Abstract
Background
Mechanism of Action
The N-methyl-
Pharmacology
As an anesthetic agent ketamine is given intravenously or intramuscularly. 3 However, for pain, the parenteral solution of ketamine can be delivered at much lower doses by the oral, intranasal, transdermal, rectal, and subcutaneous routes. 4 Onset of analgesia is 15–30 minutes by subcutaneous or oral routes. 5 Duration of action is 15 minutes to 2 hours when administered by the intramuscular or subcutaneous route, possibly longer orally. Ketamine is physically stable when mixed with morphine, low-dose dexamethasone, haloperidol, and metoclopramide. 6 Drugs that interact with CYP34A have the potential to affect ketamine metabolism (e.g., azole antifungals, macrolide antibiotics, HIV protease inhibitors, and cyclosporin). 7
Side Effects
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, hallucinations), excessive salivation, and tachycardia. Side effects at the lower doses used for pain are dose dependent, with dissociative feelings (“spaced out”), nausea, sedation, and hallucinations reported more frequently at higher doses. 8
Analgesic Effectiveness
There is an absence of large controlled trials supporting ketamine as an analgesic for cancer or neuropathic pain, but there is a large body of case reports and uncontrolled trials. Two small randomized controlled trials reported decreased morphine use and reduced neuropathic pain intensity. However, a recent systematic review found insufficient evidence that ketamine improves the effectiveness of opioid treatment in cancer pain. 9
Titration Schedule
There are no studies comparing various titration or dosing schedules, nor routes of administration. Suggested algorithms for have been proposed (see references). Depending on the clinical setting, airway monitoring and availability of resuscitation equipment may be appropriate. Note: clinicians with limited experience in using ketamine should seek expert consultation to develop an appropriate treatment and patient monitoring plan.
Summary
Low-dose ketamine (at subanesthetic doses) can be considered for use in the palliative care setting for pain refractory to opioids and adjuvant analgesics.
Footnotes
Fast Facts and Concepts are edited by Drew A. Rosielle M.D., Palliative Care Program, University of Minnesota Medical Center–Fairview Health Services, and are published by the End of Life/Palliative Education Resource Center at the Medical College of Wisconsin. For more information write to: rosi0011@umn.edu. More information, as well as the complete set of Fast Facts, is available at EPERC: 
.
Disclaimer: Fast Facts and Concepts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.