Bell Samira, Rennie Trijntje, Marwick Charis A, Davey Peter
Renal Unit, NHS Tayside, Ninewells Hospital, Dundee, UK, DD1 9SY.
Cochrane Database Syst Rev. 2018 Nov 29;11(11):CD011274. doi: 10.1002/14651858.CD011274.pub2.
Nonsteroidal anti-inflammatory drugs (NSAIDs) provide effective analgesia during the post-operative period but can cause acute kidney injury (AKI) when used peri-operatively (at or around the time of surgery). This is an update of a Cochrane review published in 2007.
This review looked at the effect of NSAIDs used in the peri-operative period on post-operative kidney function in patients with normal kidney function.
We searched Cochrane Kidney and Transplant's Specialised Register to 4 January 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
All randomised controlled trials (RCTs) and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the use of NSAIDs versus placebo for the treatment of post-operative pain in patients with normal kidney function were included.
Data extraction was carried out independently by two authors as was assessment of risk of bias. Disagreements were resolved by a third author. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). Meta-analyses were used to assess the outcomes of AKI, change in serum creatinine (SCr), urine output, renal replacement therapy (RRT), death (all causes) and length of hospital stay.
We identified 26 studies (8835 participants). Risk of bias was high in 17, unclear in 6and low in three studies. There was high risk of attrition bias in six studies.Only two studies measured AKI. The use of NSAIDs had uncertain effects on the incidence of AKI compared to placebo (7066 participants: RR 1.79, 95% CI 0.40 to 7.96; I = 59%; very low certainty evidence). One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group. Moreover, both of these studies were examining NSAIDs for indications other than analgesia and therefore utilised relatively low doses.Compared to placebo, NSAIDs may slightly increase serum SCr (15 studies, 794 participants: MD 3.23 μmol/L, 95% CI -0.80 to 7.26; I = 63%; low certainty evidence). Studies displayed moderate to high heterogeneity and had multiple exclusion criteria including age and so were not representative of patients undergoing surgery. Three of these studies excluded patients if their creatinine rose post-operatively.NSAIDs may make little or no difference to post-operative urine output compared to placebo (6 studies, 149 participants: SMD -0.02, 95% CI -0.31 to 0.27). No reliable conclusions could be drawn from these studies due to the differing units of measurements and measurement time points.It is uncertain whether NSAIDs leads to the need for RRT because the certainty of this evidence is very low (2 studies, 7056 participants: RR 1.57, 95% CI 0.49 to 5.07; I = 26%); there were few events and the results were inconsistent.It is uncertain whether NSAIDs lead to more deaths (2 studies, 312 participants: RR 1.44, 95% CI 0.19 to 11.12; I = 38%) or increased the length of hospital stay (3 studies, 410 participants: MD 0.12 days, 95% CI -0.48 to 0.72; I = 24%).
AUTHORS' CONCLUSIONS: Overall NSAIDs had uncertain effects on the risk of post-operative AKI, may slightly increase post-operative SCr, and it is uncertain whether NSAIDs lead to the need for RRT, death or increases the length of hospital stay. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further larger studies using the Kidney Disease Improving Global Outcomes definition for AKI including patients with co-morbidities are required to confirm these findings. .
非甾体抗炎药（NSAIDs）在术后阶段可提供有效的镇痛作用，但围手术期（手术时或手术前后）使用时可导致急性肾损伤（AKI）。这是2007年发表的一篇Cochrane系统评价的更新版。
本系统评价旨在探讨围手术期使用NSAIDs对肾功能正常患者术后肾功能的影响。
我们通过与信息专家联系，使用与本系统评价相关的检索词，检索了截至2018年1月4日的Cochrane肾脏和移植专业注册库。专业注册库中的研究通过检索Cochrane系统评价数据库、MEDLINE、EMBASE、会议论文集、国际临床试验注册平台（ICTRP）检索入口以及ClinicalTrials.gov来识别。
纳入所有比较NSAIDs与安慰剂用于治疗肾功能正常患者术后疼痛的随机对照试验（RCT）和半随机对照试验（通过交替分配、使用交替病历、出生日期或其他可预测方法进行治疗分配的RCT）。
由两位作者独立进行数据提取以及偏倚风险评估。分歧由第三位作者解决。二分变量结果以相对危险度（RR）报告，连续变量结果以均差（MD）及其95%置信区间（CI）报告。采用Meta分析评估AKI、血清肌酐（SCr）变化、尿量、肾脏替代治疗（RRT）、死亡（各种原因）和住院时间的结果。
我们纳入了26项研究（8835名参与者）。17项研究的偏倚风险高，6项研究偏倚风险不明确，3项研究偏倚风险低。6项研究存在高失访偏倚风险。仅两项研究测量了AKI。与安慰剂相比，使用NSAIDs对AKI发生率的影响不确定（7066名参与者：RR 1.79，95%CI 0.40至7.96；I² = 59%；极低确定性证据）。一项研究因NSAIDs组AKI发生率增加，被数据监测委员会提前终止。此外，这两项研究均考察NSAIDs用于镇痛以外的适应证，因此使用的剂量相对较低。与安慰剂相比，NSAIDs可能会使血清SCr略有升高（15项研究，794名参与者：MD 3.23 μmol/L，95%CI -0.80至7.26；I² = 63%；低确定性证据）。研究显示中度至高度异质性，并有包括年龄在内的多个排除标准。因此，这些研究不具有手术患者的代表性。其中三项研究如果患者术后肌酐升高则将其排除。与安慰剂相比，NSAIDs对术后尿量可能几乎没有影响或无差异（6项研究, 149名参与者：标准化均差 -0.02，95%CI -0.31至0.27）。由于测量单位和测量时间点不同，这些研究无法得出可靠结论。NSAIDs是否导致需要进行RRT尚不确定，因为此证据的确定性非常低（2项研究，7056名参与者：RR 1.57，95%CI 0.49至5.07；I² = 26%）；事件很少，结果不一致。NSAIDs是否导致更多死亡（2项研究，312名参与者：RR 1.44，95%CI 0.19至11.12；I² = 38%）或延长住院时间（3项研究，410名参与者：MD 0.12天，95%CI -0.48至0.72；I² = 24%）尚不确定。
总体而言，NSAIDs对术后AKI风险的影响不确定，可能会使术后SCr略有升高，NSAIDs是否导致需要进行RRT、死亡或延长住院时间尚不确定。因此，现有数据不能证实NSAIDs在手术患者中的安全性。需要进一步开展更大规模的研究，采用改善全球肾脏病预后组织（KDIGO）对AKI的定义，纳入合并症患者，以证实这些发现。
