Role of ketamine in acute postoperative pain management: a narrative review

Brian M Radvansky, Khushbu Shah, Anant Parikh, Anthony N Sifonios, Vanny Le, Jean D Eloy, Brian M Radvansky, Khushbu Shah, Anant Parikh, Anthony N Sifonios, Vanny Le, Jean D Eloy

Abstract

Objectives: The objective of this narrative review was to examine the usage of ketamine as a postoperative analgesic agent across a wide variety of surgeries.

Design: A literature search was performed using the phrases "ketamine" and "postoperative pain." The authors analyzed the studies that involved testing ketamine's effectiveness at controlling postoperative pain. Effectiveness was assessed through various outcomes such as the amount of opiate consumption, visual analog scale (VAS) pain scores, and persistent postoperative pain at long-term follow-up.

Results: While many different administration protocols were evaluated, delivering ketamine both as a pre- or perioperative bolus and postoperative infusion for up to 48 hours appeared to be the most effective. These effects are dose-dependent. However, a number of studies analyzed showed no benefit in using ketamine versus placebo for controlling postoperative pain. While ketamine is a safe and well-tolerated drug, it does have adverse effects, and there are concerns for possible neurotoxicity and effects on memory.

Conclusions: In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption. More randomized controlled trials are necessary to determine the surgical procedures and administrations (i.e., intravenous, epidural) that ketamine is best suited for.

