Skip to main content
Erschienen in: Intensive Care Medicine 2/2005

01.02.2005 | Review

Current recommendations for treatment of severe toxic alcohol poisonings

verfasst von: Bruno Mégarbane, Stephen W. Borron, Frédéric J. Baud

Erschienen in: Intensive Care Medicine | Ausgabe 2/2005

Einloggen, um Zugang zu erhalten

Abstract

Background

Ethylene glycol (EG) and methanol are responsible for accidental, suicidal, and epidemic poisonings, resulting in death or permanent sequelae. Toxicity is due to the metabolic products of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. Conventional management of these intoxications consists of ethanol and hemodialysis. Fomepizole, a potent ADH inhibitor, has largely replaced antidotal ethanol use in France and two recent prospective U.S. trials definitively established its efficacy. Fomepizole appears safer than ethanol and while no comparative study of efficacy exists, fomepizole is recommended as the first-line antidote.

Focus

Fomepizole, administered early in EG intoxication, prevents renal injury. In the absence of renal failure, EG clearance is rapid, avoiding the need for prolonged fomepizole administration. The long elimination half-life of methanol poisonings, with absent hemodialysis, necessitates prolonged administration of fomepizole. In the U.S. trials, patients were dialyzed when plasma EG or methanol concentrations were ≥0.5 g/l. However, EG-poisoned patients treated with fomepizole prior to the onset of significant acidosis may not require hemodialysis. Indeed, fomepizole may also obviate the need for hemodialysis in selected methanol-poisoned patients, in the absence of neurological and ocular impairment or severe acidosis. When dialysis is indicated, 1 mg·kg·h continuous infusion of fomepizole should be provided to compensate for its elimination.

