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Isopropanol Jolliff2016
Isopropanol Jolliff2016
Isopropanol Jolliff2016
Heath A. Jolliff
OH NAD+ NADH O
for CNS depression. Acetone is known to cause
CNS depression [26–30]. The literature also
H3C CH CH3 Alcohol H3C C CH3
reports cases of patients with initial CNS depres-
Isopropanol Dehydrogenase Acetone
sion whose mental status improved despite
Fig. 1 Conversion of isopropanol to its primary metabo- increasing acetone levels [8, 31]. Therefore it
lite acetone. Small amounts of isopropanol are excreted seems likely that both compounds are responsible
unchanged in the urine and expired air for the CNS depression seen with IPA toxicity.
Based on animal studies, IPA is estimated to
ketone (acetone) but not to a carboxylic acid (see have twice the intoxicating effect of ethanol at
Fig. 1). similar serum concentrations [32]. This effect
may be due to the higher molecular weight of
Pharmacokinetics of Isopropyl Alcohol IPA compared with ethanol [13] or perhaps the
Volume of distribution: 0.45–0.7 L/kg additive toxicodynamic effect of the acetone
Protein binding: negligible metabolite.
Mechanism of clearance: hepatic alcohol Respiratory depression and hypotension may
dehydrogenase metabolism, first-order accompany coma resulting from IPA intoxication
kinetics [13, 17, 23–25, 33, 34]. These effects are most
Half-life: isopropyl alcohol, 2–8 h; acetone, likely the result of peripheral vasodilation and
7.7–27.7 h depression of the brain stem [8, 13, 14, 17, 20,
Solubility: miscible in water 23, 25, 35]. Tachycardia is common and may be a
Vapor pressure: 33 mmHg compensatory response to hypotension [36].
Data from references: [13, 14, 16, 17] Common CNS effects of ethanol ingestion,
such as ataxia, nystagmus, and dysarthria, occur
but are not as common in IPA toxicity [36,
37]. Diminished reflexes are commonly seen in
comatose patients with IPA toxicity [17, 31,
Pathophysiology 36]. Seizures are rare but have been reported in
infants [35].
Central Nervous System Depression
not the IPA level, should be used to judge toxicity. levels in patients with acetone in their serum [5,
Levels should be drawn at least 30–60 min after 31, 60–63]. Serum osmolality and an osmolar
the exposure to identify peak IPA levels [5, 13, 17, gap may be determined. Caution must be used,
22]. The best method for measuring serum IPA however, because not only are acetone and IPA
levels is headspace gas chromatography with osmotically active compounds, but other sub-
flame ionization or proton nuclear magnetic reso- stances, such as methanol and ethylene glycol,
nance imaging [5]. If IPA levels are determined by are as well [64, 65]. The absence of an elevated
ADH-based enzymatic assays, the assay may osmolar gap does not rule out the presence of
interpret IPA as ethanol and give a falsely low either compound and, in clinical practice, is not
IPA level [5, 44]. Although IPA may be detected useful [66, 67].
with breathalyzers used to measure ethanol, these
levels are unreliable [56]. A possible erroneous
diagnosis of IPA poisoning may occur in patients Treatment
with diabetic ketoacidosis. Cases of measurable
IPA in these patients have been reported, although As with all toxic ingestions, treatment should
no exposure to IPA was known [57]. It has been focus on the overall clinical condition of the
theorized that the acetone produced with diabetic patient. The primary treatment centers on support-
ketoacidosis might be reduced to IPA via ADH [5, ive care. Because IPA is a CNS depressant, the
58]. It is also possible that in these cases, there was clinician must be vigilant with respect to the abil-
an unrecognized IPA exposure or that a laboratory ity of a patient to maintain his/her airway. If the
error occurred. patient is unable to maintain a patent airway,
Serum IPA levels greater than 120 mg/dL endotracheal intubation should be performed and
(20 mmol/L) have been associated with deep mechanical ventilation maintained. These patients
coma [14, 19, 48, 54]. An ingestion of 90 mL warrant continuous cardiac monitoring and pulse
(3 oz) of 70 % IPA can theoretically produce a oximetry. In patients who are initially able to
serum IPA level of 100 mg/dL (16.7 mmol/L) in a maintain a patent airway, close monitoring for
70-kg patient. As with ethanol, chronic alcoholics respiratory compromise is advised.
