Last October 2023, Hollywood was shocked by the passing of “Friends” sitcom star Matthew Perry. Perry had been battling drug addiction for decades and had been receiving ketamine infusion therapy for depression and anxiety.
Toxicology reports found his death was caused by the “acute effects of ketamine” (Dalton, 2023). Use of ketamine to treat depression has been on the rise in the last decade and while studies have shown it can rapidly improve treatment-resistant depression (Thase & Connolly, 2023), Perry’s death remind us that ketamine is a potent drug and that its effects cannot be underestimated. Let’s look at ketamine, how it works, the risks versus rewards, and what nurses need to know about this potent drug.
What is ketamine?
Ketamine hydrochloride is a “dissociative anesthetic hallucinogen” that produces a state of sedation, immobility, relief from pain, and amnesia (United States Drug Enforcement Administration [DEA], n.d.). It alters the perception of sight and sound and makes the individual feel separated from their pain and environment. Ketamine is approved by the Federal Drug Administration (FDA) as an injectable, short-acting general anesthetic either alone or in combination with other medications. Esketamine (Spravato®), a derivative of ketamine, was approved by the FDA in 2019 in nasal spray form to treat resistant depression in adults, in conjunction with an oral antidepressant (DEA, n.d.; Facts and Comparisons, 2023b) as well as depressive symptoms in adults with major depressive disorder with suicidal thoughts or actions.
Off-label Uses of Ketamine (Facts and Comparisons, 2023a)
Ketamine has been studied and recommended by professional medical societies for off-label use to treat a variety of disorders which include the following:
- Severe agitation and violent behavior
- Pain (neuropathic, peripheral nerve injury, fibromyalgia, cancer, musculoskeletal injury)
- Depressive episode (severe, treatment resistant) associated with major depressive disorder (unipolar): ketamine produces an antidepressant response lasting about 7 days.
- Analgesia/sedation/agitation in mechanically ventilated patients in the intensive care unit (ICU)
- Rapid sequence intubation outside the operating room
- Status epilepticus, refractory
Ketamine and Esketamine Dosing (Facts and Comparisons, 2023a)
Dosing will vary based on desired effect, patient’s age, and underlying conditions. Children metabolize ketamine faster than adults and may need a higher dose. Elderly patients metabolize ketamine slowly requiring a lower dose. Dosage adjustment is necessary if used in combination with other drugs such as IV benzodiazepines or narcotics. Consult your facility policy or a reputable drug reference for specific dosing information and important clinical considerations.
Esketamine (Spravato®) can only be administered at healthcare settings certified in the Spravato® Risk Evaluation and Mitigation Strategy (REMS) Program due to a high risk of sedation and dissociation, and the potential for abuse and misuse (FDA, 2019).
Nursing Considerations (Facts and Comparisons, 2023a; Thace & Connolly, 2023)
- Ketamine and esketamine
- Patients on either drug should be under the care of a psychiatrist to assess appropriateness of the drug and monitor treatment effectiveness; they should only be administered by experienced personnel
- Contraindicated in conditions in which an increase in blood pressure would be dangerous (aortic dissection, uncontrolled hypertension, myocardial infarction, or aneurysm)
- Use with caution in patients with
- Increased intraocular pressure (IOP)
- Elevated cerebrospinal fluid (CSF) pressure
- Chronic alcohol use disorder
- Both drugs are Schedule III controlled substances under the US Controlled Substances Act. Illegal use of ketamine includes snorting or inhalation and ingested in food.
- Ketamine
- Be prepared for intubation when administering ketamine.
- To decrease risk of respiratory depression and apnea, administer IV bolus doses over 30 to 60 seconds.
- Avoid or use with caution in patients with substance use disorder.
- Prior to administration, assess patient risk for abuse or misuse, psychosis, and cardiovascular and cerebrovascular considers.
- When treating refractory unipolar depression, administer ketamine IV over 40 minutes.
- Ketamine may be useful in hypotensive patients or patients likely to develop hypotension.
- Emergence delirium may be mitigated by decreasing the recommended dose, using it in combination with benzodiazepines, and/or reducing noise and tactile stimulation during administration. Diazepam 2 to 5 mg IV over 1 minute can reduce emergence delirium (Rosenbaum, Gupta, Patel & Palacios, 2023).
- Do not mix ketamine directly with barbiturates or diazepam as precipitation may occur.
- Esketamine
- Advise patient to avoid food for at least 2 hours and liquids at least 30 minutes prior to administration.
- Do not administer within 1 hour of medications administered nasally such as nasal steroids or decongestants.
- Patients self-administer the nasal spray under the supervision of a health care provider, and the spray cannot be taken home.
- Esketamine may worsen suicidal thinking/behavior, psychosis, ulcerative or interstitial cystitis, and hepatic impairment.
- Patients should not drive, use heavy machinery, or perform other hazardous activities for up to 24 hours after administration.
Monitoring
- Vital signs: heart rate, blood pressure, respiratory rate, oxygen saturation
- Esketamine: monitor respiratory status for at least 2 hours after each treatment.
- Level of sedation
- Cardiac function
- Liver function tests (LFTs), alkaline phosphatase, and gamma glutamyl transferase (baseline and periodically)
- Pain control (when treating pain)
- Closely monitor for worsening of depression and signs of suicidal thoughts and behaviors.
For complete information on both ketamine and esketamine, please consult the drug’s specific package insert or the
Nursing2024 Drug Handbook® + Drug Updates.
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