Analgesia Nociception Index: an Evidence-Based Review
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Published:
Sep 26, 2019
Main Article Content
Abstract
The aims of general anesthesia consisted of
unconsciousness, immobility and analgesia. One of the
main analgesic drugs is opioids which are usually titrated
by clinical surrogates of nociception and experiences of
health care providers. The under-dosage or over-dosage
of intraoperative analgesia could occur, resulting in
nausea, vomiting, respiratory depression and opioidinduced
hyperalgesia. Nociception is not a subjective
feeling but the whole physiological process of nociceptive
stimuli. The new non-invasive objective tools, Analgesia
Nociception Index (ANI), has been developed to achieve
objective pain assessment during intraoperative or patients
who unable to communicate. ANI measures heart rate
variability from EKG monitoring. The results are
continuously showed as a number from 0 to 100 through
spectral analysis. The number indicates the balance
between parasympathetic and sympathetic outflows. Most
of studies exhibited favorable results in patients under
anesthesia in terms of decreased dose of intraoperative
opioids and good correlation with hemodynamic reactivity.
However, the overall expected benefits including better
postoperative pain scores correlation or less undesirable
adverse events of opioids were until questionable. There
are some limitations of use and confounding factors that
might interfere with interpretation.
Article Details
Section
Review articles
References
Brown EN, Lydic R, Schiff ND. General anesthesia, sleep,
and coma. N Engl J Med 2010;363(27):2638-50.
2. Brown EN, Pavone KJ, Naranjo M. Multimodal General
Anesthesia: Theory and Practice. Anesth Analg 2018;127(5):
1246-58.
169
Evans JM. Pain and awareness during general anaesthesia.
Lancet 1987;2(8566):1033.
4. Fechner J, Ihmsen H, Schuttler J, Jeleazcov C. The impact
of intra-operative sufentanil dosing on post-operative pain,
hyperalgesia and morphine consumption after cardiac
surgery. Eur J Pain 2013;17(4):562-70.
5. Task Force of the European Society of Cardiology and the
North American Society of Pacing and Electrophysiology.
Heart rate variability. Standards of measurement, physiological
interpretation, and clinical use. Eur Heart J 1996;17(3):354-81.
6. Miu AC, Heilman RM, Miclea M. Reduced heart rate variability
and vagal tone in anxiety: trait versus state, and the effects
of autogenic training. Auton Neurosci 2009;145(1-2):99-103.
7. Jeanne M, Logier R, De Jonckheere J, Tavernier B. Heart
rate variability during total intravenous anesthesia: effects of
nociception and analgesia. Auton Neurosci 2009;147(1-2):
91-6.
8. Jeanne M, Logier R, De Jonckheere J, Tavernier B. Validation
of a graphic measurement of heart rate variability to assess
analgesia/nociception balance during general anesthesia.
Conf Proc IEEE Eng Med Biol Soc 2009;2009:1840-3.
9. Logier R, Jeanne M, De Jonckheere J, Dassonneville A,
Delecroix M, Tavernier B. PhysioDoloris: a monitoring device
for analgesia / nociception balance evaluation using heart
rate variability analysis. Conf Proc IEEE Eng Med Biol Soc
2010;2010:1194-7.
10. Lavand’homme P, Estebe JP. Opioid-free anesthesia:
a different regard to anesthesia practice. Curr Opin
Anaesthesiol 2018;31(5):556-61.
11. Upton HD, Ludbrook GL, Wing A, Sleigh JW. Intraoperative
“Analgesia Nociception Index”-Guided Fentanyl Administration
During Sevoflurane Anesthesia in Lumbar Discectomy and
Laminectomy: A Randomized Clinical Trial. Anesth Analg
2017;125(1):81-90.
12. Daccache G, Caspersen E, Pegoix M, et al. A targeted
remifentanil administration protocol based on the analgesia
nociception index during vascular surgery. Anaesth Crit Care
Pain Med 2017;36(4):229-32.
13. Dundar N, Kus A, Gurkan Y, Toker K, Solak M. Analgesia
nociception index (ani) monitoring in patients with thoracic
paravertebral block: a randomized controlled study. J Clin
Monit Comput 2018;32(3):481-6.