may tolerate higher IPA levels [7, 59]. Any patient with altered mental status should
Serum ketone or acetone concentrations may have a rapid bedside assessment of the serum glu-
be helpful in the diagnosis of IPA toxicity. Ace- cose to rule out hypoglycemia. Hypoglycemia can
tone is not usually detected in the serum until be treated with intravenous dextrose. Intravenous
30–60 min post-ingestion [8, 13, 43]. Detection access allows for normal saline administration to
in the urine is usually delayed for at least 3 h post- maintain blood pressure and ensure adequate
ingestion [13]. An initial non-detectable urine hydration and urine output. At least 100 mg of
acetone level should be repeated in patients if thiamine should be administered intravenously or
there is a high index of suspicion for IPA inges- intramuscularly to any patient in whom nutritional
tion. Acetone levels increase as ADH metabolizes status is uncertain and who may be at risk for the
IPA. Acetone should be measurable even after IPA development of Wernicke–Korsakoff syndrome
levels are undetectable. (grade III recommendation).
Laboratory tests useful in the management of Hypotension can be treated initially with intra-
IPA-poisoned patients include serum electro- venous fluids. In adults, normal saline can be
lytes, creatinine, glucose, and creatine phospho- bolused in doses of 250–500 mL each. When the
kinase. If a significant metabolic acidosis is total amount of intravenous fluids has reached
present, other causes must be considered (see approximately 2000 mL, one should be cautious
chapter on “Acid–Base Disorders”). Acetone not to fluid overload the patient. If the hypoten-
interferes with certain colorimetric assays used sion does not respond to intravenous normal
to determine serum creatinine levels; this has led saline, an intravenous pressor is the logical next
to reports of falsely elevated serum creatinine step. Adequacy of cardiac pump function can be
Isopropyl Alcohol 5
Special Populations
Key Points in Isopropyl Alcohol Poisoning
1. Toxicity may occur after oral, inhalational,
Pediatric Patients
rectal, or dermal exposure.
2. Isopropyl alcohol can be a potent central
Children may have a different susceptibility to
nervous system depressant.
dermal IPA absorption than adults owing to
3. The hallmark of IPA toxicity is ketosis
their larger body surface ratio and thin dermis.
without metabolic acidosis.
IPA has been applied dermally to reduce fever
4. Isopropyl alcohol toxicity may cause gas-
in children, with resultant significant toxicity
tritis as with other alcohols.
[45, 46, 54, 55]. It is unclear if the toxicity is
5. Treatment should focus on supportive care.
due solely to the dermal absorption or possibly
to a combination of dermal and inhalational
absorption. Infants have become toxic when
IPA was applied chronically to the umbilicus References
for cleaning [35]. Coma, hypotension, and sei-
zures all have been reported in children with 1. Richard J, Lewis S. Sax’s dangerous properties of
IPA toxicity [33, 35]. Children also have been industrial materials, vol. 1–5. 12th ed. New York:
Wiley; 2012.
noted to experience dermal irritation and chem- 2. Ashford RD. Ashford’s dictionary of industrial
ical burns when IPA was applied to the skin chemicals. 3rd ed. London: Cornwell/Wavelength;
[77]. Unlike ethanol, hypoglycemia has not 2012.
3. O’Neil MJ, Heckelman PE, Dobbelaar PH. The Merck
been reported to occur in children intoxicated
index. 15th ed. London: RSC Publishing; 2013.
with IPA [78–80]. A rare case of hemorrhagic 4. Leikin JB, Paloucek FP. Poisoning & toxicology hand-
gastritis has been reported in a pediatric patient book. 4th ed. Boca Raton: CRC Press; 2008.
with IPA toxicity [81]. 5. Slaughter RJ, Mason RW, Beasley DMG, Vale JA,
Schep LJ. Isopropanol poisoning. Clin Toxicol
(Phila). 2014;52(5):470–8.
6. Ford MD. Isopropanol. In: Clinical toxicology. Phila-
Pregnant Patients delphia: W B Saunders Company; 2001. p. 769–73.
7. Alexander CB, McBay AJ, Hudson RP. Isopropanol
and isopropanol deaths-ten years’ experience. J Foren-
Based on the size of the molecule, its solubility, sic Sci. 1982;27(3):541–8.
and its similarity to ethanol, IPA is expected to 8. Gaudet MP, Fraser GL. Isopropanol ingestion: case
cross the placenta. Hypotension in the mother is a report with pharmacokinetic analysis. Am J Emerg
Med. 1989;7(3):297–9.
concern for the overall status of the fetus. Sup-
9. Emadi A, Coberly L. Intoxication of a hospitalized
portive care for the mother is paramount for patient with an isopropanol-based hand sanitizer. N
protecting the fetus. IPA is not considered a Engl J Med. 2007;356(5):530–1.
human carcinogen, and its teratogenicity to 10. Kawai T, Yasugi T, Horiguchi S, et al. Biological mon-
itoring of occupational exposure to isopropyl alcohol
humans is unknown [82].
vapor by urinalysis for acetone. Int Arch Occup Envi-
ron Health. 1990;62(5):409–13.
