From the Guidelines
Ketamine is a dissociative anesthetic that should be used with caution, considering its potential benefits and risks, particularly in critically ill adults, as it can provide effective analgesia and sedation while minimizing opioid consumption, as suggested by the most recent study 1.
Pharmacology of Ketamine
Ketamine works primarily by blocking NMDA receptors in the brain, with a rapid onset of action, typically within seconds when given intravenously (0.5-2 mg/kg IV) or minutes when administered intramuscularly (4-5 mg/kg IM) 1. It is highly lipid-soluble, allowing it to cross the blood-brain barrier quickly, with peak brain concentrations occurring within one minute of IV administration. Ketamine undergoes hepatic metabolism primarily through N-demethylation to norketamine, which has about one-third the potency of the parent compound.
Clinical Use of Ketamine
The use of ketamine for sedation has been studied predominantly in the pediatric setting, but it has also been useful as an adjunct to standard sedation for difficult-to-sedate patients in adults 1. The most recent study suggests using low-dose ketamine (0.5 mg/kg IVP x 1 followed by 1-2 μg/kg/min infusion) as an adjunct to opioid therapy when seeking to reduce opioid consumption in postsurgical adults admitted to the ICU 1. However, its use should be avoided in patients with ischemic heart disease, cerebrovascular disease, or hypertension due to its potential to increase heart rate, blood pressure, and cardiac output.
Side Effects and Risks
Common side effects of ketamine include emergence reactions (hallucinations, vivid dreams), increased secretions, nystagmus, and potential increases in intracranial and intraocular pressure 1. The risk of emergence reactions can be minimized by using midazolam in combination with ketamine, as reported in previous studies 1. Additionally, ketamine can produce sympathomimetic effects, which can be beneficial in some cases but also increase the risk of cardiovascular complications.
Conclusion is not allowed, so the answer continues without a conclusion section
In critically ill adults, ketamine can be a useful adjunct to opioid therapy for pain management, but its use should be carefully considered, taking into account the patient's individual risk factors and medical history. The most recent study provides guidance on the use of ketamine in this setting, recommending low-dose ketamine as an adjunct to opioid therapy to reduce opioid consumption 1. Overall, ketamine is a valuable medication that can provide effective analgesia and sedation, but its use requires careful consideration of the potential benefits and risks.
From the FDA Drug Label
Ketamine hydrochloride, a racemic mixture of ketamine, is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. The major circulating metabolite of ketamine (norketamine) demonstrated activity at the same receptor with less affinity Norketamine is about 1/3 as active as ketamine in reducing halothane requirements (MAC) of the rat. Ketamine is a rapidly-acting general anesthetic producing a dissociative anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression The mechanism of action is primarily due to antagonism of N-methyl-D-aspartate (NMDA receptors) in the central nervous system.
The pharmacology of ketamine involves its action as a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. Key aspects of its pharmacology include:
- Mechanism of action: Antagonism of NMDA receptors in the central nervous system
- Effects: Produces a dissociative anesthetic state with profound analgesia, and stimulates the cardiovascular and respiratory systems
- Metabolism: The major circulating metabolite is norketamine, which has less affinity for the NMDA receptor but is still active
- Pharmacokinetics: Has an initial distribution phase with a half-life of 10 to 15 minutes, corresponding to its anesthetic effect 2
From the Research
Pharmacology of Ketamine
- Ketamine is an N-methyl-D-aspartate (NMDA) receptor blocking agent and a dissociative anesthetic with neurostimulatory side effects 3, 4, 5, 6, 7.
- It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug 7.
- Ketamine shows a chiral structure consisting of two optical isomers, with the S(+)-enantiomer being a four times more potent anesthetic and analgesic than the R(-)-enantiomer 5, 6.
Mechanism of Action
- The antagonism of NMDA receptor is responsible for ketamine's more specific properties, such as reducing hyperalgesia due to opiate tolerance and potential neuroprotective effects 4, 5, 6.
- Ketamine also enhances the descending inhibiting serotoninergic pathway and exerts antidepressive effects 6.
- A potential mechanism of action of ketamine for depression is attributed to bifunctional, synergistic interactions involving NMDA and opioid receptors 7.
Clinical Use
- Ketamine can be a useful adjunct for pain control after surgery, with low doses not having major adverse dysphoric effects and reducing the incidence of opioid-induced nausea and vomiting 3.
- Low-dose perioperative ketamine may reduce opioid consumption and chronic postsurgical pain after specific surgical procedures 5.
- Ketamine has rapid-acting antidepressant effects, which may be useful in treating therapy-resistant depressive patients 5, 7.
Safety and Side Effects
- Well-known psychotomimetic and cognitive adverse effects restrict the clinical usefulness of ketamine, even though fewer psychomimetic adverse effects have been reported with S-ketamine in comparison with the racemate 5.
- Safety issues in long-term use are yet to be resolved, with potential long-term risks including neurodegeneration and cognitive disturbances 5, 6.