Update in the Use of Ketamine for Anesthetists: An Evidence-Based Review
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Published:
Aug 18, 2021
Keywords:
Analgesics, Anesthetics, Ketamine, Premedication, Shivering
Main Article Content
Abstract
Ketamine has been mainly used as an anesthetic. It contains a unique property that it stimulates several receptors combining with the analgesic property, which is distinct to other anesthetics, and it does not suppress the cardiovascular system. However, it is limited in that it consists of a psychological side effect. Ketamine has been widely used for anxiolytic premedication in children. It has been reported that ketamine provides superior efficacy comparing to other anesthetics or placebo. Moreover, ketamine can be used in the outpatient setting without significant adverse outcomes. In trauma, there is a lack of evidence showing the superiority of ketamine to other drugs in terms of mortality or hospital stay. Ketamine has been shown to decrease postoperative shivering. It is potent analgesia in both acute and chronic phases. It can also be used as an alternative drug to control seizure when the standard medication is not effective.
Article Details
Section
Review articles
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
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metabolite pharmacology: Insights into therapeutic
mechanisms. Pharmacol Rev2018;70:621-60.
2. Abdel-Ghaffar HS, Kamal SM, El Sherif FA, Mohamed SA.
Comparison of nebulised dexmedetomidine, ketamine, or
midazolamforpremedicationinpreschoolchildrenundergoing
bone marrow biopsy. Br J Anaesth2018;121:445-52.
3. Oriby ME. Comparison of intranasal dexmedetomidine and
oral ketamine versus intranasal midazolam premedication
for children undergoing dental rehabilitation. Anesth Pain
Med 2019;9:e85227.
4. Sruthi S, Mandal B, Rohit MK, Puri GD. Dexmedetomidine
versus ketofol sedation for outpatient diagnostic
transesophageal echocardiography: A randomized
controlled study. Ann Card Anaesth2018;21:143-50.
5. Goswami D, Nisa N, Sharma A, Dadhwal V, Baidya DK,
Arora M. Low-dose ketamine for outpatient hysteroscopy:
A prospective, randomised, double-blind study. Turk J
Anaesthesiol Reanim 2020;48:134-41.
6. Schmitz A, Weiss M, Kellenberger C, et al. Sedation for
magneticresonanceimaging using propofol withor without
ketamineat inductionin pediatrics-a prospectiverandomized
double-blinded study. Paediatr Anaesth2018;28:264-74.
7. Upchurch CP, Grijalva CG, Russ S, et al. Comparison of
etomidateand ketaminefor induction during rapid sequence
intubationofadult trauma patients. Ann EmergMed 2017;69:
24-33.e2.
8. Baekgaard JS, Eskesen TG, Sillesen M, Rasmussen LS,
SteinmetzJ. Ketamineasarapid sequenceinductionagent
inthetrauma population: A systematicreview. Anesth Analg
2019;128:504-10.
9. Lakhe G, Adhikari KM, Khatri K, Maharjan A, Bajracharya A,
Khanal H. Preventionof shivering during spinalanesthesia:
Comparison betweentramadol,ketamineand ondansetron.
JNMA J Nepal Med Assoc2017;56:395-400.
10. Xue X,Lv Y, Zhao Y,Leng Y, Zhang Y. Efficacyof prophylactic
epiduralketamineforreducingshiveringinpatientsundergoing
caesareansection withcombined spinal-epiduralanesthesia.
Biomed Rep 2018;8:485-90.
11. Schwenk ES, Viscusi ER, Buvanendran A,etal. Consensus
guidelines on the use of intravenous ketamine infusions for
acute pain management from the american society of
regional anesthesia and pain medicine, the american
academy of pain medicine, and the american society of
anesthesiologists. Reg Anesth Pain Med 2018;43:456-66.
12. Xu J, Herndon C, Anderson S, et al. Intravenous ketamine
infusion for complex regional pain syndrome: Survey,
consensus, and a reference protocol. Pain Med 2019;20:
323-34.
13. Golub D, Yanai A, Darzi K, Papadopoulos J, Kaufman B.
Potential consequences of high-dose infusion of ketamine
for refractorystatusepilepticus: Casereportsand systematic
literaturereview. AnaesthIntensive Care2018;46:516-28.
