for metastatic epidural spinal cord
compression (MESCC) secondary to preoperative unknown primary tumor (pre-op UPT) compared to MESCC
secondary to preoperative known primary tumor (pre-op KPT).
Materials and Methods: is retrospective cohort study reviewed all consecutive MESCC patients who underwent
surgical decompression with or without stabilization within 72 hours of admission during 2010 to 2016. Survival
was compared between the pre-op UPT and pre-op KPT groups, and preoperative and postoperative prognostic
factors for survival were analyzed.
Results: A total of 169 patients (pre-op UPT: 51, and pre-op KPT: 118) were enrolled. e survival rate at 3, 6, and
12 months was 84.3%, 58.8%, and 47.1% in the pre-op UPT group, and 72.0%, 48.3%, and 34.7% in the pre-op KPT
group, respectively. e median survival time secondary to lung cancer was signicantly longer in the pre-op UPT
group (6.0±1.4 months) than in the pre-op KPT group (3.6±0.2 months) (p=0.031). Multivariate analysis revealed
survival time to be inuenced by preoperative known or unknown primary tumor status, revised Tokuhashi score,
the adjuvant therapy, and postoperative complications, including myocardial infarction, gastrointestinal bleeding,
and urinary tract infection.
Conclusion: MESCC secondary to preoperative unknown primary tumor patients who had the clinical presentation
with acute progressive neurological decits who need urgency spine surgery has comparable survival to MESCC
secondary to preoperative known primary tumors.
Keywords: Metastasis; spinal cord compression; unknown primary tumor; survival time; prognosis; urgency
decompression (Siriraj Med J 2022; 74: 684-692)
Corresponding author: Monchai Ruangchainikom
E-mail: monchai.ortho@gmail.com
Received 30 April 2022 Revised 12 September 2022 Accepted 13 September 2022
ORCID ID:http://orcid.org/0000-0003-0525-6390
http://dx.doi.org/10.33192/Smj.2022.80
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Cancer is one of the leading causes of death.1 Spinal
metastasis was found in seventy percent of cancer death
undergoing autopsy, and 10% of spinal metastasis patients
developed neurological decits.2,3
Metastatic epidural spinal cord compression (MESCC)
patients who can realize potential benet from surgical
decompression should be urgently treated to improve
patient functional status, mental status and to prevent
persistent loss of motor and/or sensory function.4,5 Surgical
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management is usually considered in patients who have
a life expectancy of greater than 3 months.6
Survival time prediction has important clinical
implications, including decision-making relative to the
potential benet of surgical treatment or palliative cancer
therapies. ere are many scales/scoring systems for
predicting the prognosis of MESCC patients, especially
Tomita7 and revised Tokuhashi8, which are the most
widely accepted scoring systems. ese assessment tools
are useful when standard diagnostic strategy is complete,
to include tumor marker, Tc-99m bone scan, positron
emission tomography (PET) scan, chest-abdomen-pelvis
computed tomography (CT) scan, magnetic resonance
imaging (MRI) of the spine with contrast, and tissue
biopsy. However, these investigations take time that may
delay proper management of spinal metastasis patients
who have acute neurological decit as the rst clinical
presentation. ese patients whose primary tumor was
initially not denitively known were described as MESCC
with preoperative unknown primary tumor (MESCC
with pre-op UPT).
Urgent surgical decompression is quite common
in MESCC patients with pre-op UPT. To the best of
our knowledge, there is no study that has compared
survival time between MESCC with pre-op UPT and
MESCC with the preoperative known primary tumor
(MESCC with pre-op KPT) in this urgent neurological
compromise setting.
us, survival analysis of all consecutive MESCC
with pre-op UPT or pre-op KPT who underwent surgical
decompression was the main objective of this study. e
secondly aim was to identify prognostic factors associated
with median survival time in both groups.
MATERIALS AND METHODS
is retrospective cohort study reviewed all 193
consecutive MESCC patients who underwent surgical
decompression with or without stabilization within 72
hours of admission to Siriraj Hospital during 2010 to
2016. is study was approved by Siriraj Institutional
Review Board (SIRB) of the Faculty of Medicine Siriraj
Hospital, Mahidol University, Bangkok, ailand (Si
013/2016).
To be eligible for inclusion, MESCC patients who
underwent surgical decompression must have had all of
the following components of preoperative management:
1) complete medical history and physical examination; 2)
standard laboratory analysis, including tumor markers;
3) plain radiography of involved bone and chest X-ray;
and, 4) MRI spine with contrast medium, with imaging
of the whole spine the sagittal view. MESCC patients with
incomplete data or who died from a non-cancer-related
cause were excluded.
Patient survival time was investigated by telephone
call and a review of medical records. Preoperative and
postoperative assessment parameters were reviewed and
recorded, as follows: general demographic data, smoking
or nonsmoking, American Spinal Injury Association
(ASIA) impairment scale score, site of pathologic spinal
level, number of spinal metastases, pre-op KPT, pre-
op UPT, nal identied primary tumor site, revised
Tokuhashi score aer complete investigation, adjuvant
therapy, operative time and operative complications.
Statistical analysis
Chi-square test was used to compare categorical
variables (results shown as number and percentage),
and Student’s t-test was used for continuous variables
(results shown as mean plus/minus standard deviation).
Survival analyses were performed by Kaplan-Meier
method, with subsequent group comparison by log-rank
test. Prognostic factors associated with survival time
were identied by Cox proportional hazards model.
A p-value of < 0.05 was considered statistically signicant.
SPSS for Windows version 18.0 was used for all statistical
analyses.
RESULTS
Participants
Of the 193 MESCC patients that were evaluated for
eligibility, 24 were excluded. Of those, 19 were excluded
for having incomplete patient data or because we could
not determine their postoperative status. Another 5
cases were excluded because they died of a non-cancer-
related cause (3 suicides, 1 trauma, and 1 murder). e
remaining 169 MESCC patients were included in our
nal analysis (Fig 1).
Descriptive data
e baseline characteristics of the 169 enrolled
MESCC patients (101 males, 68 females) were evaluated
and compared between the pre-op UPT and pre-op KPT
groups. e mean age of study patients was 54.9±12.8
years. Fiy-one cases (30.2%) with preoperative unknown
primary tumor site were identied. All MESCC patients
presented with incomplete spinal cord lesion, and most
(59.2%) had ASIA impairment scale grade D. Almost
three-quarters (69.2%) of MESCC patients who underwent
urgent spinal decompression presented with more than
one level of spinal metastasis, and the most commonly
aected spinal region was thoracic spine (50.3%). Regarding
the postoperative revised Tokuhashi score aer complete
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Fig 1. Flow chart describing the patient enrollment process.
investigation according to the standard diagnostic strategy,
most patients (55.6%) had a score that fell into the 0-8
group.
e distribution of identied primary tumor site
in the pre-op UPT and pre-op KPT groups is shown in
Table 2. e most common identied primary tumor
site was the lung in both groups. From histological study,
eight of nine cases in the cancer of unknown primary
site (CUP) patients were adenocarcinoma, and the other
was undierentiated carcinoma.
Survival aer surgery
e median survival time between groups was not
signicantly dierent, but there was a trend towards longer
survival time in the pre-op UPT group (8.4 months, 95%
CI: 0.8-16.1) than in the pre-op KPT group (5.1 months,
95% CI: 3.5-6.8) (p=0.127). Kaplan-Meier survival method
and log-rank test were used to estimate survival and
compare the results between groups (Fig 2). e survival
rate at 3, 6, and 12 months was 84.3%, 58.8%, and 47.1%
in the pre-op UPT group, and 72.0%, 48.3%, and 34.7%
in the pre-op KPT group, respectively.
Concerning the lung being the most common primary
tumor site in both groups, the median survival time
secondary to lung cancer was 3.6 months (95% CI: 3.2-
4.0) in the pre-op KPT group, and 6.0 months (95% CI:
3.3-8.7) in the pre-op UPT group (p=0.031) (Fig 3).
Prognostic factors associated with survival time
Univariate analysis (Table 3) showed the following
prognostic factors to be signicantly associated with
survival time: American Spinal Injury Association (ASIA)
Impairment Scale at presentation, patient smoking status,
number of levels of spinal involvement, revised Tokuhashi
score aer inclusion of all standard diagnostic data
(especially identication of the type of metastatic tumor
from histologic nding), adjuvant treatment aer surgical
intervention, and postoperative complications, including
cerebral infarction (stroke), myocardial infarction (MI),
gastrointestinal bleeding (GI bleeding), urinary tract
infection (UTI), and pressure ulcer.
Multivariate analysis (Table 4) revealed preoperative
primary tumor of known or unknown status, adjuvant
therapy, revised Tokuhashi score aer collection of all
standard diagnostic data, and the postoperative complications
MI, GI bleeding, and UTI to be independent prognostic
factors associated with survival.
DISCUSSION
Interest in the predicted survival time of MESCC
patients has increased over the last few years because it is
one of the most important factors for guiding decision-
making in MESCC patients relative to whether patients
with neurological decit that require urgent care should
be given palliative care or operative management. In this
study, the prevalence of MESCC patients who presented
with acute progressive neurological decit that indicated
for spinal decompression was common with secondary
to primary unknown tumor. Moreover, we observed a
comparable between median survival time in the pre-op
UPT group and in the pre-op KPT group. Regarding lung
as the primary tumor site, which was the most common
primary tumor site in the pre-op UPT group (37.3%), we
found a signicantly longer median survival time in the
pre-op UPT group than in the pre-op KPT group. is
is an interesting nding, especially since patients with
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TABLE 1. Demographic and clinical characteristics compared between the preoperative unknown primary tumor
site group (Pre-op UPT) and the known primary tumor site group (Pre-op KPT).
Characteristics Pre-op UPT Pre-op KPT
(n=51) (n=118)
P-value
Gender, n (%)
Male 39 (76.5%) 62 (52.5%) 0.003
Female 12 (23.5%) 56 (47.5%)
Age
Mean age (±SD) 54.9±11.5 54.9±13.3 0.986
ASIA impairment scale
B 9 (17.7%) 19 (16.1%) 0.418
C 9 (17.7%) 32 (27.1%)
D 33 (64.7%) 67 (56.8%)
Pathologic spinal level
Cervical spine 7 (13.7%) 14 (11.9%) 0.917
Thoracic spine 27 (52.9%) 58 (49.2%)
T-L junction (T12-L1) 9 (17.7%) 24 (20.3%)
L2-3 or cord level 8 (15.7%) 22 (18.6%)
Revised Tokuhashi score
Score 0-8 28 (54.9%) 66 (55.9%) 0.116
Score 9-11 20 (39.2%) 33 (28.0%)
Score 12-15 3 (5.9%) 19 (16.1%)
Number of levels of spinal metastasis
1 level 19 (37.3%) 33 (28.0%) 0.296
2 levels 15 (29.4%) 31(26.3%)
≥3 levels 17 (33.3%) 54 (45.8%)
Adjuvant therapy
None 7 (13.7%) 11 (9.3%) 0.092
Chemotherapy (CMT) 2 (3.9%) 3 (2.5%)
Radiotherapy (RT) 26 (51.0%) 42 (35.6%)
CMT and RT 16 (31.4%) 62 (52.5%)
Abbreviation: ASIA indicated American Spinal Injury Association
the lung as the primary tumor site are given the lowest
score of 0, the poorest prognosis primary tumor origin
category, when using the Tokuhashi scoring system.8
MESCC with preoperative unknown primary tumor
with acute progressive neurological decits presents a
major decision-making challenge for a spine surgeon,
and it makes it dicult for the surgeon to oer the patient
accurate information specic to prognosis, survival,
and management. ese unknowns can lead to surgeon
reluctance to perform urgent spinal decompression and
stabilization, but a failure to do so can lead to adverse
outcomes for the patient compared to those who receive
urgent intervention. e general recommendation is to
perform surgery only in patients with a life expectancy
of greater than 3 months, and the common survival
prediction scoring systems are commonly based on
primary tumor, performance status, number of levels
of spine metastasis, neurological status, and presence
of visceral metastases.6-9 A recent guideline from the
Netherlands Comprehensive Cancer Organization relative
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TABLE 2. Distribution of identied primary tumor sites compared between the pre-op UPT and pre-op KPT groups.