14. Le Gall L, David A, Carles P, et al. Benefits of intraoperative
analgesia guided by the Analgesia Nociception Index (ANI)
in bariatric surgery: An unmatched case-control study.
Anaesth Crit Care Pain Med 2019;38(1):35-9.
15. Szental JA, Webb A, Weeraratne C, Campbell A, Sivakumar H,
Leong S. Postoperative pain after laparoscopic cholecystectomy
is not reduced by intraoperative analgesia guided
by analgesia nociception index (ANI(R)) monitoring:
a randomized clinical trial. Br J Anaesth 2015;114(4):640-5.
16. Jiao Y, He B, Tong X, Xia R, Zhang C, Shi X. Intraoperative
monitoring of nociception for opioid administration:
a meta-analysis of randomized controlled trials. Minerva
Anestesiol 2019;85(5):522-30.
17. Boselli E, Jeanne M. Analgesia/nociception index for the
assessment of acute postoperative pain. Br J Anaesth
2014;112(5):936-7.
18. Gazi M, Abitagaoglu S, Turan G, Koksal C, Akgun FN, Ari
DE. Evaluation of the effects of dexmedetomidine and
remifentanil on pain with the analgesia nociception index in
the perioperative period in hysteroscopies under general
anesthesia. A randomized prospective study. Saudi Med J
2018;39(10):1017-22.
19. Bollag L, Ortner CM, Jelacic S, Rivat C, Landau R, Richebe
P. The effects of low-dose ketamine on the analgesia
nociception index (ANI) measured with the novel PhysioDoloris
analgesia monitor: a pilot study. J Clin Monit Comput
2015;29(2):291-5.
20. Gruenewald M, Ilies C, Herz J, et al. Influence of nociceptive
stimulation on analgesia nociception index (ANI) during
propofol-remifentanil anaesthesia. Br J Anaesth 2013;110(6):
1024-30.
21. Sriganesh K, Theerth KA, Reddy M, Chakrabarti D, Rao GSU.
Analgesia nociception index and systemic haemodynamics
during anaesthetic induction and tracheal intubation:
A secondary analysis of a randomised controlled trial. Indian
J Anaesth 2019;63(2):100-5.
22. Boselli E, Bouvet L, Begou G, Torkmani S, Allaouchiche B.
Prediction of hemodynamic reactivity during total intravenous
anesthesia for suspension laryngoscopy using Analgesia/
Nociception Index (ANI): a prospective observational study.
Minerva Anestesiol 2015;81(3):288-97.
23. Ledowski T, Averhoff L, Tiong WS, Lee C. Analgesia
Nociception Index (ANI) to predict intraoperative haemodynamic
changes: results of a pilot investigation. Acta
Anaesthesiol Scand 2014;58(1):74-9.
24. Weber F, Geerts NJE, Roeleveld HG, Warmenhoven AT,
Liebrand CA. The predictive value of the heart rate variabilityderived
Analgesia Nociception Index in children anaesthetized
with sevoflurane: An observational pilot study. Eur J Pain
2018;22(9):1597-605.
W, Stefaniak ME, Krauze T, et al. Measures of
Heart Rate Variability in 24-h ECGs Depend on Age but Not
Gender of Healthy Children. Front Physiol 2017;8:311.
26. Boselli E, Logier R, Bouvet L, Allaouchiche B. Prediction of
hemodynamic reactivity using dynamic variations of
Analgesia/Nociception Index (ANI). J Clin Monit Comput
2016;30(6):977-84.
27. Logier R, De Jonckheere J, Delecroix M, et al. Heart rate
variability analysis for arterial hypertension etiological
diagnosis during surgical procedures under tourniquet. Conf
Proc IEEE Eng Med Biol Soc 2011;2011:3776-9.
28. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines
for the management of pain, agitation, and delirium in adult
patients in the intensive care unit. Crit Care Med 2013;41(1):
263-306.