14. Hirota K,Lambert DG. Ketamine: Its mechanism(s)ofaction
and unusualclinicaluses. Br J Anaesth1996;77:441-4.
15. Mion G, Villevieille T. Ketamine pharmacology: An update
(pharmacodynamics and molecular aspects, recent
findings). CNS NeurosciTher2013;19:370-80.
16. Olofsen E, Noppers I, Niesters M, et al. Estimation of the
contributionofnorketaminetoketamine-induced acute pain
relief and neurocognitive impairment in healthy volunteers.
Anesthesiology2012;117:353-64.
17. Dahan A, Olofsen E, Sigtermans M, et al. Population
pharmacokinetic-pharmacodynamic modeling ofketamineinduced painreliefofchronic pain. EurJ Pain2011;15:258-67.
18. Clements JA, Nimmo WS. Pharmacokinetics and analgesic
effectof ketaminein man. Br J Anaesth1981;53:27-30.
19. DundeeJW, Bovill J. Ketamine.Lancet1970;2:310-1.
20. Yanagihara Y, OhtaniM, Kariya S,etal. Plasmaconcentration
profilesof ketamineand norketamineafteradministrationof
variousketamine preparationstohealthyjapanesevolunteers.
Biopharm Drug Dispos2003;24:37-43.
21. Desta Z, Moaddel R, Ogburn ET, et al. Stereoselective and
regiospecific hydroxylation of ketamine and norketamine.
Xenobiotica2012;42:1076-87.
22. RaoLK,FlakerAM,FriedelCC,KharaschED.Roleofcytochrome
p4502b6 polymorphisms in ketamine metabolism and
clearance. Anesthesiology2016;125:1103-12.
23. Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and
s-norketamine plasma concentrations after nasal and i.V.
Administration in anesthetized children. Paediatr Anaesth
2004;14:983-8.
24. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical
practice guideline for emergency department ketamine
dissociative sedation: 2011 update. Ann Emerg Med 2011;
57:449-61.
25. Gao M, Rejaei D, Liu H. Ketamine use in current clinical
practice. Acta Pharmacol Sin2016;37:865-72.
26. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann
M. Response of chronic neuropathic pain syndromes to
ketamine: A preliminary study. Pain1994;56:51-7.
27. EideK,StubhaugA,OyeI,BreivikH.Continuoussubcutaneous
administrationof then-methyl-d-asparticacid (nmda) receptor
antagonist ketamine in the treatment of post-herpetic
neuralgia. Pain1995;61:221-8.
28. Goldberg ME, Schwartzman RJ, Torjman MC, Wainer IW.
Ketamine infusion successful in some patients. Pain
Physician2010;13:E371-2;author reply E2-3.
29. Traber DL,Wilson RD, PrianoLL.Theeffectof bea-adrenergic
blockade on the cardiopulmonary response to ketamine.
Anesth Analg 1970;49:604-13.
30. Drayna PC, Estrada C, Saville BR, Arnold DH. Ketamineand
intraocular pressure. Acad Emerg Med 2013;20:424.
31. Wadia S, Bhola R, Lorenz D, Padmanabhan P, Gross J,
Stevenson M. Ketamineand intraocular pressureinchildren.
Ann Emerg Med 2014;64:385-8.e1.
32. Green SM, AndolfattoG, Krauss BS. Ketamineand intracranial
pressure: No contraindication except hydrocephalus. Ann
Emerg Med 2015;65:52-4.
33. Traivaree C, Jindakam W, Monsereenusorn C, Rujkijyanont
P, Lumkul R. The factors of ketamine that affect sedation in
children with oncology procedures: Parent satisfaction
perspective. J Med AssocThai2014;97 Suppl2:S19-24.
34. Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.
A review ofketamineabuseand diversion. Depress Anxiety
2016;33:718-27.
35. Buonanno P,Laiola A, Palumbo C, Spinelli G,Terminiello V,
Servillo G. Italian validation of the amsterdam preoperative
anxiety and information scale. Minerva Anestesiol 2017;83:
705-11.
