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Three Part Question

[In patients presenting with suspected renal colic to the ED] [is the administration of an intravenous non-steroidal anti-inflammatory drug better than intravenous opioids]at [providing adequate analgesia]?

Clinical Scenario

You are called to see a middle aged man with an acute onset of severe, colicky, left-sided loin pain. Clinical examination rules out peritonitis while urinalysis reveals '+ + +' microscopic haematuria. You strongly suspect a diagnosis of ureteric stone disease.
In such circumstances, impacted renal calculi trigger the production of prostaglandins which subsequently stimulate pain. While opiates can offer pain relief by subduing patients' awareness of these stimuli, NSAID's can actually treat the pathophysiological mechanisms that cause them in the first place. You wonder whether they would be more effective at providing analgesia?

Search Strategy

Medline database using Ovid interface: 1966–November 2005.
The Cochrane Database of Systematic Reviews was also searched.
{{{(exp Injections, Intravenous/ or intravenous. mp.) AND {(exp Analgesics/ or analgesics. mp.) OR (exp Analgesia/ or analgesia. mp.)}} AND {(exp Cyclooxygenase Inhibitors/ or exp Anti-Inflammatory Agents, non-Steroidal/ or exp Anti-Inflammatory Agents/ or non-steroidal anti-inflammatory drugs. mp.) OR (exp Analgesics, Opioid/ or opioid analgesics. mp.)}} AND {(exp Ureter/ or exp. Kidney Diseases/ or exp. Kidney Calculi/ or renal colic. mp. or exp. Ureteral Calculi/ or exp. Urinary Calculi/) OR (Ureteral diseases/ or ureteric colic. mp.)}} LIMIT to human and English Language.
Cochrane: NSAIDS and renal colic.

Search Outcome

230 papers were found of which 225 were irrelevant, of insufficient quality, or concerned drugs that are not licensed for use in the USA and UK, eg. Dipyrone. All five remaining papers had been meta-analysed by the Cochrane Collaboration.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Holdgate A & Pollock T 2004 UK	448 patients taken from 5 prospective, double-blind, randomised control trials. Adults aged 16 -79 who were diagnosed with acute renal/uretertic colic were randomised to receive either IV NSAID or IV Opiate. Patients in whom calculi could not be diagnosed; those who had already taken analgesics; those who passed the offending stone; and those with common CI's to NSAID's were excluded.	Meta-analysis Study 1: (Lehtonen at al, 1983) Indometacin Vs Pethidine Study 2: (Jonsson et al, 1987) Indomethacin Vs Oxycone/Papaverine Study 3: (Curry and Kelly, 1995) Tenoxicam Vs Pethidine Study 4: (Al-Sahlawi and Tawfik, 1996) Indomethacin Vs Aspirin Vs Pethidine Study 5: (Cordell et al, 1996) Ketorolac Vs Meperidine	Effectiveness (based on pain relief scores and/or reduction of pain intensity scores 20-30 min after administration of 1st dose of drug)	Study1: Ind = Peth; Study2: Ind = Oxy/Pap; Study3: Ten = Peth; Study4: Ind > Asp (P = 0.05), Peth > Asp (P = 0.01), Ind = Peth; Study5: Ket > Mep (P < 0.001)	Randomisation details were unclear in Studies 1, 2, and 4. Only Study 5 performed intention-to-treat analysis (NSAID was still more efficacious than Opiate at 30 min, P<0.001). Studies 1 - 4 lack statistical analysis of the differences in additional analgesia requirement & adverse effects between the various groups of drugs.
			% of patients requiring additional analgesia 20 – 30 min after 1st dose of drug	Study1: Ind 21%, Peth 26%; Study2: Ind 54%, Oxy/Pap 73%; Study3: Ten 18%, Peth 17%; Study4: Ind 4%, Asp 26%, Peth 0%; Study5: Ket 64%, Mep 89% (p = 0.04)
			% of patients with adverse effects	Study1: Ind 27%, Peth 55%; Study2: Ind 60%, Peth 73%; Study3: Ten 0%, Peth 18%; Study4: Ind 4%, Asp 0%, Peth 0%; Study5: Ket 37%, Mep 55% (p = 0.07)

Comment(s)

In terms of analgesia, the critical phase in the treatment of acute renal colic is the first 20 -30 minutes after admission. While studies 1 – 4 show no significant advantage in using opiates over NSAID's during this period, Study 5 (Cordell et al, 1996) clearly demonstrates a statistically significant advantage in favour of NSAID's (p = 0.04). This becomes even more significant on an intention-to-treat basis (p<0.001), which of course is the most likely scenario to be encountered in the ED, where the diagnosis will not have been confirmed prior to treatment. Beyond the first 20 – 30 min, Studies 1, 2, 3, and 5 also show that a considerable number of patients in both groups require additional analgesia, but in studies 1, 2, and 5, a greater proportion of opiate patients require it in comparison to NSAID patients (p = 0.04 in Study 5). Study 5 further demonstrates that patients receiving opiates require additional analgesia at earlier times and in greater doses than patients receiving NSAID's (p= 0.004 and p< 0.001, respectively). In terms of adverse effects, Studies 1, 2, 3, and 5 do show that they are more frequently associated with opiates, but not with statistical significance.

Clinical Bottom Line

Intravenous NSAID's should be the first-line treatment for patients presenting to the ED with acute renal colic.

References

1. Holdagate A & Pollock T Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic. The Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD004137.pub3. DOI: 10.1