Ketamine Hydrochloride and Caffeine

• Generic Name: ketamine
• Dosage Forms: n.a.
• Other Brand Names: Ketalar

Used IV or IM for induction of anesthesia prior to administration of other general anesthetic agents.

Used as the sole anesthetic agent for diagnostic and surgical procedures that do not require skeletal muscle relaxation; although best suited for brief procedures, may be used for longer procedures with additional (i.e, maintenance) dosing.

Also may be used to supplement low-potency agents (e.g., nitrous oxide).

Produces dissociative anesthesia (i.e., a trance-like cataleptic state characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability), which differs markedly from the anesthetic state produced by other general anesthetics (e.g., barbiturates, benzodiazepines, propofol, inhalation anesthetics).

Due to risk of emergence reactions (see Boxed Warning) and availability of other anesthetic agents, current use generally limited to certain patient populations (e.g., hemodynamically compromised patients) and settings (e.g., prehospital environments that lack appropriate monitoring and respiratory support) where the drug's unique pharmacologic properties may be particularly advantageous.

Produces sympathomimetic effects and may be particularly useful in hemodynamically unstable patients (e.g., those with traumatic injury or septic shock) or in poor-risk patients with depressed vital functions.

Because of its bronchodilating effects, generally considered the induction agent of choice in patients with reactive airway disease (e.g., asthma) or active bronchospasm.

Although currently FDA-labeled for use in adults only, has been used widely in pediatric patients.

Used to produce dissociative sedation for short painful or emotionally disturbing procedures (e.g., fracture reduction, laceration repair, abscess drainage, emergency cardioversion, chest tube insertion, central line placement) in the emergency department.

Commonly used for procedural sedation in pediatric patients; used less frequently in adults because of increased risk of emergence delirium.

Administration of a single IV or IM dose can effectively provide dissociation for approximately 5–10 or 20–30 minutes, respectively, while maintaining cardiovascular stability, spontaneous respiration, and protective airway reflexes.

Has a well-established role in burn patients undergoing painful procedures (e.g., dressing changes, debridement, grafts).

Availability of the IM route is advantageous in patients in whom IV administration may be difficult (e.g., severely agitated or combative patients, young children, patients with extensive burns).

Has been used in combination with propofol (commonly referred to as “ketofol”) to counteract adverse effects of the drugs (i.e., ketamine mitigating propofol-induced hypotension and propofol mitigating ketamine-induced vomiting and recovery agitation).

Has been used in low (i.e., subanesthetic or subdissociative) doses as part of a multimodal regimen for postoperative pain in adults and pediatric patients.

Efficacy of low-dose ketamine in the postoperative setting is well established; clinical studies have demonstrated reduced opiate requirements and, in some cases, additional reductions in pain.

Appears to provide most benefit for patients undergoing procedures associated with severe postoperative pain (e.g., thoracic, abdominal, orthopedic surgeries). Some experts state that benefit not demonstrated in patients undergoing procedures associated with mild postoperative pain (e.g., tonsillectomy, head and neck surgery); for such procedures, standard analgesia with low dosages of opiates, NSAIAs, and local anesthetics can usually provide adequate pain relief.

May be particularly useful in the management of opiate-tolerant or opiate-dependent patients undergoing surgery. Also may be considered as an adjunct to reduce postoperative opiate requirements in patients with increased risk of opiate-related respiratory depression (e.g., those with obstructive sleep apnea).

Has been used (in subanesthetic doses) alone or as an adjunct to other analgesics (e.g., opiates) for relief of acute pain in emergency department or prehospital settings. Reported to provide comparable reduction in pain scores to IV morphine.

When used as an adjunct to opiate analgesics, ketamine may reduce pain scores and/or decrease opiate requirements.

Studies evaluating subanesthetic ketamine for acute pain generally conducted in the adult population. However, low or subanesthetic doses of ketamine also have been used for analgesia in pediatric patients ≥3 months of age presenting to the emergency department.

Although evidence is limited, ketamine may be useful in opiate-dependent patients with acute exacerbations of chronic pain conditions (e.g., sickle cell disease).

Has been used as an adjunct analgesic for management of chronic pain of various etiologies, including complex regional pain syndrome (CRPS), neuropathic pain associated with spinal cord injury, phantom limb pain, fibromyalgia, ischemic pain, cancer pain, and migraine.