36. Lienhart A, Fiez N, Deriaz H. [postoperative shivering:
Analysisof mainassociated factors]. AnnFr Anesth Reanim
1992;11:488-95.
37. Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic
review of intravenousketaminefor postoperativeanalgesia.
CanJ Anaesth2011;58:911-23.
38. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative
ketamine reduces perioperative opiate consumption in
opiate-dependent patients with chronic back pain
undergoing backsurgery. Anesthesiology2010;113:639-46.
39. Mulier JP. Perioperative opioids aggravate obstructive
breathing in sleep apnea syndrome: Mechanisms and
alternative anesthesia strategies. Curr Opin Anaesthesiol
2016;29:129-33.
40. Vadivelu N, Schermer E, Kodumudi V, Belani K, Urman RD,
Kaye AD. Role of ketamine for analgesia in adults and
children. J Anaesthesiol Clin Pharmacol2016;32:298-306.
41. Pendi A, Field R, Farhan SD, Eichler M, Bederman SS.
Perioperative ketamine for analgesia in spine surgery: A
meta-analysis of randomized controlled trials. Spine (Phila
Pa1976)2018;43:E299-e307.
42. Bell RF. Ketamine for chronic noncancer pain: Concerns
regardingtoxicity.CurrOpinSupportPalliatCare2012;6:183-7.
43. Reich DL, Silvay G. Ketamine: An update on the first
twenty-five years of clinical experience. Can J Anaesth
1989;36:186-97.
44. Andolfatto G,Willman E,Joo D,etal. Intranasalketaminefor
analgesia in the emergency department: A prospective
observational series. Acad Emerg Med 2013;20:1050-4.
45. Assouline B, Tramèr MR, Kreienbühl L, Elia N. Benefit and
harm ofadding ketaminetoanopioid ina patient-controlled
analgesia device for the control of postoperative pain:
Systematic review and meta-analyses of randomized
controlled trials withtrialsequentialanalyses. Pain2016;157:
2854-64.
46. Trinka E, Cock H, Hesdorffer D, et al. A definition and
classificationofstatusepilepticus--reportof theilaetaskforce
on classification of status epilepticus. Epilepsia 2015;56:
1515-23.
47. Naylor DE, Liu H, Niquet J, Wasterlain CG. Rapid surface
accumulation of nmda receptors increases glutamatergic
excitation during statusepilepticus. Neurobiol Dis2013;54:
225-38.
48. FujikawaDG.Neuroprotectiveeffectofketamineadministered
after statusepilepticusonset. Epilepsia1995;36:186-95.
metabolite pharmacology: Insights into therapeutic
mechanisms. Pharmacol Rev2018;70:621-60.
2. Abdel-Ghaffar HS, Kamal SM, El Sherif FA, Mohamed SA.
Comparison of nebulised dexmedetomidine, ketamine, or
midazolamforpremedicationinpreschoolchildrenundergoing
bone marrow biopsy. Br J Anaesth2018;121:445-52.
3. Oriby ME. Comparison of intranasal dexmedetomidine and
oral ketamine versus intranasal midazolam premedication
for children undergoing dental rehabilitation. Anesth Pain
Med 2019;9:e85227.
4. Sruthi S, Mandal B, Rohit MK, Puri GD. Dexmedetomidine
versus ketofol sedation for outpatient diagnostic
transesophageal echocardiography: A randomized
controlled study. Ann Card Anaesth2018;21:143-50.
5. Goswami D, Nisa N, Sharma A, Dadhwal V, Baidya DK,
Arora M. Low-dose ketamine for outpatient hysteroscopy:
A prospective, randomised, double-blind study. Turk J
Anaesthesiol Reanim 2020;48:134-41.
6. Schmitz A, Weiss M, Kellenberger C, et al. Sedation for
magneticresonanceimaging using propofol withor without
ketamineat inductionin pediatrics-a prospectiverandomized
double-blinded study. Paediatr Anaesth2018;28:264-74.
7. Upchurch CP, Grijalva CG, Russ S, et al. Comparison of
etomidateand ketaminefor induction during rapid sequence
intubationofadult trauma patients. Ann EmergMed 2017;69:
24-33.e2.
