Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes

Ketamine, an anesthetic and short-acting analgesic used for nearly 30 years, has renewed clinical interest as an NMDA receptor antagonist for pain management. This review of randomized, double-blind, controlled trials from 1966 to 1998 examined low-dose ketamine for acute postoperative pain, defined as a bolus less than 2 mg/kg intramuscularly or less than 1 mg/kg intravenously or epidurally, or a continuous intravenous rate of 20 µg/kg per minute or less. The evidence suggests low-dose ketamine may improve postoperative pain management and reduce opioid-related adverse effects when used as an adjunct to local anesthetics, opioids, or other analgesics. Further research is needed on dosing, optimal routes, S(+)-ketamine, long-term outcomes, stability, spinal toxicity, and cognitive effects.

Study at a glance

Abstract

Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.