Afshar Kourosh, Jafari Siavash, Marks Andrew J, Eftekhari Arash, MacNeily Andrew E
Department of Urology, University of British Columbia, British Columbia's Children's Hospital, Children's Ambulatory Care Building, Urology Clinic, K0-134, 4480 Oak Street, Vancouver, BC, Canada, V6H 3V4.
Cochrane Database Syst Rev. 2015 Jun 29;2015(6):CD006027. doi: 10.1002/14651858.CD006027.pub2.
Renal colic is acute pain caused by urinary stones. The prevalence of urinary stones is between 10% and 15% in the United States, making renal colic one of the common reasons for urgent urological care. The pain is usually severe and the first step in the management is adequate analgesia. Many different classes of medications have been used in this regard including non-steroidal anti-inflammatory drugs and narcotics.
The aim of this review was to assess benefits and harms of different NSAIDs and non-opioids in the treatment of adult patients with acute renal colic and if possible to determine which medication (or class of medications) are more appropriate for this purpose. Clinically relevant outcomes such as efficacy of pain relief, time to pain relief, recurrence of pain, need for rescue medication and side effects were explored.
We searched the Cochrane Renal Group's Specialised Register (to 27 November 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
Only randomised or quasi randomised studies were included. Other inclusion criteria included adult patients with a clinical diagnosis of renal colic due to urolithiasis, at least one treatment arm included a non-narcotic analgesic compared to placebo or another non-narcotic drug, and reporting of pain outcome or medication adverse effect. Patient-rated pain by a validated tool, time to relief, need for rescue medication and pain recurrence constituted the outcomes of interest. Any adverse effects (minor or major) reported in the studies were included.
Abstracts were reviewed by at least two authors independently. Papers meeting the inclusion criteria were fully reviewed and relevant data were recorded in a standardized Cochrane Renal Group data collection form. For dichotomous outcomes relative risks and 95% confidence intervals were calculated. For continuous outcomes the weighted mean difference was estimated. Both fixed and random models were used for meta-analysis. We assessed the analgesic effects using four different outcome variables: patient-reported pain relief using a visual analogue scale (VAS); proportion of patients with at least 50% reduction in pain; need for rescue medication; and pain recurrence. Heterogeneity was assessed using the I² test.
A total of 50 studies (5734 participants) were included in this review and 37 studies (4483 participants) contributed to our meta-analyses. Selection bias was low in 34% of the studies or unclear in 66%; performance bias was low in 74%, high in 14% and unclear in 12%; attrition bias was low in 82% and high in 18%; selective reporting bias low in 92% of the studies; and other biases (industry funding) was high in 4%, unclear in 18% and low in 78%.Patient-reported pain (VAS) results varied widely with high heterogeneity observed. For those comparisons which could be pooled we observed the following: NSAIDs significantly reduced pain compared to antispasmodics (5 studies, 303 participants: MD -12.97, 95% CI -21.80 to - 4.14; I² = 74%) and combination therapy of NSAIDs plus antispasmodics was significantly more effective in pain control than NSAID alone (2 studies, 310 participants: MD -1.99, 95% CI -2.58 to -1.40; I² = 0%).NSAIDs were significantly more effective than placebo in reducing pain by 50% within the first hour (3 studies, 197 participants: RR 2.28, 95% CI 1.47 to 3.51; I² = 15%). Indomethacin was found to be less effective than other NSAIDs (4 studies, 412 participants: RR 1.27, 95% CI 1.01 to 1.60; I² = 55%). NSAIDs were significantly more effective than hyoscine in pain reduction (5 comparisons, 196 participants: RR 2.44, 95% CI 1.61 to 3.70; I² = 28%). The combination of NSAIDs and antispasmodics was not superior to NSAIDs only (9 comparisons, 906 participants: RR 1.00, 95% CI 0.89 to 1.13; I² = 59%). The results were mixed when NSAIDs were compared to other non-opioid medications.When the need for rescue medication was evaluated, Patients receiving NSAIDs were significantly less likely to require rescue medicine than those receiving placebo (4 comparisons, 180 participants: RR 0.35, 95% CI 0.20 to 0.60; I² = 24%) and NSAIDs were more effective than antispasmodics (4 studies, 299 participants: RR 0.34, 95% CI 0.14 to 0.84; I² = 65%). Combination of NSAIDs and antispasmodics was not superior to NSAIDs (7 comparisons, 589 participants: RR 0.99, 95% CI 0.62 to 1.57; I² = 10%). Indomethacin was less effective than other NSAIDs (4 studies, 517 participants: RR 1.36, 95% CI 0.96 to 1.94; I² = 14%) except for lysine acetyl salicylate (RR 0.15, 95% CI 0.04 to 0.65).Pain recurrence was reported by only three studies which could not be pooled: a higher proportion of patients treated with 75 mg diclofenac (IM) showed pain recurrence in the first 24 hours of follow-up compared to those treated with 40 mg piroxicam (IM) (60 participants: RR 0.05, 95% CI 0.00 to 0.81); no significant difference in pain recurrence at 72 hours was observed between piroxicam plus phloroglucinol and piroxicam plus placebo groups (253 participants: RR 2.52, 95% CI 0.15 to12.75); and there was no significant difference in pain recurrence within 72 hours of discharge between IM piroxicam and IV paracetamol (82 participants: RR 1.00, 95% CI 0.65 to 1.54).Side effects were presented inconsistently, but no major events were reported.
AUTHORS' CONCLUSIONS: Although due to variability in studies (inclusion criteria, outcome variables and interventions) and the evidence is not of highest quality, we still believe that NSAIDs are an effective treatment for renal colic when compared to placebo or antispasmodics. The addition of antispasmodics to NSAIDS does not result in better pain control. Data on other types of non-opioid, non-NSAID medication was scarce.Major adverse effects are not reported in the literature for the use of NSAIDs for treatment of renal colic.
