Killing off ketorolac

ED doctors are perversely masochistic – we love to beat ourselves up over just about anything. Oligo-analgesia one day, too much discharge opioid prescribing the next. Too many unnecessary IV cannulations and then not enough screening blood tests. Too much radiation, too little radiation. The list goes on. The latest round of self-admonishment at my shop revolved around the use of ketorolac. One clinician tried to temper the masochism by reminding us that anaesthetists use parecoxib by the bucket load, and so we shouldn’t feel too guilty. I couldn’t resist joining in however, because it seemed like an easy debate to settle: I don’t think we should beat ourselves up over use of ketorolac – I think we should just stop using it.

Anaesthetists prescribing and administering IV COX-2s intra-operatively doesn’t provide a justification for emergency physicians using IM/IV ketorolac in order to persuade a patient to go home because “they needed an injection” in order to facilitate discharge. There are other therapies bereft of evidence supporting their use in the ED (PPIs in upper GI bleeding, octreotide in variceal bleeding) however in the interests of maintaining positive relationships with inpatient teams we often administer these therapies anyway; they keep people happy/not anxious and grease the wheels of the patient flow wagon.

But NSAIDs are a different kettle of fish – acute pain management is part of our core business and this is usually undertaken without input from other services. I think we should therefore aspire and strive to be the best-practicing clinicians we can be. I think the assumptions around this debate are as follows:

1) Some NSAIDs are more potent than others
There is ample literature demonstrating an analgesic and anti-inflammatory ceiling effect of NSAIDs. Furthermore, as the pharmacodynamics of various non-COX2 NSAIDs are identical, the only differentiating features of the drugs are economic (cost), pharmacokinetic (half-life, bioavailability, route of administration), and toxicity (GI, CVS). A 2010 systematic review in the Journal of Rheumatology and Arthritis showed that the GI toxicity of ketorolac was much worse than any other NSAIDs. The data in that article was nicely graphed in a 2011 review article from International Rheumatology.

Conaghan PG. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy and toxicity. Rheumatol Int 2012;32:1491-502

I think it is pretty self-evident. The n= in the graph refers to the number of studies included to come up with the RR.

2) My patient needs an injection to benefit from that efficacious 30% placebo effect.
To debunk this belief see Schwartz NA, Turturro MA, Istvan DJ, et al. Patients’ perceptions of route of nonsteriodal anti-inflammatory drug administration and its effect on analgesia. Acad Emerg Med 2000;7:857-61.
In my 5 minutes worth of ED experience, I have yet to find a patient respond in other than a positive fashion when I provide them with a structured pain management plan (of oral analgesics) and an honest explanation (including expectation management) to go with it, even when they have arrived rooted in the belief that only a needle would save them and that “nothing ever works”.

3) We need IV/IM NSAIDs to remain in the ED formulary for the vomiting renal colic patient
Probably the least non-evidenced based argument that shrouds ketorolac mythology. But taking into account the costs, kinetics and toxicity of ketorolac I think we can still throw it out. The severely bilious patients doing the renal-colic squirm invariably get a double-tap of intravenous morphine/fentanyl and ondansetron. Aggressive titration-to-effect of these medications achieves good results. When they fail, addition of analgesic ketamine is going to safely take them out of the hurt locker a whole lot quicker, safer and cheaper than ketorolac. Once pain is controlled, the nausea and vomiting usually settles and you can get that oral NSAID down range to help facilitate discharge pain management.

To summarise my boorish rant, I can’t really say it better than Mel Herbert and Sanjay Arora:
The belief that IM/IV medications are perceived as being stronger than oral medications and therefore result in a more powerful placebo effect has also been shown to be false. With the exception of 1 study in post-op patients with a significantly flawed study design*, the evidence overwhelmingly shows that inexpensive and relatively safe oral ibuprofen has equal efficacy to the more expensive and potentially dangerous IM or IV ketorolac.

* This study was ludicrous – 20 in each arm and a ridiculous protocol

Viva la ibuprofen!

References:

Chris Bond and his superb 2013 NSAID trilogy posted on the SOCMOB blog. (Standing on the corner, minding my own business in the ER)

Conaghan PG. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy and toxicity. Rheumatol Int 2012;32:1491-502

González M, et al. Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis & Rheumatism 2010; 62: 1592–1601.

Schwartz NA, Turturro MA, Istvan DJ, et al. Patients’ perceptions of route of nonsteriodal anti-inflammatory drug administration and its effect on analgesia. Acad Emerg Med 2000;7:857-61.

Staquet MJ. A double-blind study with placebo control of intramuscular ketorolac tromethamine in the treatment of cancer pain. J Clin Pharmacol 1989; 29(11):1031-6.

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