A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic☆
Renal colic is a common, acute presentation of urolithiasis that requires immediate pain relief. European Association of Urology guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) as the preferred analgesia. However, the fear of NSAID adverse effects and the uncertainty about superior analgesic effect have maintained the practice of advocating intravenous opioids as the initial analgesia.
Objective
The objective of this systematic review and meta-analysis was to compare the safety and efficacy of NSAIDs with opioids and paracetamol (acetaminophen) for the management of acute renal colic.
Evidence acquisition
Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, Google Scholar, and the reference list of retrieved articles were searched up to December 2016 without language restrictions. Two reviewers independently assessed eligible studies using the Cochrane Collaboration tool for assessing and reporting the risk of bias and abstracted data using predefined data fields.
Evidence synthesis
From 468 potentially relevant studies, 36 randomized controlled trials (RCTs) including 4887 patients, published between 1982 and 2016, were included in this systematic review. The treatment effect observed indicated marginal benefit of NSAIDs over opioids in initial pain reduction at 30 min (11 RCTs, n = 1985, mean difference [MD] –5.58, 95% confidence interval [CI] –10.22 to –0.95; heterogeneity I2 = 81%). In the subgroup analyses by the route of administration, NSAIDs required fewer rescue treatments (seven RCTs, n = 541, number needed to treat [NNT] 11, 95% CI 6–75) and had lower vomiting rates compared with opioids (five RCTs, n = 531, NNT 5, 95% CI 4–8). Comparisons of NSAIDs with paracetamol showed no difference for both drugs at 30 min (four RCTs, n = 1325, MD –5.67, 95% CI –17.52 to 6.18, p = 0.35; I2 = 89%). Patients treated with NSAIDs required fewer rescue treatments (two trials, n = 1145, risk ratio 0.56, 95% CI 0.42–0.74, p < 0.001; I2 = 0%).
Conclusions
NSAIDs were equivalent to opioids or paracetamol in the relief of acute renal colic pain at 30 min. There was less vomiting and fewer requirements for rescue analgesia with NSAIDs compared with opioids. Patients treated with NSAIDs required less rescue analgesia compared with paracetamol. Despite observed heterogeneity among the included studies and the overall quality of evidence, the findings of a lower need for rescue analgesia and fewer adverse events, in conjunction with the practical advantages of ease of delivery, suggest that NSAIDs should be the preferred analgesic option for patients presenting to the emergency department with renal colic.
Patient summary
In kidney stone–related acute pain episodes in patients with adequate renal function, treatment with nonsteroidal anti-inflammatory drugs offers effective and most sustained pain relief, with fewer side effects, when compared with opioids or paracetamol.
Introduction
Renal colic is a common abdominal complaint with millions of emergency department visits worldwide due to excruciating pain. The reported prevalence of kidney stone varies widely from 0.1% to 18.5% [1], with a recurrence of stone in about 50% of cases over 5–10 yr.
Acute pain management is the main expectation of patients in severe pain from renal colic. The most important factors deciding the choice of initial analgesia include the safety, efficacy, cost, and availability of a drug, in addition to patient and clinician preferences [2]. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been recommended as the first-line analgesic [3], [4], [5], [6] based on the mechanism of action of prostaglandin synthesis inhibition and supported by the evidence of effectiveness [7]. However, NSAID use as the first-line analgesic in clinical practice has repeatedly been challenged, and many clinicians continue to prefer opioid treatment [8], [9]. The practice of using opioids as the preferred analgesic in renal colic is advocated based on the advantage of titrating the dose according to pain severity and lack of adverse events such as renal failure and gastrointestinal (GI) bleeding reported with NSAID treatment [8]. Following the last Cochrane review [7] concluding that NSAID treatment achieved higher pain reductions with a superior adverse effect profile compared with opioids, some randomized controlled trials (RCTs) with contrary evidence have been published [10], [11], [12]. In addition, alternative analgesics including paracetamol have been studied. Paracetamol (acetaminophen) has been reported to provide equal [13], [14] or better [15], [16] analgesia than opioids for the treatment of renal colic.
The uncertainty evident in current clinical practice requires an assessment review of the efficacy and safety of analgesics commonly used in renal colic. Therefore, we aimed to compare the efficacy and safety of NSAIDs against opioids or paracetamol for the management of acute renal colic.
Section snippets
Evidence acquisition
The protocol for this systematic review was registered on PROSPERO (CRD42016047559), and the detailed methodology was published [17] following the Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations for reporting of protocols (PRISMA-P).