Identied primary tumor site Pre-op KPT Pre-op UPT
(n=118) (n=51)
CA Lung 28 (23.7%) 19 (37.3%)
CA Breast 28 (23.7%) 1 (2.0%)
CA Prostate 10 (8.5%) 5 (9.8%)
Hematologic malignancy 10 (8.5%) 9 (17.6%)
CA Nasopharynx 8 (6.8%) 1 (2.0%)
CA Liver 7 (5.9%) 4 (7.8%)
CA Cervix 7 (5.9%) 0 (0.0%)
CA Colon 6 (5.1%) 0 (0.0%)
CA Thyroid 4 (3.4%) 1 (2.0%)
CA Kidney 2 (1.7%) 0 (0.0%)
CA Bladder 1 (0.8%) 0 (0.0%)
Others 7 (5.9%) 2 (3.9%)
Cancer of unknown primary site (CUP) - 9 (17.6%)
Fig 2. Kaplan-Meier survival graphs compared between pre-op
unknown primary tumor site group (Pre-op UPT, green line) and
the pre-op known primary tumor site group (Pre-op KPT, blue line).
Fig 3. Kaplan-Meier survival graphs compared between those with
pre-op unknown primary tumor site with post-op determination of
primary lung cancer (lung CA) (Pre-op UPT, green line) and those
with pre-op primary tumor site known to be the lung (Pre-op KPT,
blue line).
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TABLE 3. Univariate analysis for prognostic factors that predict survival time in MESCC patients who underwent
surgical decompression within 72 hours of hospital admission.
Variables n Univariate Analysis
HR 95% CI P-value
Preoperative primary tumor
known 118 1.334 0.920 – 1.933 0.129
unknown 51 1
Gender: males/females 101/68 1.088 0.777 – 1.523 0.625
Age
17 – 40 years 26 1.641 0.871 – 3.091 0.125
41 – 50 years 34 1.105 0.595 – 2.054 0.751
51 – 60 years 50 1.206 0.678 – 2.146 0.523
60 – 70 years 39 0.864 0.468 – 1.594 0.640
> 70 years 20 1
ASIA impairment scale
B 28 1.998 1.276 – 3.129 0.002*
C 41 1.108 0.737 – 1.664 0.622
D 100 1
Adjuvant therapy
None 18 2.344 1.345 – 4.086 0.003*
Chemotherapy(CMT) 5 1.186 0.371 – 3.787 0.774
Radiotherapy(RT) 68 1.092 0.763 – 1.563 0.630
Combined CMT and RT 78 1
Smoker (+/-) 43/126 1.471 1.010 – 2.142 0.044*
Pathologic level
Cervical spine 30 1 0.888 – 2.720 0.122
Thoracic spine 21 1.554 0.670 – 2.424 0.460
T-L junction (T12-L1) 85 1.274 0.718 – 2.532 0.353
L2-3 or cord level 33 1.3481
Spinal related symptom period
< 1 week 101 0.992 0.450 – 2.190 0.985
1 – 4 weeks 61 0.812 0.362 – 1.820 0.613
>4 weeks 7 1
Morbidity stage
ASA 1 7 1
ASA 2 85 0.990 0.430 – 2.281 0.982
ASA 3 75 1.233 0.532 – 2.858 0.625
ASA 4 2 2.2461 0.449 – 11.233 0.325
Group Tokuhashi score
Score 0-8 94 5.308 2.909 – 9.686 < 0.001*
Score 9-11 53 1.623 0.862 – 3.053 0.133
Score 12-15 22 1
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TABLE 3. Univariate analysis for prognostic factors that predict survival time in MESCC patients who underwent
surgical decompression within 72 hours of hospital admission. (Continued)
Variables n Univariate Analysis
HR 95% CI P-value
Number of spinal level involvement
1 level 52 1
2 levels 46 1.652 1.063 – 2.567 0.025*
≥ 3 levels 71 1.713 1.141 – 2.572 0.009*
Group operative time (hours)
< 3 hours 12 1
3 – 4 hours 60 0.758 0.391 – 1.467 0.410
4 – 5 hours 54 1.028 0.531 – 1.992 0.934
5 – 6 hours 26 1.042 0.501 – 2.170 0.912
> 6 hours 17 1.074 0.491 – 2.345 0.859
Post-op complications
Cerebral infarction (+/-) 3/166 3.754 1.172 – 12.028 0.026*
Myocardial infarction (+/-) 11/158 2.307 1.209 – 4.402 0.011*
Pneumonia (+/-) 42/127 2.803 1.925 – 4.081 <0.001*
Gastrointestinal bleeding (+/-) 11/158 3.973 2.108 – 7.489 <0.001*
Urinary tract infection (+/-) 68/101 1.650 1.177 – 2.313 0.004*
Thromboembolism (+/-) 18/151 1.590 0.942 – 2.686 0.083
Pressure ulcer (+/-) 54/115 1.521 1.072 – 2.157 0.019*
Abbreviations: ASIA; indicated American Spinal Injury Association, ASA; American Society of Anesthesiologists grade of physical status
to MESCC secondary to preoperative unknown primary
tumor recommends that, if it is possible, MRI of the
whole spine and PET-CT of the thorax/abdomen should
be performed, and that tissue biopsy should be obtained
within 1 day.10 An attempt to complete all recommended
investigations and tissue biopsy would delay the critical
time needed for recovery of injured neural tissue. e
results of our study revealed a survival time of greater
than 3 months in 72.0%-84.3% of MESCC patients.
Yalamanchili, et al. found that rapid progression is
common in patients who present with neurological
decit. ey found that 30% of patients with weakness
could progress to paraplegia within 1 week, and that
the likelihood of regaining neurological function was
very poor when paraplegia was present for more than
24 hours.11 Preserving the remaining functional neural
tissue, increasing the chance of neural tissue injury
recovery, and improving ambulatory status all play an
important role in patient survival and quality of life and
mental status.5 A meta-analysis of spinal metastasis by
Luksanapruksa, et al. found neurological decits and
ambulatory status to be commonly reported prognostic
factors for survival.12-15
Cancer of unknown primary site (CUP) was not
uncommon (17.6%) in this study, and the most common
histopathologic nding was adenocarcinoma. is is
similar to previous studies that reported a prevalence
of CUP in patients with MESCC of 13.4%-14.5%, and
the tissue pathology was usually adenocarcinoma.16,17
CUP is usually associated with more aggressive behavior
and shorter survival time, which are derived from both
biologic condition, such as prior immunoediting and/
or featuring a high degree of immunosuppression, and
lack of a specic guideline for clinical management.17,18
Our univariate analysis revealed several potential
prognostic factors signicantly associated with survival
time. Subsequent multivariate analysis that included those
factors revealed independent prognostic factors for survival
time. Among those, we found preoperative primary tumor
of known or unknown status to play an important role
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TABLE 4. Multivariate analysis for prognostic factors that predict survival time in MESCC patients who underwent
surgical decompression within 72 hours of hospital admission.
Variables n Multivariate analysis
HR 95% CI P-value
Pre-op primary tumor
known 118 1.657 1.060 – 2.590 0.027*
unknown 51 1
ASIA impairment scale
B 28 0.992 0.583 – 1.689 0.978
C 41 0.752 0.472 – 1.197 0.229
D 100 1
Adjuvant therapy
None 18 3.359 1.760 – 6.414 <0.001*
Chemotherapy(CMT) 5 2.401 0.691 – 8.346 0.168
Radiotherapy(RT) 68 0.944 0.616 – 1.447 0.792
Combined CMT and RT 78 1
Smoker (+/-) 43/126 1.435 0.930 – 2.214 0.103
Pathologic level
Cervical spine 30 1
Thoracic spine 21 1.855 0.978 – 3.518 0.058
T-L junction (T12-L1) 85 0.892 0.443 – 1.798 0.750
L2-3 or cord level 33 1.987 0.983 – 4.017 0.056
Group Tokuhashi score
Score 0-8 94 6.854 3.351 – 14.016 <0.001*
Score 9-11 53 1.892 0.973 – 3.679 0.060
Score 12-15 22 1
Number of spinal level involvement
1 level 52 1
2 levels 46 1.259 0.731 – 2.169 0.407
≥ 3 levels 71 0.937 0.542 – 1.622 0.817
Post-op complications
Cerebral infarction (+/-) 3/166 1.427 0.354 – 5.752 0.618
Myocardial infarction (+/-) 11/158 3.104 1.450 – 6.648 0.004*
Pneumonia (+/-) 42/127 1.402 0.870 – 2.260 0.165
GI bleeding (+/-) 11/158 3.565 1.702 – 7.465 0.001*
Urinary tract infection (+/-) 68/101 1.519 1.018 – 2.265 0.041*
Thromboembolism (+/-) 18/151 0.960 0.498 – 1.850 0.904
Pressure ulcer (+/-) 54/115 1.262 0.824 – 1.935 0.285
Abbreviation: ASIA indicated American Spinal Injury Association
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in survival time. We also found independent association
between the revised Tokuhashi score and survival. Similar
to other studies16,17, adjuvant therapy was identied as
an important prognostic factor for survival; however,
dierences in survival were reported among dierent
adjuvant treatments and dierent types of tumors.19-21
Lastly, we also found postoperative complications, including
myocardial infarction, gastrointestinal bleeding, and
urinary tract infection, to be independent prognostic
factors to decreased life expectancy. A systematic review
by Bakar, et al. found a high prevalence of various types
of postoperative complications in MESCC patients that
ranged in prevalence from 5% to 42.6%.22
Limitations
is study has some mentionable limitations. First,
our study’s retrospective design suggests the potential for
missing or incomplete data. However, we endeavored to
exclude all cases with incomplete data. Second, the small
number of each identied primary tumor type except for
lung cancer means that Kaplan-Meier survival analysis
could only be performed for MESCC secondary to lung
cancer. ird and last, the ndings of this study could
not analyze the decision making for adjuvant treatments
in various types of primary tumor and ununiformed
optimal chemotherapy in the period of this study with
rapid development of chemotherapy.
CONCLUSION
Survival time of MESCC patients who had the
clinical presentation with acute progressive neurological
decits depends on multiple prognostic factors, however;
the preoperative unknown primary tumor origin is not
negative factor for survival in palliative spine surgery.
ACKNOWLEDGEMENTS
We thank the personnel from the Siriraj Hospital
record and research section for their assistance, the
Department of Orthopedic Surgery, Faculty of Medicine
Siriraj Hospital, Mahidol University, Bangkok, ailand
for their support, and Mr. Pongsathorn Samphaotong
for assisting in journal submission process.
Conict of interest: e authors declare that there is
no conict of interest.
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Original Article SMJ
Ravit Ruangtrakool, M.D., Cholapa Pintawekiat, M.D.
Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.
Types and Levels of Colostomy in Children with
Anorectal Malformation
ABSTRACT
Objective: Divided colostomy for anorectal management is oen recommended due to reports of higher complications
associated with loop colostomy. is study was conducted to compare outcomes and complications in colostomies
in children with anorectal malformations according to type and level of colostomy.
Materials and Methods: A retrospective study was performed in children with anorectal malformations who
underwent a colostomy at Siriraj Hospital between December 2003 and June 2018.
Results: Out of 167 patients, 159 had a loop colostomy while 8 had a divided colostomy. Overall complication
rates were 33.3% for loop colostomy and 62.5% for divided colostomy (p = 0.100). Urinary tract infection was the
most frequently encountered complication in both loop and divided colostomies, at 23.7% and 50%, respectively
(p = 0.094). e prolapse rate in the loop colostomy group was 8.8 % and 0% in the divided colostomy group (p =
0.376). Overall complication rates with respect to location of stoma also did not dier (p = 0.706). Prolapse rates
were 15.8 % in transverse colostomy and 7.1 % in sigmoid colostomy (p = 0.231). Overall complications rates of
colostomy closure in loop and divided colostomy was 7.5% and 12.5%, respectively (p = 0.672). Non-inferiority was
demonstrated by the dierences in overall complications of loop and divided colostomy (p = 0.008).