29. Payen JF, Gelinas C. Measuring pain in non-verbal critically
ill patients: which pain instrument? Crit Care 2014;18(5):554.
30. Broucqsault-Dedrie C, De Jonckheere J, Jeanne M, Nseir S.
Measurement of Heart Rate Variability to Assess Pain in
Sedated Critically Ill Patients: A Prospective Observational
Study. PloS one 2016;11(1):e0147720.
31. Chanques G, Tarri T, Ride A, et al. Analgesia nociception
index for the assessment of pain in critically ill patients: a
diagnostic accuracy study. Br J Anaesth 2017;119(4):812-20.
32. Charier D, Vogler MC, Zantour D, et al. Assessing pain in the
postoperative period: Analgesia Nociception Index(TM)vs
pupillometry. Br J Anaesth 2019;123(2):e322-e32733.
33. Papaioannou V, Chouvarda I, Gaertner E, et al. Heart rate
variability and cardiac baroreflex inhibition-derived index
predicts pain perception in burn patients. Burns 2016;42(7):
1445-54.
34. Issa R, Julien M, Decary E, et al. Evaluation of the analgesia
nociception index (ANI) in healthy awake volunteers. Can J
Anaesthesia 2017;64(8):828-35.
35. Yan Q, An HY, Feng Y. Pain assessment in conscious healthy
volunteers: a crossover study evaluating the analgesia/
nociception index. Br J Anaesth 2017;118(4):635-6.
36. Boselli E, Musellec H, Martin L, et al. Effects of hypnosis on
the relative parasympathetic tone assessed by ANI
(Analgesia/Nociception Index) in healthy volunteers:
a prospective observational study. J Clin Monit Comput
2018;32(3):487-92.
37. Boselli E, Musellec H, Bernard F, et al. Effects of conversational
hypnosis on relative parasympathetic tone and patient
comfort during axilary brachial plexus blocks for ambulatory
upper limb surgery: a quasiexperimental pilot study. Int J
Clin Exp Hypn 2018;66(2):134-46.
38. Julien-Marsollier F, Rachdi K, Caballero MJ, et al. Evaluation
of the analgesia nociception index for monitoring intraoperative
analgesia in children. Br J Anaesth 2018;121(2):462-8.
39. Gall O, Champigneulle B, Schweitzer B, et al. Postoperative
pain assessment in children: a pilot study of the usefulness
of the analgesia nociception index. Br J Anaesth
2015;115(6):890-5.
40. Boselli E, Bouvet L, Begou G, et al. Prediction of immediate
postoperative pain using the analgesia/nociception index: a
prospective observational study. Br J Anaesth 2014;112(4):
715-21.
41. Sabourdin N, Arnaout M, Louvet N, Guye ML, Piana F,
Constant I. Pain monitoring in anesthetized children: first
assessment of skin conductance and analgesia-nociception
index at different infusion rates of remifentanil. Paediatr
Anaesth 2013;23(2):149-55.
42. Avez-Couturier J, De Jonckheere J, Jeanne M, Vallee L,
Cuisset JM, Logier R. Assessment of Procedural Pain in
Children Using Analgesia Nociception Index: A Pilot Study.
Clin J Pain 2016;32(12):1100-4.
43. Cremillieux C, Makhlouf A, Pichot V, Trombert B, Patural H.
Objective assessment of induced acute pain in neonatology
with the Newborn Infant Parasympathetic Evaluation index.
Eur J Pain 2018;22(6):1071-9.
44. De Jonckheere J, Storme L. NIPE is related to parasympathetic
activity. Is it also related to comfort? J Clin Monit Comput
2019. [Internet]. Available at: https://link.springer.com/article/
10.1007/s10877-019-00276-1. Access on Jul 30, 2019.
45. Weber F, Roeleveld HG, Geerts NJE, Warmenhoven AT,
Schroder R, de Leeuw TG. The heart rate variability-derived
Newborn Infant Parasympathetic Evaluation (NIPE) Index in
pediatric surgical patients from 0 to 2 years under sevoflurane
anesthesia-A prospective observational pilot study. Paediatr
Anaesth 2019;29(4):377-84.
