Background

The effect of nitric oxide (NO) on renal function is controversial in critical illness. We performed a systematic meta-analysis and trial sequential analysis to determine the effect of NO gas on renal function and other clinical outcomes in patients requiring cardiopulmonary bypass (CPB). The primary outcome was the relative risk (RR) of acute kidney injury (AKI), irrespective of the AKI stage. The secondary outcome was the mean difference (MD) in the length of ICU and hospital stay, the RR of postoperative hemorrhage, and the MD in levels of methemoglobin. Trial sequential analysis (TSA) was performed for the primary outcome.

Results

54 trials were assessed for eligibility and 5 studies (579 patients) were eligible for meta-analysis. NO was associated with reduced risk of AKI (RR 0.76, 95% confidential interval [CI], 0.62 to 0.93, I² = 0%). In the subgroup analysis by NO initiation timing, NO did not decrease the risk of AKI when started at the end of CPB (RR 1.20, 95% CI 0.52–2.78, I² = 0%). However, NO did significantly reduce the risk of AKI when started from the beginning of CPB (RR 0.71, 95% CI 0.54–0.94, I² = 10%). We conducted TSA based on three trials (400 patients) using KDIGO criteria and with low risk of bias. TSA indicated a CI of 0.50–1.02 and an optimal information size of 589 patients, suggesting a lack of definitive conclusion. Furthermore, NO does not affect the length of ICU and hospital stay or the risk of postoperative hemorrhage. NO slightly increased the level of methemoglobin at the end of CPB (MD 0.52%, 95% CI 0.27–0.78%, I² = 90%), but it was clinically negligible.

Conclusions

NO appeared to reduce the risk of postoperative AKI in patients undergoing CPB. Additional studies are required to ascertain the finding and further determine the dosage, timing and duration of NO administration.

中文翻译：

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一氧化氮对体外循环患者术后急性肾损伤的影响：系统评价和荟萃分析与试验序贯分析

 背景

一氧化氮（NO）对危重病肾功能的影响存在争议。我们进行了系统的荟萃分析和试验序贯分析，以确定 NO 气体对需要体外循环 (CPB) 的患者的肾功能和其他临床结果的影响。主要结局是急性肾损伤 (AKI) 的相对风险 (RR)，无论 AKI 分期如何。次要结果是 ICU 和住院时间的平均差 (MD)、术后出血的 RR 以及高铁血红蛋白水平的 MD。对主要结局进行试验序贯分析（TSA）。

 结果

54 项试验进行了资格评估，其中 5 项研究（579 名患者）符合荟萃分析的条件。 NO 与 AKI 风险降低相关（RR 0.76，95% 可信区间 [CI]，0.62 至 0.93， I ² = 0%）。在按 NO 起始时间进行的亚组分析中，在 CPB 结束时开始 NO 并不会降低 AKI 风险（RR 1.20，95% CI 0.52–2.78， I ² = 0%）。然而，从 CPB 开始时，NO 确实显着降低了 AKI 风险（RR 0.71，95% CI 0.54–0.94， I ² = 10%）。我们根据三项试验（400 名患者）使用 KDIGO 标准进行了 TSA，且偏倚风险较低。 TSA 表明 CI 为 0.50-1.02，最佳信息量为 589 名患者，表明缺乏明确的结论。此外，NO不会影响ICU的时间和住院时间或术后出血的风险。 NO 会略微增加 CPB 结束时的高铁血红蛋白水平（MD 0.52%，95% CI 0.27–0.78%， I ² = 90%），但临床上可以忽略不计。

 结论

NO 似乎可以降低接受 CPB 的患者术后 AKI 的风险。需要进行更多研究来确定这一发现并进一步确定 NO 给药的剂量、时间和持续时间。