References

    1. Johansen A., Romundstad L., Nielsen C. S., Schirmer H., Stubhaug A. Persistent postsurgical pain in a general population: prevalence and predictors in the Tromso study. Pain. 2012;153(7):1390–1396. doi: 10.1016/j.pain.2012.02.018.
    1. Meera A. Pain and opioid dependence: is it a matter of concern. Indian Journal of Palliative Care. 2011;17(4):S36–S38. doi: 10.4103/0973-1075.76240.
    1. Suzuki M. Role of N-methyl-D-aspartate receptor antagonists in postoperative pain management. Current Opinion in Anaesthesiology. 2009;22(5):618–622. doi: 10.1097/ACO.0b013e32832e7af6.
    1. Himmelseher S., Durieux M. E. Ketamine for perioperative pain management. Anesthesiology. 2005;102(1):211–220. doi: 10.1097/00000542-200501000-00030.
    1. Domino E. F., Chodoff P., Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clinical Pharmacology and Therapeutics. 1965;6:279–291.
    1. Aroni F., Iacovidou N., Dontas I., Pourzitaki C., Xanthos T. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. Journal of Clinical Pharmacology. 2009;49(8):957–964. doi: 10.1177/0091270009337941.
    1. Persson J. Ketamine in pain management. CNS Neuroscience & Therapeutics. 2013;19(6):396–402. doi: 10.1111/cns.12111.
    1. Naughton M., Clarke G., O'Leary O. F., Cryan J. F., Dinan T. G. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. Journal of Affective Disorders. 2014;156:24–35. doi: 10.1016/j.jad.2013.11.014.
    1. Lapidus K. A. B., Levitch C. F., Perez A. M., et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biological Psychiatry. 2014;76(12):970–976. doi: 10.1016/j.biopsych.2014.03.026.
    1. Azari P., Lindsay D. R., Briones D., Clarke C., Buchheit T., Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26(3):215–228. doi: 10.2165/11595200-000000000-00000.
    1. Bell R. F., Eccleston C., Kalso E. A. Ketamine as an adjuvant to opioids for cancer pain. The Cochrane Database of Systematic Reviews. 2012;(11) doi: 10.1002/14651858.CD003351.pub2.CD003351
    1. Leppert W. Ketamine in the management of cancer pain. Journal of Clinical Oncology. 2013;31(10, article 1374) doi: 10.1200/jco.2012.47.5939.
    1. Krystal J. H., Madonick S., Perry E., et al. Potentiation of low dose ketamine effects by naltrexone: potential implications for the pharmacotherapy of alcoholism. Neuropsychopharmacology. 2006;31(8):1793–1800. doi: 10.1038/sj.npp.1300994.
    1. Krupitsky E., Burakov A., Romanova T., Dunaevsky I., Strassman R., Grinenko A. Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment. 2002;23(4):273–283. doi: 10.1016/s0740-5472(02)00275-1.
    1. Krupitsky E. M., Burakov A. M., Dunaevsky I. V., Romanova T. N., Slavina T. Y., Grinenko A. Y. Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence. Journal of Psychoactive Drugs. 2007;39(1):13–19. doi: 10.1080/02791072.2007.10399860.
    1. Jat K. R., Chawla D. Ketamine for management of acute exacerbations of asthma in children. The Cochrane Database of Systematic Reviews. 2012;11CD009293
    1. Jat K. R., Azad C., Guglani V. Use of ketamine for refractory wheezing in an infant. Indian Pediatrics. 2012;49(7):587–588. doi: 10.1007/s13312-012-0101-x.
    1. Wang M., Wang Q., Yu Y. Y., Wang W. S. An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study. Annales Francaises d'Anesthesie et de Reanimation. 2013;32(9):e103–e106. doi: 10.1016/j.annfar.2013.06.013.
    1. Katalinic N., Lai R., Somogyi A., Mitchell P. B., Glue P., Loo C. K. Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. The Australian and New Zealand Journal of Psychiatry. 2013;47(8):710–727. doi: 10.1177/0004867413486842.
    1. Oye I., Paulsen O., Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. Journal of Pharmacology and Experimental Therapeutics. 1992;260(3):1209–1213.
    1. Mion G., Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings) CNS Neuroscience & Therapeutics. 2013;19(6):370–380. doi: 10.1111/cns.12099.
    1. Clements J. A., Nimmo W. S., Grant I. S. Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans. Journal of Pharmaceutical Sciences. 1982;71(5):539–542. doi: 10.1002/jps.2600710516.
    1. Grant I. S., Nimmo W. S., McNicol L. R., Clements J. A. Ketamine disposition in children and adults. British Journal of Anaesthesia. 1983;55(11):1107–1111. doi: 10.1093/bja/55.11.1107.
    1. Woolf C. J., Thompson S. W. N. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991;44(3):293–299. doi: 10.1016/0304-3959(91)90100-C.
    1. Rosseland L. A., Stubhaug A., Sandberg L., Breivik H. Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain, demonstrates large variation in need of analgesics, and finds no analgesic effect of IA ketamine compared with IA saline. Pain. 2003;104(1-2):25–34. doi: 10.1016/S0304-3959(02)00463-3.
    1. Niesters M., Khalili-Mahani N., Martini C., et al. Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. Anesthesiology. 2012;117(4):868–877. doi: 10.1097/aln.0b013e31826a0db3.