Quantity of evidence identified
A total of 36 RCTs [10], [11], [12], [16], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55] (including 4887 patients), published from 16 countries between 1982 and 2016, were included in this systematic review (Fig. 1). Five articles were published in non-English literature (three in Spanish [30], [43], [46], one in Norwegian [29], and one in Danish [40]
Conclusions
NSAIDs were at least equivalent to opioids and paracetamol for the relief of acute renal colic pain at 30 min after delivery. There was less vomiting and fewer requirements for rescue analgesia compared with opioids. NSAIDs required less rescue analgesia compared with paracetamol. Despite observed heterogeneity among the included studies and the overall quality of evidence, the findings of lower need for rescue analgesia and fewer adverse events, in conjunction with the practical advantages of
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The integration of acupuncture with intramuscular injection of diclofenac sodium can expedite the onset of analgesia in treating acute renal colic caused by urolithiasis. However, it remains unclear whether acupuncture can accelerate pain relief constantly until complete remission. This study aimed to explore the extent to which acupuncture can expedite the onset time of response or complete pain relief in treating acute renal colic, and the predictive value of patient characteristics for treatment efficacy.
This secondary analysis utilized data from a prior randomized controlled trial. Eighty patients with acute renal colic were randomly assigned 1:1 to the acupuncture group or the sham acupuncture group. After intramuscular injection of diclofenac sodium, acupuncture or sham acupuncture was delivered to patients. The outcomes included time to response (at least a 50 % reduction in pain) and complete pain relief. Between-group comparison under the 2 events was estimated by Kaplan-Meier methodology. Subgroup analysis was performed utilizing the Cox proportional hazards model.
The median response time and complete pain relief time in the acupuncture group were lower than those in the sham acupuncture group (5 vs 30 min, Log Rank P < 0.001; 20 min vs not observed, Log Rank P < 0.001, respectively). Hazard Ratios (HRs) for response across all subgroups favored the acupuncture group. All HRs for complete pain relief favored acupuncture, expect large stone and moderate pain at baseline. No interaction was found in either event.
Acupuncture can accelerate the response time and complete pain relief time for patients with acute renal colic, with the efficacy universally.
This study has been registered at Chinese Clinical Trial Registry: ChiCTR1900025202.
The optimal pain relief method for acute renal colic in the emergency department remains controversial.
We compared the safety and efficacy of intradermal sterile water injection (ISWI) to treatment with intramuscular (IM) diclofenac, intravenous (IV) opioids, and IV paracetamol in patients with acute renal colic.
This randomized, single-blind study included 320 patients with renal colic to one of four treatment groups. The first group received ISWI at four different points around the most painful flank area. Patients in the DI, PARA, and TRAM groups received 75 mg IM diclofenac, 1 g IV paracetamol, and 100 mg IV tramadol, respectively. Pain intensity was measured using a visual analog scale (VAS) before treatment and 15, 30, and 60 min after treatment.
VAS scores 15 and 30 min after treatment were significantly lower in group ISWI than in groups DI, PARA, and TRAM. However, there were no significant differences in the decrease in the pain score at baseline and at 60 min after treatment. In addition, fewer patients required rescue analgesia in group ISWI than in group TRAM. However, no significant differences were observed between group ISWI and group DI or PARA in terms of the need for rescue analgesia. Finally, there were significantly fewer adverse events in group ISWI than in groups DI and TRAM.
ISWI had similar efficacy, faster pain relief, and lower need for rescue analgesia compared with diclofenac, paracetamol, and tramadol for the management of acute renal colic. In addition, ISWI was well-tolerated and had no adverse effects.
El cólico nefrítico es una consulta frecuente en los servicios de urgencias, se trata de un dolor severo y limitante que necesita atención urgente y, en muchos casos, medicación parenteral. Se deben hacer estudios complementarios que incluyan analítica de sangre y orina y pruebas de imagen para descartar complicaciones que necesiten de cirugía urgente con descompresión de la vía urinaria, utilizando nefrostomía percutánea o ureteroscopia con stents. El tratamiento analgésico es el pilar principal, y se basa en el uso de antiinflamatorios no esteroideos, en primer lugar, y opiáceos según la respuesta clínica de cada paciente. Se utiliza también tratamiento facilitador expulsivo con tamsulosina. La mayoría de los pacientes pueden ser dados de alta con revisión en consultas de atención primaria y/o urología para su tratamiento definitivo.
