- Email: [email protected]
Isopropanol
SPECIFIC SUBSTANCES
Isopropanol
myopathy and haemolytic anaemia. Development of hypotension is a poor prognostic feature5,15 and can herald cardiac arrest.5,14
Allister Vale
Management There is no evidence that gastric lavage is of value in reducing absorption, nor would this be expected, as absorption is rapid. The mainstay of treatment is supportive care. In addition, since isopropanol has a small volume of distribution (0.45e0.55 litre/kg)4 and is responsible together with its metabolite, acetone, for toxicity, there is a role for haemodialysis in the management of severely poisoned patients with very high plasma isopropanol concentrations. Isopropanol clearance during haemodialysis was 137 ml/min;15 58,325 milligrams isopropanol was removed over 3 hours. Acetone is also removed effectively by haemodialysis.15 No advantage is gained by administering fomepizole to block alcohol dehydrogenase, as such treatment will prolong isopropanol elimination and thereby enhance toxicity. A
Abstract Isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase. The effects on the central nervous system are similar to those of ethanol but probably more severe. Coma and respiratory depression are the major sequelae after substantial exposure. The mainstay of treatment is supportive care, although in severe cases haemodialysis will remove isopropanol and acetone effectively.
Keywords Acetone; haemodialysis; isopropanol
Introduction Isopropanol is found in aftershave lotions, disinfectants and window-cleaning solutions, and is used as a sterilizing agent and ‘rubbing’ alcohol. It is usually ingested, but inhalation1 and topical exposure2 have led to poisoning; there is one report of the accidental use of an isopropanol-containing enema leading to coma and death.3 Isopropanol poisoning has recently been reviewed.4
REFERENCES 1 Vicas IMO, Beck R. Fatal inhalational isopropyl alcohol poisoning in a neonate. J Toxicol Clin Toxicol 1993; 31: 473e81. 2 McFadden SW, Haddow JE. Coma produced by topical application of isopropanol. Pediatrics 1969; 43: 622e3. 3 Haviv YS, Safadi R, Osin P. Accidental isopropyl alcohol enema leading to coma and death. Am J Gastroenterol 1998; 93: 850e1. 4 Slaughter RJ, Mason RW, Beasley DMG, et al. Isopropanol poisoning. Clin Toxicol 2014; 52: 470e8. 5 Abramson S, Singh AK. Treatment of the alcohol intoxications: ethylene glycol, methanol and isopropanol. Curr Opin Nephrol Hypertens 2000; 9: 695e701. 6 Stremski E, Hennes H. Accidental isopropanol ingestion in children. Pediatr Emerg Care 2000; 16: 238e40. 7 Parker KM, Lera Jr TA. Acute isopropanol ingestion: pharmacokinetic parameters in the infant. Am J Emerg Med 1992; 10: 542e4. 8 Gaudet MP, Fraser GL. Isopropanol ingestion: case report with pharmacokinetic analysis. Am J Emerg Med 1989; 7: 297e9. 9 Vale A. Alcohols and glycols. Medicine 2016; 44: 128e32. 10 Pappas AA, Ackerman BH, Olsen KM, Taylor EH. Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data. J Toxicol Clin Toxicol 1991; 29: 11e21. 11 Mecikalski MB, Depner TA. Peritoneal dialysis for isopropanol poisoning. West J Med 1982; 137: 322e5. 12 Trullas JC, Aguilo S, Castro P, Nogue S. Life-threatening isopropyl alcohol intoxication: is hemodialysis really necessary? Vet Hum Toxicol 2004; 46: 282e4. 13 Dyer S, Mycyk MB, Ahrens WR, Zell-Kanter M. Hemorrhagic gastritis from topical isopropanol exposure. Ann Pharmacother 2002; 36: 1733e5. 14 Lacouture PG, Wason S, Abrams A, Lovejoy Jr FH. Acute isopropyl alcohol intoxication. Diagnosis and management. Am J Med 1983; 75: 680e6. 15 Rosansky SJ. Isopropyl alcohol poisoning treated with hemodialysis: kinetics of isopropyl alcohol and acetone removal. J Toxicol Clin Toxicol 1982; 19: 265e71.
Toxicokinetics After ingestion, peak serum isopropanol concentrations are reached after 15e30 minutes.5,6 Isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase;6,7 hence, fomepizole inhibits isopropanol metabolism. Isopropanol and acetone are both excreted primarily in the urine with minimal amounts through the lungs;6 the odour of acetone can be detected on the breath. The elimination half-life of isopropanol is usually 5.8e7.3 hours,7,8 although the reported range is 2.5 and 8.0 hours; the elimination of acetone is often slower, with a half-life following isopropanol ingestion of 7.7e27 hours.4
Mechanisms of toxicity The effects of isopropanol on the nervous system are similar to those of ethanol (see Alcohols and Glycols on pages 128e132 of this issue),9 but often more severe and more persistent.
Features Coma10,11 and respiratory depression10e12 are the major sequelae following substantial exposure. Coma can be prolonged due to the relatively slow metabolism of isopropanol and the subsequent generation of acetone. The most common metabolic effects are an increased osmolal gap, ketonaemia and ketonuria. Other features following ingestion include haemorrhagic gastritis (although this has also been reported after topical application),13 haematemesis, hypotension,10,12,14 hypothermia, sinus tachycardia,8 frequent premature ventricular beats,8 renal tubular necrosis, acute Allister Vale MD FRCP FRCPE FRCPG FFOM FAACT FBTS FBPhS FEAPCCT is Director of the National Poisons Information Service (Birmingham Unit) at City Hospital, Birmingham, and Honorary Professor, University of Birmingham, UK. Competing interests: none declared.
MEDICINE 44:3
179
Ó 2016 Published by Elsevier Ltd.
