Isopropyl Alcohol Intoxication Jaime Rich, MD; Richard T. Scheife, PharmD; Nathaniel Katz, MD; Louis R. Caplan, MD
\s=b\ Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and labora-
tory findings. (Arch Neurol. 1990;47:322-324)
intoxication is an extremely "p^thanol common social and medical prob¬
lem whose symptoms are well known to laymen. Some alcoholics also abuse cheap substitute intoxicants. The toxic effects of methanol (Sterno) and ethylene glycol (antifreeze) have been well described, but isopropyl al¬ cohol (IPA) (rubbing alcohol, "blue heaven") toxicity is less well known. Patients with IPA intoxication present in two different situations: stupor in a known alcoholic, and as an encephalopathy of unknown cause in individuals who hide their addiction. We describe three patients who pro¬ vide examples of these presentations, and review the scant literature on the clinical and laboratory features and treatment of IPA intoxication. even
Accepted
for publication June 5,1989. From the Department of Neurology, Tufts University, 750 Washington St, Boston, Mass. Reprint requests to Department of Neurology, Tufts University, 750 Washington St, Boston, MA 02111 (Dr Caplan).
REPORT OF CASES
nary acetone
44-year-old black man came department because of epigastric, joint, and muscle pain that had been present for 4 days. He was an alcoholic who had been admitted to another hospital 3 weeks previously after alcohol with¬ drawal seizures. After discharge, he conva¬ lesced at his sister's house; she, along with the patient, insisted that he had had no ac¬ cess to ethanol during the preceding 2 weeks. The sister reported that for a few days he had been uncharacteristically apa¬ thetic, and his speech, walking, and mem¬ ory had deteriorated. The patient also com¬ plained of a constant headache and loss of visual clarity. He vigorously denied re¬ cently drinking alcohol, Sterno, rubbing al¬ Case 1.—A
to the emergency
cohol, or antifreeze. On examination, there
odor of alcohol. The patient was alert but slow and abulie. His speech was dysarthric and terse, with frequent omis¬ sion of words and perseverations during repetition of sentences. His speech compre¬ hension was normal. His short-term mem¬ ory was very poor: he recalled none of three objects after 2 minutes. A short attention span and distractibility made testing of reading, writing, drawing, and copying dif¬ ficult. The patient's cranial nerves were normal, except for sluggish pupils and prominent horizontal nystagmus. His strength was normal, but he had appendicular and gait ataxia. Deep tendon reflexes were exaggerated and plantar responses were extensor. Pin and touch perception were decreased in a stocking distribution. was no
Computed tomographic findings
were
normal. A sample of cerebrospinal fluid was normal except for a protein content of 0.61 g/L. Serum amylase and creatine kinase levels were elevated. After admission, the patient had a grand mal seizure. His think¬ ing, memory, and gait gradually improved, and by day 4, his examination results were nearly normal. The next day, however, he was found wandering around the hospital, confused, with recurrence of dysarthria and ataxia. A nurse alertly noticed that his bedside rubbing alcohol bottle was missing. At that time, admission studies were re¬ ported and showed an acetone level of 41710 Mmol/L and an IPA level of 3 mmol/L. Uri-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/19/2015
was
absent. Serum electro¬
lyte levels, carbon dioxide content, and anion gap were normal. The patient then admitted to long-term IPA abuse and said that he had drunk rubbing alcohol in his sister's house, as well as in the hospital. Case 2.—A-38-year-old white man was admitted for sudden stupor after a head in¬
jury. He had a long history of alcoholism complicated by seizures and delirium tremens and took phenytoin sodium and phé¬
