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Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning: A Systematic Review and Consensus Statement

Roberts, Darren M. PhD, FRACP1,2; Yates, Christopher MD3; Megarbane, Bruno MD4; Winchester, James F. MD5; Maclaren, Robert PharmD6; Gosselin, Sophie MD7; Nolin, Thomas D. PharmD, PhD8,9; Lavergne, Valéry MD10; Hoffman, Robert S. MD11; Ghannoum, Marc MD12on behalf of the Extracorporeal Treatments in Poisoning Workgroup

doi: 10.1097/CCM.0000000000000708
Review Article
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Objective: Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning.

Design and Methods: Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus.

Results: Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage.

Conclusion: Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.

Supplemental Digital Content is available in the text.

1School of Medicine, University of Queensland, Brisbane, QLD, Australia.

2Drug Health Services, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

3Emergency Medicine Department/Clinical Toxicology Unit, Hospital Universitari Son Espases, Palma de Mallorca, Spain.

4Réanimation Médicale et Toxicologique, Hôpital Lariboisière, INSERM U1144, Université Paris-Diderot, Paris, France.

5Division of Nephrology, Mount Sinai Beth Israel, New York, NY.

6University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO.

7Department of Emergency Medicine, Medical Toxicology Service, McGill University Health Centre, McGill University, Montréal, QC, Canada.

8School of Pharmacy, University of Pittsburgh, Pittsburgh, PA.

9School of Medicine, University of Pittsburgh, Pittsburgh, PA.

10Département de Microbiologie Médicale et Infectiologie, Hôpital du Sacré-Coeur de Montréal, Montréal, QC, Canada.

11Division of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, New York, NY.

12University of Montreal, Verdun Hospital, Montreal, QC, Canada.

Represented organizations include the following: American Academy of Clinical Toxicology, European Renal Best Practice, American College of Medical Toxicology, European Society of Emergency Medicine, American Society of Nephrology, European Society of Intensive Care Medicine, American Society of Pediatric Nephrology, French Language Society of Resuscitation, Asia Pacific Association of Medical Toxicology, German Society of Nephrology, Australian and New Zealand Intensive Care Society, International Pediatric Nephrology Association, Australian and New Zealand Society of Nephrology, International Society of Nephrology, Brazilian Association of Information Centres and Toxicologic Assistance, Latin American Society of Nephrology and Hypertension, Brazilian Society of Nephrology, National Kidney Foundation, Brazilian Society of Toxicology, Pediatric Continuous Renal Replacement Therapy, Canadian Association of Poison Control Centres, Pediatric Critical Care Medicine, Canadian Association of Emergency Physicians, Quebec Association of Emergency Physicians, Canadian Society of Nephrology, Quebec Association of Specialists in Emergency Medicine, Chinese College of Emergency Physicians, Quebec Society of Nephrology, Renal Association, Society of Critical Care Medicine, Spanish Clinical Toxicology Foundation, Chinese Medical Doctor Association, and European Association of Poison Centres and Clinical Toxicologists.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Roberts received support for travel from Amgen (Australia); the Research Institute from Verdun Hospital (Montreal, QC, Canada); and the Royal Australasian College of Physicians, Australia and New Zealand Society of Nephrology, University of Cambridge, and Amgen (Australia) (In 2011, Dr. Roberts was a recipient of a fellowship to support work in Cambridge in renal medicine and was otherwise unrestricted). Dr. Yates received support for travel from the Research Institute from Verdun Hospital; is employed by Hospital Universitari Son Espases; lectured for Balear School of Public Administration and Colegio de Enfermería Illes Balears (Nursing College) (lectures in toxicology courses); and received support for travel from Vlada Republike Hrvatske, Ured Za Suzbijane Zlouporabe Droga (Roughly Croatian Agency for combatting drug abuse. Travel expenses to give a talk on novel psychoactive substances). Dr. Yates and his institution received grant support from the European Commission (European Drug Emergencies Network. JUST/2012/DPIP/AG/3591 Payment for work on design, creation, and implementation of research on emergencies from recreational drugs of abuse). Dr. Bruno received support for travel from the Research Institute from Verdun Hospital. Dr. Maclaren consulted for Gordon and Rees; Kennedy Childs; and Rutherford, Mullin, and Moore (medical legal review). His institution received grant support from Hospira (investigator-initiated grant to support dexmedetomidine studies). Dr. Gosselin received support for travel from the Research Institute from Verdun Hospital, consulted for the Quebec Board of Physicians (evaluated physician adequacy for practice and licensing in emergency medicine), and lectured for the Canadian Association of Emergency Physicians and Associations des Médecins d’Urgence du Québec (travel support and honorarium for conferences and Continuing Medical Education course from these physician associations). Dr. Nolin consulted for Thrasos Innovation (member of Independent Data Monitoring Committee); is employed by the University of Pittsburgh; and received support for travel from the American Society of Nephrology (reimbursement for travel to Kidney Health Initiative and postgraduate education committee meetings). His institution received grant support from the National Institutes of Health (pending grant that is unrelated to the submitted work). Dr. Lavergne lectured for Amgen, Pfizer, Association des spécialistes en médecine interne du Québec, and Association d'Orthopédie du Québec. Dr. Hoffman received support for travel from Extracorporeal Treatments in Poisoning. Dr. Ghannoum received support for travel (airfare expense paid by organizing committee/research institution for American Society of Nephrology 2012, World Congress of Nephrology 2013, and the Society of Critical Care Medicine 2014). His institution received support for travel from unrestricted educational support only used for support of travel and received unrestricted support for payment of translators (foreign-language articles). Dr. Winchester has disclosed that he does not have any potential conflicts of interest.

For information regarding this article, E-mail: darren.roberts@uq.edu.au

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