It is “our” drug, but now it is in other hands …

It is “our” drug, but now it is in other hands …

  • Issue 71

Gabriel M. Gurman, Chief Editor
gurman@bgu.ac.il

Clinical note

This story is not new. We are already accustomed to “renting” some of our drugs to other specialties. Benzodiazepines are in current use in psychiatry and the gastroenterologists use propofol for sedating their patients.

But here it is a new trend, this time in the domain of chronic pain management. A recent congress of the American Academy of Pain Medicine had as a prime subject the use of ketamine infusion for treating patients suffering from pain of different aetiologies.

For those of our younger readers, here is a short note on the history of ketamine use. It started in 1966 as an anaesthetic miracle drug, since it did not affect the cardiovascular stability of the patient. It could be used intravenously or intramuscularly, and it was considered the drug of choice in mass casualties, since the needed level of supervision of the numerous wounded patients was considered to be lower than usual, once again because of lack of effect on blood pressure.

Later on, the anaesthesiologist community became worried about the hallucinogenic effects of ketamine, but this drawback was, at least partially, solved by premedicating the patient with a benzodiazepine. Anecdotally, some studies showed that vivid dreamers were more predisposed to develop psychogenic symptoms and the advice was not to use ketamine for this kind of patient.

But, gradually, especially after the inclusion of propofol in the drugs arsenal for induction of general anaesthesia, the use of ketamine decreased, and much smaller doses than once used for induction have been recommended in order to benefit from a drug with both hypnotic and analgesic effects.

As per today, ketamine’s place in the routine techniques of general anaesthesia is rather limited, only in small doses and in combination with other anaesthetic drugs. But recently ketamine became a subject of clinical studies in order to establish its place in the treatment of chronic pain. It has been used as a possible therapeutic alternative for neuropathic pain, regional pain syndrome, migraine, and even after spinal cord injury.

At the same time, due to the “vulgarization” of the drug, it got an unwanted place on the list of what the newspapers use to call “nightclub drugs” and a significant percentage of car accidents in the USA have been considered as being caused by inappropriate oral use of ketamine.

Some clinical trials studied the antidepressant effects of ketamine, but the secondary effects, such as nausea, headache, and dysphoria, limited its use for this medical condition. But the medical community did not abandon the idea of using ketamine for treating acute and chronic pain. A very recent study1 used ketamine in a bolus dose followed by continuous infusion of 0.1 mg/kg/hour for treating acute pain after nephrectomy and found a reduction of 33% in the necessary morphine dose.

Currently some papers have been published about the use of ketamine in various intravenous doses for treating pain after spinal cord injury or regional pain syndrome. The results showed some clear improvement in the pain scale, but some critics mentioned the fact that most of trials’ results have been hampered by the small numbers of patients included in the studies, as well as the lack of effective blinding.

So, where are we today?

First of all, a clear fact has to be emphasized: a good part of the published studies have been done by non-anaesthesiologists, which means that the authors tended to neglect, at least partially, the huge experience accumulated by our colleagues regarding the use of ketamine. Second, it seems that some guidelines are being prepared for publication with the aim of including the use of ketamine in the routine management of chronic pain. Currently ketamine is not approved in the USA for chronic pain management.

One of the participants in the mentioned congress was of an opinion that since the drug is very cheap and there is no patent protection, there would be only a slight chance to see a serious double-blind study being done and published in the near future.

Does the anaesthesiologist community have to react to this news? Although we possess the most experience regarding the use of ketamine, we do not have the monopoly in this domain. But a very interesting thing came out of this increase in use of ketamine. For some national and international organizations, ketamine became a dangerous drug and some actions were taken in order to restrict its use and impose strict control on this drug. As a reaction to this trend, WFSA coordinated a response to governments and the World Health Organization (WHO) to limit a potential threat to the availability of ketamine as an essential anaesthesia drug. This subject was debated on various occasions, and letters were sent to the WHO Expert Committee on Drug Dependence (ECDD) with the aim of clearly identifying the medical necessity of ketamine in anaesthetic practice, especially in low and middle income countries.

As a result, in December 2015 the World Health Organisation recommended against the international control of ketamine² for the fourth time since 2006. The ECDD concluded that ketamine abuse does not pose a global public health threat, while controlling it could limit access to the only anaesthetic and pain killer available in large areas of the developing world.

In conclusion, our role in the discussion regarding the use of ketamine outside the operating room is not at all limited. WFSA succeeded in convincing WHO about the place of ketamine in the anaesthesia armamentarium. But above everything, we are supposed to be ready to offer our expertise any time it would be needed, because all of us are committed to the wellbeing of our patients. And this is much more important than any kind of exaggerated professional ego.

Reference
1.Jendoubi A, Naceur IB, Bouzouita A, et al. Saudi J Anaesth 2017;11(2):177-84.
2. http://www.wfsahq.org/ketamine
3. http://newsletter.esahq.org/the-world-federation-of-societies-of-anaesthesiologists-wfsa-campaign-for-ketamine/