Ketamine in palliative care

Contents

An old drug with a new role
Clinical implications
Side-effects
Ketamine and opioids
Dosage
Summary

An old drug with a new role

Ketamine has been around for about 30 years and used by anaesthetists as a dissociative general anaesthetic. It activates the limbic system and depresses the cerebral cortex, producing profound analgesia, slight respiratory depression, cardiovascular stimulation and amnesia. The protective reflexes are maintained. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist.

It is because of the unique properties of ketamine that this drug has become of interest to palliative care physicians who are always on the lookout for drugs to assist patients with severe and sometimes difficult to control pain. It has particularly been looked at in the so called 'wind up' phenomena where there is a progressive increase in dorsal horn neuronal response to rapidly repeated, identical noxious stimuli. In clinical terms it may mean that simple touch input is converted into a painful sensation called allodynia. It can also mean that a painful response to any given painful stimuli is magnified(hyperalgesia) and prolonged. The 'wind up' appears to be mediated by the NMDA receptors and can be reduced by ketamine. It is very resistant to opioids and neuropathic agents.

Clinical implications

There is evidence that NMDA receptors are involved in the induction and maintenance of the pain response in any pain syndrome with allodynia, hyperalgesia and prolongation of the pain response as well as inflammatory pain, neuropathic pain, phantom limb pain and peripheral vascular disease pain. However it is not yet clearcut as to the exact role of ketamine in the management of these pain syndromes and it is certainly inappropriate to get over-optimistic as to the benefit of this drug at this stage. Its exact role in the palliative care setting is yet to be determined.

Side-effects

Although in palliatve care ketamine is used in subanaesthetic doses there are still the well-known side-effects seen after anaesthesia using this drug. They are confusion, delerium, vivid dreams, hallucinations and feelings of detachment from the body. Some clinicians routinely use haloperidol or a benzodiazepine to alleviate these distressing symptoms.

Ketamine and opioids

There is evidence that ketamine reverses morphine tolerance and clinically this results in the reappearance of morphine sensitivity. In practical terms this means that it is necessary to reduce the morphine dose at the same time as introducing ketamine to avoid the problems associated with morphine toxicity. It may need to be reduced by 30-50%.

Dosage

The doses recommended are 10-30mg stat, given subcutaneously (sc), then starting an infusion dose of 300mg/ 24hrs via a syringe driver, then 350mgm/24hr etc to maximum of about 700mg/24hr. Alternatively, rather than using a syringe driver intermittent doses can be given by the sc route.This may also have a role for painful wound dressings.

Summary

Ketamine may have a role to play in carefully selected patients with severe intractable pain that has not responded to conventional analgesics used appropriately in adequate doses. However research is still underway to clearly define where this drug fits into the drug therapy for palliative care patients. Other related drugs with less potential side-effects may come on to the market in the future. Until we hear more it is appropriate to just be aware that this drug is being trialled in the palliative care setting.

Andrew Binns

Reference

Marie T Fallon and John Welsh. The role of ketamine in pain control. European Journal of Palliative Care,1996:3(4) 143-146.

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