Ureteric colic is a common cause of severe pain. Anecdotally, many patients describe it as “the worst pain” they’ve experienced. In the Emergency Department (ED) pain is typically treated with either a non-steroidal anti-inflammatory drugs (NSAIDs) or an opiate or a combination of both. There are limited high-quality studies investigating whether one medication is superior to another or whether the route of medication administration makes a difference. Elucidation of the optimal agent and route would be useful in determining initial management as well as the necessity of placing an intravenous (IV) catheter.
What is the best initial analgesic medication and the optimal route of administration in patients presenting with renal colic to the ED?
Patients > 18 years of age who presented with ureteric colic and a pain scale > 4 on a Numerical pain Rating Scale (NRS).
Each patient received one of the study medications (diclofenac 75 mg IM, morphine 0.1 mg/kg IV and paracetaol 1000 mg IV) followed by two normal saline placebos representing (and appearing identical to) the other medications.
Outcome (Primary): Proportion of patients with at least a 50% reduction in initial pain score at 30 minutes after analgesia administration (the authors performed both an intention-to-treat analysis as well as a per-protocol analysis. The per-protocol analysis included only patients with ureteric calculi on imaging at the index visit)
Outcome (Secondary): Reduction of NRS score > 3 at 30 min, rescue analgesia required, persistent pain at 60 min (NRS > 2), Adverse events.
Double-blind, randomized, controlled trial with three treatment arms
Known allergy to any of the three study medications, history of asthma, known renal or liver failure or impairment, previous study enrollment, pregnancy, pain from trauma or previous analgesia within 6 hours of presentation.
- 1644 patients included in the intention-to-treat analysis
- Diclofenac (n = 547), paracetamol (n = 548), morphine (n = 549)
- 1316 (80%) patients with ureteric calculi detected (per-protocol population)
Table: Primary Outcome (50% reduction in pain @ 30 min) Odds Ratios
|Diclofenac vs. Morphine||1.35*||1.49*|
|Paracetamol vs. Morphine||1.26||1.40*|
*Statistically Significant Finding
- Primary Outcome (50% reduction in pain @ 30 minutes)
- Diclofenac: 68% (371/547)
- Paracetamol: 66% (364/548)
- Morphine: 61% (335/549)
- Dicolofenac: 69% (303/438)
- Paracetamol: 68% (295/435)
- Morphine: 60% (266/443)
- Primary Outcome Comparison
- Intention-to-Treat Analysis
- Diclofenac vs. morphine OR (diclofenac/morphine) 1.35 (CI 1.05-1.73)
- Morphine vs. paracetamol OR (paracetamol/morphine) 1.26 (CI 0.99 – 1.62)
- Per-protocol Analysis
- Diclofenac vs. morphine OR (diclofenac/morphine) 1.49 (CI 1.12-1.97)
- Morphine vs. paracetamol OR (paracetamol/morphine) 1.40 (CI 1.06 – 1.85)
- Need for rescue medication
- Diclofenac: 12% (63/547)
- Paracetamol: 20% (111/548)
- Morphine: 23% (126/549)
- Persistent Pain at 60 min
- Diclofenac: 24% (131/547)
- Paracetamol: 30% (162/548)
- Morphine: 38% (207/549)
- Adverse events
- Morphine 3% (19/549)
- Diclofenac 1% (7/547) (no episodes of renal failure or GI bleeding)
- Paracetamol 1% (7/548)
- Intention-to-Treat Analysis
- Easily the larges randomized trial investigating this particular question
- Randomization and blinding were robust. Each patient received 2 placebos in addition to their active medication
- The primary outcome is patient centered and utilized a validated pain score instrument
- Medications were appropriately dosed in all groups
- Primary outcome assessed in all but one patient (lost data form)
- The authors performed both an intention-to-treat analysis as well as a per-protocol analysis. In this study, 98% of patients had imaging performed and 80% of patients had confirmed stones
- External validity:
- Single center study with mostly young healthy patients
- Vast majority of patients (> 80%) were male bringing into question the external validity
- Primary outcome was short-term pain improvement. The study does not give any information about long-term pain relief
- A 50% pain reduction doesn’t mean the same thing in all patients. A reduction from NRS = 6 to NRS = 3 brings you below the threshold for moderate to severe pain (established as an NRS > 4). However, a reduction from NRS = 10 to NRS = 5 does not. Simply measuring a pain score < 4 at 30 minutes would have been a cleaner primary endpoint.
- Prior studies have shown high efficacy of intravenous NSAIDs (ketorolac) for pain in ureteric colic (Tramer 1998). It would be helpful to see a comparison of IV vs. IM NSAIDs
- Typical management of ureteric colic is with an NSAID AND an opioid. This likely gives better pain relief than either alone but this study does not look at this question.
- This study used diclofenac IM as the parenteral NSAID of choice but in many locations, ketorlac is preferred. Prior studies have shown that ketorlac is equivalent or superior to diclofenac in ureteric colic (Stein 1996, Kolasani 2013)
“Intramuscular non-steroidal anti-inflammatory drugs offer the most effective sustained analgesia for renal colic in the emergency department and seem to have fewer side-effects.”
Based on these results, it appears that an IM NSAID is superior to IV morphine or acetaminophen for the immediate relief of pain from ureteric colic. Additionally, acetaminophen appears equivalent in short-term analgesia to morphine.
Potential Impact To Current Practice
An IM NSAID should be first line therapy for patients presenting with renal colic that do not meet one of the exclusion criteria for this study. It appears that it is unnecessary to place an intravenous line in all patients with ureteric colic for analgesia based on the efficacy of an IM NSAID. Additionally, an IM NSAID can be provided more rapidly to a patient as IV catheter placement time is avoided.
When treating pain in patients with ureteric colic, reach for an IM NSAID unless specific contraindications exist. This approach is effective in relieving pain and may eliminate the need for an IV line in some patients.
EM Lit of Note: NSAIDs Probably Best for Renal Colic
EM Nerd: The Case of the Man Made of Staw
Tramer MR et al. Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by different routes in acute and chronic pain: A qualitative systematic review. Acta Anaesth Scand 1998;42:71-79. PMID: 9527748
Stein A et al. Single-dose intramuscular ketorolac versus diclofenac for pain management in renal colic. Am J Emerg Med 1996; 14: 385-7. PMID: 8768161
Kolasani BP, Juturu J. Intramuscular ketorolac versus diclofenac in acute renal colic: a comparative study of efficacy and safety. Indian J Basic App Med Res 2013; 8(2): 923-31. Link