[Pharmacology and clinical results with peridural and intrathecal administration of ketamine]

Abstract

The epidural and intrathecal administration of opioids has gained wide acceptance among anaesthesiologists during recent years. Ketamine, an anaesthetic agent with an unusual pharmacological profile, has also attracted some interest in this context, as in subanaesthetic doses it provides marked analgesia without inducing respiratory depression. Since the first publication on the epidural administration of ketamine in humans in 1982, various studies on the pharmacology, toxicology and clinical use of ketamine by the epidural and intrathecal routes have been published. PHARMACOLOGY. There is a large body of evidence to show that systemically administered ketamine interacts with different neurotransmitter systems and may even produce local anaesthetic effects when used for intravenous regional anaesthesia. The results of animal studies suggest that ketamine may cause complete sensory and motor blockade after intrathecal administration, which leads to high concentrations in the cerebrospinal fluid. One study investigating the effects after epidural administration showed motor blockade only after high doses of ketamine. Binding to local opiate receptors seems to play only a minor role, whereas significant analgesia after even low doses of ketamine is the result of antagonism to NMDA receptors. In vitro and animal data also suggest an involvement of the descending inhibitory pathways, mainly through inhibition of re-uptake of neurotransmitters. NEUROTOXICITY. Data relating to the neurotoxicity of ketamine after intrathecal administration are confusing. While no neurotoxic effects have been observed in studies in primates and rabbits, experimental rats and monkeys have sustained lesions: they may have been caused by a faulty puncture technique or by inherent neurotoxicity of the drug. CLINICAL RESULTS. The only study of intrathecal administration of ketamine in humans revealed local anaesthetic effects after doses of 50 mg. For epidural use, doses up to 30 mg did not give adequate pain relief after surgery in controlled studies, but had some analgesic effect in patients with chronic pain syndromes. When doses of 30 mg and over were used, postoperative analgesia was generally assessed as good. CONCLUSIONS. When administered intrathecally, ketamine shows local anaesthetic effects in both animals and humans. Unfortunately, all commercially available ketamine preparations contain disinfectant agents whose intrathecal administration is prohibited. Epidurally administered ketamine doses of 30 mg and more seem to provide adequate postoperative analgesia, while smaller doses might be effective in chronic pain syndromes. More studies investigating the neurotoxicity and clinical effects of ketamine on the spinal cord are needed before wider use of the substance by this route of administration can be recommended.