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评估静脉注射硫酸镁预防黏菌素所致急性肾损伤的效果:一项开放标签、安慰剂对照、区组随机临床试验。

Evaluating the effects of intravenous magnesium sulfate for prevention of colistin induced acute kidney injury: an open-label, placebo-controlled, block randomized clinical trial.

作者信息

Hosseini Sareh, Alavi Darzam Ilad, Amirdosara Mahdi, Zangi Masoud, Sahraei Zahra

机构信息

Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Infectious Diseases and Tropical Medicine, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4559-4570. doi: 10.1007/s00210-024-03583-w. Epub 2024 Nov 6.

Abstract

Colistin, has reinstated as a last-resort antibiotic despite its known nephrotoxicity. The aim of this study was to determine the potential nephroprotective effects of Magnesium (Mg) Sulfate during colistin therapy. This study was an open-label, placebo-controlled, block-randomized clinical trial conducted from January 2023 to February 2024 involving 87 patients eligible for colistin therapy. Patients were randomly assigned to receive either Mg sulfate (16 mEq in 100 mL of normal saline) or 100 mL of normal saline as placebo before each dose of colistin. The primary outcome of the study was the incidence of Acute Kidney Injury (AKI) during the first week of colistin therapy, while the secondary outcomes included colistin dose adjustments, length of stay in the ICU and hospital, and overall mortality. This study was registered in The Iranian Registry of Clinical Trials (IRCT20130917014693N15; 2023-01-12). A total of 87 patients (46 in Mg and 41 in control group) completed the study. Fourteen patients (30.43%) in the Mg group and twenty-one patients (51.21%) in the control group developed AKI during the first week of colistin therapy (p = 0.048). Although AKI incidence was not statistically different between the groups in unadjusted Cox regression model (HR =0.51, 95% CI =0.26-1.01, P =0.057), it became significant after adjusting for confounding factors (HR =0.40,95% CI =0.18-0.86, P =0.021). The length of hospital stay was 48.62 ± 18.82 and 44.82 ± 20.23 days for Mg and control groups respectively (p=0.373). In the Mg group, 25 out of 46 patients (54.34 %) and in the control group, 24 out of 41 patients (58.53%) eventually expired (p=0.694). This study indicates that Mg sulfate significantly reduces AKI rates and prevents hypomagnesemia, optimizing dosing and enhancing patient safety during colistin therapy.

摘要

尽管已知具有肾毒性,黏菌素仍被重新用作一种挽救生命的抗生素。本研究的目的是确定硫酸 镁在黏菌素治疗期间的潜在肾保护作用。本研究是一项开放标签、安慰剂对照、区组随机临床试验,于2023年1月至2024年2月进行,纳入了87例符合黏菌素治疗条件的患者。患者在每次给予黏菌素前,被随机分配接受硫酸镁(16 mEq加入100 mL生理盐水中)或100 mL生理盐水作为安慰剂。本研究的主要结局是黏菌素治疗第一周内急性肾损伤(AKI)的发生率,次要结局包括黏菌素剂量调整、在重症监护病房(ICU)和医院的住院时间以及总体死亡率。本研究已在伊朗临床试验注册中心注册(IRCT20130917014693N15;2023 - 01 - 12)。共有87例患者(硫酸镁组46例,对照组41例)完成了研究。硫酸镁组14例患者(30.43%)和对照组21例患者(51.21%)在黏菌素治疗第一周内发生了AKI(p = 0.048)。尽管在未调整的Cox回归模型中,两组间AKI发生率无统计学差异(HR = 0.51,95%CI = 0.26 - 1.01,P = 0.057),但在调整混杂因素后具有统计学意义(HR = 0.40,95%CI = 0.18 - 0.86,P = 0.021)。硫酸镁组和对照组的住院时间分别为48.62 ± 18.82天和44.82 ± 20.23天(p = 0.373)。硫酸镁组46例患者中有25例(54.34%)最终死亡,对照组41例患者中有24例(58.53%)最终死亡(p = 0.694)。本研究表明,硫酸镁可显著降低AKI发生率并预防低镁血症,在黏菌素治疗期间优化给药并提高患者安全性。

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