Department of Acute Medicine, Division of Medicine, Oslo University Hospital, Oslo, Norway.
University of Oslo, Oslo, Norway.
Basic Clin Pharmacol Toxicol. 2018 Dec;123(6):749-755. doi: 10.1111/bcpt.13074. Epub 2018 Jul 23.
Methanol mass poisoning is a global problem with high fatality rates and often severe sequelae in survivors. Patients typically present late to the hospital with severe metabolic acidosis followed by a rapid deterioration in their clinical status. The hypothesis 'Circulus hypoxicus' describes the metabolic acidosis following methanol poisoning as a self-enhancing hypoxic circle responsible for methanol toxicity. We wanted to test the validity of this hypothesis by an observational study based on 35 patients from the methanol outbreaks in Norway (2004) and the Czech Republic (2012). Comprehensive laboratory values, including S(serum)-methanol, S-formate, S-lactate, arterial blood gases, anion and osmolal gaps, were used in the calculations. Laboratory values and calculated gaps were compared to each other using linear regression. S-lactate and S-formate correlated better with the increased base deficit and anion gap than did S-formate alone. Base deficit rose to about 20 mmol/L and S-formate rose to 12 mmol/L prior to a significant rise in S-lactate - most likely caused by formate inhibition of mitochondrial respiration (type B lactacidosis). The further rise in S-lactate was not linear to S-formate most likely due to the self-enhancing pathophysiology, but may also be associated with hypotension in critically ill patients and variable ethanol drinking habits. Our study suggests that the primary metabolic acidosis leads to a secondary lactic acidosis mainly due to the toxic effects of formate. The following decline in pH will further increase this toxicity. As such, a vicious and self-enhancing acidotic circle may explain the pathophysiology in methanol poisoning, namely the 'Circulus hypoxicus'.
甲醇大量中毒是一个全球性的问题，死亡率高，幸存者常伴有严重的后遗症。患者通常在出现严重代谢性酸中毒后晚期到医院就诊，随后临床状况迅速恶化。“缺氧循环”假说描述了甲醇中毒后的代谢性酸中毒，认为其是导致甲醇毒性的自我增强的缺氧循环。我们希望通过一项基于挪威（2004 年）和捷克共和国（2012 年）甲醇中毒爆发的 35 名患者的观察性研究来验证该假说的有效性。综合实验室值，包括血清甲醇、血清甲酸盐、血清乳酸、动脉血气、阴离子间隙和渗透压间隙，用于计算。使用线性回归比较实验室值和计算的间隙。与单独的甲酸盐相比，血清乳酸和血清甲酸盐与增加的基础缺陷和阴离子间隙的相关性更好。基础缺陷上升到约 20mmol/L，血清甲酸盐上升到 12mmol/L，然后血清乳酸显著上升——很可能是由于甲酸盐抑制线粒体呼吸（B 型乳酸酸中毒）所致。由于自我增强的病理生理学，血清乳酸的进一步上升与血清甲酸盐不成线性关系，但也可能与危重病患者的低血压和不同的乙醇饮酒习惯有关。我们的研究表明，原发性代谢性酸中毒导致继发性乳酸酸中毒，主要是由于甲酸盐的毒性作用。随后 pH 值的下降将进一步增加这种毒性。因此，这种恶性和自我增强的酸中毒循环可能解释了甲醇中毒的病理生理学，即“缺氧循环”。