nobarbital sodium for seizures. He had been. on a "binge" for 2 weeks. A day before ad¬ mission, he was hit on the forehead, sus¬ taining a laceration that required sutures. On the day of admission, he came to the emergency department because of a nose¬ bleed and frontal headache. On arrival he was alert and walking, but smelled of eth¬ anol. He was dishevelled, unshaven, and unkempt. Findings of the medical resi¬ dent's examination were "nonfocal." Fif¬ teen minutes after the patient was seen us¬ ing the urinal, he was found unresponsive. His temperature was 37.8°C, his pulse rate was 100 beats per minute, and his blood pressure was 120/70 mm Hg. He was unre¬ sponsive to deep pain and did not move his limbs except for two brief witnessed epi¬ sodes of stiffening and trembling of the arms, lasting a few seconds. Pupils, fundi, and oculocephalic responses were normal. Tendon reflexes were normal and plantar responses were flexor. Arterial blood gas analysis showed a pH of 7.25, a Pco2 of 55 mm Hg, and a Po2 of 51 mm Hg. The patient was intubated and mechanically ventilated. A catheterized urine specimen showed blood and 1+ ke¬ tones and bilirubin. Serum urea nitrogen and electrolyte levels were normal. The se¬ rum acetone level was 1650 Mmol/L; etha¬ nol, 74 mmol/L; and IPA, 38 mmol/L. The serum phenytoin level was 15 Mmol/L and phénobarbital was not detectable. A few hours after vigorous hydration and nasogastric lavage, the patient awakened and moved his limbs. On hospital day 2, he was restless and agitated and later reported vi¬ sual hallucinations. After treatment with lorazepam and chlordiazepoxide hydrochlo¬ ride for his delirium tremens, he signed out against medical advice. Case 3.—A 44-year-old man was brought
to the hospital in coma. He was a street person who had had previous admissions
for head injury and other complications of alcoholism. At 9 AM that morning he had visited the emergency department because of a large purulent hand wound, but left, refusing treatment. At 2 pm he was found unconscious in a nearby park amid empty bottles of IPA and mouthwash. He was un¬ responsive. His temperature was 36°C, his blood pressure was 88/62 mm Hg, his pulse rate was 80 beats per minute, and his res¬ piratory rate was 24 breaths per minute. In the emergency department he became more hypotensive; his pulse rate slowed and he had a sinus arrest. Sinus rhythm returned after chest compression and bag ventila¬ tion. After the patient underwent intuba¬ tion and intravenous treatment with saline, thiamine hydrochloride, dextrose, and naloxone hydrochloride, his pulse rate and blood pressure improved and he was admit¬ ted to an intensive care unit. He did not react to painful stimuli. His pupils were initially unreactive but later were 4 mm in diameter and reacted slowly and partially. There was no response to oculocephalic or corneal stimulation. Tone was symmetrically decreased, and the deep tendon reflexes were symmetrically brisk. Plantar responses were extensor. Initial laboratory test results were as follows: se¬ rum sodium, 140 mmol/L; potassium, 3.4 mmol/L; chloride, 105 mmol/L; bicarbon¬ ate, 21 mmol/L; serum urea nitrogen, 3.0 mmol/L; IPA, 89 mmol/L; acetone, 7030 Mmol/L; and ethanol, 16 mmol/L. Hemodialysis was begun at 10 pm. Serum, urinary, and dialysate levels of IPA and acetone are noted in Table 1. At 1:30 am, the patient be¬ gan to awaken and moved all extremities. By 11:30 am he sat up and tried to remove his endotracheal tube. He was extubated the following day and left the hospital against advice early on the fourth hospital day. COMMENT
Alcoholics, like other substance abusers, often have a repertoire of agents they use. Most prefer ethanol, but abuse IPA, methanol, or ethylene access to ethanol is frus¬ trated or when funds run out. A few individuals seem to prefer IPA. The