Conclusions

Fomepizole is an effective and safe first-line recommended antidote for EG and methanol intoxication. In selected patients, fomepizole may obviate the need for hemodialysis.
Literatur
1.
Zurück zum Zitat Watson WA, Litovitz TL, Rodgers GC Jr, Klein-Schwartz W, Youniss J, Rose SR, Borys D, May ME (2003) 2002 annual report of the American Association of poison control centers toxic exposure surveillance system. Am J Emerg Med 21:353–421CrossRefPubMed Watson WA, Litovitz TL, Rodgers GC Jr, Klein-Schwartz W, Youniss J, Rose SR, Borys D, May ME (2003) 2002 annual report of the American Association of poison control centers toxic exposure surveillance system. Am J Emerg Med 21:353–421CrossRefPubMed
2.
Zurück zum Zitat Hylander B, Kjellstrand CM (1996) Prognostic factors and treatment of severe ethylene glycol intoxication. Intensive Care Med 22:546–552 Hylander B, Kjellstrand CM (1996) Prognostic factors and treatment of severe ethylene glycol intoxication. Intensive Care Med 22:546–552
3.
Zurück zum Zitat Liu JJ, Daya MR, Carrasquillo O, Kales SN (1998) Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol 36:175–181 Liu JJ, Daya MR, Carrasquillo O, Kales SN (1998) Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol 36:175–181
4.
Zurück zum Zitat Jacobsen D, McMartin KE (1997) Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol 35:127–143PubMed Jacobsen D, McMartin KE (1997) Antidotes for methanol and ethylene glycol poisoning. J Toxicol Clin Toxicol 35:127–143PubMed
5.
Zurück zum Zitat Mégarbane B, Baud F (2003) Is there a remaining place for hemodialysis in toxic alcohol poisonings treated with fomepizole? J Toxicol Clin Toxicol 41:396–397 [abstr] Mégarbane B, Baud F (2003) Is there a remaining place for hemodialysis in toxic alcohol poisonings treated with fomepizole? J Toxicol Clin Toxicol 41:396–397 [abstr]
6.
Zurück zum Zitat Baud FJ, Galliot M, Astier A, Bien DV, Garnier R, Likforman J, Bismuth C (1988) Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 319:97–100 Baud FJ, Galliot M, Astier A, Bien DV, Garnier R, Likforman J, Bismuth C (1988) Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med 319:97–100
7.
Zurück zum Zitat Borron SW, Mégarbane B, Baud FJ (1999) Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet 354:831 Borron SW, Mégarbane B, Baud FJ (1999) Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet 354:831
8.
Zurück zum Zitat Mégarbane B, Borron SW, Trout H, Hantson P, Jaeger A, Krencker E, Bismuth C, Baud FJ (2001) Treatment of acute methanol poisoning with fomepizole. Intensive Care Med 27:1370–1378CrossRefPubMed Mégarbane B, Borron SW, Trout H, Hantson P, Jaeger A, Krencker E, Bismuth C, Baud FJ (2001) Treatment of acute methanol poisoning with fomepizole. Intensive Care Med 27:1370–1378CrossRefPubMed
9.
Zurück zum Zitat Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K (1999) Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 340:832–838CrossRefPubMed Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K (1999) Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 340:832–838CrossRefPubMed
10.
Zurück zum Zitat Brent J, McMartin K, Philipps S, Aaron C, Kulig K, Methylpyrazole for Toxic Alcohols Study Group (2001) Fomepizole for the treatment of methanol poisoning. N Engl J Med 344:424–429CrossRef Brent J, McMartin K, Philipps S, Aaron C, Kulig K, Methylpyrazole for Toxic Alcohols Study Group (2001) Fomepizole for the treatment of methanol poisoning. N Engl J Med 344:424–429CrossRef
11.
Zurück zum Zitat McMartin KE, Hedström KG, Tolf BR, Ostling-Wintzell H, Blomstrand R (1980) Studies on the meatbolic interactions between 4-methylpyrazole and methanol using the monkey as an animal model. Arch Biochem Biophys 199:606–614 McMartin KE, Hedström KG, Tolf BR, Ostling-Wintzell H, Blomstrand R (1980) Studies on the meatbolic interactions between 4-methylpyrazole and methanol using the monkey as an animal model. Arch Biochem Biophys 199:606–614
12.
Zurück zum Zitat Jacobsen D, Barron SK, Sebastian CS, Blomstrand R, McMartin KE (1989) Non-linear kinetics of 4-methylpyrazole in healthy human subjects. Eur J Clin Pharmacol 37:599–604 Jacobsen D, Barron SK, Sebastian CS, Blomstrand R, McMartin KE (1989) Non-linear kinetics of 4-methylpyrazole in healthy human subjects. Eur J Clin Pharmacol 37:599–604
13.
Zurück zum Zitat Jacobsen D, Sebastian CS, Dies DF, Breau RL, Spann EG, Barron SK, McMartin KE (1996) Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans. Alcohol Clin Exp Res 20:804–809 Jacobsen D, Sebastian CS, Dies DF, Breau RL, Spann EG, Barron SK, McMartin KE (1996) Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans. Alcohol Clin Exp Res 20:804–809
14.
Zurück zum Zitat Barceloux DG, Krenzelok EO, Olson K, Watson W (1999) American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 37:537–560CrossRef Barceloux DG, Krenzelok EO, Olson K, Watson W (1999) American Academy of Clinical Toxicology practice guidelines on the treatment of ethylene glycol poisoning. J Toxicol Clin Toxicol 37:537–560CrossRef
15.
Zurück zum Zitat Barceloux DG, Bong GR, Krenzelok EP, Cooper H, Vale JA, American Academy of Clinical Toxicology ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning (2002) American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 40:415–446CrossRefPubMed Barceloux DG, Bong GR, Krenzelok EP, Cooper H, Vale JA, American Academy of Clinical Toxicology ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning (2002) American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol 40:415–446CrossRefPubMed
16.
Zurück zum Zitat Faissel H, Houze P, Baud FJ, Scherrmann JM (1995) 4-methylpyrazole monitoring during hemodialysis of ethylene glycol intoxicated patients. Eur J Clin Pharmacol 49:211–213 Faissel H, Houze P, Baud FJ, Scherrmann JM (1995) 4-methylpyrazole monitoring during hemodialysis of ethylene glycol intoxicated patients. Eur J Clin Pharmacol 49:211–213
17.
Zurück zum Zitat Jobard E, Harry P, Turcant A, Roy PM, Allain P (1996) 4-methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol 34:379–381 Jobard E, Harry P, Turcant A, Roy PM, Allain P (1996) 4-methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol 34:379–381
18.
Zurück zum Zitat Sivilotti MLA, Burns MJ, McMartin KE, Brent J (2001) Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. Ann Emerg Med 36:114–125CrossRef Sivilotti MLA, Burns MJ, McMartin KE, Brent J (2001) Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. Ann Emerg Med 36:114–125CrossRef
19.
Zurück zum Zitat Martin Caravati E, Heileson HL, Jones M (2004) Treatment of severe pediatric ethylene glycol intoxication without hemodialysis. J Toxicol Clin Toxicol 42:255–259CrossRef Martin Caravati E, Heileson HL, Jones M (2004) Treatment of severe pediatric ethylene glycol intoxication without hemodialysis. J Toxicol Clin Toxicol 42:255–259CrossRef
20.
