Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Surg Oncol. 2023 Dec;128(7):1141-1149. doi: 10.1002/jso.27412. Epub 2023 Sep 13.
Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans.
We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B.
In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium.
A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.
高热术中顺铂（HIOC）与急性肾损伤（AKI）有关。在动物模型中，高剂量镁的给药可减轻顺铂引起的 AKI（CP-AKI），但尚未在人类中进行严格检查。
我们测试了接受 HIOC 的间皮瘤患者中不同剂量镁的可行性和安全性。在初步研究 1 中，我们以 0.5 g/h 的速度连续输注 36 小时镁，目标血清镁水平在 3 至 4.8 mg/dL 之间。在初步研究 2A 中，我们给予 6 g 推注，然后以 2 g/h 的速度开始输注，滴定以达到 4 至 6 mg/dL 的水平。我们在初步研究 2B 中消除了推注。
在初步研究 1 中，所有 5 名入组患者均完成了研究；然而，术后镁中位数水平仅为 2.4 mg/dL。在初步研究 2A 中，由于推注期间心动过缓，有 4 名患者中的 2 名（50%）被撤出。在初步研究 2B 中，有两名患者完成了研究，而另外两名患者因镁而出现术后心动过缓。
36 小时以 0.5 g/h 的速度输注未达到治疗性镁水平，而以 2 g/h 的速度输注则与心动过缓有关。这些研究为一项随机临床试验提供了信息，该试验测试了静脉内 Mg 是否减轻 HIOC 相关 AKI。