Common Errors in Isopropyl Alcohol Poisoning 11. Lee EG, Harper M, Bowen RB, Slaven J. Evaluation of
Not considering isopropyl alcohol as a poten- COSHH essentials: methylene chloride, isopropanol,
and acetone exposures in a small printing plant. Ann
tial cause in an intoxicated patient
Occup Hyg. 2009;53(5):463–74.
Ruling out the diagnosis of isopropyl alco- 12. Turner P, Saeed B, Kelsey MC. Dermal absorption of
hol intoxication based on a normal osmolality isopropyl alcohol from a commercial hand rub: impli-
and osmolar gap cations for its use in hand decontamination. J Hosp
Infect. 2004;56(4):287–90.
Attributing an anion gap metabolic acidosis
13. Lacouture PG, Wason S, Abrams A, Lovejoy
to isopropyl alcohol FH. Acute isopropyl alcohol intoxication. Diagnosis
Using hemodialysis instead of good sup- and management. Am J Med. 1983;75(4):680–6.
portive care as a cornerstone of treatment 14. Natowicz M, Donahue J, Gorman L, Kane M,
McKissick J, Shaw L. Pharmacokinetic analysis of a
Isopropyl Alcohol 7
case of isopropanol intoxication. Clin Chem. 1985;31 33. Vicas IM, Beck R. Fatal inhalational isopropyl alcohol
(2):326–8. poisoning in a neonate. Clin Toxicol (Phila). 1993;31
15. Baselt R. Isopropanol. In: Disposition of toxic drugs (3):473–81.
and chemicals in man. 10th ed. Seal Beach: Biomedical 34. Adelson L. Fatal intoxication with isopropyl alcohol
Publications; 2014. p. 1073–5. (rubbing alcohol). Am J Clin Pathol. 1962;38:144–51.
16. Daniel DR, McAnalley BH, Garriott JC. Isopropyl 35. Vivier PM, Lewander WJ, Martin HF, Linakis
alcohol metabolism after acute intoxication in humans. JG. Isopropyl alcohol intoxication in a neonate through
J Anal Toxicol. 1981;5(3):110–2. chronic dermal exposure: a complication of a
17. Pappas AA, Ackerman BH, Olsen KM. Isopropanol culturally-based umbilical care practice. Pediatr
ingestion: a report of six episodes with isopropanol and Emerg Care. 1994;10(2):91–3.
acetone serum concentration time data. J Toxicol Clin 36. Kelner M, Bailey DN. Isopropanol Ingestion: interpre-
Toxicol. 1991;29(1):11–21. tation of blood concentrations and clinical findings.
18. Lewin GA, Oppenheimer PR, Wingert WA. Coma Clin Toxicol (Phila). 1983;20(5):497–507.
from alcohol sponging. JACEP. 1977;6(4):165–7. 37. Rich J, Scheife RT, Katz N, Caplan LR. Isopropyl
19. McCord WM, Switzer PK, Brill HH. Isopropyl alcohol alcohol intoxication. Arch Neurol. 1990;47(3):322–4.
intoxication. South Med J. 1948;41(7):639–42. 38. Lehman AJ, Chase HF. The acute and chronic toxicity
20. Rosansky SJ. Isopropyl alcohol poisoning treated with of isopropyl alcohol. J Lab Clin Med Elsevier. 1944;29
hemodialysis: kinetics of isopropyl alcohol and ace- (6):561–7.
tone removal. J Toxicol Clin Toxicol. 1982;19 39. Haviv YS, Safadi R, Osin P. Accidental isopropyl
(3):265–71. alcohol enema leading to coma and death. Am J
21. Lacouture PG, Heldreth DD, Shannon M, Lovejoy Gastroenterol. 1998;93(5):850–1.
FH. The generation of acetonemia/acetonuria follow- 40. Corbett J, Meier G. Suicide attempted by rectal admin-
ing ingestion of a subtoxic dose of isopropyl alcohol. istration of drug. JAMA. 1968;206(10):2320–1.
Am J Emerg Med. 1989;7(1):38–40. 41. Barnett JM, Plotnick M, Fine KC. Intoxication after an
22. Parker KM, Lera TA. Acute isopropanol ingestion: isopropyl alcohol enema. Ann Intern Med. 1990;113
pharmacokinetic parameters in the infant. Am J (8):638–9.
