1Department of Emergency Medicine, Medical Toxicology Service, Morristown Medical Center, Morristown, NJ. 2Division of Nephrology, Department of Medicine, University of California, San Francisco, CA. 3The University of Rochester Medical Center and Strong Memorial Hospital, Rochester, NY. 4Burns, Trauma and Critical Care Research Centre, School of Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia. 5Department of Medical Biology, Sacré-Coeur Hospital, University of Montreal, Montreal, QC, Canada. 6Department of Emergency Medicine, Medical Toxicology Consultation Service, McGill University Health Centre, Montreal, QC, Canada. 7Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University School of Medicine, New York, NY. 8Department of Pharmacy and Therapeutics, Center for Clinical Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA. 9Department of Nephrology, Verdun Hospital, University of Montreal, Verdun, QC, Canada.
Crit Care Med. 2015 Aug;43(8):1716-30. doi: 10.1097/CCM.0000000000001002.
Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing diverse professions, presents its systematic review and clinical recommendations for extracorporeal treatment in metformin poisoning.
A systematic literature search was performed, data extracted, findings summarized, and structured voting statements developed. A two-round modified Delphi method was used to achieve consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Anonymized votes and opinions were compiled and discussed. A second vote determined the final recommendations.
One hundred seventy-five articles were identified, including 63 deaths: one observational study, 160 case reports or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies in end-stage renal disease, yielding a very low quality of evidence for all recommendations. The workgroup concluded that metformin is moderately dialyzable (level of evidence C) and made the following recommendations: extracorporeal treatment is recommended in severe metformin poisoning (1D). Indications for extracorporeal treatment include lactate concentration greater than 20 mmol/L (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard supportive measures (1D), and decreased level of consciousness (2D). Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal treatment. Intermittent hemodialysis is preferred initially (1D), but continuous renal replacement therapies may be considered if hemodialysis is unavailable (2D). Repeat extracorporeal treatment sessions may use hemodialysis (1D) or continuous renal replacement therapy (1D).
Metformin poisoning with lactic acidosis appears to be amenable to extracorporeal treatments. Despite clinical evidence comprised mostly of case reports and suboptimal toxicokinetic data, the workgroup recommended extracorporeal removal in the case of severe metformin poisoning.
二甲双胍中毒是一种具有挑战性的临床病症，其死亡率为 30%。目前，关于血液透析等体外治疗方法的作用尚未明确。在这里，由代表不同专业的国际专家组成的体外治疗中毒工作组，对二甲双胍中毒的体外治疗进行了系统评价和临床推荐。
进行了系统的文献检索，提取数据，总结发现，并制定了结构化投票陈述。采用两轮改良 Delphi 法对投票陈述达成共识，并采用 RAND/UCLA 适宜性方法量化分歧。匿名投票和意见进行了汇编和讨论。第二次投票确定了最终建议。
共确定了 175 篇文章，包括 63 例死亡：1 项观察性研究，160 例病例报告或系列，11 项描述性队列研究，以及 3 项终末期肾病的药代动力学研究，所有建议的证据质量均非常低。工作组得出结论，二甲双胍可适度透析（证据水平 C），并提出以下建议：在严重二甲双胍中毒时推荐进行体外治疗（1D）。体外治疗的指征包括乳酸浓度大于 20mmol/L（1D）、pH 值小于或等于 7.0（1D）、休克（1D）、标准支持措施失败（1D）以及意识水平下降（2D）。应继续进行体外治疗，直到乳酸浓度小于 3mmol/L（1D）且 pH 值大于 7.35（1D），此时需要密切监测以确定是否需要额外的体外治疗疗程。最初首选间歇性血液透析（1D），但如果无法进行血液透析，则可以考虑连续肾脏替代治疗（2D）。重复进行体外治疗时可选择血液透析（1D）或连续肾脏替代治疗（1D）。
二甲双胍中毒伴乳酸性酸中毒似乎可以采用体外治疗方法。尽管临床证据主要由病例报告和不太理想的毒代动力学数据组成，但工作组建议在严重二甲双胍中毒的情况下进行体外清除。
