Renal colic is described as acute onset, flank to groin radiating pain, with or without haematuria, most commonly caused by ureteric calculi. It is described as one of the worst pains a patient can have and results in more than one million emergency department visits in the USA every year.1 In the UK, the National Health Service (NHS), England, health episode statistics data2 for 2012–13 showed 31 000 hospital admissions with a 1 day median stay and an NHS tariff cost of £19·3 million. In the UK and the USA, the incidence of ureteric colic had increased by more than 50% during the previous decade. The prevalence of renal colic is higher in the “stone belt”—the equatorial region, including southeast America, northern Africa, the Middle East, southeastern Asia, and northeastern Australia—where the estimated lifetime prevalence is 10–15%.3 The excruciating pain of patients on presentation requires effective analgesia to be administered in the shortest possible time.
Research in context
Evidence before this study
We did a MEDLINE search until Dec 21, 2015, using the terms “renal colic”, “ureteric colic”, “analgesia”, “ NSAIDs”, “opioids”, “ paracetamol”, and “pain relief” with no data or language restrictions. We identified two Cochrane systematic reviews that had appraised and meta-analysed previous randomised controlled trials of treatment with non-steroidal anti-inflammatory drugs, opioids, and non-opioids in renal colic. Meta-analysis of 20 trials comparing non-steroidal anti-inflammatory drugs against opioids, with 1613 participants, reported that because of unexplained heterogeneity, these results could not be pooled to establish the superiority of a drug. However, non-steroidal anti-inflammatory drugs were less likely to require rescue analgesia (risk ratio 0·75 [95% CI 0·61–0·93]; p= 0·007). Most trials also indicated a higher incidence of nausea and vomiting in the opioid group, although most of these trials used pethidine (meperidine), which is known to have worse adverse effect profiles and is not used frequently in current practice. Additionally, trials comparing intramuscular non-steroidal anti-inflammatory drugs to opioids had been inconclusive because of the challenges associated with concealment of randomisation and masking of assessors.
The second Cochrane review and meta-analysis of 37 studies comparing efficacy of non-steroidal anti-inflammatory drugs versus non-opioids in renal colic was again inconclusive regarding the superiority of any one drug because of the degree of variability in the studies included and the poor study designs. From previously published studies, there was uncertainty regarding the optimum analgesic for renal colic, considering the relative efficacy and safety of opioids, non-steroidal anti-inflammatory drugs, and paracetamol and the ideal route of administration.
Added value of this study
We have overcome deficiencies in previous studies by, first, designing the largest double-blind randomised controlled trial examining analgesia options for renal colic presenting to the emergency department, with robust means of concealment and masking. Second, we chose a clinically relevant and clearly defined patient-oriented primary outcome measure. Third, we tested intravenous and intramuscular routes in a pragmatic approach to consider logistic issues involved in the analgesia administration in busy emergency departments and settings facing bureaucratic challenges to opioid administration. Finally, as per our prespecified protocol, we analysed the data to assess the effectiveness of each analgesic by doing an intention-to-treat analysis, and to assess the efficacy by per-protocol analysis.
Implications of all the available evidence
We have shown that intramuscular diclofenac is superior to intravenous morphine in delivering acute pain relief to patients with renal colic. Intramuscular non-steroidal anti-inflammatory drugs can be safely used as the first-line treatment and offer the fastest, most effective, and sustained relief from renal colic in the emergency setting, and in patients with ureteric calculi; both intramuscular diclofenac and intravenous paracetamol were superior in providing acute analgesia and were associated with fewer adverse events than morphine.
The most common analgesics prescribed for renal colic are non-steroidal anti-inflammatory drugs, opioids, and paracetamol.4, 5 The choice of analgesia is not only established by evidence of its effectiveness but also by the logistics involved in rapid administration.6 On the basis of a few studies,7, 8, 9 intravenous treatment is believed to be more effective than intramuscular administration because of its faster absorption and ease of titration. However, intramuscular injectable non-steroidal anti-inflammatory drugs are commonly used, being technically easier and faster to administer, but use is limited by fears of unpredictable absorption or renal dysfunction, whereas oral pain medications have often been tried at home and take a long time to have an effect.10 Among non-steroidal anti-inflammatory drugs, diclofenac, ketoprofen, and ketorolac are commonly used parenteral preparations and are reported to be equally effective and as safe as each other.11, 12, 13 Although intravenous analgesia is frequently preferred, potential arguments against the use of intravenous opioids for excruciating pain are delays to establishing intravenous access and documentation required for dispensing narcotic analgesia. However, intravenous opioid analgesia has been associated with acute respiratory depression and adverse effects on gastrointestinal motility.14 There has also been increasing concern in developed countries about the misuse of prescription narcotics because of easy availability. Conversely, in developing countries, access to intravenous narcotics is often difficult, with overly bureaucratic restrictions.15
For renal colic, non-steroidal anti-inflammatory drugs have been reported to be better than opioids, in terms of a lower requirement for rescue analgesia and fewer side-effects.5, 16 However, comparators in these studies were pethidine (meperidine) and pentazocine that are known to have better adverse effect profiles than morphine but are less commonly used in standard practice. Additionally, trials comparing intramuscular diclofenac to opioids have been inconclusive because of challenges associated with concealment of randomisation and masking of assessors and participants.5 Paracetamol has been reported to be at least as potent as morphine in some studies, but trials were limited by small sample sizes and the primary outcome being mean difference in pain scores rather than an assessment of individual patient pain relief.17, 18, 19, 20 Clinician preference has been towards intravenous opioids despite potentially taking longer to administer rather than non-opioid alternatives because of the logistics involved.
In light of conflicting evidence and the practice of providing analgesia, we aimed to develop definitive evidence regarding the choice of initial analgesia and route of administration in patients presenting with renal colic to the emergency department. We designed a trial to assess the effectiveness of intramuscular diclofenac, intravenous paracetamol, and intravenous morphine in achieving rapid pain reduction.