Evidence of efficacy varies depending on specific chronic pain condition; some evidence supports short-term benefits of ketamine infusions for certain conditions associated with a neuropathic component.

There is weak to moderate evidence supporting use for CRPS. There is weak evidence supporting use for neuropathic pain associated with spinal cord injury. Evidence remains inconclusive for cancer-related pain, mixed neuropathic pain, phantom limb pain, postherpetic neuralgia, fibromyalgia, ischemic pain, migraine, and low-back pain.

Additional study needed to establish role of ketamine in patients with chronic pain, and to determine optimum dosages, durability of response, and long-term benefits and risks.

Has been used in low (i.e., subanesthetic) doses for the treatment of severe and treatment-resistant depression associated with major depressive disorder or bipolar disorder.

In controlled studies, single, low-dose IV infusions of ketamine resulted in approximately 37–71% response rates in patients with treatment-resistant depression. Limited clinical experience in patients with bipolar disorder; not known if such patients respond differently to ketamine than patients with major depressive disorder.

Multiple-infusion regimens of ketamine (i.e., weekly, biweekly, 3 times weekly) appear to be more effective in depressed patients than single infusions and can prolong remission. However, long-term efficacy and safety of repeated doses not fully determined. Although not observed to date, multiple-infusion regimens potentially may cause long-term cognitive impairment and/or neurotoxicity. Some clinicians suggest that short-term use of ketamine to produce rapid antidepressant and antisuicidal effects until a less invasive relapse prevention strategy can be implemented may be optimal.

Has been used in the short-term treatment of suicidal ideation. In a systematic review and meta-analysis, suicidal ideation rapidly decreased following IV infusions of ketamine even among patients whose depression did not fully respond to ketamine therapy, suggesting the drug may have a partially independent antisuicidal effect.

Preliminary evidence suggests that intranasal ketamine can rapidly improve depressive symptoms in patients with major depressive disorder and is generally well tolerated; however, further studies are needed to more clearly determine the efficacy, tolerability, and optimal dosing of this alternative route of administration. Pending further accumulation of safety data from controlled settings, the APA's Council of Research Task Force on Novel Biomarkers and Treatments currently advises against the prescription of self-administration of ketamine at home and recommends medical supervision whenever the drug is used.

Despite the increasing use of ketamine to treat patients with treatment-resistant depression and suicidality and the rapid increase in the number of facilities offering ketamine therapy (e.g., ketamine infusion centers and psychiatric clinics), some clinicians currently recommend limiting ketamine's use to controlled settings under the care of skilled clinicians. If ketamine is used outside of a controlled setting, careful screening, monitoring during treatment, and follow-up of patients are necessary.

When considering the use of ketamine for mood disorders, the APA's Council of Research Task Force on Novel Biomarkers and Treatments recommends balancing the potential benefits of ketamine infusion therapy with the potential risks of long-term exposure (e.g., neurotoxicity, cystitis, abuse potential). (See Cautions.)

Some clinicians consider electroconvulsive therapy (ECT) to be first-line therapy for patients with refractory depression and are concerned that a trial of ketamine might delay patients from being referred for an ECT consultation. Preliminary experience with the adjunctive use of ketamine in the course of ECT for depression does not suggest improved efficacy or tolerability.

Has been used by continuous IV infusion to provide short-term (i.e., < 24 hours) sedation in critically ill patients in the ICU setting; however, evidence supporting this use is generally lacking, and other agents (e.g., propofol, midazolam, dexmedetomidine) are more commonly used.

Also has been used for pain management in critically ill patients.

A known drug of abuse; prescribe and administer with caution. Subject to control under the Federal Controlled Substances Act of 1970 as a schedule III drug.

Most commonly abused by nasal insufflation (i.e., snorting) of the evaporated powder, although IV, IM, and oral routes also used. Most cases of ketamine abuse reported in the context of multidrug or polysubstance abuse.

Pharmacologic and behavioral effects of ketamine are similar to, but somewhat less intense and shorter in duration than those of phencyclidine (PCP).

Reported desired effects include feelings of dissociation and unreality, altered state of consciousness, enhanced sensory perception, hallucinations, intoxication, mild euphoria, and sensation of floating.

Although brief exposure in a hospital setting is not likely to cause addiction, the possibility exists and patients should be assessed for their risk.