Intravenous Acetaminophen Versus Placebo as an Adjuvant Therapy for Pain Management in Transsphenoidal Pituitary Surgery Patients: A Double-blinded Randomized Controlled Trial

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Surunchana Lerdsirisopon
Vorrachai Sae-phua
Kornkamon Yuwapattanawong
Lawan Tuchinda
Tharinan Tangworanigoonkit
Chayanee Srira


Background: Transsphenoidal pituitary surgery (TSS) is a neurosurgical procedure with mild to moderate postoperative pain, which is usually controlled by opioid analgesics. However, concerns about side effects associated with opioids have been challenges among these patients. Thus, multimodal analgesics are often required to optimize pain control with less undesired effects. Objective: Our study aimed to determine intravenous acetaminophen’s efficacy as an adjuvant therapy for postoperative pain management in TSS patients. Methods: We conducted a prospective, double-blinded, randomized controlled trial. Forty-six patients who had undergone elective TSS were recruited and randomly assigned to the acetaminophen or placebo group. The total fentanyl consumptions in the first 24 hours were recorded. Pain scores and adverse effects such as nausea, vomiting, and sedation were recorded. All statistical analyses were performed using STATA 14. Results: Based on the average pain scores, both groups received optimal postoperative pain management. Postoperative fentanyl consumption was 284.1±152.8 mcg in the study group and 364.4±211.7 mcg in the placebo group, respectively. Adding acetaminophen to fentanyl was associated with an opioid-sparing effect of 22% (P-value = 0.15) in the first 24 hours postoperative period. The incidences of nausea, vomit, sedation and respiratory depression were not different in both groups. Conclusion: In our study, acetaminophen administration was not associated with a reduction of postoperative fentanyl consumption. Acetaminophen had neither significant fentanyl-sparing effects nor side effects reduction for postoperative pain management in TSS patients.