Zurück zum Zitat Brown MJ, Shannon MW, Woolf A, Boyer EW (2001) Childhood methanol ingestion treated with fomepizole and hemodialysis. Pediatrics 108:77–79CrossRef Brown MJ, Shannon MW, Woolf A, Boyer EW (2001) Childhood methanol ingestion treated with fomepizole and hemodialysis. Pediatrics 108:77–79CrossRef
21.
Zurück zum Zitat Benitez JG, Swanson-Biearman B, Krenzelok EP (2000) Nystagmus secondary to fomepizole administration in a pediatric patient. J Toxicol Clin Toxicol 38:795–798CrossRef Benitez JG, Swanson-Biearman B, Krenzelok EP (2000) Nystagmus secondary to fomepizole administration in a pediatric patient. J Toxicol Clin Toxicol 38:795–798CrossRef
22.
Zurück zum Zitat Roy M, Bailey B, Chalut D, Senécal PE, Gandreault P (2003) What are the adverse effects of ethanol used as an antidote in the treatment of suspected methanol poisoning in children. J Toxicol Clin Toxicol 41:155–161CrossRef Roy M, Bailey B, Chalut D, Senécal PE, Gandreault P (2003) What are the adverse effects of ethanol used as an antidote in the treatment of suspected methanol poisoning in children. J Toxicol Clin Toxicol 41:155–161CrossRef
23.
Zurück zum Zitat Hirsch DJ, Jindal KK, Wong P, Fraser AD (2001) A simple method to estimate the required dialysis time for cases of alcohol poisoning. Kidney Int 60:2021–2024CrossRef Hirsch DJ, Jindal KK, Wong P, Fraser AD (2001) A simple method to estimate the required dialysis time for cases of alcohol poisoning. Kidney Int 60:2021–2024CrossRef
24.
Zurück zum Zitat Moreau CL, Kerns W II, Tomaszewski CA, McMartin KE, Rose SR, Ford MD, Brent J (1998) Glycolate kinetics and hemodialysis in ethylene glycol poisoining. J Toxicol Clin Toxicol 36:659–666 Moreau CL, Kerns W II, Tomaszewski CA, McMartin KE, Rose SR, Ford MD, Brent J (1998) Glycolate kinetics and hemodialysis in ethylene glycol poisoining. J Toxicol Clin Toxicol 36:659–666
25.
Zurück zum Zitat Watson WA (2000) Ethylene glycol toxicity: closing in on rational, evidence-based treatment. Ann Emerg Med 36:139–141CrossRefPubMed Watson WA (2000) Ethylene glycol toxicity: closing in on rational, evidence-based treatment. Ann Emerg Med 36:139–141CrossRefPubMed
26.
Zurück zum Zitat Porter WH, Rutter PW, Bush BA, Papas AA, Dunnington JE (2001) Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol 39:607–615CrossRef Porter WH, Rutter PW, Bush BA, Papas AA, Dunnington JE (2001) Ethylene glycol toxicity: the role of serum glycolic acid in hemodialysis. J Toxicol Clin Toxicol 39:607–615CrossRef
27.
Zurück zum Zitat Hantson P, Wallemacq P, Brau M, Vanbinst R, Haufroid V, Mahieu P (1999) Two cases of acute methanol poisoning partially treated by oral 4-methylpyrazole. Intensive Care Med 25:528–531 Hantson P, Wallemacq P, Brau M, Vanbinst R, Haufroid V, Mahieu P (1999) Two cases of acute methanol poisoning partially treated by oral 4-methylpyrazole. Intensive Care Med 25:528–531
28.
Zurück zum Zitat Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J (1997) Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med 30:829–832 Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J (1997) Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med 30:829–832
29.
Zurück zum Zitat Kerns W 2nd, Tomaszewski C, McMartin K, Ford M, Brent J, META Study Group (2003) Methylpyrazole for toxic alcohols: formate kinetics in methanol poisoning. J Toxicol Clin Toxicol 41:257–258CrossRef Kerns W 2nd, Tomaszewski C, McMartin K, Ford M, Brent J, META Study Group (2003) Methylpyrazole for toxic alcohols: formate kinetics in methanol poisoning. J Toxicol Clin Toxicol 41:257–258CrossRef
30.
Zurück zum Zitat Yip L, Jacobsen D (2002) Endogenous formate elimination and total body clearance during hemodialysis. J Toxicol Clin Toxciol 40:137–143CrossRef Yip L, Jacobsen D (2002) Endogenous formate elimination and total body clearance during hemodialysis. J Toxicol Clin Toxciol 40:137–143CrossRef
31.
Zurück zum Zitat Bekka R, Borron SW, Astier A, Sandouk P, Bismuth C, Baud FJ (2001) Treatment of methanol and isopropanol poisoning with intravenous fomepizole. J Toxicol Clin Toxicol 39:59–67CrossRef Bekka R, Borron SW, Astier A, Sandouk P, Bismuth C, Baud FJ (2001) Treatment of methanol and isopropanol poisoning with intravenous fomepizole. J Toxicol Clin Toxicol 39:59–67CrossRef
32.
Zurück zum Zitat Sivilotti ML, Burns MJ, Aaron CK, McMartin KE, Brent J (2001) Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol 39:627–631CrossRef Sivilotti ML, Burns MJ, Aaron CK, McMartin KE, Brent J (2001) Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole. J Toxicol Clin Toxicol 39:627–631CrossRef
33.
Zurück zum Zitat Essama Mbia JJ, Guerit JM, Haufroid V, Hantson P (2002) Fomepizole therapy for reversal of visual impairment after methanol poisoning: a case documented by visual evoked potentials investigation. Am J Ophtalmol 134:914–916CrossRef Essama Mbia JJ, Guerit JM, Haufroid V, Hantson P (2002) Fomepizole therapy for reversal of visual impairment after methanol poisoning: a case documented by visual evoked potentials investigation. Am J Ophtalmol 134:914–916CrossRef
34.
Zurück zum Zitat Hantson P, Mahieu P (2000) Pancreatic injury following acute methanol poisoning. J Toxicol Clin Toxicol 38:297–303CrossRef Hantson P, Mahieu P (2000) Pancreatic injury following acute methanol poisoning. J Toxicol Clin Toxicol 38:297–303CrossRef
35.
Zurück zum Zitat Borron SW, Baud FJ, Garnier R (1997) Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: a case report. Vet Hum Tox 39:26–28 Borron SW, Baud FJ, Garnier R (1997) Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: a case report. Vet Hum Tox 39:26–28
36.
Zurück zum Zitat Osterhoudt KC (2002) Fomepizole therapy for pediatric butoxyethanol intoxication. J Toxicol Clin Toxicol 40:929–930CrossRefPubMed Osterhoudt KC (2002) Fomepizole therapy for pediatric butoxyethanol intoxication. J Toxicol Clin Toxicol 40:929–930CrossRefPubMed
37.
Zurück zum Zitat Mégarbane B, Fompeydie D, Garnier R, Baud FJ (2002) Treatment of a 1,4-butanediol poisoning with fomepizole. J Toxicol Clin Toxicol 40:77–80CrossRef Mégarbane B, Fompeydie D, Garnier R, Baud FJ (2002) Treatment of a 1,4-butanediol poisoning with fomepizole. J Toxicol Clin Toxicol 40:77–80CrossRef
38.
Zurück zum Zitat Brophy PD, Tenenbein M, Gardner J, Bunchman TE, Smoyer WE (2000) Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis 35:958–962PubMed Brophy PD, Tenenbein M, Gardner J, Bunchman TE, Smoyer WE (2000) Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis 35:958–962PubMed
39.
Zurück zum Zitat Lindros KO, Stowell A, Pikkarainen P, Salaspuro M (1981) The disulfiram (antabuse) – alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res 5:528–530 Lindros KO, Stowell A, Pikkarainen P, Salaspuro M (1981) The disulfiram (antabuse) – alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res 5:528–530
Metadaten
Titel
Current recommendations for treatment of severe toxic alcohol poisonings
verfasst von
Bruno Mégarbane
Stephen W. Borron
Frédéric J. Baud
Publikationsdatum
01.02.2005
Verlag
Springer-Verlag
Erschienen in
Intensive Care Medicine / Ausgabe 2/2005
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-004-2521-0

