Increasing Nonsteroidal Anti-inflammatory Drugs and Reducing Opioids or Paracetamol in the Management of Acute Renal Colic: Based on Three-Stage Study Design of Network Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Currently, although non-steroidal anti-inflammatory drugs (NSAIDs) were recommended for acute renal colic in the 2018 European Association of Urology guidelines, there are no specific NSAIDs and no specific routes of administration in this guideline. The clinical practice of advocating intravenous opioids as the initial analgesia is still common out of the fear of adverse events from NSAIDs. Objectives: To comprehensively assess the efficacy and safety of NSAIDs, opioids, paracetamol, and combination therapy for acute renal colic. Methods: Ovid MEDLINE, Ovid EMbase, the Cochrane Library, Clinical Trials Registry Platform for Clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched through February 2, 2018. Two reviewers selected all randomized controlled trails (RCTs) regarding NSAIDs, opioids, paracetamol, combination therapy, and placebo were identified for analysis. We designed a three-stage strategy based on classification and pharmacological mechanisms in the first stage, routes of administration in the second stage, and specific drug branches with different routes in the third stage using network meta-analysis. The pain variance at 30 min was seen as the primary outcome. Results: 65 RCTs with 8633 participants were involved. Comparing different classification and pharmacological mechanisms, combination therapy with more adverse events was more efficient than NSAIDs for the primary outcomes. Opioids gave rise to more nonspecific adverse events and vomiting events. NSAIDs were superior to opioids, paracetamol, and combination therapy after a full consideration of all outcomes. Comparing different routes of administration, NSAIDs with IV or IM route ranked first from efficacy and safety perspective. Comparing different specific drug branches with different routes, ibuprofen via IV route, ketorolac via IV route and diclofenac via IM route were superior for the management of acute renal colic. The results from diclofenac using IM route were more than those from ibuprofen used with IV route and ketorolac with IV route. Conclusions: In patients with adequate renal function, diclofenac via the IM route is recommended for patients without risks of cardiovascular events. Ibuprofen and ketorolac with IV route potentially superior to diclofenac via IM route remain to be investigated. Combination therapy is an alternative choice for uncontrolled pain after the use of NSAIDs.

Intravenous morphine plus ibuprofen or ketorolac versus intravenous morphine alone in reducing renal colic pain intensity in emergency department: A randomized, double-blind clinical trial

“…showed that in the most studies, NSAIDs like ibuprofen or ketorolac were the better choice of acute renal colic management because of lower adverse effects compared to opioids alone or combination of both. [ 11 ] Different kinds of administration, different dose of morphine, and different kind of NSAIDs used in this systematic review illustrate the different findings.…”

“…revealed that in the most of the studies, NSAIDs were more effective in more than 50% renal colic pain relief than opioids, combination of both or placebo and the superiority of NSAIDs could be its direct effect on inhibition of cyclooxygenase enzyme, but the combination therapy had significant priority compared to monotherapy in patients with uncontrollable renal colic pain with NSAIDs alone also in comparison of all outcomes including pain variance at 30 min, rescue analgesic requirements and acute adverse effects. [ 11 ]…”

“…[ 7 9 ] Various studies recommended that NSAIDs as appropriate and effective alternatives reported lower adverse effects, alone or in combination with opioids for alleviating renal colic pain. [ 10 11 ] NSAIDs can control renal colic pain by reducing the glomerular filtration rate, renal pelvic pressure, ureteric peristalsis, edema, and inflammation. [ 7 12 13 ] The efficacy of the combination of NSAIDs and morphine in renal colic pain management is still at a matter of debate.…”

“…[ 15 ] A review of 65 randomized clinical trials (RCTs) showed that the combination of NSAIDs and morphine was more effective in the reduction of renal colic pain at 30 min, but NSAIDS had priority to morphine and combination therapy at full consideration of all outcomes. [ 11 ]…”

Effects of adding oral clonidine to standard treatments on pain intensity of patients with acute renal colic: A randomized clinical trial

“…The use of NSAIDs also has advantages and disadvantages. [ 7 8 ] These drugs inhibit prostaglandins and as mentioned above, prostaglandins play an important role in the development of renal colic. Disadvantages of these drugs include increasing the chances of kidney failure and gastrointestinal bleeding.…”