BACKGROUND: Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. METHODS: The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. RESULTS: Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p < 0.001) and more severely poisoned (25/40 vs. 9/41 patients with Glasgow Coma Scale (GCS) ≤ 8; p < 0.001). The median intensive care unit length of stay (4 (range 1-16) days vs. 4 (1-22) days; p = 0.703) and the number of patients with complications during the treatment (11/41 vs. 13/40 patients; p = 0.576) did not differ between the groups. The mortality was higher in the CRRT group (15/40 vs. 5/41; p = 0.008). The number of survivors without sequelae of poisoning was higher in the IHD group (23/41 vs. 10/40; p = 0.004). There was a significant association of ECTR modality with both mortality and the number of survivors with visual and CNS sequelae of poisoning, but this association was not present after adjustment for arterial blood pH and GCS on admission (all p > 0.05). CONCLUSIONS: In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of "use what you have" in situations with large outbreaks and limited dialysis capacity.

Department of Anesthesia and Intensive Care 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Biomimetic Electrochemistry J Heyrovský Institute of Physical Chemistry of CAS v v i Prague Czech Republic

Department of Occupational Medicine Toxicological Information Center 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

The Norwegian CBRNE Centre of Medicine Department of Acute Medicine Oslo University Hospital Oslo Norway

See more in PubMed

Hovda KE, Hunderi OH, Tafjord AB, Dunlop O, Rudberg N, Jacobsen D. Methanol outbreak in Norway 2002-2004: epidemiology, clinical features and prognostic signs. J Intern Med. 2005;258:181–190. doi: 10.1111/j.1365-2796.2005.01521.x. PubMed DOI

Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia: outbreak in 154 patients. Clin Toxicol. 2007;45:152–157. doi: 10.1080/15563650600956329. PubMed DOI

Hassanian-Moghaddam H, Nikfarjam A, Mirafzal A, Saberinia A, Nasehi AA, Asl HM, Memaryan N. Methanol mass poisoning in Iran: role of case finding in outbreak management. J Public Health. 2015;37:354–359. doi: 10.1093/pubmed/fdu038. PubMed DOI

Rostrup M, Edwards JK, Abukalish M, Ezzabi M, Some D, Ritter H, et al. The methanol poisoning outbreaks in Libya 2013 and Kenya 2014. PLoS ONE. 2016;11:e0152676. doi: 10.1371/journal.pone.0152676. PubMed DOI PMC

Hovda KE, McMartin KE, Jacobsen D. Methanol and formaldehyde poisoning. In: Critical care toxicology. Second Edition. Brent J, Megarbane B, Palmer R, Hatten B, Burkhart K (Eds). New York, Springer Publishing, 2017, Online Early.

Megarbane B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005;31:189–195. doi: 10.1007/s00134-004-2521-0. PubMed DOI

McMartin K, Jacobsen D, Hovda KE. Antidotes for toxic alcohol poisoning. Brit J Pharmacol. 2016;81:505–515. doi: 10.1111/bcp.12824. PubMed DOI PMC

Liesivuori J, Savolainen H. Methanol and formic-acid toxicity—biochemical mechanisms. Pharmacol Toxicol. 1991;69:157–163. doi: 10.1111/j.1600-0773.1991.tb01290.x. PubMed DOI

Sejersted OM, Jacobsen D, Ovrebo S, Jansen H. Formate concentrations in plasma from patients poisoned with methanol. Acta Med Scand. 1983;213:105–110. doi: 10.1111/j.0954-6820.1983.tb03699.x. PubMed DOI

Zakharov S, Nurieva O, Navratil T, Diblik P, Kuthan P, Pelclova D. Acute methanol poisonings: folates administration and visual sequelae. J Appl Biomed. 2014;12:309–316. doi: 10.1016/j.jab.2014.04.001. DOI

Bezdicek O, Klempir J, Liskova I, Michalec J, Vaneckova M, Seidl Z, et al. Sequelae of methanol poisoning for cognition. Cesk Slov Neurol N. 2014;77(110):320–325.

Zakharov S, Kurcova I, Navratil T, Salek T, Komarc M, Pelclova D. Is the measurement of serum formate concentration useful in the diagnostics of acute methanol poisoning? A prospective study of 38 patients. Basic Clin Pharmacol Toxicol. 2015;116:445–451. doi: 10.1111/bcpt.12338. PubMed DOI

Zakharov S, Nurieva O, Kotikova K, Urban P, Navratil T, Pelclova D. Factors predicting optic nerve axonal degeneration after methanol-induced acute optic neuropathy: a 2-year prospective study in 54 patients. Monatsh Chem. 2016;147:251–261. doi: 10.1007/s00706-015-1581-x. DOI

Nurieva O, Kotikova K, Urban P, Pelclova D, Petrik V, Navratil T, et al. Prevalence, dynamics, and biochemical predictors of optic nerve remyelination after methanol-induced acute optic neuropathy: a 2-year prospective study in 54 patients. Monatsh Chem. 2016;147:239–249. doi: 10.1007/s00706-015-1580-y. DOI

Zakharov S, Kotikova K, Vaneckova M, Seidl Z, Nurieva O, Navratil T, et al. Acute methanol poisoning: prevalence and predisposing factors of haemorrhagic and non-haemorrhagic brain lesions. Basic Clin Pharmacol Toxicol. 2016;119:228–238. doi: 10.1111/bcpt.12559. PubMed DOI

Coulter CV, Farquhar SE, McSherry CM, Isbister GK, Duffull SB. Methanol and ethylene glycol acute poisonings—predictors of mortality. Clin Toxicol. 2011;49:900–906. doi: 10.3109/15563650.2011.630320. PubMed DOI

