BACKGROUND & AIMS:
OBJECTIVE:Ringer's lactate may improve early systemic inflammation during critical illnesses like severe acute pancreatitis, which are associated with hypocalcemia. Ringer's lactate is buffered and contains lactate and calcium. We, thus analyzed extracellular calcium or lactate's effects on the mechanisms, intermediary markers, and organ failure in models mimicking human disease with nonesterified fatty acid (NEFA) elevation.
METHODS:Meta-analyses and experimental studies were performed. Experimentally, extracellular calcium and lactate were compared in their interaction with linoleic acid (LA; a NEFA increased in human severe pancreatitis), and its subsequent effects on mitochondrial depolarization and cytosolic calcium signaling resulting in cell injury. In vivo, the effect of LA was studied on organ failure, along with the effect of calcium or lactate (pH 7.4) on severe acute pancreatitis-associated organ failure. A meta-analysis of human randomized control trials comparing Ringer's lactate to normal saline was done, focusing on necrosis and organ failure.
RESULTS:Calcium reacted ionically with LA and reduced lipotoxic necrosis. In vivo, LA induced organ failure and hypocalcemia. During severe pancreatitis, calcium supplementation in saline pH 7.4, unlike lactate, prevented hypocalcemia, increased NEFA saponification, reduced circulating NEFA and C-reactive protein , reduced pancreatic necrosis adjacent to fat necrosis, and normalized shock (carotid pulse distension) and blood urea nitrogen elevation on day 1. This, however, did not prevent the later increase in serum NEFA which caused delayed organ failure. Meta-analysis showed Ringer's lactate reduced necrosis, but not organ failure, compared with normal saline.
CONCLUSION:Hypocalcemia occurs due to excess NEFA binding calcium during a critical illness. Ringer's lactate's early benefits in systemic inflammation are by the calcium it provides reacting ionically with NEFA. This, however, does not prevent later organ failure from sustained NEFA generation. Future studies comparing calcium supplemented saline resuscitation to Ringer's lactate may provide insights to this pathophysiology.
背景与目标:
目的:在严重的急性胰腺炎等严重疾病(与低钙血症有关)期间,林格氏乳酸盐可能会改善早期的全身炎症。林格氏乳酸被缓冲并且包含乳酸和钙。因此,我们在模拟非酯化脂肪酸(NEFA)升高的人类疾病的模型中,分析了细胞外钙或乳酸对机制,中介标志物和器官衰竭的影响。
方法:进行了荟萃分析和实验研究。实验上,比较了细胞外钙和乳酸与亚油酸(LA;人严重胰腺炎中NEFA升高)的相互作用,以及其对线粒体去极化和胞质钙信号传导导致细胞损伤的后续作用。在体内,研究了LA对器官衰竭的作用,以及钙或乳酸(pH 7.4)对严重急性胰腺炎相关器官衰竭的作用。对人的随机对照试验进行了荟萃分析,比较了林格氏乳酸和生理盐水,重点是坏死和器官衰竭。
结果:钙离子与LA发生离子反应,减少了脂毒性坏死。在体内,LA诱发器官衰竭和低钙血症。在严重的胰腺炎期间,与乳酸不同,在pH 7.4的盐水中补充钙可预防低血钙症,增加NEFA皂化,减少循环NEFA和C反应蛋白,减少与脂肪坏死相邻的胰腺坏死,并使休克恢复正常(颈动脉脉搏扩张)和血尿素氮在第1天升高。但是,这并不能阻止后来的血清NEFA升高而导致器官功能衰竭延迟。荟萃分析显示,与生理盐水相比,林格氏乳酸可减少坏死,但不会减少器官衰竭。
结论:低钙血症的发生是由于危重病期间过多的NEFA结合钙引起的。林格氏乳酸盐在全身性炎症中的早期益处是钙提供的钙与NEFA发生离子反应。但是,这不能防止持续的NEFA产生导致随后的器官衰竭。未来将钙补充盐水复苏与林格氏乳酸进行比较的研究可能会为这种病理生理学提供见解。