Ketamine in the treatment of chronic pain as evidence-based medicine.

Abstract

Ketamine is a noncompetitive NMDA receptor antagonist and has a large action’s mechanism, that involves receptors: AMPA, kainate, gamma-aminobutyric acid, opioids, monoamine, muscarinic and nicotinic. It is acting on voltage-dependent calcium channels, join in the synthesis and release of nitric oxide and inhibits serotonin reuptake. The interaction with these mechanisms of action makes it an important role on mechanisms of pain, inflammation, neuroprotection and opioid tolerance. In this paper we review the different routes of administration of ketamine, dosage, modes of administration, duration of treatment, indications according to levels of evidence available and side effects to set up its efficacy in the therapy of chronic pain and promote a more specific treatment, in those pathologies where it has shown greater efficacy. We perform a search in: Trip Database Population Intervention Comparison Outcome (PICO), National Guidelines Clearinghouse, Cochrane Library, Medline, CMA infobase, Health Services / Technology Assessment, New Zealand Guidelines Group and Scottish Intercollegiate Guidelines Network. Ketamine is very versatile in their routes of administration: intravenous, intramuscular, subcutaneous, sublingual, oral, rectal, nasal, transdermic, epidural and subarachnoid; as well as their ways of administration (bolus, continuous infusion). However, the oral route is the most widely used and preferred for the treatment of chronic pain. However, we do not have an oral formulation marketed, making it difficult to use. Clinical use of ketamine requires careful patient’s selection and assessment of the risk / benefit ratio. Ketamine has a potential risk of drug abuse; therefore, it should checked prior history of drug abuse. It is available evidence on the efficacy of ketamine in patients with refractory cancer pain and complex regional pain syndrome (CRPS). The use of low-dose intravenous ketamine has moderate evidence in CRPS, that does not justify its routine use in this syndrome. In neuropathic pain, ketamine has been particularly effective in controlling allodynia, hyperalgesia and hyperpathia, although there is controversy over its use. Oral ketamine may have a place in the treatment of chronic pain patients refractory to standard treatments. It is shown useful as an adjuvant to other analgesics, especially in patients treated with opioids, allowing reduction of doses and increasing pain relief in patients with chronic pain.