Zakharov Sergey, Navratil Tomas, Salek Tomas, Kurcova Ivana, Pelclova Daniela
Toxicological information center, Department of Occupational Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
Department of Biomimetic Electrochemistry, J. Heyrovsky Institute of Physical Chemistry of AS CR, v.v.i, Prague.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Dec;159(4):666-76. doi: 10.5507/bp.2015.008. Epub 2015 Mar 1.
During the 2012 outbreak of mass methanol poisonings in the Czech Republic, ethanol, in the main, was used as an antidote. The complex pharmacokinetics of ethanol made it difficult to maintain the requisite 1000-1500 mg/L serum ethanol levels (S-EtOH). The aim of this study was to measure the fluctuations in S-EtOH during the treatment.
A prospective case series in 21 patients, median age 52 (27-79 years), 13 males and 8 females. Serum ethanol, methanol and formate were measured every 2-6 hours during the treatment. Follow-up clinical examination was carried out in 15/18 survivors.
The majority of patients (17/21) were late presenters and on admission, almost half (10/21) had suffered a severe grade of intoxication according to the Poisoning Severity Score (PSS). The mean observation time was 90±20 h. The mean period of consistent maintenance of S-EtOH within the recommended therapeutic range lasted 28±7% of the total observation time. For 29±8% of the time, S-EtOH was >1500 mg/L with "peaks" of up to 3500 mg/L. For 44±10% of the observation time, S-EtOH was <1000 mg/L. The mean duration of sub-therapeutic concentration of S-EtOH and toxic serum levels of methanol >200 mg/L or formate >20 mg/L lasted 20±10% and 18±11% of the time of observation, respectively. Complications occurred in 14 (67%) of cases including significant fluctuations of S-EtOH in 9; aspiration pneumonia in 3 and delirium tremens in 2 cases. Other complications included sepsis, bleeding, acidosis rebound, intolerance and set clotting. The outcomes were: 11 survivors free of health impairment, 7 with sequelae and 3 deaths. There was no significant difference in mean duration of sub-therapeutic and supra-therapeutic concentrations of serum ethanol in patients who survived without sequelae and those with poor outcome (P > 0.05).
Administration of ethanol according to the present guidelines of the AACT/EAPCCT is effective and relatively safe in the treatment of methanol poisoning during a mass outbreak(31). Physicians have to be most aware of fluctuations in serum ethanol at the end of short sessions of IHD and after changes in route from intravenous to oral. Rigorous monitoring of serum ethanol concentrations is pivotal for severely poisoned patients with PSS 3 and where there is suspected conversion of significant amounts of methanol to formic acid.
在2012年捷克共和国大规模甲醇中毒事件爆发期间，主要使用乙醇作为解毒剂。乙醇复杂的药代动力学使得难以维持血清乙醇水平（S-EtOH）所需的1000 - 1500mg/L。本研究的目的是测量治疗期间S-EtOH的波动情况。
对21例患者进行前瞻性病例系列研究，患者年龄中位数为52岁（27 - 79岁），男性13例，女性8例。治疗期间每2 - 6小时测量血清乙醇、甲醇和甲酸水平。对15/18例幸存者进行了随访临床检查。
大多数患者（17/21）就诊较晚，入院时，根据中毒严重程度评分（PSS），几乎一半（10/21）患者中毒程度严重。平均观察时间为90±20小时。S-EtOH在推荐治疗范围内持续维持的平均时间占总观察时间的28±7%。在29±8%的时间里，S-EtOH >1500mg/L，“峰值”高达3500mg/L。在44±10%的观察时间里，S-EtOH <1000mg/L。S-EtOH低于治疗浓度以及甲醇血清水平>200mg/L或甲酸>20mg/L的毒性水平持续的平均时间分别占观察时间的20±10%和18±11%。14例（67%）患者出现并发症，其中9例S-EtOH有显著波动；3例发生吸入性肺炎，2例发生震颤谵妄。其他并发症包括败血症、出血、酸中毒反弹、不耐受和凝血异常。结果为：11例幸存者无健康损害，7例有后遗症，3例死亡。无后遗症存活患者与预后不良患者血清乙醇低于治疗浓度和高于治疗浓度的平均持续时间无显著差异（P > 0.05）。
按照AACT/EAPCCT目前的指南给予乙醇治疗大规模爆发的甲醇中毒有效且相对安全。医生必须特别注意在短时血液透析结束时以及从静脉给药改为口服给药后血清乙醇的波动情况。对于PSS为3级的严重中毒患者以及怀疑有大量甲醇转化为甲酸的患者，严格监测血清乙醇浓度至关重要。