Isopropanol
myopathy and haemolytic anaemia. Development of hypotension is a poor prognostic feature5,15 and can herald cardiac arrest.5,14
Allister Vale
Management There is no evidence that gastric lavage is of value in reducing absorption, nor would this be expected, as absorption is rapid. The mainstay of treatment is supportive care. In addition, since isopropanol has a small volume of distribution (0.45e0.55 litre/kg)4 and is responsible together with its metabolite, acetone, for toxicity, there is a role for haemodialysis in the management of severely poisoned patients with very high plasma isopropanol concentrations. Isopropanol clearance during haemodialysis was 137 ml/min;15 58,325 milligrams isopropanol was removed over 3 hours. Acetone is also removed effectively by haemodialysis.15 No advantage is gained by administering fomepizole to block alcohol dehydrogenase, as such treatment will prolong isopropanol elimination and thereby enhance toxicity. A
Abstract Isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase. The effects on the central nervous system are similar to those of ethanol but probably more severe. Coma and respiratory depression are the major sequelae after substantial exposure. The mainstay of treatment is supportive care, although in severe cases haemodialysis will remove isopropanol and acetone effectively.
Keywords Acetone; haemodialysis; isopropanol
Introduction Isopropanol is found in aftershave lotions, disinfectants and window-cleaning solutions, and is used as a sterilizing agent and ‘rubbing’ alcohol. It is usually ingested, but inhalation1 and topical exposure2 have led to poisoning; there is one report of the accidental use of an isopropanol-containing enema leading to coma and death.3 Isopropanol poisoning has recently been reviewed.4
REFERENCES 1 Vicas IMO, Beck R. Fatal inhalational isopropyl alcohol poisoning in a neonate. J Toxicol Clin Toxicol 1993; 31: 473e81. 2 McFadden SW, Haddow JE. Coma produced by topical application of isopropanol. Pediatrics 1969; 43: 622e3. 3 Haviv YS, Safadi R, Osin P. Accidental isopropyl alcohol enema leading to coma and death. Am J Gastroenterol 1998; 93: 850e1. 4 Slaughter RJ, Mason RW, Beasley DMG, et al. Isopropanol poisoning. Clin Toxicol 2014; 52: 470e8. 5 Abramson S, Singh AK. Treatment of the alcohol intoxications: ethylene glycol, methanol and isopropanol. Curr Opin Nephrol Hypertens 2000; 9: 695e701. 6 Stremski E, Hennes H. Accidental isopropanol ingestion in children. Pediatr Emerg Care 2000; 16: 238e40. 7 Parker KM, Lera Jr TA. Acute isopropanol ingestion: pharmacokinetic parameters in the infant. Am J Emerg Med 1992; 10: 542e4. 8 Gaudet MP, Fraser GL. Isopropanol ingestion: case report with pharmacokinetic analysis. Am J Emerg Med 1989; 7: 297e9. 9 Vale A. Alcohols and glycols. Medicine 2016; 44: 128e32. 10 Pappas AA, Ackerman BH, Olsen KM, Taylor EH. Isopropanol ingestion: a report of six episodes with isopropanol and acetone serum concentration time data. J Toxicol Clin Toxicol 1991; 29: 11e21. 11 Mecikalski MB, Depner TA. Peritoneal dialysis for isopropanol poisoning. West J Med 1982; 137: 322e5. 12 Trullas JC, Aguilo S, Castro P, Nogue S. Life-threatening isopropyl alcohol intoxication: is hemodialysis really necessary? Vet Hum Toxicol 2004; 46: 282e4. 13 Dyer S, Mycyk MB, Ahrens WR, Zell-Kanter M. Hemorrhagic gastritis from topical isopropanol exposure. Ann Pharmacother 2002; 36: 1733e5. 14 Lacouture PG, Wason S, Abrams A, Lovejoy Jr FH. Acute isopropyl alcohol intoxication. Diagnosis and management. Am J Med 1983; 75: 680e6. 15 Rosansky SJ. Isopropyl alcohol poisoning treated with hemodialysis: kinetics of isopropyl alcohol and acetone removal. J Toxicol Clin Toxicol 1982; 19: 265e71.
Toxicokinetics After ingestion, peak serum isopropanol concentrations are reached after 15e30 minutes.5,6 Isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase;6,7 hence, fomepizole inhibits isopropanol metabolism. Isopropanol and acetone are both excreted primarily in the urine with minimal amounts through the lungs;6 the odour of acetone can be detected on the breath. The elimination half-life of isopropanol is usually 5.8e7.3 hours,7,8 although the reported range is 2.5 and 8.0 hours; the elimination of acetone is often slower, with a half-life following isopropanol ingestion of 7.7e27 hours.4
Mechanisms of toxicity The effects of isopropanol on the nervous system are similar to those of ethanol (see Alcohols and Glycols on pages 128e132 of this issue),9 but often more severe and more persistent.
Features Coma10,11 and respiratory depression10e12 are the major sequelae following substantial exposure. Coma can be prolonged due to the relatively slow metabolism of isopropanol and the subsequent generation of acetone. The most common metabolic effects are an increased osmolal gap, ketonaemia and ketonuria. Other features following ingestion include haemorrhagic gastritis (although this has also been reported after topical application),13 haematemesis, hypotension,10,12,14 hypothermia, sinus tachycardia,8 frequent premature ventricular beats,8 renal tubular necrosis, acute Allister Vale MD FRCP FRCPE FRCPG FFOM FAACT FBTS FBPhS FEAPCCT is Director of the National Poisons Information Service (Birmingham Unit) at City Hospital, Birmingham, and Honorary Professor, University of Birmingham, UK. Competing interests: none declared.
MEDICINE 44:3
179
Ó 2016 Published by Elsevier Ltd.