Conclusion: ere was no dierence in incidence of complications between type or location of colostomy performed
in children with anorectal malformations. Loop colostomy was non-inferior to divided colostomy in respect to
overall complications.
Keywords: Anorectal malformation; loop colostomy; divided colostomy; colostomy prolapse; urinary tract infection;
complication (Siriraj Med J 2022; 74: 693-698)
Corresponding author: Ravit Ruangtrakool
E-mail: sisuped@mahidol.ac.th
Received 14 February 2022 Revised 6 July 2022 Accepted 31 July 2022
ORCID ID:http://orcid.org/0000-0001-8162-2941
http://dx.doi.org/10.33192/Smj.2022.81
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Among all congenital anomalies, the gastrointestinal
anomaly was the second most common system involved
(33.67%).1 Anorectal malformations are a common
gastrointestinal anomaly encountered by pediatric
surgeons worldwide. There is a wide spectrum of
malformations, ranging from simple cutaneous stula
to cloacal malformations. Colostomy, with subsequent
denite repair is the standard treatment in those with
non-low type anorectal malformation. Loop colostomy
was the only preferred option in Division of Pediatric
Surgery at Siriraj Hospital for more than ve decades,
until divided colostomy was rstly introduced by PeñaA,
who developed posterior sagittal anorectoplasty, the most
popular denite operation for anorectal malformation in
1982.2-5 Divided colostomy is generally preferred over
loop colostomy due to the higher rate of complications
associated with the latter, which includes prolapse, risk
of incomplete diversion of feces that causes subsequent
distension of distal rectal pouch, and possible contamination
Volume 74, No.10: 2022 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index
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of feces into the urinary tract in those with a connecting
stula between the rectum and genitourinary system.2-6
However, controversy still surrounds the higher risk of
complications associated with loop colostomies compared
to divided colostomies with previously published studies
showing debatable results.7-9 us, this study was conducted
to describe and compare outcomes and complications of
colostomies in children with anorectal malformations
according to type and level of colostomy. Outcomes
related to colostomy closure with respect to type of
colostomy were also compared.
MATERIALS AND METHODS
Following approval by the Siriraj Institutional
Review Board (Si 175/2019) a retrospective study was
conducted in children with anorectal malformations
who underwent a colostomy at Siriraj Hospital between
December 2003 to June 2018. Children with cloacal
exstrophy and major chromosomal anomalies incompatible
with life and those with incomplete medical information
were excluded from the study. Patients’ demographics,
type of malformation, location and type of colostomy
was collected. First, a colostomy was performed and this
was followed by denitive repair. Following achieving
an adequate neo-anus size as dilated by the parents,
colostomy closure was performed. Loop colostomy was
the preferred option in our division at Siriraj Hospital.
Complications during colostomy were recorded, including
prolapse, retraction, parastomal hernia, urinary tract
infection, bleeding, and skin excoriation. Upon colostomy
closure, operative time and complications were noted.
Complications during colostomy closure included wound
infection, wound dehiscence, and anastomosis leakage.
e collected data was analyzed using SPSS soware
version 18 (SPSS Inc. Released 2009. PASW Statistics for
Windows, Version 18.0. Chicago: SPSS Inc.). Continuous
data was expressed as median and IQR and categorical
data expressed as numbers and percentages. A Chi square
test or Fisher’s exact test was used to compare outcomes
in type and location of colostomy. Non-inferiority test
for dierence in overall complications between loop and
divided colostomy was conducted. Non-inferiority was
demonstrated when lower bound of the 95% one-sided
CI for dierence in overall complications was lower than
pre-specied non-inferior margin of 10%. A p-value of
<0.05 indicated statistical signicance.
RESULTS
Of the 178 patients whose medical records were
reviewed, 11 were excluded, which meant 167 patients
were included in the study. Out of the 167 patients
included, 159 underwent loop colostomies while eight
had a divided colostomy for fecal diversion. One hundred
and four out of 159 participants were male, of which 98
had a loop colostomy. Sixty-three patients were female,
of which 61 underwent a loop colostomy. For colostomy
level, there were four locations in total; ascending colon,
transverse colon, descending colon, and sigmoid colon.
e majority of patients underwent a (134 out of 167)
sigmoid loop colostomy. ere was a wide distribution
of malformation types ranging from imperforate anus
without stula to complex defects without signicant
dierences between the loop and divided colostomy
group (Table 1).
e dierences in complications found in the loop
and divided colostomy groups were not significant
(Table 2). Overall complication rates were 33.3% in
the loop colostomy group and 62.5% in the divided
colostomy group (p = 0.100). Urinary tract infections
were the most frequently observed complications in both
the loop (23.3%) and divided (50%) colostomy group.
e prolapse rate was 8.8% in the loop colostomy group
and 0% in the divided colostomy group, while skin
excoriation was 6.3% in the loop colostomy group and
12.5% in the divided colostomy group. When comparing
complications according to colostomy location, there
were no dierence in overall or individual complications
(Table 3). Interestingly, no statistically signicant dierence
was noted in overall complications or prolapse rates
between the transverse and sigmoid colostomy.
e median operative time for colostomy closures
was 160 minutes for loop colostomy and 195 minutes for
divided colostomy. e dierence was not statistically
signicant (p = 0.128). e incidence of complications
such as wound infection, wound dehiscence, and leakage
following closures in loop colostomy and divided colostomy
were not statistically signicant (Table 4).
When statistics for non-inferiority were performed,
with pre-specied non inferior margin of 10% between loop
and divided colostomies, non-inferiority was demonstrated
as the dierence in overall complications (p = 0.008).
DISCUSSION
Colostomy with subsequent definite repair is
the standard treatment in people with non-low type
malformation. Divided colostomies have been proposed
over loop colostomies due to reports of an increase in
complications associated with loop colostomy.2-6 In fact,
loop colostomy was condemned by Pena A,2,4,5 a world
authority in anorectal malformation management, due to
an increased prolapse rate, risk of incomplete diversion of
feces causing subsequent distension of distal rectal pouch,
Ruangtrakool et al.
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Original Article SMJ
TABLE 1. Comparison of the patient characteristics between the loop colostomy and the divided colostomy.
TABLE 2. Complications from colostomy, comparing between loop colostomy and divided colostomy.
Variable Loop Colostomy Divided Colostomy Total
(n = 159) (n = 8) (n = 167)
P-value
Gender, n (%) 0.711
Male 98 (61.6%) 6 (75.0%) 104 (62.3%)
Female 61 (38.4%) 2 (25.0%) 63 (37.7%)
Level of Colostomy, n (%) 0.137
Ascending 3 (1.9%) 0 (0%) 3 (1.8%)
Transverse 18 (11.3%) 1 (12.5%) 19 (11.4%)
Descending 2 (1.3%) 1 (12.5%) 3 (1.8%)
Sigmoid 134 (84.3%) 6 (75.0%) 140 (83.8%)
Type of Malformation, n (%) 0.819
Imperforate Anus Without Fistula 30 (18.9%) 3 (37.5%) 33 (19.8%)
Perineal Fistula 10 (6.3%) 0 (0%) 10 (6.0%)
Vestibular Fistula 14 (8.8%) 0 (0%) 14 (8.4%)
Rectovaginal Fistula 6 (3.8%) 0 (0%) 6 (3.6%)
Rectobulbar Urethral Fistula 26 (16.4%) 0 (0%) 26 (15.6%)
Rectoprostatic Urethral Fistula 19 (11.9%) 1 (12.5%) 20 (12.0%)
Rectobladder Neck Fistula 11 (6.9%) 1 (12.5%) 12 (7.2%)
Rectovesicle Fistula 9 (5.7%) 0 (0%) 9 (5.4%)
Persistent Cloaca < 3 Cm 13 (8.6%) 1 (12.5%) 14 (8.4%)
Persistent Cloaca > 3 Cm 7 (4.4%) 0 (0%) 7 (4.2%)
Rectal Atresia 3 (1.9%) 0 (0%) 3 (1.8%)
Complex Defect 3 (1.9%) 0 (0%) 3 (1.8%)
Loop Colostomy Divided Colostomy Total
(n = 159) (n = 8) (n = 167) P-value
Overall Complication, n (%) 53 (33.3%) 5 (62.5%) 58 (34.7%) 0.100
Prolapse 14 (8.8%) 0 (0%) 14 (8.4%) 0.376
Retraction 2 (1.3%) 0 (0%) 2 (1.2%) 0.747
Parastomal Hernia 1 (0.6%) 0 (0%) 1 (0.6%) 0.820
Urinary Tract Infection 37 (23.3%) 4 (50.0%) 41 (24.6%) 0.094
Bleeding 5 (3.1%) 0 (0%) 5 (3.0%) 0.607
Skin Excoriation 10 (6.3%) 1 (12.5%) 11 (6.6%) 0.502
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TABLE 3. Complications from colostomy, comparing among dierent sites.
TABLE 4. Outcomes at colostomy closure, comparing between loop colostomy and divided colostomy.
Ascending Transverse Descending Sigmoid
Variables colostomy colostomy colostomy colostomy P-value
(n = 3) (n = 19) (n = 3) (n = 140)
Overall Complication, n (%) 2 (66.7%) 6 (31.6%) 1 (33.3%) 50 (35.7%) 0.706
Prolapse 1 (33.3%) 3 (15.8%) 0 (0%) 10 (7.1%) 0.231
Retraction 0 (0%) 0 (0%) 0 (0%) 2 (1.4%) 0.948
Parastomal Hernia 0 (0%) 0 (0%) 0 (0%) 1 (0.7%) 0.981
Urinary Tract Infection 2 (66.7%) 5 (26.3%) 1 (33.3%) 34 (24.3%) 0.409
Bleeding 0 (0%) 0 (0%) 0 (0%) 5 (3.6%) 0.820
Skin Excoriation 1 (33.3%) 0 (0%) 0 (0%) 10 (7.1%) 0.168
Variable Loop Colostomy Divided Colostomy Total
(n = 159) (n = 8) (n = 167)
P-value
Operative time (min) 0.128
Median (min. max) 160 (35, 457) 195 (120, 215) 160 (35, 157)
Complications, n (%) 12 (7.5%) 1 (12.5%) 13 (7.7%) 0.672
Wound Infection 8 (5.0%) 1 (12.5%) 9 (5.39%) 0.410
Wound Dehiscence 1 (0.6%) 0 (0%) 1 (0.6%) 0.814
Leakage 1 (0.6%) 0 (0%) 1 (0.6%) 0.814
Gut Obstruction 3 (1.9%) 0 (0%) 3 (1.8%) 0.682
Incisional Hernia 1 (0.6%) 0 (0%) 1 (0.6%) 0.814
TABLE 5. Overall complications in loop and divided colostomy.
Loop colostomy Divided colostomy Difference Non-inferiority test
(n=159) (n=8) (95% one-sided CI) (P-value)
Overall complications 53 (33.3%) 5 (62.5%) -28.5% (-1.7, ∞)* 0.008**
*Non-inferiority was demonstrated (lower bound of the 95% one-sided CI for dierence in overall complications between loop and divided
colostomy was lower than pre-specied non-inferiority margin of 10%)
**Non-inferiority was demonstrated and p-value of non-inferiority test was less than signicant level of 0.05
Ruangtrakool et al.
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Original Article SMJ
and possible contamination of feces into the urinary tract
in patients with a connecting stula between the rectum
and genitourinary system.2-5 However, in our study,
there was no statistically signicant dierence between
the loop and divided colostomy group regarding overall
complications. e complication rate associated with loop
colostomies in this study was consistent with previously
published studies at about 20%-30%.3,7,9 However, this
study elicited a higher rate of complications in divided
colostomies compared to other studies (62.5% vs. 8%-
30%).3,7,9
e prolapse rate of loop colostomies was quite low
in our study (8.8%) compared to other published studies
which reported rates of up to 18%.3,9 A low prolapse
rate in loop colostomies in our institution might be the
result of the stoma creation technique used at our center
where loop colostomy was performed at the descending-
sigmoid colonic junction and the proximal and distal
limb of colostomy site were sutured together prior to
exteriorization and xation at sheath and skin. e suturing
of the proximal and distal limb may have decreased the
mobility of colon.
