Amidst a burgeoning body of research, we’re continually unravelling new facets of the versatile drug ketamine. A case in point is recent studies indicating another feather in ketamine’s cap: treating severe alcohol withdrawal that proves stubborn to benzodiazepines. Now, the somewhat surprising proposition here is utilising ketamine as a go-to treatment for severe alcohol withdrawal. High levels of ethanol compete for, and inhibit, NMDA receptors, while the unregulated NMDA receptors lead to excitatory withdrawal symptoms.
Ketamine, an NMDA receptor antagonist, addresses ethanol withdrawal at a receptor that’s not a typical target for conventional treatment. Furthermore, ketamine has a relatively muted propensity to depress respiration. A retrospective observational study of 63 patients recently published found that ketamine infusion in patients with delirium tremens was associated with reduced requirements for GABA-agonists (benzodiazepines and phenobarbital), shorter ICU stays, and fewer intubations. Alongside the standard symptom-triggered GABA agonist dose, 0.15 to 0.3 mg/kg/hr of ketamine was administered until delirium was allayed.
In this article, we delve into the most critical clinical insights into ketamine. Ketamine hydrochloride, an FDA-approved general anaesthesia for diagnostic and surgical procedures not requiring skeletal muscle relaxation, can be employed solely or as an adjunct to other anaesthetics. Despite having a short duration of effect, ketamine can be administered to children as young as three months. However, the FDA categorises ketamine as a Schedule III (3) non-narcotic drug due to its hallucinogenic and sedative properties, positioning it as a potential substance of abuse. Ketamine works by non-competitively and reversibly inhibiting N-methyl-D-aspartate (NMDA) receptors. This blockade reduces the synthesis of glutamate (an excitatory neurotransmitter) in the central nervous system, resulting in dissociative anaesthetic and analgesic effects.
Therapeutic Applications of Ketamine
Ketamine is typically used in combination with other general anaesthetics to induce general anaesthesia for brief, emergency procedures. It poses less risk of hypotension or respiratory depression compared to opioids. The onset of action is within 30 seconds when administered intravenously, lasting between 5 to 30 minutes. Given its bronchodilatory properties, it’s the preferred treatment for patients with bronchospasm.
Pain Management – At moderate doses, ketamine can augment opioid therapy to manage both acute and chronic pain in opioid-tolerant patients. Studies have shown that combining ketamine with opioids inhibits opioid-induced hyperalgesia and acute opioid tolerance. The 2018 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU (PADIS) cites low-dose ketamine for reducing opioid consumption in post-surgical adults in the ICU (conditional recommendation, low quality of evidence).
Ketamine for Depression and Suicidal Thoughts – While the FDA regards the clinical use of ketamine to treat depression and suicidal thoughts as off-label, numerous studies testify to ketamine’s effectiveness in addressing depression. By controlling emotion and cognition, it could be beneficial for individuals with mood disorders and elevated glutamate levels in the brain. In 2019, the FDA approved Spravato (esketamine), the S-enantiomer of ketamine, in conjunction with another oral antidepressant for treatment-resistant depression.
Risks, Side Effects, and Clinical Limitations of Ketamine
While ketamine offers a slew of benefits, it’s not without risks and side effects, including nausea, delirium, hallucinations, hypoventilation, pruritus, and sedation. Furthermore, ketamine may induce emergence delirium, a sudden state of confusion which can present as disorientation, hallucinations, restlessness, and hyperactivity upon recovery from anaesthesia.
Pharmaceutical Interactions – Ketamine amplifies the sedative effects of alcohol, opioids, benzodiazepines, and other CNS depressants. While this is the principal concern in terms of ketamine drug interactions, medication interactions via CYP enzymes are typically not a worry as they’re not seen as a primary mechanism of metabolism.
Contraindications and Precautions – Ketamine is contraindicated for patients with poorly controlled hypertension, stroke, severe cardiovascular disease, increased intracranial or intraocular pressure, severe liver disease, and active phase psychosis. Caution is advised in patients who have consumed alcohol.