Weitere Artikel der Ausgabe 2/2005

Intensive Care Medicine 2/2005 Zur Ausgabe

Häusliche Gewalt in der orthopädischen Notaufnahme oft nicht erkannt

28.05.2024 Traumatologische Notfälle Nachrichten

In der Notaufnahme wird die Chance, Opfer von häuslicher Gewalt zu identifizieren, von Orthopäden und Orthopädinnen offenbar zu wenig genutzt. Darauf deuten die Ergebnisse einer Fragebogenstudie an der Sahlgrenska-Universität in Schweden hin.

Fehlerkultur in der Medizin – Offenheit zählt!

Darüber reden und aus Fehlern lernen, sollte das Motto in der Medizin lauten. Und zwar nicht nur im Sinne der Patientensicherheit. Eine negative Fehlerkultur kann auch die Behandelnden ernsthaft krank machen, warnt Prof. Dr. Reinhard Strametz. Ein Plädoyer und ein Leitfaden für den offenen Umgang mit kritischen Ereignissen in Medizin und Pflege.

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

17.05.2024 Klinik aktuell Nachrichten

Sie sei „ethisch geboten“, meint Gesundheitsminister Karl Lauterbach: mehr Transparenz über die Qualität von Klinikbehandlungen. Um sie abzubilden, lässt er gegen den Widerstand vieler Länder einen virtuellen Klinik-Atlas freischalten.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.