Ketamine was introduced commercially in 1970 as a rapidly acting, nonbarbiturate general anesthetic useful for short procedures. With the help of its unique pharmacological properties and newly found beneficial properties, ketamine remains used in a variety of clinical scenarios, including a strong application in anesthetic contexts [1]. Ketamine presents a number of advantages and disadvantages compared to other anesthetics.

Ketamine is a phencyclidine derivative that is both water- and lipid-soluble, which is rapidly broken down and redistributed to peripheral tissues. It is eventually metabolized in the liver.

Its mechanism of action is mainly via noncompetitive antagonism of N-methyl D-aspartic acid (NMDA) receptors. It also interacts, however, with opioid receptors, as well as monoamine, cholinergic, purinergic and adrenoreceptor systems in addition to its local anesthetic effects [2].

Ketamine has a number of advantages compared to other anesthetics, including a rapid onset of action, hemodynamic stability, and minimal impact on airway and breathing. In addition, it is a non-opioid drug with pain-relieving effects and is relatively low cost.

Ketamine has a rapid onset of action, which makes it an attractive option for procedures that require quick anesthesia induction. A 10 mg/kg (5 mg/lb) dose usually produces 12 to 30 minutes of surgical anesthesia with an onset period of 3 to 5 minutes [3]. Ketamine is also generally associated with hemodynamic stability [4]. This means that it does not typically cause significant changes in blood pressure or heart rate.

Studies have not found that ketamine is a major cause of airway or respiratory challenges, though anesthesia providers should still use standard techniques for the prevention of aspiration and maintenance of a patent airway. Ketamine has had a reputation for resulting in increased rates of laryngeal spasm, but many of these reports may be obfuscated by partial airway obstructions, which is very common with ketamine and usually responds to simple airway maneuvers [5]. Overall, pooled data do not support its link to heightened respiratory challenges [6].

Ketamine is known for its solid analgesic effects, thereby reducing the need for additional pain medications during and after a procedure. In particular, subanesthetic ketamine doses improve pain scores and reduce perioperative opioid consumption across a broad range of surgical procedures. Finally, ketamine is a relatively inexpensive medication, making it a particularly attractive option in certain resource-poor settings.

However, ketamine also has its disadvantages compared to other anesthetics. A number of contraindications to its use exist. First, for a range of reasons, ketamine is contraindicated in patients with vascular disease, uncontrolled hypertension, and globe injuries, among others [7]. Second, due to ketamine’s metabolism, caution should be exercised in patients with renal or hepatic dysfunction [7]. Some patients may be at risk of developing abnormal liver function during prolonged low-dose ketamine infusions.

In addition, bladder complaints ranging from urinary frequency to ulcerative cystitis have been reported among patients with prolonged exposure to ketamine, although this remains to be confirmed in short-term perioperative contexts [8]. Finally, ketamine may be potentially fatal in alcohol-intoxicated patients [3].

Though ketamine is used clinically for its anesthetic and analgesic effects, it can also cause dissociative and hallucinogenic effects, which may be disturbing and require additional monitoring. Relatedly, ketamine might make people feel detached from their environment or produce hallucinations, which has led to cases of ketamine misuse [9]. Ketamine is thus not recommended in patients with a history of psychosis. Another potential side effect of ketamine is nausea and vomiting, which can be uncomfortable for patients and may require further medications to manage [9].

Finally, like with many other medications, tolerance to ketamine can develop over time, resulting in the need for higher doses to provide the same effect. A study in rhesus macaques suggested that the combination of low dose ketamine and high dose dexmedetomidine may be a potential alternative, as that mix provided a 30-min window of anesthesia with a degree of analgesia appropriate for mild to moderately painful procedures [10].

Additional targeted research is required in order to clarify the detailed mechanisms of action of ketamine in anesthetic contexts. This will help clarify and specify its role and advantages as an anesthetic in perioperative contexts compared to other medications [11].

References

1) Kurdi, M. S., Theerth, K. A. & Deva, R. S. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth. Essays Res. 8, 283 (2014). DOI: 10.4103/0259-1162.143110
2) Persson, J. Wherefore ketamine? Curr. Opin. Anaesthesiol. 23, 455–460 (2010). DOI: 10.1097/ACO.0b013e32833b49b3
3) Rosenbaum, S. B., Gupta, V., Patel, P. & Palacios, J. L. Ketamine. StatPearls (2022).
4) H., H., M., E., M., V. & S.E.J., G. Hemodynamic stability during induction of anesthesia in elderlypatients: Propofol + ketamine versus propofol + etomidate. J. Cardiovasc. Thorac. Res. (2013). DOI: 10.5681/jcvtr.2013.011
5) Craven, R. Ketamine. Anaesthesia 62, 48–53 (2007). DOI: 10.1111/j.1365-2044.2007.05298.x
6) Green, S. M. & Li, J. Ketamine in adults: What emergency physicians need to know about patient selection and emergence reactions. Academic Emergency Medicine (2000). doi:10.1111/j.1553-2712.2000.tb01076.x
7) Gorlin, A. W., Rosenfeld, D. M. & Ramakrishna, H. Intravenous sub-anesthetic ketamine for perioperative analgesia. J. Anaesthesiol. Clin. Pharmacol. 32, 160 (2016). doi: 10.4103/0970-9185.182085.
8) Chiew, Y. W. & Yang, C. S. Disabling frequent urination in a young adult. Ketamine-associated ulcerative cystitis. Kidney Int. 76, 123–124 (2009). doi: 10.1038/ki.2009.139.
9) Ketamine: What Is It, uses, treatments, effects, and more effects. Available at: https://www.medicalnewstoday.com/articles/302663. (Accessed: 31st March 2023)
10) Killoran, K. E., Walsh, C. A., Asher, J. L., Tarleton, M. B. & Wilson, S. R. Rapid Recovery and Short Duration Anesthesia after Low Dose Ketamine and High Dose Dexmedetomidine in Rhesus Macaques (Macaca mulatta). J. Am. Assoc. Lab. Anim. Sci. 60, 337 (2021). doi: 10.30802/AALAS-JAALAS-20-000112.
11) Rascón-Martínez, D., Carrillo-Torres, O., Ramos-Nataren, R. & Rendón-Jaramillo, L. Advantages of ketamine as a perioperative analgesic. Rev. Médica del Hosp. Gen. México (2016). doi:10.1016/j.hgmx.2016.10.007