46. Ledowski T. Objective monitoring of nociception: a review
of current commercial solutions. Br J Anaesth 2019;123(2):
e312-21.
47. Silke B, Guy S, Riddell JG. Effects of beta-adrenoceptor
agonists and antagonists on heart-rate variability in normal
subjects assessed using summary statistics and nonlinear
procedures. J Cardiovasc Pharmacol 1997;30(6):817-23.
48. Mdolaris Medical Systems. ANI Monitor V2 product brochure.
[Internet]. Available at: URL:https://www.mdoloris.com/en/
technologies/ani-analgesia-nociception-index/?b5-file=
1201&b5-folder=228. Access on May 27, 2019.
and coma. N Engl J Med 2010;363(27):2638-50.
2. Brown EN, Pavone KJ, Naranjo M. Multimodal General
Anesthesia: Theory and Practice. Anesth Analg 2018;127(5):
1246-58.
169
Evans JM. Pain and awareness during general anaesthesia.
Lancet 1987;2(8566):1033.
4. Fechner J, Ihmsen H, Schuttler J, Jeleazcov C. The impact
of intra-operative sufentanil dosing on post-operative pain,
hyperalgesia and morphine consumption after cardiac
surgery. Eur J Pain 2013;17(4):562-70.
5. Task Force of the European Society of Cardiology and the
North American Society of Pacing and Electrophysiology.
Heart rate variability. Standards of measurement, physiological
interpretation, and clinical use. Eur Heart J 1996;17(3):354-81.
6. Miu AC, Heilman RM, Miclea M. Reduced heart rate variability
and vagal tone in anxiety: trait versus state, and the effects
of autogenic training. Auton Neurosci 2009;145(1-2):99-103.
7. Jeanne M, Logier R, De Jonckheere J, Tavernier B. Heart
rate variability during total intravenous anesthesia: effects of
nociception and analgesia. Auton Neurosci 2009;147(1-2):
91-6.
8. Jeanne M, Logier R, De Jonckheere J, Tavernier B. Validation
of a graphic measurement of heart rate variability to assess
analgesia/nociception balance during general anesthesia.
Conf Proc IEEE Eng Med Biol Soc 2009;2009:1840-3.
9. Logier R, Jeanne M, De Jonckheere J, Dassonneville A,
Delecroix M, Tavernier B. PhysioDoloris: a monitoring device
for analgesia / nociception balance evaluation using heart
rate variability analysis. Conf Proc IEEE Eng Med Biol Soc
2010;2010:1194-7.
10. Lavand’homme P, Estebe JP. Opioid-free anesthesia:
a different regard to anesthesia practice. Curr Opin
Anaesthesiol 2018;31(5):556-61.
11. Upton HD, Ludbrook GL, Wing A, Sleigh JW. Intraoperative
“Analgesia Nociception Index”-Guided Fentanyl Administration
During Sevoflurane Anesthesia in Lumbar Discectomy and
Laminectomy: A Randomized Clinical Trial. Anesth Analg
2017;125(1):81-90.
12. Daccache G, Caspersen E, Pegoix M, et al. A targeted
remifentanil administration protocol based on the analgesia
nociception index during vascular surgery. Anaesth Crit Care
Pain Med 2017;36(4):229-32.
13. Dundar N, Kus A, Gurkan Y, Toker K, Solak M. Analgesia
nociception index (ani) monitoring in patients with thoracic
paravertebral block: a randomized controlled study. J Clin
Monit Comput 2018;32(3):481-6.
14. Le Gall L, David A, Carles P, et al. Benefits of intraoperative
analgesia guided by the Analgesia Nociception Index (ANI)
in bariatric surgery: An unmatched case-control study.
Anaesth Crit Care Pain Med 2019;38(1):35-9.
15. Szental JA, Webb A, Weeraratne C, Campbell A, Sivakumar H,
Leong S. Postoperative pain after laparoscopic cholecystectomy
is not reduced by intraoperative analgesia guided
by analgesia nociception index (ANI(R)) monitoring:
a randomized clinical trial. Br J Anaesth 2015;114(4):640-5.
