Fast Fact and Concept #132: Ketamine Use in Palliative Care

Author(s): Eric Prommer, MD

Ketamine is FDA approved as 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. This Fast Fact reviews the use of ketamine in palliative care as an analgesic.

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, Drugs that interact with CYP34A have the potential to affect ketamine metabolism (e.g. azole antifungals, macrolide antibacterials, HIV protease inhibitors, and cyclosporin). U ndesirable 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: There is an absence of large controlled trials supporting ketamine as an analgesic for cancer or neuropathic pain, but 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. 1

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 (sub-anesthetic doses) can be considered for use in the palliative care setting for pain refractory to opioids and adjuvant analgesics.

References

• Bell RF, Eccleston C, Kalso E. Ketamine as adjuvant to opioids for cancer pain. A qualitative systematic review. J Pain Symptom Manage. 2003 Sep; 26(3):867-75.
• Kotlinska-Lemieszek A, Luczak J. Subanesthetic ketamine: an essential adjuvant for intractable cancer pain. J Pain Symptom Manage. 2004 Aug; 28(2):100-2.
• Fine PG. Low-dose ketamine in the management of opioid nonresponsive terminal cancer pain. J Pain Symptom Manage. 1999 Apr; 17(4):296-300
• Fisher K, Hagen NA. Analgesic effect of oral ketamine in chronic neuropathic pain of spinal origin: a case report. J Pain Symptom Manage. 1999 Jul;18(1):61-6.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information : Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Prommer, E. Ketamine in Palliative Care. Fast Fact and Concepts #132. March, 2005. End-of-Life / Palliative Education Resource Center @ www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information; this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in 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.

Creation Date: 3/2005

Purpose: Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain>non-opioids