Divided colostomies were preferred over loop
colostomies due to risk of fecal contamination into the
distal rectourinary stula in the latter.2,4 Although urinary
tract infection was the most common complication,
there was no signicant dierence between the loop
and divided colostomy group in this study. is nding
was consistent with previously published studies.3,7 A
loop colostomy conducted in the proper way was able
to complete fecal diversion and was not dierent from
divided colostomy.
Regarding location of colostomy, no statistically
signicant dierence in complication rates was elicited
in this study. However, our study had higher rates of
overall complications for both transverse and sigmoid
colostomies compared to results published by van den
Hondel et al9 and Demirogullari et al.10 is might be the
result of including urinary tract infection as a complication
in our study while other studies did not include it. Previous
literatures have revealed that transverse colostomies have
a higher prolapse rate than other colostomy locations.9-11
Regarding transverse colostomies, our study had a lower
prolapse rate than others. As mentioned previously,
this might be due to our surgical technique of placing
sutures between the proximal and distal limb of colon
prior to exteriorization of stoma at sheath and skin. Also,
we had more experience performing a loop colostomy
regardless of location when compared to other studies.
Since there were no significant differences in
complications in loop and divided colostomies, we
attempted to determine whether loop colostomy was
non-inferior compared to divided colostomy in respect
to complication rates. e non-inferior margin was
pre-determined to be 10%. Interestingly, we found that
non-inferiority, which was shown as a p-value in the
non-inferiority test, to be less than the signicant level
of 0.05. is had not been shown in previously published
studies.
Since there was no dierence in complications
between loop and divided colostomies during the stoma
creation period, outcomes during and aer colostomy
closure were investigated to demonstrate the advantage
of one stoma over the other. e operative time for
colostomy closure seemed shorter for loop colostomy at 160
minutes compared to 195 minutes for divided colostomy.
However, there was no signicant dierence to suggest
easier closure in loop colostomy. Complications such as
wound infection, wound dehiscence and anastomotic
leakage were also not signicantly dierent.
e limitation of this study was its retrospective
design which means some information might be missing.
Moreover, the number of subjects was relatively small at
167 patients. Also, there were a smaller number of divided
colostomy patients compared to the loop colostomy
group as it is our division’s preference to perform the
latter. is made comparison between the two groups
dicult in the study. However, our results were similar
to previously published studies in which loop colostomy
had good results compared to divided colostomy. A
multicenter study may be performed in the future to
increase the number of patients and data of divided
colostomy cases.
CONCLUSION
Loop colostomy is non-inferior to divided colostomy
in terms of overall complications and is a feasible diversion
procedure for anorectal malformation. Proper technique
and experience with loop colostomy helps achieve complete
diversion of feces with outcomes similar to that of divided
colostomy.
ACKNOWLEDGEMENTS
We would like to thank Dr. Sasima Tongsai from
the Division of Clinical Epidemiology, Department of
Research and Development, Faculty of Medicine Siriraj
Hospital, Mahidol University for her continuous help
with data processing and statistical analysis.
Conicts of interest: e authors have no conicts of
interest to declare.
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REFERENCES
1. Sahoo S, Ganguly R, Dash M, Pradhan A, Priya TG, Mohanty.
Study of Congenital Malformation in a Tertiary Care Teaching
Hospital.Siriraj Med J. 2021;73(9):609-13.
2. Pena A, Migotto-Krieger M, Levitt MA. Colostomy in anorectal
malformations: a procedure with serious but preventable
complications. J Pediatr Surg. 2006;41(4):748-56.
3. Oda O, Davies D, Colapinto K, Gerstle JT. Loop versus divided
colostomy for the management of anorectal malformations.
J Pediatr Surg. 2014;49(1):87-90.
4. Levitt MA, PeñaA.Imperforate anus and cloacal malformations.
In:Holcomb III GW, Murphy JA, ed.Ashcra’s Pediatric
Surgery, 5th edition, Philadelphia: Saunders Elsevier; 2010.p.468-
90.
5. WilkinsS,PeñaA. e role of colostomy in the management
of anorectal malformations.Pediatr Surg Int.1988;3:105-9.
6. Gardikis S, Antypas S, Mamoulakis C, Demetriades D, Dolatzas T,
Tsalkidis A, et al. Colostomy type in anorectal malformations:
10-years experience. Minerva Pediatr 2004; 56(4):425-9.
7. Liechty ST, Barnhart DC, Huber JT, Zobell S, Rollins MD.
e morbidity of a divided stoma compared to a loop colostomy
in patients with anorectal malformation. J Pediatr Surg. 2016;
51(1):107-10
8. Patwardhan N, Kiely EM, Drake DP, Spitz L, Pierro A. Colostomy
for anorectal anomalies: high incidence of complications. J
Pediatr Surg. 2001;36(5):795-8.
9. van den Hondel D, Sloots C, Meeussen C, Wijnen R. To split or
not to split: colostomy complications for anorectal malformations
or hirschsprung disease: a single center experience and a
systematic review of the literature. Eur J Pediatr Surg. 2014;24(1):
61-9.
10. Demirogullari B, Yilmaz Y, Yildiz GE, Ozen IO, Karabulut R,
Turkyilmaz Z, et al. Ostomy complications in patients with
anorectal malformations. Pediatr Surg Int. 2011;27(10):1075-8.
11. Almosallam OI, Aseeri A, Shanafey SA. Outcome of loop versus
divided colostomy in the management of anorectal malformations.
Ann Saudi Med. 2016;4:352-5.
Ruangtrakool et al.
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Original Article SMJ
Sukhum Jiamton, M.D., Ph.D.*, Nuttagarn Jantanapornchai, M.D*, Ya-Nin Nokdhes, M.D.*, Poramin Patthamalai,
M.D., Ph.D.*, Ploypailin Tantrapornpong, M.D.*, Yanisorn Nanchaipruek, M.D. *, Pichaya Limpoka, M.D.*
*Sexually Transmitted Disease and HIV Division, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok
10700, ailand.
Lidocaine Reducing Pain from Benzathine Penicillin
Injection: A Controlled Trial
ABSTRACT
Objective: is study aimed to investigate the ecacy and safety of benzathine penicillin G (BPG) injection
compared between dilution with 1% lidocaine hydrochloride and dilution with sterile water to reduce pain in ai
male syphilis patients.
Materials and Methods: is randomized, split-buttock, double-blind controlled trial was conducted at the Sexually
Transmitted Disease and HIV Division, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol
University, Bangkok, ailand during September 2018 to July 2019. Aer randomization, 20 le and 20 right
buttocks were injected with 1.2 million-unit BPG (half dose) with lidocaine as the diluent. e other 20 le and
20 right buttocks were then injected with 1.2 million-unit BPG (half dose) with sterile water as the diluent. Pain at
each buttock was measured by numeric rating scale during and immediately aer the injection, and at 5 minutes,
20 minutes, and 24 hours aer injection.
Results: Forty males (mean age: 30.6±10.3 years) were included. Compared to sterile water diluent, we found that
dilution with 1% lidocaine signicantly reduced pain during and immediately aer injection, and at 5-minutes and
20-minutes post-injection (all p<0.001). ere was no signicant improvement in pain at 24-hours post-injection.
Minor adverse events were observed in 37.5% of patients, including generalized rash, pruritus, and fever. One
patient experienced minor drug allergy.
Conclusion: One percent lidocaine as a diluent of BPG was found to be eective for reducing pain during and
aer BPG injection.
Keywords: Ecacy; 1% lidocaine hydrochloride; sterile water; pain; benzathine penicillin G injection; syphilis
(Siriraj Med J 2022; 74: 699-704)
Corresponding author: Sukhum Jiamton
E-mail: sukhum.jia@mahidol.ac.th
Received 14 March 2022 Revised 11 September 2022 Accepted 13 September 2022
ORCID ID:http://orcid.org/0000-0003-1068-1586
http://dx.doi.org/10.33192/Smj.2022.82
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Syphilis is a bacterial infectious disease that is caused
by Treponema pallidum subspecies pallidum.1 Eective
treatment is intramuscular (IM) penicillin G for all stages
of the disease. In adults, one IM injection of benzathine
penicillin G (BPG) 2.4 million units is recommended for
early syphilis treatment, including primary, secondary,
and early latent syphilis. ree doses (once a week for 3
consecutive weeks) of BPG 2.4 million units is suggested
for late latent and tertiary syphilis without neurosyphilis
treatment.1
BPG that is diluted with sterile water causes pain
during and aer injection at the injection sites. e local
pain and discomfort associated with the injection tend to
decrease compliance, especially in children and adolescents.2,3
To reduce pain and improve patient compliance in those
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700
requiring 3 injections, we set forth to investigate the
ecacy and safety of BPG injection compared between
dilution with 1% lidocaine hydrochloride and dilution
with sterile water to reduce pain in ai male syphilis
patients.
MATERIALS AND METHODS
This randomized, split-buttock, double-blind
controlled trial in syphilis patients aged 18 years or older
was conducted at the Sexually Transmitted Disease and
HIV Division of the Department of Dermatology, Faculty
of Medicine Siriraj Hospital, Mahidol University, Bangkok,
ailand during September 2018 to July 2019. Patients
with allergy to lidocaine or penicillin were excluded.
e protocol for this study was approved by the Siriraj
Institutional Review Board (SIRB) (Si 635/2017), and
written informed consent was obtained from all study
participants.
Both buttocks of each patient were randomized
using block randomization with a block size of four. It
was used to determine which side of the buttock was
intervention or control. us, for instance, BPG diluted
with lidocaine mean intervention or BPG diluted with
sterile water mean control (Fig 1). e dilution was 1.2
million-unit BPG whether with 4.0 ml of lidocaine or
with 4.0 ml of sterile water. One dermatologist prepared
medication for administration. However, only the rst
dose of injection was examined in those required three
doses of injection.
A 20-gauge 1.5-inch-long needle was used for injection.
One blinded dermatologist performed drug injection at
each buttock intramuscularly. All participants were blinded.
Pain was assessed using a numeric rating scale, with a
zero indicating no pain, and a ten indicating the most
severe pain. Pain was assessed during and immediately
aer the injection, and at 5 minutes, 20 minutes, and
24 hours aer the injection. Adverse eects and events
were recorded. e same blinded dermatologist assessed
pain score and adverse eect.
Statistical methods
e data were analyzed using Statistical Package for
the Social Sciences (SPSS, Inc., Chicago, IL, USA) version
18. Categorical data are reported as number and percentage,
and continuous data are reported as mean plus/minus
standard deviation. Paired t-test was used to compare
the pain score between the two diluent formulations
at during and immediately aer the injection, and at 5
minutes, 20 minutes, and 24 hours aer the injection.
A p-value less than 0.05 was considered statistically
signicant for all tests.
Fig 1. Flow diagram of the
randomized clinical trial of
benzathine penicillin G (BPG).
Jiamton et al.
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Original Article SMJ
Fig 2. Mean numeric pain score over time compared between injection of BPG diluted with 1% lidocaine and injection of BPG diluted with
sterile water.
RESULTS
Forty Thai males that were recruited from our
outpatient dermatology clinic were included. e age of
patients ranged from 18 to 59 years, and the mean age was
30.6±10.3 years. Half of patients reported being homosexual,
and 15% were bisexual. No patients reported that they
always use a condom during intercourse. Fiy-ve and
forty percent of patients were in the late latent stage or
secondary stage of syphilis, respectively. irty-three of
37 patients had a Venereal Disease Research Laboratory
(VDRL) titer higher than 1:16, and all patients had a
positive Treponema pallidum particle agglutination assay
(TPHA) result (Table 1). Compared to sterile water diluent,
we found that dilution with 1% lidocaine signicantly
reduced pain during and immediately aer injection, and
at 5-minutes and 20-minutes post-injection (all p<0.001)
(Table 2). ere was no signicant improvement in pain
at 24-hours post-injection. Minor adverse events were
observed in 37.5% of patients, including generalized
rash, pruritus, and fever. One patient experienced minor
drug allergy (Table 3). However, there was no local
adverse event so the local adverse event between study
and control group could not done.