Emerg Med. 1992;10(6):542–4. 42. Chapin MA. Isopropyl alcohol poisoning with acute
23. King LH, Bradley KP, Shires DL. Hemodialysis for renal insufficiency. J Maine Med Assoc. 1949;40
isopropyl alcohol poisoning. JAMA. 1970;211 (10):288–90.
(11):1855–1855. 43. Ashkar FS, Miller R. Hospital ketosis in the alcoholic
24. Martinez TT, Jaeger RW, deCastro FJ, Thompson MW, diabetic: a syndrome due to isopropyl alcohol intoxi-
Hamilton MF. A comparison of the absorption and cation. South Med J. 1971;64(11):1409–11.
metabolism of isopropyl alcohol by oral, dermal and 44. Vasiliades J, Pollock J, Robinson CA. Pitfalls of the
inhalation routes. Vet Hum Toxicol. 1986;28(3):233–6. alcohol dehydrogenase procedure for the emergency
25. Freireich AW, Cinque TJ, Xanthaky G, Landau assay of alcohol: a case study of isopropanol overdose.
D. Hemodialysis for isopropanol poisoning. N Engl J Clin Chem. 1978;24(2):383–5.
Med. 1967;277(13):699–700. Hemodialysis for 45. Visudhiphan P, Kaufman H. Increased cerebrospinal
Isopropanol Poisoning – NEJM. 1967;277 fluid protein following isopropyl alcohol intoxication.
(13):699–700. N Y State J Med. 1971;71(8):887–8.
26. Ross DS. Acute acetone intoxication. Occup Health 46. McFadden SW, Haddow JE. Coma produced by topical
(Lond). 1975;27(3):120–4. application of isopropanol. Pediatrics. 1969;43
27. Gamis AS, Wasserman GS. Acute acetone intoxication (4):622–3.
in a pediatric patient. Pediatr Emerg Care. 1988;4 47. Juncos L, Taguchi JT. Isopropyl alcohol intoxication.
(1):24–6. Report of a case associated with myopathy renal fail-
28. Gitelson S, Werczberger A, Herman JB. Coma and ure, and hemolytic anemia. JAMA. 1968;204
hyperglycemia following drinking of acetone. Diabe- (8):732–4.
tes. 1966;15(11):810–1. 48. Manring E, Meggs W, Pape G, Ford M. Toxicity of an
29. Ramu A, Rosenbaum J, Blaschke TF. Disposition of intravenous infusion of isopropyl alcohol. J Toxicol
acetone following acute acetone intoxication. West J Clin Toxicol. 1997;35(5):503.
Med. 1978;129(5):429–32. 49. Dhillon S, Von Burg R. Isopropyl alcohol. J Appl
30. Oliver JS, Watson JM. Abuse of solvents “for kicks”. A Toxicol. 1995;15(6):501–6.
review of 50 cases. Lancet. 1977;1(8002):84–6. 50. Wasilewski C. Allergic contact dermatitis from isopro-
31. Mydler TT, Wasserman GS, Watson WA, Knapp pyl alcohol. Arch Dermatol. 1968;98(5):502–4.
JF. Two-week-old infant with isopropanol intoxication. 51. Ludwig E, Hausen BM. Sensitivity to isopropyl alco-
Pediatr Emerg Care. 1993;9(3):146–8. hol. Contact Dermatitis. 1977;3(5):240–4.
32. Wallgreen H. Relative intoxicating effects on rats of 52. Fuller HC, Hunter OB. Isopropyl alcohol-an investiga-
ethyl, propyl and butyl alcohols. Acta Pharmacol tion of its physiologic properties. J Lab Clin Med.
Toxicol (Copenh). 1960;16:217–22. 1927;12:326–49.
8 H.A. Jolliff
53. Wills JH, Jameson EM, Coulston F. Effects on man of 68. Albertson TE, Dawson A, de Latorre F, et al. TOX-
daily ingestion of small doses of isopropyl alcohol. ACLS: toxicologic-oriented advanced cardiac life sup-
Toxicol Appl Pharmacol. 1969;15(3):560–5. port. Ann Emerg Med. 2001;37 Suppl 4:S78–90.
54. Senz EH, Goldfarb DL. Coma in a child following use 69. Light FB, Marx GF. The value of gastric aspiration in a
of isopropyl alcohol in sponging. J Pediatr. 1958;53 comatose child. Anesthesiology. 1969;31(5):478–80.
(3):322–3. 70. Watkins AM, Keogh EJ. Alcohol burns in the neonate.