    1. Rogers R., Wise R. G., Painter D. J., Longe S. E., Tracey I. An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging. Anesthesiology. 2004;100(2):292–301. doi: 10.1097/00000542-200402000-00018.
    1. Smith D. J., Bouchal R. L., DeSanctis C. A., et al. Properties of the interaction between ketamine and opiate binding sites in vivo and in vitro. Neuropharmacology. 1987;26(9):1253–1260. doi: 10.1016/0028-3908(87)90084-0.
    1. Hustveit O., Maurset A., Oye I. Interaction of the chiral forms of ketamine with opioid, phencyclidine, sigma and muscarinic receptors. Pharmacology & Toxicology. 1995;77(6):355–359. doi: 10.1111/j.1600-0773.1995.tb01041.x.
    1. Maurset A., Skoglund L. A., Hustveit O., Øye I. Comparison of ketamine and pethidine in experimental and postoperative pain. Pain. 1989;36(1):37–41. doi: 10.1016/0304-3959(89)90109-7.
    1. Stella L., Crescenti A., Torri G. Effect of naloxone on the loss of consciousness induced by I.V. anaesthetic agents in man. British Journal of Anaesthesia. 1984;56(4):369–373. doi: 10.1093/bja/56.4.369.
    1. Pacheco D. D. F., Romero T. R. L., Duarte I. D. G. Central antinociception induced by ketamine is mediated by endogenous opioids and μ- And δ-opioid receptors. Brain Research. 2014;1562:69–75. doi: 10.1016/j.brainres.2014.03.026.
    1. de Bartolomeis A., Sarappa C., Buonaguro E. F., et al. Different effects of the NMDA receptor antagonists ketamine, MK-801, and memantine on postsynaptic density transcripts and their topography: role of Homer signaling, and implications for novel antipsychotic and pro-cognitive targets in psychosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;46:1–12. doi: 10.1016/j.pnpbp.2013.06.010.
    1. Subramaniam K., Subramaniam B., Steinbrook R. A. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesthesia and Analgesia. 2004;99(2):482–495.
    1. Lavand'homme P., De Kock M., Waterloos H. Intraoperative epidural analgesia combined with ketamine provides effective preventive analgesia in patients undergoing major digestive surgery. Anesthesiology. 2005;103(4):813–820. doi: 10.1097/00000542-200510000-00020.
    1. Jha A. K., Bhardwaj N., Yaddanapudi S., Sharma R. K., Mahajan J. K. A randomized study of surgical site infiltration with bupivacaine or ketamine for pain relief in children following cleft palate repair. Paediatric Anaesthesia. 2013;23(5):401–406. doi: 10.1111/pan.12124.
    1. Eghbal M. H., Taregh S., Amin A., Sahmeddini M. A. Ketamine improves postoperative pain and emergence agitation following adenotonsillectomy in children. A randomized clinical trial. Middle East Journal of Anesthesiology. 2013;22(2):155–160.
    1. Cho H. K., Kim K. W., Jeong Y. M., Lee H. S., Lee Y. J., Hwang S. H. Efficacy of ketamine in improving pain after tonsillectomy in children: meta-analysis. PLoS ONE. 2014;9(6) doi: 10.1371/journal.pone.0101259.e101259
    1. Nitta R., Goyagi T., Nishikawa T. Combination of oral clonidine and intravenous low-dose ketamine reduces the consumption of postoperative patient-controlled analgesia morphine after spine surgery. Acta Anaesthesiologica Taiwanica. 2013;51(1):14–17. doi: 10.1016/j.aat.2013.03.003.
    1. Hadi B. A., Daas R., Zelkó R. A randomized, controlled trial of a clinical pharmacist intervention in microdiscectomy surgery—low dose intravenous ketamine as an adjunct to standard therapy. Saudi Pharmaceutical Journal. 2013;21(2):169–175. doi: 10.1016/j.jsps.2012.08.002.
    1. Kim S. H., Kim S. I., Ok S. Y., et al. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery. Korean Journal of Anesthesiology. 2013;64(6):524–528. doi: 10.4097/kjae.2013.64.6.524.
    1. Pestieau S. R., Finkel J. C., Junqueira M. M., et al. Prolonged perioperative infusion of low-dose ketamine does not alter opioid use after pediatric scoliosis surgery. Paediatric Anaesthesia. 2014;24(6):582–590. doi: 10.1111/pan.12417.
    1. Cengiz P., Gokcinar D., Karabeyoglu I., Topcu H., Cicek G. S., Gogus N. Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial. Journal of the College of Physicians and Surgeons—Pakistan. 2014;24(5):299–303.
    1. Guará Sobrinho H., Garcia J. B. S., Vasconcelos J. W., Sousa J. C. A., Ferro L. S. G. Analgesic efficacy of the intra-articular administration of S(+)- ketamine in patients undergoing total knee arthroplasty. Revista Brasileira de Anestesiologia. 2012;62(5):665–675. doi: 10.1016/s0034-7094(12)70165-4.
    1. D'Alonzo R. C., Bennett-Guerrero E., Podgoreanu M., D'Amico T. A., Harpole D. H., Shaw A. D. A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery. Journal of Anesthesia. 2011;25(5):672–678. doi: 10.1007/s00540-011-1206-4.
    1. Nesher N., Serovian I., Marouani N., Chazan S., Weinbroum A. A. Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects. Pharmacological Research. 2008;58(1):38–44. doi: 10.1016/j.phrs.2008.06.003.