DISCUSSION
Our study showed that BPG injection using 1%
lidocaine as the diluent signicantly reduces pain at
injection sites during and immediately aer the injection,
and at 5 minutes and 20 minutes aer the injection.
Interestingly, however, the pain score in the lidocaine
group increased by the 24-hour time point to very near
the pain score in the sterile water group. is study also
found intramuscular injection with BPG to be associated
with two distinct episodes of pain during and immediately
aer injection, and at 24 hours aer injection. is
reemergence of pain aer a decrease in pain at 5-minutes
and 20-minutes post-injection is likely due to the fact
that the elimination half-life of lidocaine is biphasic
within a range of 90-120 minutes in most patients.4
Pain during intramuscular injection is a problem
in clinical practice.5 Reducing intramuscular injection
pain may be achieved by combining drugs with local
anesthetics, such as lidocaine.6 Lidocaine is a sodium-
channel blocking drug with rapid onset of action, and
it has a minimal toxicity prole.2,7 Four milliliters of 1%
lidocaine was used in this study for a total dose of 2 mg.
is is less than the maximum dose of lidocaine without
Volume 74, No.10: 2022 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index
702
TABLE 1. Demographic and clinical characteristics of the 40 included syphilis patients.
Characteristics n %
Age (years)
Mean ± SD 30.6 ± 10.3 -
Range 18-59 -
Sexual orientation
Homosexual 20 50.0
Heterosexual 14 35.0
Bisexual 6 15.0
Frequency of condom use
Always 0 0.0
Sometimes 37 92.5
Never 3 7.5
Underlying medical condition
Yes 7 17.5
No 33 82.5
HIV infection 23 57.5
Stage of syphilis
Primary syphilis 0 0.0
Secondary syphilis 16 40.0
Early latent syphilis 2 5.0
Late latent syphilis 22 55.0
Tertiary Syphilis 0 0.0
Presence history of known contact disease 11 30.8
Recurrent syphilis 9 19.2
TPHA reactive at diagnosis (titer) 38 100.0
>1:80 38 100.0
VDRL reactive at diagnosis (titer) 37 92.5
1:1 2 5.4
1:2 1 2.7
1:4 1 2.7
1:16 3 8.1
1:32 7 18.9
1:64 8 21.6
1:128 11 29.7
1:256 4 10.8
Jiamton et al.
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Original Article SMJ
TABLE 2. Mean pain visual analogue scale (VAS) at dierent time points compared between injection of benzathine
penicillin G diluted with 1% lidocaine and injection of benzathine penicillin G diluted with sterile water.
TABLE 3. Adverse events and complication at 24 hours
aer treatment among the 40 included syphilis patients.
1% Lidocaine side Sterile water side
(mean±SD) (mean±SD) P-value
During and immediately after injection 2.25±1.85 7.93±1.95 1.45 x 10-18*
5 minutes after injection 0.60±1.43 3.45±2.64 4.55 x 10-8*
20 minutes after injection 0.35±1.21 2.20±2.15 7.12 x 10-6*
24 hours after injection 2.80±1.94 3.13±2.08 0.156
*A p-value<0.05 indicates statistical signicance
Adverse events and complication n (%)
Adverse events
No 25 62.5%
Yes 15 37.5%
Generalized rash 9 60.0%
Generalized pruritus 8 53.3%
Fever 8 53.3%
Complication
No 39 97.5%
Yes 1 2.5%
Minor drug allergy 1 100.0%
epinephrine, which was reported to be 300 mg.8 All
patients in this study were observed for lidocaine toxicity,
and no signs of toxicity were observed. Previous studies
reported no adverse pharmacokinetic eects of lidocaine
on IM penicillin.2,9 It was also reported that the BPG
combined with lidocaine did not change the concentration
of penicillin in body uid.2 No local adverse event was
observed in our study. e adverse events in our study
were generalized symptoms such as rash, pruritus, and
fever. Because participants received both interventions
and all of them had no history of allergy from penicillin10
or lidocaine11, so these recorded generalized symptoms
might be from penicillin or lidocaine.
CONCLUSION
One percent lidocaine as a diluent of BPG was found
to be eective for signicantly reducing pain during and
immediately aer BPG injection, and at 5-minutes and
20-minutes post-injection. We recommend the use of
1% lidocaine as a diluent for BPG in this clinical setting.
ACKNOWLEDGEMENTS
e authors gratefully acknowledge the patients
that generously agreed to participate in this study, and
the statistician for assistance with statistical analysis.
Funding disclosure: is study was funded by a grant
from the Siriraj Research Development Fund (Managed
by Routine to Research: R2R) (COA no. [IO] R01613501).
Conict of interest: All authors declare they have no
personal or professional conicts of interest relating to
any aspect of this study.
REFERENCES
1. Workowski KA, Bachmann LH, Chan PA, Johnston CM,
Muzny CA, Park I, et al. Sexually Transmitted Infections
Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):
1-187.
2. Amir J, Ginat S, Cohen YH, Marcus TE, Keller N, Varsano I.
Lidocaine as a diluent for administration of benzathine penicillin
G. Pediatr Infect Dis J. 1998;17(10):890-3.
3. Matthapan L, Bunyaratavej S, Leeyaphan C, Rujitharanawong C,
Limphoka P, Prasong W, et al. Clinical Application of Toothbrush
Technique for Specimen Collection of Tinea Capitis. Siriraj
Med J [Internet]. 2019 Mar 28. Available from: https://he02.
tcithaijo.org/index.php/sirirajmedj/article/view/180764
4. omson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn
W, Cudihee R, et al. Lidocaine Pharmacokinetics in Advanced
Heart Failure, Liver Disease, and Renal Failure in Humans.
Ann Intern Med. 1973;78(4):499-508.
Volume 74, No.10: 2022 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index
704
5. Morsy MMF, Mohamed MA, Abosedira MM, Al-Harbi K,
Abdelaziz NA, Hal SQK, et al. Lidocaine as a diluent for
benzathine penicillin G reduces injection pain in patients with
rheumatic fever: A prospective, randomized double-blinded
crossover study. Australian Journal of Basic and Applied
Sciences. 2012;6:236-40.
6. Russell K, Nicholson R, Naidu R. Reducing the pain of intramuscular
benzathine penicillin injections in the rheumatic fever population
of Counties Manukau District Health Board. J Paediatr Child
Health. 2014;50(2):112-7.
7. Razavi BM, Fazly Bazzaz BS. A review and new insights to
antimicrobial action of local anesthetics. Eur J Clin Microbiol
Infect Dis. 2019;38(6):991-1002.
8. Physicians’ desk reference. Montvale, N.J. Medical Economics
Co., 1996.
9. Schichor A, Bernstein B, Weinerman H, Fitzgerald J, Yordan E,
Schechter N. Lidocaine as a diluent for ceriaxone in the treatment
of gonorrhea. Does it reduce the pain of the injection? Arch
Pediatr Adolesc Med. 1994;148(1):72-5.
10. Yip DW, Gerriets V. Penicillin. [Updated 2021 Sep 30]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2022 Jan-.Available from: https://www.ncbi.nlm.nih.gov/
books/NBK554560/
11. Cherobin ACFP, Tavares GT. Safety of local anesthetics.Anais
Brasileiros de Dermatologia 2020;95:82-90.
Jiamton et al.
Volume 74, No.10: 2022 Siriraj Medical Journal
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Review Article SMJ
anathip Suenghataiphorn, M.D.*, Sakdipat Songwisit, M.D.*, Surapa Tornsatitkul, M.D.**, Pawit Somnuke,
M.D., Ph.D.***
*Faculty of Medicine Siriraj Hospital, **Department of Pharmacology, Faculty of Pharmacy, ***Department of Anesthesiology, Faculty of Medicine,
Siriraj Hospital, Mahidol University, Bangkok 10700, ailand.
An Overview on Postoperative Cognitive
Dysfunction; Pathophysiology, Risk Factors,
Prevention and Treatment
ABSTRACT
Postoperative cognitive dysfunction (POCD) is an event that alarms medical personnel owing to its adverse
eects, including heightened morbidity and mortality rates, prolonged recovery times, and increased lengths of
hospital stay and healthcare expenditure. e populations at high risk are elderly, critical patients, or complicated
cases that need prolonged surgery in which the hemodynamics are not stable. Although guidelines have been
established to facilitate the early diagnosis of POCD, its prevention is recommended for good patient outcomes. A
preoperative assessment is a prerequisite for patient optimization before surgery. Intraoperative, enhanced-recovery
protocols have been widely adopted to promote recovery following surgery. Frequent, postoperative assessments of
patients’ vital signs and cognitive functions are required for early POCD detection. Patients diagnosed with POCD
need regular follow-up, and proper patient counselling is paramount.
Keywords: Diagnostic and Statistical Manual of Mental Disorders (DSM-5); Enhanced Recovery Aer Surgery
(ERAS); Montreal Cognitive Assessment Scale (MoCA); Neurocognitive disorder, Postoperative cognitive dysfunction
(POCD) (Siriraj Med J 2022; 74: 705-713)
Corresponding author: Pawit Somnuke
E-mail: Pawit-pup@hotmail.com
Received 5 June 2022 Revised 5 July 2022 Accepted 6 July 2022
ORCID ID:http://orcid.org/0000-0002-6773-1882
http://dx.doi.org/10.33192/Smj.2022.83
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
Postoperative cognitive dysfunction (POCD) is
a condition that can occur during the postoperative
or postanesthetic periods.1 Previous study reported
that upon discharge, 41.4% of patients aged over 60
years developed POCD and, notably, up to 12.7% of
those patients were detected with POCD at 3 months.1
Morbidity of the patients with POCD at 3 months and
1 year aer surgery was 25.8% and 10%, respectively.2
e etiologies can be categorized into (1) patient factors:
age > 60 years old, low education level, American Society
of Anesthesiologists (ASA) physical status ≥ 3, and
comorbidities, for example, cerebrovascular disease,
anemia (preoperative hemoglobin ≤ 11 g/dl), preexisting
cognitive dysfunction, poor functional capacity, severe
illness, postoperative respiratory complications and
postoperative infection (2) surgical factors: complex and
complicated surgeries or complications during surgery,
type of surgery and time of surgery ≥ 4 hours and (3)
anesthetic factors: intraoperative use of benzodiazepines
and Isourane volatile anesthetic agent, intraoperative
hypotension and oxygen desaturation during anesthetic
induction.3-7 POCD contributes to declined general
health, longer length of hospitalization, longer length
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706
of postsurgical recovery, and an increase in 1-year post-
surgical mortality rate.8,9 e prevention of POCD requires
cooperation between medical specialties throughout the
preoperative, perioperative and postoperative periods.9
e best strategy for combatting POCD is to prevent
before it occurs. It is paramount that medical personnel
have a thorough understanding about POCD so that they
are capable of planning how to prevent POCD and also
to enhance patients’ postoperative recovery and quality
of life.
is review discusses and summarizes the details of
POCD by using evidence-based medicine covering POCD
denitions, clinical symptoms, diagnosis, pathophysiology,
risk factors, prevention, treatment, and prognosis.
Denition
e Diagnostic and Statistical Manual of Mental
Disorders (DSM-5) has yet to issue a formal denition of
POCD. However, the International Society of Postoperative
Cognitive Dysfunction (ISPOCD) denes it as a condition
that can develop when ≥ 1 abnormality in a discrete
area of mental state such as memory, consciousness
or attention is discovered, which can occur anytime
from immediate postoperative period to 6 months later.
Usually, the onset of impaired memory and intellectual
disability ranges from weeks to months postoperatively
while recovery is within days to weeks.1,10 POCD can be
diagnosed by comparing the dierences in the results of
baseline preoperative and postoperative psychometric
testing.9
In 2018, the new consensus among international
medical doctors and scientists was published in the
British Journal of Anesthesia.11 e clearer denition of
POCD was introduced to facilitate research and education
endeavors: (1) delayed neurocognitive recovery (within 30
days postoperatively) and (2) postoperative neurocognitive
disorder (between 30 days and 12 months postoperatively).
