Tuesday, 12 August 2014

Sub-Dissociative Ketamine for pain in the ED? The Enthusiasm Exceeds the Science.

All emergency physicians love ketamine. Under the right circumstances, it is a fabulous agent for procedural sedation and as an induction agent for RSI or DSI.

Recently there has been a lot of enthusiasm to use sub-dissociative doses of ketamine for pain. Everybody seems to be talking up the greatness of ketamine. But this study was a bit different and looked at the intra-nasal administration of ketamine as a primary analgesic agent for adults with moderate to severe pain. Crazy you say? Well, yes probably so.

This was a prospective observational study. To be clear, this was not a trial and did not compare any different analgesic agents. Adult patients with a VAS of >6 were included. There were lots of reasonable exclusion criteria including administration of opiates in the previous 4 hours. Patients were given an initial dose of 0.7mg/kg (this was increased to 1mg/kg after 6 months) with a secondary dose of 0.5mg/kg after 15 minutes if pain did not improve.

The primary outcome was the change in VAS at 30 minutes and the percentage of patients reporting what they called clinically significant reduction in the VAS of >20mm. (This cut-off could certainly be debated.)

A total of 72 patients were included in the data analysis. Unfortunately there was quite a lot of heterogeneity in the painful conditions treated and this may have made the response to therapy different. There were 4 patients with renal colic and I would question the ethics of their inclusion.

The bottom line? It didn’t work very well and there were lots of side effects.

The median reduction in VAS rating at 30 minutes was 24mm. 56% reported a VAS reduction of >20mm. Therefore it failed about half the time (if you take their primary outcome at face value.) I wonder if placebo would have had a similar response.

The satisfaction rate at 30 minutes was 60% which is absolutely abysmal. In general, most people report very high levels of satisfaction in studies regardless of the eventual outcome. This is why it is always a challenge to use changes in satisfaction as a study outcome measure.

About 80% of the subjects reported some adverse events. These were reported to be relatively minor such as dizziness and “spaced out.” But in trauma patients and those with undifferentiated conditions, this might make evaluation quite difficult.

Overall this study definitely provides us with some useful information and the medical student lead author is to be congratulated. Nevertheless, there were a few issues with the methods of statistical analysis (but this is probably irrelevant anyway.) A power calculation was probably not necessary as this was not a trial.

It is a bit difficult to understand the key conclusions as stated in the paper since they are a bit contradictory when comparing the abstract, text and key findings. But I think the data speaks for itself. Sub-dissociative doses of ketamine as the primary agent of analgesia does not work that well and causes lots of side effects. Although not studied here, ketamine may have a role as an adjunct to opiates or in individuals who are chronically habituated.

If the intranasal (IN) route of administration you want, then fentanyl is your drug! Despite the text of the paper, fentanyl is available in Australia in a concentrated vial of 600mcg/2ml and therefore suitable in adults as well as children. I am unaware of any published head-to-head comparison of IN ketamine vs. fentanyl but given previous experience I think this would be an absolute waste of time.

In the end, I don’t understand why we are trying to fix something that is not broken. In general we know that opiates are great drugs as the primary agent for acute painful conditions. There are those that proclaim we need to “spare opiates.” But what is so wrong with opiates? They are a known entity, generally safe, reversible and work in the vast majority of patients when dosed appropriately. Opiates are certainly better when compared to the side effect profile and the lack of efficacy of sub-dissociative ketamine. How about we save our enthusiasm for what we know works.


Covering:


Yeaman, F, Meek, R, Egerton-Warburton D, et al. Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients. Emerg Med Aust. 2014; 26:237-242.




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