肾绞痛是由尿路结石引起的急性疼痛。在美国,尿路结石的患病率在10%至15%之间,这使得肾绞痛成为紧急泌尿科护理的常见原因之一。疼痛通常很严重,治疗的第一步是充分镇痛。在这方面已经使用了许多不同种类的药物,包括非甾体抗炎药和麻醉药。
本综述的目的是评估不同非甾体抗炎药和非阿片类药物在治疗成年急性肾绞痛患者中的益处和危害,并在可能的情况下确定哪种药物(或药物类别)更适合此目的。探讨了疼痛缓解疗效、疼痛缓解时间、疼痛复发、急救药物需求和副作用等临床相关结局。
我们通过与试验检索协调员联系,使用与本综述相关的检索词检索了Cochrane肾脏组专业注册库(至2014年11月27日)。
仅纳入随机或半随机研究。其他纳入标准包括临床诊断为尿路结石引起肾绞痛的成年患者,至少一个治疗组包括与安慰剂或另一种非麻醉药物相比的非麻醉性镇痛药,以及疼痛结局或药物不良反应的报告。通过经过验证的工具进行的患者自评疼痛、缓解时间、急救药物需求和疼痛复发构成了感兴趣的结局。纳入研究中报告的任何不良反应(轻微或严重)均包括在内。
摘要由至少两名作者独立审查。符合纳入标准的论文进行了全面审查,并将相关数据记录在标准化的Cochrane肾脏组数据收集表中。对于二分法结局,计算相对风险和95%置信区间。对于连续结局,估计加权平均差。固定模型和随机模型均用于荟萃分析。我们使用四个不同的结局变量评估镇痛效果:使用视觉模拟量表(VAS)患者报告的疼痛缓解;疼痛至少减轻50%的患者比例;急救药物需求;以及疼痛复发。使用I²检验评估异质性。
本综述共纳入50项研究(5734名参与者),37项研究(4483名参与者)纳入我们的荟萃分析。34% 的研究选择偏倚低,66% 不清楚;74% 的研究实施偏倚低,14% 高,12% 不清楚;82% 的研究失访偏倚低以及18% 高;92% 的研究选择性报告偏倚低;4% 的研究存在其他偏倚(行业资助)高,18% 不清楚,78% 低。患者报告的疼痛(VAS)结果差异很大,观察到高度异质性。对于那些可以合并的比较,我们观察到以下情况:与解痉药相比,非甾体抗炎药显著减轻疼痛(5项研究,303名参与者:MD -12.97,95% CI -21.80至-4.14;I² = 74%),非甾体抗炎药加解痉药的联合治疗在疼痛控制方面比单独使用非甾体抗炎药显著更有效(2项研究,310名参与者:MD -1.99,95% CI -2.58至-1.40;I² = 0%)。在第一小时内,非甾体抗炎药在将疼痛减轻50%方面显著比安慰剂更有效(3项研究,197名参与者:RR 2.28,95% CI 1.47至3.51;I² = 15%)。发现吲哚美辛比其他非甾体抗炎药效果差(4项研究,412名参与者:RR 1.27,95% CI 1.01至1.60;I² = 55%)。在减轻疼痛方面,非甾体抗炎药比东莨菪碱显著更有效(5项比较,196名参与者:RR 2.44,95% CI 1.61至3.70;I² = 28%)。非甾体抗炎药和解痉药的联合使用并不优于仅使用非甾体抗炎药(9项比较,906名参与者:RR 1.00,95% CI 0.89至1.13;I² = 59%)。当非甾体抗炎药与其他非阿片类药物比较时,结果不一。当评估急救药物需求时,接受非甾体抗炎药的患者比接受安慰剂的患者显著更不需要急救药物(4项比较,180名参与者:RR 0.35,95% CI 0.20至0.60;I² = 24%),并且非甾体抗炎药比解痉药更有效(4项研究,299名参与者:RR 0.34,95% CI 0.14至0.84;I² = 65%)。非甾体抗炎药和解痉药的联合使用并不优于非甾体抗炎药(7项比较,589名参与者:RR 0.99,95% CI 0.62至1.57;I² = 10%)。吲哚美辛比其他非甾体抗炎药效果差(4项研究,517名参与者:RR 1.36,95% CI 0.96至1.94;I² = 14%),除了赖氨酸乙酰水杨酸(RR 0.15,95% CI 0.04至0.65)。只有三项研究报告了疼痛复发,无法合并:与接受40mg吡罗昔康(肌肉注射)治疗的患者相比,接受75mg双氯芬酸(肌肉注射)治疗的患者在随访的前24小时内疼痛复发比例更高(60名参与者:RR 0.05,至95% CI 0.00至0.81);吡罗昔康加间苯三酚组和吡罗昔康加安慰剂组在72小时时疼痛复发无显著差异(253名参与者:RR 2.52,95% CI 0.15至12.75);肌肉注射吡罗昔康和静脉注射对乙酰氨基酚在出院后72小时内疼痛复发无显著差异(82名参与者:RR 1.00,95% CI 0.65至1.54)。副作用报告不一致,但未报告重大事件。
尽管由于研究存在变异性(纳入标准、结局变量和干预措施)且证据质量不是最高的,但我们仍然认为与安慰剂或解痉药相比,非甾体抗炎药是治疗肾绞痛的有效方法。在非甾体抗炎药中添加解痉药并不能更好地控制疼痛。关于其他类型非阿片类、非非甾体抗炎药药物的数据很少。文献中未报告使用非甾体抗炎药治疗肾绞痛的重大不良反应。