POCD can be dierentiated from other diseases, such
as delirium or dementia, as outlined in Table 1.1,12-14
Pathophysiology
Although the pathophysiology of POCD is still
not elucidated, it is, by evidence-based, associated with
neuroinammation, disruption of blood-brain barrier
(BBB) integrity, neurosynaptic damage, mitochondrial
dysfunction and oxidative stress.15-19 Other mechanisms
including hyperventilation, hypotension or cerebral
microemboli were also proposed to involve POCD.10
Surgical stimuli induce the expression of the inammatory
mediator, high mobility group box-1 (HMGB1), which
interacts with the pattern recognition receptor (PRR) on
macrophages causing downstream activation of innate
immunity. Also, the S100 calcium-binding protein
A12 (S100A12) level increases aer the operation and
thus resulting in intracephalic signal transduction and
inammation.20 Upon surgical stimulation, intracellular
RNA released from the damaged tissue is detected by the
immune cells therefore inammatory process is initiated.
Proinammatory cytokines from macrophages including
tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6)
TABLE 1. Dierential diagnoses of postoperative cognitive dysfunction.
Parameters Delirium POCD Dementia
Onset
Duration
Attention
Consciousness
Symptoms
Activities of
daily living
Within 3 days
Days to weeks
Decreased
Altered
Fluctuation within the day;
alteration of consciousness;
can be hypoactive or hyperactive
Increased risk of functional
decline
Within a few months
Weeks to months
Decreased
Normal
Memory decline or cognitive
decline
No risk of functional decline
Months to years
Months till death
Decreased
Normal
Memory decline; executive
function decline; changes in
behavior and abilities
Increased risk of functional
decline
Abbreviation: POCD, Postoperative cognitive dysfunction
Suenghataiphorn et al.
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Review Article SMJ
and IL-1β are upregulated in the blood circulation.21-24 ese
cytokines can breach through the BBB via vagus nerve
or paraventricular areas of the BBB leading to activation
of cerebrovascular endothelial cells which will produce
secondary messenger to secrete more proinammatory
cytokines.25 An increase in brain-specic inammatory
markers such as serum S100 calcium-binding protein B
(S100B) and neuron-specic enolase (NSE) aer surgery
also supports that brain inammation could lead to
POCD.10,12,26,27 Albeit playing smaller role than surgery,
anesthesia is involved in the pathophysiology of POCD.
Past study demonstrated that isourane caused apoptosis
in human neuronal cell lines and mouse brain potentially
through the accumulation of amyloid β peptide. Randomized
controlled studies also reported higher incidence of
POCD and level of proinammatory markers in groups
anesthetized under volatile anesthesia implying that
volatile might involve in POCD mechanism.28,29
Risk factors
e risk factors of POCD can be divided into patient,
surgical, and anesthetic factors.
1. Patient factors
Old age1,30
Age is a major factor of POCD especially in the
elderly aged > 60 years old. Studies have shown that
older age has various eects on the brain, for instance,
decreased brain volume, decreased BBB density, decreased
neurogenesis, reduced cognitive reserve, increased brain
inammation, and increased brain-vessel degeneration.
e medial temporal lobe atrophy as well as the white
matter hyperintensity as seen by magnetic resonance
imaging (MRI) in the elderly were well correlated with
clinical cognitive decline.31
Low level of education9,32
Many higher-educated people are prone to engage in
greater levels of complex thinking, leading to heightened
usage of the brain neural network. is extra utilization
may result in the prevention of brain decay due to a
corresponding increase in the cognitive reserve and
improvements to the eciency of neuronal replacement.
Education levels may therefore be employed to indicate
cognitive reserves as each additional year of study has
been demonstrated to result in around a 10% reduction
in the incidence of POCD.
Preexisting cerebrovascular disease1,33
e patients with preexisting cerebral infarction
were reported to be 18.2% at risk of POCD compare with
4.9% in the control group. erefore, cerebrovascular
disease was considered the potential non-modiable
risk factors of POCD.
Preexisting Systemic Lupus Erythematosus (SLE)34
A correlation between cognitive impairment and
underlying SLE had been reported previously. However,
the incidence of cognitive dysfunction was not dependent
on SLE duration, activity or evidence of preexisting
neuropsychiatric involvement.
Presence of insulin resistance35
Preexisting insulin resistance was independently
associated with the incidence of POCD. It has been shown
that insulin resistance reects metabolic disease which
is related to neuropathological process regarding aging
and cognitive function. A reduction in insulin receptor
on the BBB according to insulin resistance results in
decreased insulin transport into the brain causing POCD
and Alzheimer’s disease.
Genetics36
The Human Apolipoprotein E (ApoE) gene is
located on chromosome 19. E4 allele of the APOE gene is
evidenced to account for Alzheimer’s disease, cognitive
dysfunction and atherosclerosis. To date there are no
studies conrming the eect of sex dierence on POCD.
However, men who are the carriers of APOE4 alleles were
reported to have higher risk of POCD than women with
APOE4.
Alcoholism37
e elderly with history of alcohol abuse could
pose a higher risk for POCD especially in the domains
related to visuospatial and executive functions.
2. Surgical factors1,6,38
Complicated and prolonged surgeries > 4 hours,
complications during the peri- or postoperative periods,
and procedures needing multiple surgeries are all risk
factors which could result in POCD. Cardiac surgery
with the application of cardiopulmonary bypass pump
(CPB) is a predisposing factor to POCD. Prolonged
arterial cross clamping time in cardiac surgery plays
an important role in POCD according to poor cerebral
hypoperfusion.
3. Anesthetic factors
Factors such as a prolonged anesthetic period causing
disequilibrium of uids and electrolytes, acute blood
loss, oxygen desaturation, and peri- or postoperative
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708
anesthetic complications account for POCD. Studies
have also demonstrated that various anesthetic agents
can aect POCD; for example, midazolam may lead to
memory impairment than propofol or remifentanil.39
Medications aecting the cholinergic system can increase
the POCD risk. On the other hand, previous studies have
found that the perioperative usage of dexmedetomidine
may result in a lower POCD risk by reducing the levels
of IL-6 and S100B.40-42 Intraoperative use of volatile
anesthesia especially isourane and sevourane had
been reported to inuence higher risk of POCD when
compared with intravenous propofol.29
Assessment
Assessment of POCD is not straightforward. Variations
among assessors, dierent POCD denitions or diagnostic
tools used, the timing of evaluation, emotion, degree of
pain, medication prole, and environmental setting are
common factors contributing to dierent assessment
results. 43 Many studies have assessed POCD by observing
changes in patients’ neuropsychological signs. e Mini-
Mental State Examination (MMSE) assesses orientation
(time and place), memory (immediate and short-term),
calculation, language (naming, repetition, listening, reading
comprehension, and writing), visuospatial awareness,
concentration, and attention while the Montreal Cognitive
Assessment tool (MoCA) focuses on visuospatial and
executive function (alternate trail-making test, copy the
cube, and clock drawing), language ability, attention
and calculation, delayed recall, and abstract thinking.44
ese tools are the most common clinical screening
tests for POCD. However, they are not suitable for
cognitive follow-up evaluation.45 Other test batteries
that are designed to evaluate cognitive status include
various neuropsychological tests (NPT) which determine
specied cognitive domains such as Digit span test, Trail
Making Test, Groove Pegboard Test, etc.
Several screening tests for POCD with comparable
sensitivity and specicity at dierentiating mild cognitive
impairment (MCI) from dementia are Addenbrooke’s
Cognitive Exam (ACE-III), Quick Mild Cognitive
Impairment Screening (Qmci), Saint Louis University
Mental Status (SLUMS), Mini-cog, Rowland Universal
Dementia Assessment Scale (RUDAS) and Abbreviate
Mental Test (AMT) (Table 2).3,46-55
e new consensus for POCD diagnosis recommends
applying the diagnostic criteria for a neurocognitive
disorder from DSM-5.11 Neurocognitive assessment relies
on a subjective test (based on the responses of the patient
or close relatives), an objective test (standardized NPT)
as well as an assessment of the patient’s ability to perform
the activities of daily living (ADL). is new approach
provides a more accurate POCD diagnosis compared with
the previous recommendation where only an objective
test was considered. Recent publication reported the use
of the ai version of RUDAS to screen for POCD at
postoperative day 5-9 through real-time video stream
over mobile phone internet connection. Even though the
test consumed longer time, almost 30 minutes per each
patient, than usual face-to-face evaluation, this method
encouraged the use of telemedicine in geriatric patients
especially who were not well complied with clinical
follow-up.56
Prevention
ere are currently 2 main strategies for POCD
prevention:1,9
1. Patient factors
Comprehensive geriatric assessment and preoperative
assessment to stratify and optimize risks before proceeding
to operations are recommended during the preoperative
period.
2. Surgical and anesthetic factors
The Enhanced Recovery after Surgery (ERAS)
protocol has been reported to improve postoperative
recovery and to reduce rate of postoperative hospitalization
and morbidity. e general principles of ERAS involve
limited uid intake, preference of laparoscopic surgery,
appropriate anesthetic agent administration, adequate pain
medications, early feeding, and early mobilization. e
ERAS protocol covers the preoperative, intraoperative,
and postoperative states, as outlined below.3,42,57-64
a. Preoperative state
• Controlling patients’ underlying diseases,
optimizing the risk factors, and providing
preoperative counselling and prehabilitation.
• Recognizing the risks contributing to worsening
outcomes such as major surgery, immobilization,
and prolonged hospitalization.
• Encouraging social and moderate physical
activities to improve cognitive function.
• Implementation of prehabilitation program
at 6-8 weeks preoperatively which involves
processes designed to improve the preoperative
functional status of the patients by:
- Adequate and appropriate exercise including breathing
exercises or resistance training.
- Supplementary dietary intake to improve malnutrition.
- Giving education and advice especially to elderly patients.
- Treatment of comorbidities e.g., atrial brillation which
could relate to POCD.
b. Immediate preoperative state
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Review Article SMJ
TABLE 2. Neuropsychological tests for the assessment of postoperative cognitive dysfunction.
Parameters MMSE MoCA ACE-III Qmci
Parameters SLUMS Mini-cog RUDAS AMT
Total score
Cut off Score for
MCI
Average time to
complete
Sensitivity (%)
Specicity (%)
Advantages
Disadvantages
Total score
Cut off Score for
MCI
Average time to
complete
Sensitivity (%)
Specicity (%)
Advantages
Disadvantages
30
< 24
10 min
79.8%
81.3%
- Less time consuming
- Easy to use
- Low sensitivity and
not suitable to screen
for MCI
30
< 27
7 min
98
98
- High sensitivity and
specicity
- May be affected in
patients with ≤ 6 years
of education and non-
white ethnicity
- New tool, not widely
used
30
< 26
15 min
90
87
- High sensitivity
- Can identify MCI and
cognitive dysfunction
in Alzheimer’s and
Parkinson’s diseases
- Designed for MCI
rather than dementia
5
< 4
3 min
85.7
79.4
- Less time consuming
- Can be used in pri-
mary care setting
- Cannot be used in
patients with visual
impairment or difculty
to hold the pen/pencil
100
< 82–88
16 min
84–93
100
- Can differentiate MCI
from early dementia
- Provides scores for
different cognitive do-
mains with correlation
to NPT
- Cannot differentiate
dementia subtypes
100
< 25
10 min
76.2
75
- Can differentiate MCI
from dementia and
normal cognition
- May be affected in
patients with ≤ 6 years
of education
100
< 62
5 min
90
87
- Less time consuming
- High sensitivity
- Useful test to detect MCI
and dementia
- Maybe inaccurate when
used in certain subgroups
e.g., post stroke patients
10
< 9
3-5 min
91.5
82.4
- Less time consuming
- Can be used as rst line
screening in acute setting
- Normal AMT may not
exclude MCI therefore it
cannot be used as a rule-
out test
Abbreviations: ACE-III, Addenbrooke's Cognitive Examination III; AMT, Abbreviated Mental Test; MCI, Mild cognitive impairment;
MOCA, e Montreal Cognitive Assessment tool; NPT, Neuropsychological test; Qmci, e Quick Mild Cognitive Impairment; RUDAS,
Rowland Universal Dementia Assessment Scale; SLUMPS, Saint Louis University Mental Status
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710
• Reducing the fasting time is benecial since
prolonged starvation stimulates stress and
anxiety. Maintaining patients in an euvolemic
state is recommended.
