围手术期阿司匹林和可乐定与急性肾损伤风险：一项随机临床试验。

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

机构信息

London Health Sciences Centre and Western University, London, Ontario, Canada.

Cleveland Clinic, Cleveland, Ohio.

出版信息

JAMA. 2014 Dec 3;312(21):2254-64. doi: 10.1001/jama.2014.15284.

DOI:10.1001/jama.2014.15284

PMID:25399007

Abstract

IMPORTANCE

Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.

OBJECTIVE

To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury.

DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013.

INTERVENTIONS

Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery.

MAIN OUTCOMES AND MEASURES

Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery.

RESULTS

Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58).

CONCLUSIONS AND RELEVANCE

Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01082874.

摘要

背景

急性肾损伤是手术常见的并发症，与不良预后和高医疗成本相关。一些研究表明，围手术期给予阿司匹林或可乐定可降低急性肾损伤的风险；然而，这些影响尚不确定，每种干预措施都有可能造成伤害。

目的

确定阿司匹林与安慰剂相比，可乐定与安慰剂相比，是否改变围手术期急性肾损伤的风险。

设计、设置和参与者：这是一项在 88 个中心的 22 个国家开展的、6905 例非心脏手术患者的 2×2 析因随机、双盲、临床试验，连续患者于 2011 年 1 月至 2013 年 12 月期间入组。

干预措施

患者被分配服用阿司匹林（200 mg）或安慰剂，于术前 2 至 4 小时；然后阿司匹林（100 mg）或安慰剂，每天一次，持续至术后 30 天。患者还被分配服用口服可乐定（0.2 mg）或安慰剂，于术前 2 至 4 小时；然后使用透皮可乐定贴片（每片提供 0.2 mg/d 的可乐定）或安慰剂贴片，直至术后 72 小时。

主要结局和测量指标

急性肾损伤主要定义为手术 48 小时内血清肌酐浓度较术前浓度增加 0.3 mg/dL 或更多（≥26.5 μmol/L），或 7 天内增加 50%或更多。

结果

与安慰剂相比，阿司匹林（n=3443）并未改变急性肾损伤的风险（分别为 13.4%和 12.3%；调整后相对风险，1.10；95%CI，0.96-1.25）。可乐定（n=3453）与安慰剂（n=3452）相比，也未改变急性肾损伤的风险（分别为 13.0%和 12.7%；调整后相对风险，1.03；95%CI，0.90-1.18）。阿司匹林增加了大出血的风险。在一项事后分析中，大出血与随后发生急性肾损伤的风险增加相关（存在出血时为 23.3%，不存在出血时为 12.3%；调整后危险比，2.20；95%CI，1.72-2.83）。同样，可乐定增加了临床重要性低血压的风险。在一项事后分析中，临床重要性低血压与随后发生急性肾损伤的风险增加相关（低血压存在时为 14.3%，不存在时为 11.8%；调整后危险比，1.34；95%CI，1.14-1.58）。