55. Garrison RF. Acute poisoning from use of isopropyl J Paediatr Child Health. 1992;28(4):306–8.
alcohol in tepid sponging. J Am Med Assoc. 1953;152 71. Burkhart KK, Martinez MA. The adsorption of
(4):317–8. isopropanol and acetone by activated charcoal. J
56. Logan BK, Gullberg RG, Elenbaas JK. Isopropanol Toxicol Clin Toxicol. 1992;30(3):371–5.
interference with breath alcohol analysis: a case report. 72. Wiener SW. Toxic alcohols. In: Hoffman R, editor.
J Forensic Sci. 1994;39(4):1107–11. Goldfrank’s toxicologic emergencies. 10th ed. -
57. Bailey DN. Detection of isopropanol in acetonemic New York: McGraw Hill Professional; 2014.
patients not exposed to isopropanol. J Toxicol Clin p. 1346–57.
Toxicol. 1990;28(4):459–66. 73. Trullas JC, Aguilo S, Castro P, Nogue S. Life-
58. Jones AE, Summers RL. Detection of isopropyl alco- threatening isopropyl alcohol intoxication: is hemodi-
hol in a patient with diabetic ketoacidosis. J Emerg alysis really necessary? Vet Hum Toxicol. 2004;46
Med. 2000;19(2):165–8. (5):282–4.
59. Mendelson J, Wexler D, Leiderman PH, Solomon P. A 74. Mecikalski MB, Depner TA. Peritoneal dialysis for
study of addiction to nonethyl alcohols and other poi- isopropanol poisoning. West J Med. 1982;137
sonous compounds. Q J Stud Alcohol. 1957;18 (4):322–5.
(4):561–80. 75. Bekka R, Borron SW, Astier A, Sandouk P, Bismuth C,
60. Hawley PC, Falko JM. “Pseudo” renal failure after Baud FJ. Treatment of methanol and isopropanol poi-
isopropyl alcohol intoxication. South Med J. 1982;75 soning with intravenous fomepizole. J Toxicol Clin
(5):630–1. Toxicol. 2001;39(1):59–67.
61. Watkins PJ. The effect of ketone bodies on the deter- 76. Lee SL, Shih HT, Chi YC, Li YP, Yin SJ. Oxidation of
mination of creatinine. Clin Chim Acta. 1967;18 methanol, ethylene glycol, and isopropanol with
(2):191–6. human alcohol dehydrogenases and the inhibition by
62. Adla MR, Gonzalez-Paoli JA, Rifkin SI. Isopropyl ethanol and 4-methylpyrazole. Chem Biol Interact.
alcohol ingestion presenting as pseudorenal failure 2011;191(1–3):26–31.
due to acetone interference. South Med J. 2009;102 77. Schick JB, Milstein JM. Burn hazard of isopropyl
(8):867–9. alcohol in the neonate. Pediatrics. 1981;68(4):587–8.
63. Killeen C, Meehan T, Dohnal J, Leikin JB. Pseudorenal 78. Ricci LR, Hoffman SA. Ethanol-induced hypoglyce-
insufficiency with isopropyl alcohol ingestion. Am J mic coma in a child. Ann Emerg Med. 1982;11
Ther. 2011;18(4):e113–6. (4):202–4.
64. Chan KM, Wong ET, Matthews WS. Severe 79. Cummins LH. Hypoglycemia and convulsions in chil-
isopropanolemia without acetonemia or clinical mani- dren following alcohol ingestion. J Pediatr.
festations of isopropanol intoxication. Clin Chem. 1961;58:23–6.
1993;39(9):1922–5. 80. Hornfeldt CS. A report of acute ethanol poisoning in a
65. Monaghan MS, Ackerman BH, Olsen KM, Farmer C, child: mouthwash versus cologne, perfume and after-
Pappas AA. The use of delta osmolality to predict shave. Clin Toxicol. 1992;30(1):115–21.
serum isopropanol and acetone concentrations. Phar- 81. Dyer S, Mycyk MB, Ahrens WR, Zell-Kanter
macotherapy. 1993;13(1):60–3. M. Hemorrhagic gastritis from topical isopropanol
66. Glaser DS. Utility of the serum osmol gap in the exposure. Ann Pharmacother. 2002;36(11):1733–5.
diagnosis of methanol or ethylene glycol ingestion. 82. IARC monographs: isopropanol. Vol 71. Lyon:
Ann Emerg Med. 1996;27(3):343–6. WHO/International Agency for Research on Cancer;
67. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank 2008. p. 1027–36.
LR. Osmol gaps revisited: normal values and limita-
tions. J Toxicol Clin Toxicol. 1993;31(1):81–93.