• Oral carbohydrate preloading is suggested to
stimulate the neuroendocrine response to
stress.
• romboprophylaxis is recommended for all
patients either by intermittent pneumatic
compression devices, compression stockings
or encouraging early mobilization. e risk
of bleeding needs to be evaluated before
anticoagulant administration.
• Antibiotic prophylaxis should be given 60
minutes before skin incisions.
c. Intraoperative state
• Preanesthetic sedatives and anxiolytics are
not routinely administered.
Short-acting opioids are recommended.
• Sevourane, desurane, intravenous thiopental,
and propofol infusions are recommended to
reduce risks for POCD.
• Monitoring of anesthetic depth and cerebral
oxygenation during surgery.
• Anesthetic agents with small molecular
structures, isourane and desurane, could
create amyloid β-oligomerization which
involve POCD. A large molecular agent like
propofol, if administered with smaller molecular
agents, could also result in amyloid
β-oligomerization production.
• Avoidance of prolonged nitric oxide usage.
• Laparoscopic surgeries are recommended,
given the decreased levels of bowel distention
and lower incidences of postoperative nausea
and vomiting.
• Low tidal volume ventilation (5–7 mL/kg) and
real-time hemodynamic monitoring via an
esophageal doppler are recommended.
• A high level of oxygen can increase blood ow
to the anastomotic site, lessen the risk of delayed
wound healing, and lower the incidences of
postoperative nausea and vomiting.
• Epidural analgesia is recommended for open
surgical procedures.
• Avoidance of drains or nasogastric tubes as
they hinder early mobilization.
• Administration of a local anesthetic around
the wound helps reduce pain and urinary
retention.
• Fluids overloading should be avoided according
to poor intestinal anastomosis, prolonged
bowel ileus, and systemic edema.
• Balanced salt solutions are recommended
because saline overload leads to metabolic
acidosis and hyperchloremia.
• Hypotension from central neuraxial blockade
and general anesthesia should be resolved by
vasoconstrictors rather than uid resuscitation.
• Keeping normothermia as hypothermia may
result in increased metabolic demand, altered
drug metabolism, and impaired immunity
and coagulation.
d. Postoperative state
• Opioids should be used rationally. Paracetamol
and NSAIDs are encouraged for pain control.
• Epidural anesthesia should be given continuously.
• Oral uids should be given 2 hours aer surgery,
and intravenous uids should be administered
cautiously to reduce anastomotic dehiscence
and infection.
• Maintenance of blood glucose between 180–200
mg/dl.
• Early mobilization is encouraged. Nasogastric
tubes, abdominal drains, opioids, and epidural
catheters should therefore not be used from
the second day onwards unless necessary.
• The patients should be settled in a calm
environment and properly advised before
their discharge.
Treatment
POCD treatment is usually based on 2 major
principles:1,10
1. POCD can be mimicked by POCD-like conditions
(e.g., myocardial infarction, septic shock, medication or
toxic-substance abuse, electrolyte imbalance, a hypo- or
hyperglycemic state, endocrine or liver dysfunction, and
neurological decits). Hypoglycemia can be treated with
an intravenous glucose solution. iamine is the proper
treatment if Wernicke encephalopathy is suspected.
2. e general principles of surgical patient care can be
adapted for POCD patients. Some essential methods include
the provision of adequate ventilation and oxygenation,
hemodynamic support, or adequate postoperative pain
control. Pain control is critical and consequently requires
sucient patient counselling. Monitoring of vital signs,
electrolytes, and the cardiovascular and pulmonary
functions is suggested for enhanced recovery. When
POCD is resolved, patients may recall fragments of
memories during their POCD episodes which may create
stress. It is therefore necessary that medical personnel
give appropriate advice and counselling.
Suenghataiphorn et al.
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Review Article SMJ
CONCLUSION
POCD is a condition that warrants early detection
and treatment. e best measure to is to prevent it before
the resulting cognitive dysfunction develops. Proper
pre-, intra- and postoperative patient care should be
considered to reduce the risks of POCD. Preoperative
assessments are necessary to identify patients at risk and
to optimize patients’ condition for particular surgical
procedures. According to the ERAS protocol, hemodynamic
stabilization, adequate uid administration, avoidance of
excessive anesthetic agents, and appropriate management
of hypotension or hypothermia are measures for POCD
risk reduction. Adequate postoperative pain control,
breathing exercise, and early mobilization are essential
to prevent POCD and improve patients’ outcomes.
Additionally, appropriate environmental settings and
frequent postoperative POCD assessments are encouraged.
Once POCD develops, patients should be treated promptly,
scheduled for regular follow-ups, and given proper
counselling.
ACKNOWLEDGMENTS
e authors thank Dr. Arunotai Siriussawakul,
M.D., for her advice and support with the content review
and development of the nal revision. We also gratefully
acknowledge the administrative assistance provided by
Miss Chanita Janoonsong.
Conicts of interest: e authors declare that there are
no conicts of interest.
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714
I Putu Eka Widyadharma, M.D., Ph.D., Eric Hartono Tedyanto, M.D.
Department of Neurology, Faculty of Medicine, Universitas Udayana, Bali, Indonesia.
Serum Neurolament Light Chain: A Potential
Biomarker for Peripheral Neuropathy
ABSTRACT
In some neurological diseases, advanced examinations can be used as diagnostic tools. Several indicators have
also been discovered that can be used to assess the severity of neuronal damage and neurological disease progression.
Neurolament light chain (NfL) is a cytoskeleton protein that makes up the structure of neuron axons and is released
when a neuron is injured, allowing it to assess neuronal injury severity. NfL was rst used to diagnose central nervous
system disorders like dementia, multiple sclerosis, and other neurodegenerative diseases. But, NfL levels have also
been elevated in peripheral nervous system disorders, like in several neuropathic conditions, including amyloid
neuropathy, HIV-associated neuropathy, diabetic peripheral neuropathy, leprosy neuropathy, and other neuropathy,
according to various investigations. eoretically, all abnormalities induced by axonal injury will increase blood
NfL levels, allowing NfL testing to be utilized as a measurement tool. NfL levels can also be a predictive indicator
to monitor treatment ecacy and peripheral neuropathy progression.
Keywords: Biomarker; neurolament light chain; peripheral neuropathy; prognostic (Siriraj Med J 2022; 74: 714-720)
Corresponding author: Eric Hartono Tedyanto
E-mail: erichartonoo@gmail.com
Received 28 April 2022 Revised 15 August 2022 Accepted 16 August 2022
ORCID ID:http://orcid.org/0000-0002-4554-0348
http://dx.doi.org/10.33192/Smj.2022.84
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
INTRODUCTION
In recent years, neurology has made signicant
technological innovations. A variety of neuroimaging
methods can generate accurate images of the brain.
Moreover, various biomarkers have been developed
which may be used in clinical trials to estimate the level of
neuronal damage. One of them is the neurolament light
chain (NfL). NfL is released into the CSF and bloodstream
whenever there is damage to neurons.1
Since it is an indicator of axonal damage, the serum
neurolament light chain (NfL) is a potential diagnostic
in neurological diseases. Previously, NfL has only been
detected in CSF. e NfL can still be detected in the
blood due to the new advanced technologies, making
it simpler to detect and avoiding traumatic procedures
like a lumbar puncture. A neurologist can use NfL as
a prospective diagnostic as an accurate sign of nerve
injury. If the cardiologist has troponin, the neurologist
has the neurolament light chain (NfL).2
NfL concentrations in the normal population are
rarely reported. Tobias et al revealed that NfL levels in
normal populations are 7.3 (±3) pg/mL in serum and 416
(±191) pg/mL in CSF. In patients with Multiple Sclerosis,
NfL levels are 16.4 (±14.4) pg/mL in serum and 2368
(±1947) pg/mL in CSF. e levels of NfL are aected by
age, BMI, and renal function. e association between
age and NfL concentration was positive (r = 0.325;
p-value <0.0001), while the correlation between BMI
and NfL concentration was negative (r = 0.227; p-value
<0.0001). No signicant dierences exist between NfL
concentration and gender. In addition, there was a strong
correlation between NF-L levels and renal function. NfL
concentration and eGFR were also found to have a very
strong connection (r = − 0.492; p-value <0.0001).3-5
Widyadharma et al.
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CSF and serum NfL levels were higher in patients
with a central or peripheral nervous system injury. is
increase has been linked to neurological diseases, according
to certain studies. e NfL can also be used to predict
future outcomes. Because it can be easily detected and
non-invasively in the blood, NfL is a promising biomarker
for monitoring the progression of neurological diseases
and evaluating the ecacy of therapy.6
Peripheral neuropathy aects approximately 2.4
percent of the population, with symptoms varying
depending on what type of nerve ber is aected, the
type of neuron injury, and the severity of the injury.
Peripheral neuropathy is most commonly caused by
diabetes. However, HIV can also directly or indirectly
induce peripheral neuropathy through antiretroviral
(ARV) medications. Systemic disease, infection, and
malnutrition are also all potential causes of peripheral
neuropathy.7
A neurologist might conduct an electrophysiological
evaluation of nerve conduction velocity to diagnose
peripheral neuropathy. However, nerve conduction
velocity may not be able to accurately assess the severity
and progression of neuropathy in some conditions,
requiring the use of additional biomarkers to determine
prognostic value. On the other hand, NfL has lately
undergone massive research and can be utilized as a
biomarker for peripheral nerve injury. Serum NfL levels
are known to be elevated in cases of peripheral neuropathy
and correlate with disease severity.8 In this review, we
provide the role of the neurolament light chain (NfL)
as a biomarker of peripheral neuropathy.
Neurolament light chain (NfL)
e essential features of neurons are neurolaments,
built up of protein triplets and present on nerve axons
(Fig 1). e neurolament core cannot functionally work
without the neurolament light chain (NfL) subunit.
Almost every neuron component contains the protein
neurofilament light chain (NfL). The diameter and
speed of nerve conduction from peripheral nerves are
determined by NfL accumulation, linked to axon growth
during myelination.9 Depending on the severity of axonal
damage in peripheral nerves, NfL can be released into the
extracellular space and bloodstream. An apophagocytotic
process releases NfL into the CSF and bloodstream when
neurons in the central nervous system are damaged. NfL
will enter the CSF through direct drainage and then
enter the bloodstream through arachnoid granulation
and lymphatic ow in the subarachnoid space, making
it detectable in both the CSF and the blood.10 According
to some studies, the amount of NfL in CSF is 500 times
higher than in blood because CSF is directly related
to the central nervous system. NfL concentrations in
the blood are too low to be detected by an ELISA test.
