In recent years, ketamine has seen an exponential rise in use due to its unique pharmacological properties. Although initially developed as a dissociative anesthetic, its primary mechanism of action is a noncompetitive antagonist of the N-methyl-D-aspartate receptor in the central nervous system. However, ketamine has also been found to interact with opioid receptors, monoaminergic receptors, muscarinic receptors, and voltage-sensitive calcium channels. These functions explain ketamine’s influence on the human body and its potential uses.
In the context of airway management, ketamine has a rapid onset of action with a relatively short duration of effect. This makes it a viable option for rapid sequence intubation or procedural sedation. Fortunately, this amnesia and analgesia come without significant respiratory depression. This explains why patients with severe alcohol withdrawal on continuous ketamine infusions have decreased ICU length of stay and intubation rates.1 The ability to allow for continued spontaneous breathing and muscle relaxation can be explained by its effects on the genioglossus muscle activity, respiratory rate, and breathing cycle. This helps preserve airway reflexes such as coughing and swallowing, as well as overall airway patency, which is a critical advantage over other sedatives. This makes it an ideal choice for managing difficult or unstable airways.
Ketamine has also been used to treat asthma and bronchospasm, as few prospective control trials have validated its use in patients with severe asthma.2 This is believed to be done by reducing airway resistance and relaxation of airway smooth muscle, thereby reducing mean peak airway pressure and improving lung compliance. Although patients may experience hypersalivation as a side effect, the agitation-tachypnea cycle resets due to its analgesic properties, and patients have been found to avoid intubation.
Ketamine may also have neuroprotective properties through its antiinflammatory and antioxidant effects. It could be utilized in neurological critical care situations like traumatic brain injury or status epilepticus, as it does not increase intracranial pressure.3 Furthermore, its analgesic properties allow patients to decrease their opioid needs, thereby limiting respiratory depression.4 This may explain why ICU patients treated with ketamine have a lower incidence and duration of delirium.5
Similarly, its sympathomimetic properties allow it to increase blood pressure, heart rate, and cardiac output while preserving respiratory activity. This makes it particularly useful in patients who are critically ill who may not tolerate the hypotensive effects of other sedatives, so it is often combined with them.6 When comparing etomidate with ketamine as sedation for emergency intubation, ketamine was found to be a safe and valuable alternative, particularly in patients who were septic due to the higher percentage of adrenal insufficiency seen in the etomidate group.7 A more recent study demonstrated that etomidate use was associated with higher hospital mortality than was the use of ketamine.8
In critical care, the sedative choice is as vital as the decision to intubate. Often, intensivists balance the need for adequate sedation with hemodynamics and respiratory depression. The rise of ketamine use expands the analgesia-sedative alternatives that could provide personalized patient care.
References
1. Pizon AF, Lynch MJ, Benedict NJ, et al. Adjunct ketamine use in the management of severe ethanol withdrawal. Crit Care Med. 2018;46(8):e768-e771.
2. Esmailian M, Koushkian Esfahani M, Heydari F. The effect of low-dose ketamine in treating acute asthma attack; a randomized clinical trial. Emerg (Tehran). 2018;6(1):e21.
3. Aitkenhead AR, Smith G, Rowbotham DJ, eds. Textbook of Anaesthesia. Elsevier Health Sciences; 2007.
4. Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2012;11:CD003351.
5. Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain 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(5):521-546.
6. Merelman AH, Perlmutter MC, Strayer RJ, et al. Alternatives to rapid sequence intubation: contemporary airway management with ketamine. West J Emerg Med. 2019;20(3):466-471.
7. Jabre P, Combes X, Lapostolle F, et al; KETASED Collaborative Study Group. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293-300.
8. Wunsch H, Bosch NA, Law AC, et al. Evaluation of etomidate use and association with mortality compared with ketamine among critically ill patients. Am J Respir Crit Care Med. 2024;210(10):1243-1251.