Ketamine is a parenterally administered, rapid-acting dissociative general anesthetic. However, in the past 10 years there have been numerous reports of ketamine, administration via various routes, for pain control.

Mechanism of action: The N-methyl-D-aspartate/glutamate receptor (NMDA) is a calcium channel closely involved in the development of central (dorsal horn) sensitization. This channel has a role in opioid-resistant pain, neuropathic pain, allodynia, and hyperalgesia. Ketamine enters and blocks the open channel at a phencyclidine site, thereby inhibiting the excitatory effects of glutamate and aspartate. Ketamine also interacts with nicotinic, muscarinic, and opioid receptors.

Pharmacology: As an anesthetic agent ketamine is given IV or IM. However, for pain, the parenteral solution of ketamine can be delivered, using much lower doses, by the oral, intranasal, transdermal, rectal, and subcutaneous routes.
Onset of analgesia is 15-30 minutes by subcutaneous or oral routes.
Duration of action is 15 minutes to 2 hours when administered by the IM or SQ route, possibly longer PO.
Ketamine is physically stable when mixed with morphine, low-dose dexamethasone, haloperidol, and metoclopramide.

Undesirable effects of high dose ketamine used for general anesthesia (1-2 mg/kg IV or 6.5-13 mg/kg IM) include psychotomimetic phenomena (dysphoria, blunted affect, psychomotor retardation, nightmares, and hallucinations), excessive salivation and tachycardia.

Analgesic effectiveness: While there is a large body of case reports, retrospective surveys, and uncontrolled trials suggesting that ketamine effectively relieves cancer and noncancer pain from neuropathy, ischemia, bone metastasis, or mucositis, smaller controlled trials have had mixed results. If used as an analgesic, a short term “burst” treatment (e.g., appropriate ketamine dosing given over 2-4 days) should be considered, as evidence suggests the analgesic effects of “burst” treatment can extend several weeks.

Titration schedule: There are no studies comparing various titration or dosing schedules, nor routes of administration. Usual initial analgesic oral dose in adults is 10-25 mg TID to QID with titration in steps of 10-25 mg. The maximum reported oral dose is 200 mg QID. A common initial IV dose in adults is 50-100 mg/day, with titration at increments of 25-50 mg/day, and a usual effective dose of 100-300 mg/day. Careful monitoring of blood pressure, heart rate, and psychotomimetic effects should occur. Drowsiness may ensue when patients are on background opioids; consequently, some clinicians empirically reduce opioid doses by 25-50% when starting IV ketamine.

Depending on the clinical setting, airway monitoring and availability of resuscitation equipment may be appropriate.

See reference for details.

Adapted from Prommer E. Palliative Care Network of Wisconsin. Fast facts and concepts #132. Ketamine use in palliative care. Internet. Accessed on January 25, 2016.