16. Jiao Y, He B, Tong X, Xia R, Zhang C, Shi X. Intraoperative
monitoring of nociception for opioid administration:
a meta-analysis of randomized controlled trials. Minerva
Anestesiol 2019;85(5):522-30.
17. Boselli E, Jeanne M. Analgesia/nociception index for the
assessment of acute postoperative pain. Br J Anaesth
2014;112(5):936-7.
18. Gazi M, Abitagaoglu S, Turan G, Koksal C, Akgun FN, Ari
DE. Evaluation of the effects of dexmedetomidine and
remifentanil on pain with the analgesia nociception index in
the perioperative period in hysteroscopies under general
anesthesia. A randomized prospective study. Saudi Med J
2018;39(10):1017-22.
19. Bollag L, Ortner CM, Jelacic S, Rivat C, Landau R, Richebe
P. The effects of low-dose ketamine on the analgesia
nociception index (ANI) measured with the novel PhysioDoloris
analgesia monitor: a pilot study. J Clin Monit Comput
2015;29(2):291-5.
20. Gruenewald M, Ilies C, Herz J, et al. Influence of nociceptive
stimulation on analgesia nociception index (ANI) during
propofol-remifentanil anaesthesia. Br J Anaesth 2013;110(6):
1024-30.
21. Sriganesh K, Theerth KA, Reddy M, Chakrabarti D, Rao GSU.
Analgesia nociception index and systemic haemodynamics
during anaesthetic induction and tracheal intubation:
A secondary analysis of a randomised controlled trial. Indian
J Anaesth 2019;63(2):100-5.
22. Boselli E, Bouvet L, Begou G, Torkmani S, Allaouchiche B.
Prediction of hemodynamic reactivity during total intravenous
anesthesia for suspension laryngoscopy using Analgesia/
Nociception Index (ANI): a prospective observational study.
Minerva Anestesiol 2015;81(3):288-97.
23. Ledowski T, Averhoff L, Tiong WS, Lee C. Analgesia
Nociception Index (ANI) to predict intraoperative haemodynamic
changes: results of a pilot investigation. Acta
Anaesthesiol Scand 2014;58(1):74-9.
24. Weber F, Geerts NJE, Roeleveld HG, Warmenhoven AT,
Liebrand CA. The predictive value of the heart rate variabilityderived
Analgesia Nociception Index in children anaesthetized
with sevoflurane: An observational pilot study. Eur J Pain
2018;22(9):1597-605.
W, Stefaniak ME, Krauze T, et al. Measures of
Heart Rate Variability in 24-h ECGs Depend on Age but Not
Gender of Healthy Children. Front Physiol 2017;8:311.
26. Boselli E, Logier R, Bouvet L, Allaouchiche B. Prediction of
hemodynamic reactivity using dynamic variations of
Analgesia/Nociception Index (ANI). J Clin Monit Comput
2016;30(6):977-84.
27. Logier R, De Jonckheere J, Delecroix M, et al. Heart rate
variability analysis for arterial hypertension etiological
diagnosis during surgical procedures under tourniquet. Conf
Proc IEEE Eng Med Biol Soc 2011;2011:3776-9.
28. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines
for the management of pain, agitation, and delirium in adult
patients in the intensive care unit. Crit Care Med 2013;41(1):
263-306.
29. Payen JF, Gelinas C. Measuring pain in non-verbal critically
ill patients: which pain instrument? Crit Care 2014;18(5):554.
30. Broucqsault-Dedrie C, De Jonckheere J, Jeanne M, Nseir S.
Measurement of Heart Rate Variability to Assess Pain in
Sedated Critically Ill Patients: A Prospective Observational
Study. PloS one 2016;11(1):e0147720.
31. Chanques G, Tarri T, Ride A, et al. Analgesia nociception
index for the assessment of pain in critically ill patients: a
diagnostic accuracy study. Br J Anaesth 2017;119(4):812-20.
32. Charier D, Vogler MC, Zantour D, et al. Assessing pain in the
postoperative period: Analgesia Nociception Index(TM)vs
pupillometry. Br J Anaesth 2019;123(2):e322-e32733.