    1. Abdolahi M., Soltani H. A., Montazeri K., Soleymani B. Preemptive low-dose of ketamine does not effective on anesthetic consumption, perioperative analgesic requirement and postoperative pain, nausea and vomiting in painful ophthalmic surgery. Journal of Research in Medical Sciences. 2013;18:583–587.
    1. Suppa E., Valente A., Catarci S., Zanfini B. A., Draisci G. A study of low-dose S-ketamine infusion as ‘preventive’ pain treatment for cesarean section with spinal anesthesia: benefits and side effects. Minerva Anestesiologica. 2012;78(7):774–781.
    1. Zakine J., Samarcq D., Lorne E., et al. Postoperative ketamine administration decreases morphine consumption in major abdominal surgery: a prospective, randomized, double-blind, controlled study. Anesthesia & Analgesia. 2008;106(6):1856–1861. doi: 10.1213/ane.0b013e3181732776.
    1. de Kock M., Lavand'homme P., Waterloos H. 'Balanced analgesia' in the perioperative period: Is there a place for ketamine? Pain. 2001;92(3):373–380. doi: 10.1016/s0304-3959(01)00278-0.
    1. Laskowski K., Stirling A., McKay W. P., Lim H. J. A systematic review of intravenous ketamine for postoperative analgesia. Canadian Journal of Anesthesia. 2011;58(10):911–923. doi: 10.1007/s12630-011-9560-0.
    1. Elia N., Tramèr M. R. Ketamine and postoperative pain—a quantitative systematic review of randomised trials. Pain. 2005;113(1-2):61–70. doi: 10.1016/j.pain.2004.09.036.
    1. McCartney C. J. L., Sinha A., Katz J. A qualitative systematic review of the role of N-methyl-D-aspartate receptor antagonists in preventive analgesia. Anesthesia & Analgesia. 2004;98(5):1385–1400.
    1. Thomas M., Tennant I., Augier R., Gordon-Strachan G., Harding H. The role of pre-induction ketamine in the management of postoperative pain in patients undergoing elective gynaecological surgery at the University Hospital of the West Indies. The West Indian Medical Journal. 2012;61:224–229.
    1. Bilgen S., Köner Ö., Türe H., Menda F., Fiçicioğlu C., Aykaç B. Effect of three different doses of ketamine prior to general anaesthesia on postoperative pain following caesarean delivery: a prospective randomized study. Minerva Anestesiologica. 2012;78(4):442–449.
    1. Katz J., Schmid R., Snijdelaar D. G., Coderre T. J., McCartney C. J. L., Wowk A. Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use. Pain. 2004;110(3):707–718. doi: 10.1016/j.pain.2004.05.011.
    1. Morgan C. J. A., Curran H. V. Ketamine use: a review. Addiction. 2012;107(1):27–38. doi: 10.1111/j.1360-0443.2011.03576.x.
    1. Strayer R. J., Nelson L. S. Adverse events associated with ketamine for procedural sedation in adults. The American journal of emergency medicine. 2008;26(9):985–1028. doi: 10.1016/j.ajem.2007.12.005.
    1. Smith H. S. Ketamine-induced urologic insult (KIUI) Pain Physician. 2010;13(6):E343–E346.
    1. Noppers I. M., Niesters M., Aarts L. P. H. J., et al. Drug-induced liver injury following a repeated course of ketamine treatment for chronic pain in CRPS type 1 patients: a report of 3 cases. Pain. 2011;152(9):2173–2178. doi: 10.1016/j.pain.2011.03.026.
    1. Scallet A. C., Schmued L. C., Slikker W., Jr., et al. Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons. Toxicological Sciences. 2004;81(2):364–370. doi: 10.1093/toxsci/kfh224.
    1. Jevtovic-Todorovic V., Wozniak D. F., Benshoff N. D., Olney J. W. A comparative evaluation of the neurotoxic properties of ketamine and nitrous oxide. Brain Research. 2001;895(1-2):264–267. doi: 10.1016/S0006-8993(01)02079-0.
    1. Dong C., Anand K. J. S. Developmental neurotoxicity of ketamine in pediatric clinical use. Toxicology Letters. 2013;220(1):53–60. doi: 10.1016/j.toxlet.2013.03.030.
    1. Paule M. G., Li M., Allen R. R., et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicology and Teratology. 2011;33(2):220–230. doi: 10.1016/j.ntt.2011.01.001.
    1. Chang L. C., Raty S. R., Ortiz J., Bailard N. S., Mathew S. J. The emerging use of ketamine for anesthesia and sedation in traumatic brain injuries. CNS Neuroscience & Therapeutics. 2013;19(6):390–395. doi: 10.1111/cns.12077.
    1. Michalczyk K., Sullivan J. E., Berkenbosch J. W. Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children. Pediatric Critical Care Medicine. 2013;14(3):e149–e155. doi: 10.1097/PCC.0b013e3182720459.
    1. Gaspard N., Foreman B., Judd L. M., et al. Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. Epilepsia. 2013;54(8):1498–1503. doi: 10.1111/epi.12247.
    1. Karpinski N., Dunn J., Hansen L., Masliah E. Subpial vacuolar myelopathy after intrathecal ketamine: report of a case. Pain. 1997;73(1):103–105. doi: 10.1016/s0304-3959(97)00068-7.
    1. Perry E. B., Jr., Cramer J. A., Cho H.-S., et al. Psychiatric safety of ketamine in psychopharmacology research. Psychopharmacology. 2007;192(2):253–260. doi: 10.1007/s00213-007-0706-2.

Source: PubMed

3
Subskrybuj