Paasma R, Hovda KE, Hassanian-Moghaddam H, Brahmi N, Afshari R, Sandvik L, et al. Risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes—a multicenter study. Clin Toxicol. 2012;50:823–831. doi: 10.3109/15563650.2012.728224. PubMed DOI

Liu JJ, Daya MR, Carrasquillo O, Kales SN. Prognostic factors in patients with methanol poisoning. J Toxicol-Clin Toxicol. 1998;36:175–181. doi: 10.3109/15563659809028937. PubMed DOI

Hubacek JA, Pelclova D, Seidl Z, Vaneckova M, Klempir J, Ruzicka E, et al. Rare alleles within the CYP2E1 (MEOS system) could be associated with better short-term health outcome after acute methanol poisoning. Basic Clin Pharmacol Toxicol. 2015;116:168–172. doi: 10.1111/bcpt.12310. PubMed DOI

Abramson S, Singh AK. Treatment of the alcohol intoxications: ethylene glycol, methanol and isopropanol. Curr Opin Nephrol Hypertens. 2000;9:695–701. doi: 10.1097/00041552-200011000-00017. PubMed DOI

Bayliss G. Dialysis in the poisoned patient. Hemodial Int. 2010;14:158–167. doi: 10.1111/j.1542-4758.2009.00427.x. PubMed DOI

Chebrolu SB, Hariman A, Eggert CH, Patel S, Kjellstrand CM, Ing TS. Phosphorus-enriched hemodialysis for the treatment of patients with severe methanol intoxication. Int J Artif Organs. 2005;28:270–274. PubMed

Peces R, Alvarez R. Effectiveness of hemodialysis with high-flux polysulfone membrane in the treatment of life-threatening methanol intoxication. Nephron. 2002;90:216–218. doi: 10.1159/000049046. PubMed DOI

Kan G, Jenkins I, Rangan G, Woodroffe A, Rhodes H, Joyce D. Continuous haemodiafiltration compared with intermittent haemodialysis in the treatment of methanol poisoning. Nephrol Dial Transplant. 2003;18:2665–2667. doi: 10.1093/ndt/gfg432. PubMed DOI

Zakharov S, Pelclova D, Navratil T, Belacek J, Kurcova I, Komzak O, et al. Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning. Kidney Int. 2014;86:199–207. doi: 10.1038/ki.2014.60. PubMed DOI PMC

Zakharov S, Pelclova D, Navratil T, Belacek J, Latta J, Pisar M, et al. Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning. Clin Toxicol. 2017;55:123–132. doi: 10.1080/15563650.2016.1250901. PubMed DOI

Roberts DM, Yates C, Megarbane B, Winchester JF, Maclaren R, Gosselin S, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med. 2015;43:461–472. doi: 10.1097/CCM.0000000000000708. PubMed DOI

Zakharov S, Pelclova D, Urban P, Navratil T, Diblik P, Kuthan P, et al. Czech mass methanol outbreak 2012: epidemiology, challenges and clinical features. Clin Toxicol. 2014;52:1013–1024. doi: 10.3109/15563650.2014.974106. PubMed DOI

Zakharov S, Pelclova D, Diblik P, Urban P, Kuthan P, Nurieva O, et al. Long-term visual damage after acute methanol poisonings: longitudinal cross-sectional study in 50 patients. Clin Toxicol. 2015;53:884–892. doi: 10.3109/15563650.2015.1086488. PubMed DOI

Urban P, Zakharov S, Diblík P, Pelclova D, Ridzon P. Visual evoked potentials in patients after methanol poisoning. IJOMEH. 2016;29:471–478. doi: 10.13075/ijomeh.1896.00452. PubMed DOI

Vaneckova M, Zakharov S, Klempir J, Ruzicka E, Bezdicek O, Brozova H, et al. Imaging findings after methanol intoxication (cohort of 46 patients) Neuroendocrinol Lett. 2015;36:737–744. PubMed

Vaneckova M, Zakharov S, Klempir J, Ruzicka E, Bezdicek O, Brozova H, et al. Methanol intoxication on magnetic resonance imaging—case reports. Cesk Slov Neurol N. 2014;77(110):235–239.

Zakharov S, Navratil T, Pelclova D. Fomepizole in the treatment of acute methanol poisonings: experience from the Czech mass methanol outbreak 2012-2013. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158:641–649. PubMed

Zakharov S, Pelclova D, Navratil T, Belacek J, Komarc M, Eddleston M, et al. Fomepizole versus ethanol in the treatment of acute methanol poisoning: comparison of clinical effectiveness in a mass poisoning outbreak. Clin Toxicol. 2015;53:797–806. doi: 10.3109/15563650.2015.1059946. PubMed DOI

Zakharov S, Navratil T, Salek T, Kurcova I, Pelclova D. Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159:666–676. PubMed

Hovda KE, Andersson KS, Urdal P, Jacobsen D. Methanol and formate kinetics during treatment with fomepizole. Clin Toxicol. 2005;43:221–227. doi: 10.1081/CLT-58936. PubMed DOI

Zakharov S, Kotikova K, Nurieva O, Hlusicka J, Kacer P, Urban P, et al. Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning. Clin Toxicol. 2017;55:249–259. doi: 10.1080/15563650.2017.1284332. PubMed DOI

Bezdicek O, Michalec J, Vaneckova M, Klempir J, Liskova I, Seidl Z, et al. Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective. Alcohol. 2017;59:27–35. doi: 10.1016/j.alcohol.2016.12.003. PubMed DOI

Rulisek J, Balik M, Polak F, Waldauf P, Pelclova D, Belohlavek J, et al. Cost-effectiveness of hospital treatment and outcomes of acute methanol poisoning during the Czech Republic mass poisoning outbreak. J Crit Care. 2017;39:190–198. doi: 10.1016/j.jcrc.2017.03.001. PubMed DOI