8. Baekgaard JS, Eskesen TG, Sillesen M, Rasmussen LS,
SteinmetzJ. Ketamineasarapid sequenceinductionagent
inthetrauma population: A systematicreview. Anesth Analg
2019;128:504-10.
9. Lakhe G, Adhikari KM, Khatri K, Maharjan A, Bajracharya A,
Khanal H. Preventionof shivering during spinalanesthesia:
Comparison betweentramadol,ketamineand ondansetron.
JNMA J Nepal Med Assoc2017;56:395-400.
10. Xue X,Lv Y, Zhao Y,Leng Y, Zhang Y. Efficacyof prophylactic
epiduralketamineforreducingshiveringinpatientsundergoing
caesareansection withcombined spinal-epiduralanesthesia.
Biomed Rep 2018;8:485-90.
11. Schwenk ES, Viscusi ER, Buvanendran A,etal. Consensus
guidelines on the use of intravenous ketamine infusions for
acute pain management from the american society of
regional anesthesia and pain medicine, the american
academy of pain medicine, and the american society of
anesthesiologists. Reg Anesth Pain Med 2018;43:456-66.
12. Xu J, Herndon C, Anderson S, et al. Intravenous ketamine
infusion for complex regional pain syndrome: Survey,
consensus, and a reference protocol. Pain Med 2019;20:
323-34.
13. Golub D, Yanai A, Darzi K, Papadopoulos J, Kaufman B.
Potential consequences of high-dose infusion of ketamine
for refractorystatusepilepticus: Casereportsand systematic
literaturereview. AnaesthIntensive Care2018;46:516-28.
14. Hirota K,Lambert DG. Ketamine: Its mechanism(s)ofaction
and unusualclinicaluses. Br J Anaesth1996;77:441-4.
15. Mion G, Villevieille T. Ketamine pharmacology: An update
(pharmacodynamics and molecular aspects, recent
findings). CNS NeurosciTher2013;19:370-80.
16. Olofsen E, Noppers I, Niesters M, et al. Estimation of the
contributionofnorketaminetoketamine-induced acute pain
relief and neurocognitive impairment in healthy volunteers.
Anesthesiology2012;117:353-64.
17. Dahan A, Olofsen E, Sigtermans M, et al. Population
pharmacokinetic-pharmacodynamic modeling ofketamineinduced painreliefofchronic pain. EurJ Pain2011;15:258-67.
18. Clements JA, Nimmo WS. Pharmacokinetics and analgesic
effectof ketaminein man. Br J Anaesth1981;53:27-30.
19. DundeeJW, Bovill J. Ketamine.Lancet1970;2:310-1.
20. Yanagihara Y, OhtaniM, Kariya S,etal. Plasmaconcentration
profilesof ketamineand norketamineafteradministrationof
variousketamine preparationstohealthyjapanesevolunteers.
Biopharm Drug Dispos2003;24:37-43.
21. Desta Z, Moaddel R, Ogburn ET, et al. Stereoselective and
regiospecific hydroxylation of ketamine and norketamine.
Xenobiotica2012;42:1076-87.
22. RaoLK,FlakerAM,FriedelCC,KharaschED.Roleofcytochrome
p4502b6 polymorphisms in ketamine metabolism and
clearance. Anesthesiology2016;125:1103-12.
23. Weber F, Wulf H, Gruber M, Biallas R. S-ketamine and
s-norketamine plasma concentrations after nasal and i.V.
Administration in anesthetized children. Paediatr Anaesth
2004;14:983-8.
24. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical
practice guideline for emergency department ketamine
dissociative sedation: 2011 update. Ann Emerg Med 2011;
57:449-61.
25. Gao M, Rejaei D, Liu H. Ketamine use in current clinical
practice. Acta Pharmacol Sin2016;37:865-72.
26. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann
M. Response of chronic neuropathic pain syndromes to
ketamine: A preliminary study. Pain1994;56:51-7.
27. EideK,StubhaugA,OyeI,BreivikH.Continuoussubcutaneous
administrationof then-methyl-d-asparticacid (nmda) receptor
antagonist ketamine in the treatment of post-herpetic
neuralgia. Pain1995;61:221-8.