33. Papaioannou V, Chouvarda I, Gaertner E, et al. Heart rate
variability and cardiac baroreflex inhibition-derived index
predicts pain perception in burn patients. Burns 2016;42(7):
1445-54.
34. Issa R, Julien M, Decary E, et al. Evaluation of the analgesia
nociception index (ANI) in healthy awake volunteers. Can J
Anaesthesia 2017;64(8):828-35.
35. Yan Q, An HY, Feng Y. Pain assessment in conscious healthy
volunteers: a crossover study evaluating the analgesia/
nociception index. Br J Anaesth 2017;118(4):635-6.
36. Boselli E, Musellec H, Martin L, et al. Effects of hypnosis on
the relative parasympathetic tone assessed by ANI
(Analgesia/Nociception Index) in healthy volunteers:
a prospective observational study. J Clin Monit Comput
2018;32(3):487-92.
37. Boselli E, Musellec H, Bernard F, et al. Effects of conversational
hypnosis on relative parasympathetic tone and patient
comfort during axilary brachial plexus blocks for ambulatory
upper limb surgery: a quasiexperimental pilot study. Int J
Clin Exp Hypn 2018;66(2):134-46.
38. Julien-Marsollier F, Rachdi K, Caballero MJ, et al. Evaluation
of the analgesia nociception index for monitoring intraoperative
analgesia in children. Br J Anaesth 2018;121(2):462-8.
39. Gall O, Champigneulle B, Schweitzer B, et al. Postoperative
pain assessment in children: a pilot study of the usefulness
of the analgesia nociception index. Br J Anaesth
2015;115(6):890-5.
40. Boselli E, Bouvet L, Begou G, et al. Prediction of immediate
postoperative pain using the analgesia/nociception index: a
prospective observational study. Br J Anaesth 2014;112(4):
715-21.
41. Sabourdin N, Arnaout M, Louvet N, Guye ML, Piana F,
Constant I. Pain monitoring in anesthetized children: first
assessment of skin conductance and analgesia-nociception
index at different infusion rates of remifentanil. Paediatr
Anaesth 2013;23(2):149-55.
42. Avez-Couturier J, De Jonckheere J, Jeanne M, Vallee L,
Cuisset JM, Logier R. Assessment of Procedural Pain in
Children Using Analgesia Nociception Index: A Pilot Study.
Clin J Pain 2016;32(12):1100-4.
43. Cremillieux C, Makhlouf A, Pichot V, Trombert B, Patural H.
Objective assessment of induced acute pain in neonatology
with the Newborn Infant Parasympathetic Evaluation index.
Eur J Pain 2018;22(6):1071-9.
44. De Jonckheere J, Storme L. NIPE is related to parasympathetic
activity. Is it also related to comfort? J Clin Monit Comput
2019. [Internet]. Available at: https://link.springer.com/article/
10.1007/s10877-019-00276-1. Access on Jul 30, 2019.
45. Weber F, Roeleveld HG, Geerts NJE, Warmenhoven AT,
Schroder R, de Leeuw TG. The heart rate variability-derived
Newborn Infant Parasympathetic Evaluation (NIPE) Index in
pediatric surgical patients from 0 to 2 years under sevoflurane
anesthesia-A prospective observational pilot study. Paediatr
Anaesth 2019;29(4):377-84.
46. Ledowski T. Objective monitoring of nociception: a review
of current commercial solutions. Br J Anaesth 2019;123(2):
e312-21.
47. Silke B, Guy S, Riddell JG. Effects of beta-adrenoceptor
agonists and antagonists on heart-rate variability in normal
subjects assessed using summary statistics and nonlinear
procedures. J Cardiovasc Pharmacol 1997;30(6):817-23.
48. Mdolaris Medical Systems. ANI Monitor V2 product brochure.
[Internet]. Available at: URL:https://www.mdoloris.com/en/
technologies/ani-analgesia-nociception-index/?b5-file=
1201&b5-folder=228. Access on May 27, 2019.