anks to recent technological advancements, a new
method, SIMOA (Single-Molecule Assay (SiMoA), has
been developed to detect NfL down to a single-digit
picogram per millimeter unit.11
NfL in neurological cases
Axonal damage in the central and peripheral nervous
systems, such as stroke, head trauma, multiple sclerosis,
ALS, Alzheimer’s disease, frontotemporal dementia,
Fig 1. Structure of neurolament.6
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716
and peripheral neuropathy, can be identied by NfL
measurement. Previous studies linked increased NfL
levels in CSF and serum to neurodegenerative and
neuroinammatory processes, indicating demyelination
and axonal damage.12-16
Neurological patients have much greater NfL levels
in their CSF and blood than healthy or non-neurological
patients. NfL is a test that can identify neurological
problems caused by axonal damage. It can tell the dierence
between varying degrees of axonal damage, progression,
and whether or not it is a neurodegenerative condition. As
a result, the NfL examination is utilized as a biomarker to
validate the diagnosis aer a full neurological examination
or other biomarker and neuroimaging procedures.6 In
the event of peripheral neuropathy, NfL can be utilized
as a non-invasive diagnostic technique to determine
therapy success and progression.8
It is unclear how long the duration of NfL levels
increases in patients with peripheral neuropathy. In
studies on multiple sclerosis, traumatic brain injury,
and stroke, NfL levels peak 3–4 weeks aer a clinical
relapse and remain elevated for 6–12 months. Further
studies on how long NfL levels increase in peripheral
neuropathy need to be done for prognostic purposes.17
NfL in peripheral neuropathy
Peripheral neuropathy has become a global health
concern, aecting 2.4 percent of the world’s population,
or around 10 million people in the European Union and
7 million in the United States. Measurement of nerve
conduction velocity is the gold standard for diagnosing
peripheral neuropathy. However, it cannot be used as a
monitor for the success of therapy or disease progression
in some cases. As a result, a peripheral nerve damage
biomarker is required. On the other hand, NfL has
recently undergone extensive research and can be used as
a biomarker for peripheral nerve damage. NfL levels have
been shown to increase in peripheral neuropathy patients’
blood and correlate with disease severity, implying that
the NfL is involved in disease progression and can be
used as a prognostic factor in peripheral nerve damage.8,18
Neuronal neurolament breakdown is thought to
use a combination of ubiquitin-mediated proteasomal
and apophagocytotic mechanisms. Based on the
transport of other CNS-degraded proteins, it is likely
that neurolament fragments drain directly into CSF and
blood via numerous pathways. ese include lymphatic
outow into subarachnoid and perivascular regions
and direct draining into CSF and blood via arachnoid
granulations. Once NfL enters the bloodstream, the
half-life is a crucial factor with consequences for disease
activity monitoring frequency. In a longitudinal study of
NfL levels before and aer implantation of an intrathecal
catheter, NfL levels in both CSF and serum peaked one
month aer surgery and returned to baseline six to nine
months later.2
Other biomarkers besides NfL can be used to
diagnose peripheral neuropathy, including Brain Derived
Neurotrophic Factor (BDNF), Nerve Growth Factor
(NGF), and other inammatory markers such as IL-1,
6,10, 18, and TNF-alpha. Low BDNF levels were correlated
with CIPN in 91 multiple myeloma patients treated
Fig 2. Pathophysiology of neurolament light chain in cerebrospinal uid (CSF) and blood.
Widyadharma et al.
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with bortezomib, and a cut-point of 9.11 ng/ml was 76%
sensitive and 71% specic for identifying Chemotherapy-
induced Peripheral Neuropathy (CIPN). Nonetheless,
another study found no correlation between BDNF and
the incidence of CIPN. In one investigation, a correlation
was shown between decreasing NGF and the severity of
neuropathy as measured by nerve conduction velocity
testing. High levels of IFN-, IL-1, and IL-8, but low levels
of IL-10 and IL-6, were linked to peripheral neuropathy
symptoms. Due to the inconsistency and expense of these
biomarkers, NfL testing is recommended to monitor
peripheral neuropathy.19
Sandelius et al. suggested that the cut-o value
of NfL for peripheral neuropathy was 20 pg/mL with
a sensitivity of 71% and specicity of 75%. Increased
serum NfL concentration is not specic to peripheral
neuropathy because other neurological disorders such
as multiple sclerosis, Alzheimer’s disease, stroke, and
Amyotrophic Lateral Sclerosis (ALS) also reported
increases. NfL is not useful for diagnosis, but it may be
useful to measure axonal damage and could serve as a
biomarker of progressivity of the disease for monitoring
and response to treatment. NfL is sensitive to detecting
axonal damage and correlates with disease severity and
progressivity.18
Several studies have reported elevated levels of NfL
in amyloid neuropathy, HIV-associated neuropathy,
diabetic peripheral neuropathy, chemotherapy-induced
peripheral neuropathy, and pyridoxine-induced sensory
neuropathy.
Amyloid neuropathy
Amyloidosis patients with polyneuropathy experience
axonal degeneration, which results in elevated serum NfL
levels. Axonal degeneration is caused by the accumulation
of amyloid brils in the endoneurium and direct toxicity
to the nerve’s prebrillar oligomers.20-22 Patients with
symptomatic polyneuropathy, as well as those who are
asymptomatic, have elevated serum NfL levels. Serum
NfL levels can be used as a marker for early-stage axonal
damage in asymptomatic or subclinical amyloidosis, making
it essential to diagnose, treat, and monitor the progress
and success of amyloidosis therapy.23 e AUC between
asymptomatic and symptomatic amyloid neuropathy
patients was 0.99 (p .001), and a NfL concentration
of 10.6 pg/mL distinguished these individuals with a
sensitivity of 96.2% and a specicity of 93.8%.20 Serum
NfL levels increase the most in patients with abnormal
EMG results. is demonstrates that serum NfL is a
sensitive marker for early detection of polyneuropathy
and is strongly associated with the disease.14
HIV-associated neuropathy
HIV-associated neuropathy manifests as distal
symmetrical polyneuropathy and toxic antiretroviral
neuropathy (ATN), which is dicult to distinguish
clinically and electrophysiologically regardless of the
use of antiretroviral drugs or the onset of symptoms.
HIV-associated neuropathy is linked to the patient’s
viral load and CD4+ cell count. e use of dNRTIs like
stavudine, didanosine, or zalcitabine has been linked
to ATN. Aer antiretroviral therapy, the symptoms of
HIV-related polyneuropathy improve as the viral load
decreases. Aer a year of ARV treatment, the symptoms
of ATN will worsen.24
NFL is a structural component of myelinated axons
that have been used as a marker of axonal damage in
neurodegenerative diseases in several studies. Axonal
damage also occurs in HIV-associated neuropathy, but
research on elevated serum NfL levels in HIV-associated
neuropathy is uncommon. e HIV in Dementia study
is the most widely conducted. Compared to HIV patients
without dementia, NfL levels were signicantly higher
in HIV patients with dementia. e levels of plasma NfL
and CSF NfL did not dier signicantly. Damian et al.
conducted a study to see if NfL levels were elevated in
HIV-associated neuropathy patients. e researchers
discovered an increase in NfL levels in both CSF and serum
in 26 of 54 patients with neuropathy, which correlates
to the severity of the neuropathy.25 NfL levels are not
only used as markers of damage to the central nervous
system but also in the peripheral nervous system, such
as neuropathy, according to these studies.26
Chemotherapy induced peripheral neuropathy (CIPN)
CIPN is a side eect of chemotherapy in some cancers.
Proper diagnosis, treatment, and dosage adjustments
are required to avoid permanent nerve damage. Because
CIPN is an axonopathy, it can mimic the symptoms
of polyneuropathy. Previous research has discovered
that elevated serum NfL levels are linked to peripheral
neuropathy and the severity of nerve damage, allowing
NfL levels to be measured in CIPN patients. In a mouse
model given the cytostatic drug vincristine (VCR) 0.2
mg/kg intravenously four times per week, serum NfL
levels increased fourfold, with signs of axonopathy on
neurophysiological and pathological examinations. e
presence of the NfL in the blood can determine the
severity of CIPN.27-29
Other chemotherapy drugs, such as oxaliplatin, can
cause neuronal cell death and neuropathy in the dorsal
ganglion. One study found a link between serum NfL
levels and changes in nerve amplitude aer treatment with
Volume 74, No.10: 2022 Siriraj Medical Journal https://he02.tci-thaijo.org/index.php/sirirajmedj/index
718
oxaliplatin. Serum NfL levels were signicantly higher
in 5 patients with grade 3 OIPN (oxaliplatin-induced
peripheral neuropathy) than in grades 0-2 (80 percent
sensitivity and 86 percent specicity with a cut-o value
of 195 pg/mL). Based on the ndings of these studies,
serum NfL can be used as a monitor for the severity of
OIPN.30
Diabetic peripheral neuropathy (DPN)
An observational study used Serum NfL as a non-
invasive diagnostic tool to detect diabetic peripheral
neuropathy and its progression. NfL levels are related
to the neuropathy disability score (NDS) and decreased
nerve conduction velocity in some nerves. e AUC for
serum NfL was 0.564, and the DPN cut-o point was
12.6 pg/ml. NfL is also associated with the hyperalgesia
phenotype and is positively correlated with the severity
of DPN.31,32
NfL mRNA levels have also been elevated in prediabetic
patients with peripheral neuropathy. is supports the
hypothesis that NfL mRNA levels are signicantly higher
in prediabetic patients when small-diameter nociceptive
aerent C bers are interfered with in hyperglycemic
conditions, causing axon damage and neuropathic pain
symptoms. is level is positively correlated with DN4
questionnaire score.9,33
Leprosy neuropathy
Mycobacterium leprae can damage both myelinated
and unmyelinated nerve bers. Patients with leprosy may
develop painful neuropathy symptoms. e pathogenesis
of neuropathy in leprosy includes infection of the Schwann
cells, demyelination, and damage to the axons, leading
to atrophy. In tuberculoid and borderline leprosy, axon
damage is caused by inammation of the endoneurial
membrane, which destroys nerve structures and causes
nerve damage. According to the results of a nerve biopsy,
axons and myelin are lost in patients with leprosy.
Electromyography also revealed axonal polyneuropathy.
Axon damage is a focus of research into the mechanism
of leprosy neuropathy. Biomarkers such as NfL can be
used with other tests to help determine prognosis and
treatment success.35,36
Post-herpetic neuralgia
Aer the reactivation of the varicella-zoster virus,
which damages the cell body and axons, post-herpetic
neuralgia (PHN) develops. e pathology of PHN is
associated with peripheral axonal damage, sensory neuron
degeneration, and dorsal horn atrophy. However, several
theories suggest that aer viral reactivation, axonal damage
occurs due to inammation in PHN. e role of NfL in
post-herpetic neuralgia has rarely been studied. More
research on the NfL as a biomarker of post-herpetic
neuralgia is needed.37
Pyridoxine-induced sensory neuropathy (PISN)
According to a study, NfL levels in the CSF and
blood increased on day four aer rats received pyridoxine
therapy. Pyridoxine’s primary target is the cell body of
TABLE 1. Summarize how NfL is used in various peripheral neuropathy diseases.
Disease NfL levels Indication Sensitivity Specicity AUC Reference
Peripheral neuropathy 20 pg/mL Prognostic 71% 75% 0.755 18
Amyloid neuropathy 10.6 pg/mL Prognostic 96.2% 93.8% 0.99 20
CIPN 195 pg/mL Prognostic, 80% 86% N/A 30
treatment
response
Diabetic peripheral 12.6 pg/ml Prognostic, 77.6% 86.3% 0.564 32
neuropathy treatment
response
ALS 93 pg/ml Prognostic 80.5% 90.9% 0.85 38
Post-stroke cognitive 46.12 pg/ml Prognostic 71% 81.5% 0.785 39
impairment
Widyadharma et al.
Volume 74, No.10: 2022 Siriraj Medical Journal
https://he02.tci-thaijo.org/index.php/sirirajmedj/index 719
Review Article SMJ
DRG neurons, which is followed by secondary nerve ber
degeneration. NfL is released directly from the DRG to
the CSF via the subarachnoid space from the neuronal
cell body and surrounding nerve bers.34
Summarize
As described above, NfL can help determine the
progression and response to peripheral neuropathy
treatment. Here we provide a table summarizing how
NfL is used in various peripheral neuropathy diseases
discussed in the manuscript (Table 1). We also compared
diseases such as ALS and post-stroke cognitive impairment.
No studies determine the cut-o value for some types
of peripheral neuropathy. Further research on cut-o
NfL levels needs to be done.
CONCLUSION
Serum NfL can be used as a diagnostic tool for
peripheral neuropathy aer a careful history and physical
examination. In addition, NfL levels can also be used as a
monitor for the success of therapy and the progression of
peripheral neuropathy to be used as a prognostic value.
Further studies regarding when serum NfL levels begin
to elevate, how long they last, and clear cut-o points
for each type of peripheral neuropathy are needed to
strengthen the diagnostic value and specicity of serum
NfL.
Conict of interest: No conict of interest
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