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1. Suksompong S, Chaikittisilpa N, Rutchadawong T, Chankaew E,
von Bormann B. Pain after major craniotomy in a university
hospital: a prospective cohort study. J Med Assoc Thai
2. Gottschalk A, Berkow LC, Stevens RD, et al. Prospective
evaluation of pain and analgesic use following major elective
intracranial surgery. J Neurosurg 2007;106:210-6.
3. Morad A, Winters B, Stevens R, et al. The efficacy of
intravenous patient-controlled analgesia after intracranial
surgery of the posterior fossa: a prospective, randomized
controlled trial. Anesth Analg 2012;114:416-23.
4. Xiong W, Li L, Bao D, et al. Postoperative analgesia of scalp
nerve block with ropivacaine in pediatric craniotomy patients:
a protocol for a prospective, randomized, placebocontrolled, double-blinded trial. Trials 2020;21:580.
5. Basali A, Mascha EJ, Kalfas I, Schubert A. Relation between
perioperative hypertension and intracranial hemorrhage
after craniotomy. Anesthesiology 2000;93:48-54.
6. Cold GE, Felding M. Even small doses of morphine might
provoke “luxury perfusion” in the postoperative period after
craniotomy. Neurosurgery 1993;32:327.
7. Shay JE, Kattail D, Morad A, Yaster M. The postoperative
management of pain from intracranial surgery in pediatric
neurosurgical patients. Paediatr Anaesth 2014;24:724-33.
8. Singer AJ, Mynster CJ, McMahon BJ. The effect of IM
ketorolac tromethamine on bleeding time: a prospective,
interventional, controlled study. Am J Emerg Med 2003;21:
9. Palmer JD, Sparrow OC, Iannotti F. Postoperative hematoma:
a 5-year survey and identification of avoidable risk factors.
Neurosurgery 1994;35:1061-4.
10. Magni G, La Rosa I, Melillo G, Abeni D, Hernandez H, Rosa G.
Intracranial hemorrhage requiring surgery in neurosurgical
patients given ketorolac: a case-control study within a cohort
(2001-2010). Anesth Analg 2013;116:443-7.
11. Richardson MD, Palmeri NO, Williams SA, et al. Routine
perioperative ketorolac administration is not associated with
hemorrhage in pediatric neurosurgery patients. J Neurosurg
Pediatr 2016;17:107-15.
12. Nair S, Rajshekhar V. Evaluation of pain following supratentorial
craniotomy. Br J Neurosurg 2011;25:100-3.
13. de Gray LC, Matta BF. Acute and chronic pain following
craniotomy: a review. Anaesthesia 2005;60:693-704.
14. Remy C, Marret E, Bonnet F. Effects of acetaminophen on
morphine side-effects and consumption after major surgery:
meta-analysis of randomized controlled trials. Br J Anaesth
2005 Apr; 94:505-13.
15. McNicol ED, Tzortzopoulou A, Cepeda MS, Francia MB,
Farhat T, Schumann R. Single-dose intravenous paracetamol
or propacetamol for prevention or treatment of postoperative
pain: a systematic review and meta-analysis. Br J Anaesth
16. McNicol ED, Ferguson MC, Haroutounian S, Carr DB,
Schumann R. Single dose intravenous paracetamol or
intravenous propacetamol for postoperative pain. Cochrane
Database Syst Rev 2016;(5):CD007126.
17. Apfel CC, Turan A, Souza K, Pergolizzi J, Hornuss C.
Intravenous acetaminophen reduces postoperative nausea
and vomiting: a systematic review and meta-analysis. Pain
18. Hong JY, Kim WO, Koo BN, Cho JS, Suk EH, Kil HK. Fentanylsparing effect of acetaminophen as a mixture of fentanyl in
intravenous parent-/nurse-controlled analgesia after pediatric
ureteroneocystostomy. Anesthesiology 2010;113:672-7.
19. Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous
paracetamol reduced the use of opioids, extubation time,
and opioid-related adverse effects after major surgery in
intensive care unit. J Crit Care 2010;25:458-62.
20. Kemppainen T, Kokki H, Tuomilehto H, Seppä J, Nuutinen
J. Acetaminophen is highly effective in pain treatment after
endoscopic sinus surgery. Laryngoscope 2006;116:2125-8.
21. Ghaffarpasand F, Dadgostar E, Ilami G, et al. Intravenous
acetaminophen (paracetamol) for post-craniotomy pain;
systematic review and meta-analysis of randomized clinical
trials. World Neurosurg 2020;134:569-76.
22. Ong CK, Seymour RA, Lirk P, Merry AF. Combining
paracetamol (acetaminophen) with nonsteroidal antiinflammatory
drugs: a qualitative systematic review of analgesic efficacy
for acute postoperative pain. Anesth Analg 2010;110:1170-9.
23. McGlothlin AE, Lewis RJ. Minimal clinically important
difference: defining what really matters to patients. JAMA
24. Shepherd DM, Jahnke H, White WL, Little AS. Randomized,
double-blinded, placebo-controlled trial comparing two
multimodal opioid-minimizing pain management regimens
following transsphenoidal surgery. J Neurosurg 2018;128:
25. Banerjee U, Hagan K, Bhavsar S, et al. Association between
intravenous acetaminophen and reduction in intra-operative
opioid consumption during transsphenoidal surgery for
pituitary tumors. J Anaesthesiol Clin Pharmacol 2018;34:
26. Taniguchi H, Nagahuchi M, Kamada T, et al. Effect of scheduled
intravenous acetaminophen on postoperative nausea and
vomiting in patients undergoing laparoscopic gynecologic
surgery. J Anesth 2020;34:502-11.
27. Flynn BC, Nemergut EC. Postoperative nausea and vomiting
and pain after transsphenoidal surgery: a review of 877
patients. Anesth Analg 2006;103:162-7.
28. Chowdhury T, Prabhakar H, Bithal PK, Schaller B, Dash HH.
Immediate postoperative complications in transsphenoidal
pituitary surgery: a prospective study. Saudi J Anaesth