Renal colic is a common consultation in emergency departments. It is severe, limiting pain that requires urgent care and, in many cases, parenteral medication. Additional tests must be done, including a blood test, urinalysis, and imaging tests, to rule out complications that necessitate urgent surgery with decompression of the urinary tract through percutaneous nephrostomy or ureteroscopy with stents. Analgesic treatment is the main pillar and is based on the use of non-steroidal anti-inflammatory drugs first and opioids according to each patient's clinical response. Expulsive treatment with tamsulosin is also used. Most patients can be discharged with a follow-up appointment in the primary care and/or urology department for definitive treatment.
The acute situation, caused by an obstructive stone, is defined by a renal colic that may be uncomplicated, complicated, or at risk in specific conditions. Its management may be medical or require interventional treatment by extracorporeal shockwave lithotripsy, endoscopic removal, or ureteroscopy.
These recommendations were developed using two methods, the Clinical Practice Recommendations (CPR) and the ADAPTE method, in function of whether the question was considered in the European Association of Urology (EAU) recommendations (https://uroweb.org/guidelines/urolithiasis) [EAU Guidelines on urolithiasis. 2022] and whether they could be adapted to the French context.
La situation aiguë, liée à un calcul obstructif, se manifeste par une colique néphrétique qui peut être simple, compliquée ou à risque sur terrain particulier. Son traitement peut être seulement médical ou avoir recours à un traitement interventionnel par Lithotripsie extra corporelle (LEC), drainage endoscopique ou urétéroscopie.
Ces recommandations ont été élaborées selon deux méthodes : la méthode Recommandation pour la pratique clinique (RPC) et la méthode ADAPTE, en fonction de la considération ou non de la question dans les recommandations de l’EAU (https://uroweb.org/guidelines/urolithiasis) [EAU Guidelines on urolithiasis. 2022] et de leur adaptabilité au contexte français.
Renal colic is a disease in which a calculus obstructs the urinary tract, resulting in severe pain do ureteric peristaltic movements. Other symptoms, such as hematuria, nausea, and vomiting, may accompany the pain. This network meta-analysis aimed to compare the efficacy and safety of different analgesic agents for the treatment of acute renal colic.
Medline, Embase, and CENTRAL databases were searched. Randomized controlled trials (RCTs) that compared different analgesic agents, either alone or in combination were included. For the management of acute renal colic, analgesic agents were selected based on the current standard medical practice. The medications included intravenous acetaminophen, ketamine, ketorolac, and morphine. This study sought to evaluate the pain score on the visual analog scale (VAS) at 15, 30, and 60 min; adverse events; and the utilization of rescue therapy. The efficacy of different analgesic agents was explored through a frequentist network meta-analysis using the Netmeta statistical package in R software. All treatments were ranked using the Netrank function, yielding P-scores.
Twelve RCTs were deemed eligible. As per the P-scores, acetaminophen was the most effective in reducing pain score at 15 min (P-score = 0.74). Ketorolac was the most effective in reducing the pain score at 30 and 60 min (P-score = 0.84) (P-score = 0.99), whereas morphine was the least effective (P-score = 0.07). Moreover, morphine was correlated with the highest odds of adverse events after treatment (P-score = 0.89). Morphine was the most frequently required rescue therapy in cases of suboptimal pain relief (P-score = 0.96).
This network meta-analysis demonstrated that ketorolac and acetaminophen were the most effective analgesic agents according to the pain score. Morphine showed the highest adverse event profile and the highest rate at which rescue therapy was required for the management of acute renal colic.
Different international associations have proposed their own guidelines on urolithiasis. However, the focus is primarily on an overview of the principles of urolithiasis management rather than step-by-step technical details for the procedure. The International Alliance of Urolithiasis (IAU) is releasing a series of guidelines on the management of urolithiasis. The current guideline on shockwave lithotripsy (SWL) is the third in the IAU guidelines series and provides a clinical framework for urologists and technicians performing SWL. A total of 49 recommendations are summarized and graded, covering the following aspects: indications and contraindications; preoperative patient evaluation; preoperative medication; prestenting; intraoperative analgesia or anesthesia; intraoperative position; stone localization and monitoring; machine and energy settings; intraoperative lithotripsy strategies; auxiliary therapy following SWL; evaluation of stone clearance; complications; and quality of life. The recommendations, tips, and tricks regarding SWL procedures summarized here provide important and necessary guidance for urologists along with technicians performing SWL.
For kidney and urinary stones of less than 20 mm in size, shockwave lithotripsy (SWL) is an approach in which the stone is treated with shockwaves applied to the skin, without the need for surgery. Our recommendations on technical aspects of the procedure provide guidance for urologists and technicians performing SWL.
