Ketamine

Introduction

Ketamine is as an anaesthetic agent with well-recognised analgesic properties, due to its action as an antagonist at the N-Methyl D-Aspartate (NMDA) glutamate receptor2-5, and is widely, and effectively, used parenterally in trauma situations for severe, acute pain1. Oral Ketamine has been used as an analgesic in cancer and chronic non-malignant pain . There is evidence10 that the NMDA  receptor is  important in the pathogenesis of some chronic pain states. There are few  clinical trials on the use of Ketamine in the long-term6 and its use is  based on its known efficacy in the short term9, case study evidence and clinical experience. Ketamine has found a limited clinical role in the treatment of refractory neuropathic pain conditions and some  complex nociceptive pain situations.2-7

Preparation

It is available as an unlicensed  an oral preparation in the UK, and the  intravenous preparations is effective orally, though this is an off-license use. 

Safety

There is understandable public and professional concern focused on safety, dependence, misuse, licensing issues, diversion, side-effects, monitoring and the arrangement of care. Side-effects include central nervous effects, cardiovascular changes, bladder inflammation and rarely liver disorder. Ketamine should be initiated in specialist centres because of the complexity of patient assessment, decision-making and initial monitoring. 

NICE and the FPM does not recommend these for chronic primary pain [NG193]. The FPM recommend that ketamine is principally considered for complex neuropathic pain problems in specialised units. 

Monitoring and shared care

Monitoring for longer term prescribing and the roles of General Practice and Secondary care is a matter for local arrangement/policy. It is the prescribing practitioner who carries the legal responsibility for a prescribed medicine and must be competent in this task.  Key monitoring issues include safety, clinical effectiveness, prescriber safeguard, public risk management and other clinical governance arrangements. Family practitioners are understandably cautious about entering into shared-care agreements but shared care arrangements can be put in place.8

Local arrangements on prescribing must be enabled by appropriate liaison, education and support  between specialist centres and general practitioners. Most commonly Ketamine is prescribed as a specialist 'red flag' product by pain specialists familiar with its use who have developed local care arrangements.

 

References

  1. De Rocquigny G., Dubecq C., Martinez T., Peffer J, Cauet A., Travers S., Pasquier P. Use of ketamine for prehospital pain control on the battlefield: A systematic review. Journal of  Trauma Acute Care Surg 2020; 88(1):180-185. Available from: 
    doi: 10.1097/TA.0000000000002522
  2. Quibell R., Fallon M., Mihalyo M., Twycross R., Wilcock A.  Ketamine. Journal of Pain & Symptom Management. 2015; 50(2):268-78.
  3. Twycross R., Wilcock A., Charlesworth S., Dickman A., Thorp,S. Palliative Care Formulary 2 (2nd Edition). Radcliffe Medical Press 2002.
  4. Fallon MT., Welsh J. The role of Ketamine in pain control. European Journal of Palliative Care 1996; 3:143-146.
  5. Fisher K., Coderre TJ., Hagen NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions. Journal of Pain and Symptom Management 2000; 20:358-373. 
  6. Rae FB., Eccleston C., Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Systematic Review . Published: 28 June 2017. Available from:  https://doi.org/10.1002/14651858.CD003351.pub3
  7. Persson J. Ketamine in Pain Management. CNS Neurosciences and Therapeutics. 2013; 19: 396-402.
  8. Akporehwe NA., Wilkinson PR., Quibell R., Akporehwe KA. Ketamine: a misunderstood analgesic?  BMJ 2006; 332(75556): 1466. Available from: doi: 10.1136/bmj.332.7556.1466
  9. Jonkman, K., Dahan, A., van de Donk, T., Aarts, L., Niesters, M., van Velzen, M. Ketamine for Pain. Ketamine for pain [version 1; peer review: 2 approved]. F1000Research. 2017, 6(F1000 Faculty Rev):1711 Available from: https://doi.org/10.12688/f1000research.11372.1
  10. Eide, P.K. Wind-up and the NMDA receptor complex from a clinical perspective. European Journal of Pain, 2000; 4: 5-15. Available from:  https://doi.org/10.1053/eujp.1999.0154 

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