It has long held that non-steroidal anti-inflammatory treatment is specifically ideal for symptomatic ureterolithiasis – leading to the popularity of such treatments as intravenous and intramuscular ketorolac, diclofenac, and the like.
However, I hadn’t quite seen as large and well-designed comparative efficacy trial as this, as recently published in The Lancet. This trial, a placebo-control, double-blind, randomized trial compared 75mg intramuscular diclofenac, 1g intravenous paracetamol, and 0.1mg/kg intravenous morphine for patients with acute renal colic. This means, most impressively, every patient received three injections – one active and two placebo. The primary outcome was 50% reduction in initial pain score by 30 minutes, with relevant secondary outcomes of persistent pain and need for secondary analgesia.
Based on an analysis only of those who ultimately had confirmed diagnosis of stone on imaging (CT or ultrasound), both diclofenac and paracetamol were similar or superior to morphine, with fewer adverse effects. Pain scores were halved in 68% of diclofenac, 66% of paracetamol, and 61% of morphine. Most importantly, need for rescue medication in this trial was only 12% with the intramuscular diclofenac, an important consideration when potentially forgoing an IV start. The authors actually probably understate the advantage of diclofenac here, as time zero is the time of study medication administration, not time of ED arrival, as an intramuscular injection can be provided much more rapidly than one requiring an IV.
Generalizability may be limited, as it is a single-center study from Qatar in which 80+% of patients were male. At least however, the nationality of patients were quite diverse, representing Indian, Egyptian, Nepalese, Pakistani, Bangladeshi, Sri Lankan, and many others.
“Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial”
https://www.ncbi.nlm.nih.gov/pubmed/26993881
The dose of morphine is unrealistically low so I think a lot of drugs would do better. Because of that, their conclusion is unwarranted.
Perhaps; 0.1mg/kg isn't usually trivial, though exceeding it does improve pain control – while also increasing adverse effects. Many factors contribute to the effectiveness of a particular dose of morphine.
Would the results have been much different using, say, 0.15mg/kg morphine? I still think diclofenac would have performed statistically similarly to morphine – which would support their conclusion of potentially using it first-line for suspected renal colic.
Ryan,
Glad to see you reviewed this paper.
All of the drugs seemed to work pretty well. But as you mentioned, the need for rescue analgesia was quite a bit lower in the IM NSAID group. Let's face it, this is probably the best outcome measure of efficacy.
But in the end, will this change practice? Why not give NSAIDS, plus a decent rapid titrated dose of morphine? I can't see what I have been doing for years is broken.
I think intravenous ketorolac is so effective in renal colic that it is nearly diagnostic. I would love to see a study of this. So one might wonder if the NSAIDs when given IV rather than IM might even be better.
I don't want to be overly critical… this was an excellent paper.
Unrealistically low? What do you mean?
That is the standard initial dose for most of us, and certainly the standard dose in most modern pain trials. I think in terms of research standards, 0.1 mg/kg of MS is perfectly appropriate design wise, and given the precedence in the literature using this dose, completely justifies their conclusion.
How much Morphine do you start with?
Tramer et al 1998 (http://www.ncbi.nlm.nih.gov/pubmed/9527748) found that IV NSAIDs acted quickest so I agree it would be good to see this trial using IV ketorolac. There are I think 2 other studies that found IV paracetamol equivalent to this dose of morphine in renal colic. My first line is ketorolac + IV paracetamol. I use opiates 2nd line but it is rare that I need them after that starting combo.