Ketamine is a well-known drug used to induce anesthesia and reduce pain in humans and animals.1 People also use ketamine recreationally, because at high doses it has hallucinogenic, tranquilizing and dissociative effects.1 Recent research has focused on ketamine as a treatment for severe depression2 or as a solution to nerve pain caused by chemotherapy.3 In hospitals or clinics, health professionals generally use ketamine for premedication, sedation, induction and maintenance of general anesthesia4 and perioperative analgesia.5 Given the various contraindications of ketamine5 and its abuse potential,1 anesthesia providers should study ketamine’s pharmacology, effects and anesthetic uses thoroughly before providing it to patients.
Ketamine is a phencyclidine (PCP) derivative and an antagonist of the brain’s N-methyl-D-aspartate (NMDA) receptor.6 The ketamine molecule shows chirality, meaning it has two isomers, one of which (S-ketamine) is four times more potent in anesthesia and analgesia than the other.6 Liver enzymes mediate the body’s metabolism of ketamine.4 When administered orally, ketamine’s bioavailability is limited.6 On the other hand, nasal administration of ketamine produces rapid drug concentrations and high bioavailability.6 For medical purposes, ketamine is usually given through intramuscular injection or an intravenous (IV) line, both of which allow for high bioavailability.1 The half-life of ketamine, or time it requires to reduce ketamine’s plasma concentration to 50 percent, is approximately 45 minutes.7
Though ketamine’s mechanism of action is not well understood,7 it produces a variety of visible effects in patients. It tends to decrease central sensitization, pain wind-up (i.e., development of ongoing, worsening or chronic pain) and pain memory.7 It also has antidepressant effects that outlast detectable drug levels in the body,8 and can help with chronic pain even after just one administration.7 It causes bronchodilation (i.e., increased air flow) and stimulates the sympathetic nervous system and cardiovascular system, activating a stress response.4 Clinicians should consider ketamine’s range of effects, which is not limited to anesthesia and analgesia, before administration.
Ketamine has many uses in anesthesia and analgesia, as it produces hemodynamically stable anesthesia without affecting respiratory function.6 A study by Mylavarapu et al. showed that ketamine in combination with dexmedetomidine in pediatric patients did not reduce airway caliber or morphology when compared to dexmedetomidine alone.9 Tang et al.’s review on ketamine in obstetric anesthesia showed that IV ketamine is safe for general anesthesia in parturient patients.10 Ketamine can also be combined with midazolam or propofol for sedation and pain relief in intensive care patients.4 Additionally, many studies have found that sub-anesthetic doses of ketamine can be useful for analgesia. Gorlin et al. found that sub-anesthetic ketamine can have analgesic effects throughout the entire perioperative period,5 and Tang et al.’s review showed that epidural ketamine produced analgesic effects in obstetric patients.10 A meta-analysis by McNicol et al. found that low-dose ketamine can reduce postoperative pain,11 while Peltoniemi et al.’s review cites its use in decreasing opioid consumption and chronic pain after certain surgical procedures.6 Evidently, ketamine has a variety of uses in anesthesia and analgesia depending on dosage.
Recent research shows ketamine’s efficacy in depression, chronic pain, anesthesia and analgesia. Anesthesia providers should be aware of ketamine’s pharmacodynamics and pharmacokinetics, as well as its general effects, before administering it to patients. Ketamine’s uses in anesthesiology range from general anesthesia to sub-anesthetic perioperative analgesia. Future research should investigate the long-term effects of ketamine as an anesthetic, as well as its uses in low-resource settings where no anesthesiology practitioners are available.12
1. Davis K. What are the uses of ketamine? October 12, 2017; https://www.medicalnewstoday.com/articles/302663.php#a_final_word.
2. Collins S. What You Need to Know About Ketamine’s Effects. 2019; https://www.webmd.com/depression/features/what-does-ketamine-do-your-brain#1.
3. Ketamine hydrochloride. In: National Cancer Institute, ed. NCI Dictionary of Cancer Terms. Bethesda, MD: National Institutes of Health; 2019.
4. Sinner B, Graf BM. Ketamine. In: Schüttler J, Schwilden H, eds. Modern Anesthetics. Berlin, Heidelberg: Springer Berlin Heidelberg; 2008:313–333.
5. Gorlin AW, Rosenfeld DM, Ramakrishna H. Intravenous sub-anesthetic ketamine for perioperative analgesia. Journal of Anaesthesiology, Clinical Pharmacology. 2016;32(2):160–167.
6. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clinical Pharmacokinetics. 2016;55(9):1059–1077.
7. Rosenbaum SB, Palacios JL. Ketamine. StatPearls. February 21, 2019.
8. Li D-J, Wang F-C, Chu C-S, et al. Significant treatment effect of add-on ketamine anesthesia in electroconvulsive therapy in depressive patients: A meta-analysis. European Neuropsychopharmacology. 2017;27(1):29–41.
9. Mylavarapu G, Fleck R, Subramanyam R, Frimpong-Manso M, Amin R, Mahmoud MA. Effect of a Combination of Dexmedetomidine and Ketamine Anesthesia on the Upper Airway Caliber in Normal Children. When Kids Cannot Sleep (Or Breathe): American Thoracic Society; 2017:A4121.
10. Tang Y, Liu R, Zhao P. Ketamine: An update for obstetric anesthesia. Translational Perioperative and Pain Medicine. 2017;4(4):1–12.
11. McNicol ED, Schumann R, Haroutounian S. A systematic review and meta-analysis of ketamine for the prevention of persistent post-surgical pain. Acta Anaesthesiologica Scandinavica. 2014;58(10):1199–1213.
12. Villegas S, Suarez S, Owuor J, et al. Intraoperative awareness and experience with a ketamine-based anaesthesia package to support emergency and essential surgery when no anaesthetist is available. African Journal of Emergency Medicine. 2019;9:S56–S60.