28. Goldberg ME, Schwartzman RJ, Torjman MC, Wainer IW.
Ketamine infusion successful in some patients. Pain
Physician2010;13:E371-2;author reply E2-3.
29. Traber DL,Wilson RD, PrianoLL.Theeffectof bea-adrenergic
blockade on the cardiopulmonary response to ketamine.
Anesth Analg 1970;49:604-13.
30. Drayna PC, Estrada C, Saville BR, Arnold DH. Ketamineand
intraocular pressure. Acad Emerg Med 2013;20:424.
31. Wadia S, Bhola R, Lorenz D, Padmanabhan P, Gross J,
Stevenson M. Ketamineand intraocular pressureinchildren.
Ann Emerg Med 2014;64:385-8.e1.
32. Green SM, AndolfattoG, Krauss BS. Ketamineand intracranial
pressure: No contraindication except hydrocephalus. Ann
Emerg Med 2015;65:52-4.
33. Traivaree C, Jindakam W, Monsereenusorn C, Rujkijyanont
P, Lumkul R. The factors of ketamine that affect sedation in
children with oncology procedures: Parent satisfaction
perspective. J Med AssocThai2014;97 Suppl2:S19-24.
34. Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M.
A review ofketamineabuseand diversion. Depress Anxiety
2016;33:718-27.
35. Buonanno P,Laiola A, Palumbo C, Spinelli G,Terminiello V,
Servillo G. Italian validation of the amsterdam preoperative
anxiety and information scale. Minerva Anestesiol 2017;83:
705-11.
36. Lienhart A, Fiez N, Deriaz H. [postoperative shivering:
Analysisof mainassociated factors]. AnnFr Anesth Reanim
1992;11:488-95.
37. Laskowski K, Stirling A, McKay WP, Lim HJ. A systematic
review of intravenousketaminefor postoperativeanalgesia.
CanJ Anaesth2011;58:911-23.
38. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative
ketamine reduces perioperative opiate consumption in
opiate-dependent patients with chronic back pain
undergoing backsurgery. Anesthesiology2010;113:639-46.
39. Mulier JP. Perioperative opioids aggravate obstructive
breathing in sleep apnea syndrome: Mechanisms and
alternative anesthesia strategies. Curr Opin Anaesthesiol
2016;29:129-33.
40. Vadivelu N, Schermer E, Kodumudi V, Belani K, Urman RD,
Kaye AD. Role of ketamine for analgesia in adults and
children. J Anaesthesiol Clin Pharmacol2016;32:298-306.
41. Pendi A, Field R, Farhan SD, Eichler M, Bederman SS.
Perioperative ketamine for analgesia in spine surgery: A
meta-analysis of randomized controlled trials. Spine (Phila
Pa1976)2018;43:E299-e307.
42. Bell RF. Ketamine for chronic noncancer pain: Concerns
regardingtoxicity.CurrOpinSupportPalliatCare2012;6:183-7.
43. Reich DL, Silvay G. Ketamine: An update on the first
twenty-five years of clinical experience. Can J Anaesth
1989;36:186-97.
44. Andolfatto G,Willman E,Joo D,etal. Intranasalketaminefor
analgesia in the emergency department: A prospective
observational series. Acad Emerg Med 2013;20:1050-4.
45. Assouline B, Tramèr MR, Kreienbühl L, Elia N. Benefit and
harm ofadding ketaminetoanopioid ina patient-controlled
analgesia device for the control of postoperative pain:
Systematic review and meta-analyses of randomized
controlled trials withtrialsequentialanalyses. Pain2016;157:
2854-64.
46. Trinka E, Cock H, Hesdorffer D, et al. A definition and
classificationofstatusepilepticus--reportof theilaetaskforce
on classification of status epilepticus. Epilepsia 2015;56:
1515-23.
47. Naylor DE, Liu H, Niquet J, Wasterlain CG. Rapid surface
accumulation of nmda receptors increases glutamatergic
excitation during statusepilepticus. Neurobiol Dis2013;54:
225-38.
48. FujikawaDG.Neuroprotectiveeffectofketamineadministered
after statusepilepticusonset. Epilepsia1995;36:186-95.