glycol when
of IPA is rubbing alcohol, which contains a 70% solution of IPA. Rubbing alcohol is used widely in hospitals and medical facilities and is readily available in many stores. In hospitals, IPA is often colored with blue dye to distinguish it visually from many other clear and colorless liquids; this practice has led to the designation blue heaven by abusers. Two of our pa¬ tients ingested IPA in hospital facili¬ ties, one in the emergency department, and the other in his room, from his bedside rubbing alcohol bottle. The other patient drank IPA in a nearby park. One of us (L.R.C.), during an in¬ ternship at the Boston (Mass) City most common
source
Hospital, observed
many alcoholics
Table 1.—Levels of
Isopropyl Alcohol (IPA)
and Acetone
IPA, mmol/L Serum
Urine
(Patient 3)
Acetone, Mmol/L Serum
Dialysate
Urine
Dialysate
Day 1, before dialysis Day 2, after dialysis 28
1 AM
4:30
17 460
am
5800
15
2
31980
PM
Day 3, Day 4,
4
am
840
4 am
Table 2.—Differential Characteristics of Alcohol Intoxications*
Isopropyl Methanol Characteristic
Ethanol
Ethylene Glycol
Alcohol
Yes
Yes
Yes
No
Onset
Rapid (30-60 min)
Rapid (30-60 min)
Rapid (30-60 min)
Late effects Metabolic
Severe (24 h) Severe (lactate
Mild to moderate
Absent
Rapid (30-60 min) Severe (48 h) Severe (lactate,
odor
acidosis
formate)
(lactic)
or
slight
(lactic)
oxalate,
glycolate) Ketones
Ketobutyric
Acetoacetic
Anion gap >12 mmol/L
Large
Moderate
Serum
Each 80 mg/dL adds 27 mOsm
Each 350
Acetone
hydroxybutyrate
osmolarity
mg/dL
adds 80 mOsm
Slight
Large
Each 340 mg/dL adds 60 mOsm, and each 55
Each 21 mg/dL adds 3.5 mOsm
mg/dL
of acetone adds 10
mOsm Serum
Amylase increased Hypoglycemia
Hypoglycemia
Hypocalcemia
Other
Dilated nonreactive
Gastritis,
Oxalic acid
findings
pupils, retinal
hematemesis
crystalluria
edema, blindness Modified from chart in LaCoutre et al."
drinking blue thermometer fluid (IPA) in the emergency department when they believed themselves to be unob¬
served. Since the first case of IPA intoxica¬ tion was reported in 1948 by McCord et al,1 much has been learned about the pharmacologie effects of this agent. The acute potency of IPA as a central nervous system depressant is about twice that of ethanol. The fatal inges¬ tion dose is about 250 mL in a nonalco¬ holic patient, but alcoholics clearly have a higher tolerance to its toxic effects.24 Essentially, all of an ingested dose is absorbed within 30 minutes, but massive doses may take somewhat longer to absorb. Isopropyl alcohol is eliminated from the body by firstorder kinetics; ie, its half-life is not dependent on the size of the dose.4"7 It has a volume of distribution of 0.6 to 0.7 L/kg.8 The primary metabolite of IPA is acetone. In one study that ex¬ amined the kinetics of IPA and acetone in a nonalcoholic patient, the serum
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/19/2015
half-lives of IPA and acetone in the were similar to those in the serum.4 Alcoholics metab¬ olize IPA more quickly than do nonalcoholics, showing a half-life of 3 to 4 hours6-8; this rapid clearance probably at least partially accounts for toler¬
cerebrospinal fluid
ance.
Ingestion of IPA can cause severe pain, with gastritis and frequent nausea and vomiting, occa¬ sionally with hematemesis.2·8"" Our pa¬ tient 1 had prominent intestinal symp¬ toms mimicking or associated with pancreatitis. Early nervous system abdominal
symptoms of IPA intoxication
are
qualitatively similar to those of etha¬ nol intoxication, but the initial phase
of exhilaration often described after ethanol use is conspicuously absent after IPA use. Dizziness, ataxia, head¬ ache, and confusion are reported. Iso¬ propyl alcohol can rapidly produce coma (as in patients 2 and 3). Coma rarely persists for more than 12 hours in nonfatal cases.812 Death after a
large ingestion of IPA is usually pre¬ ceded by respiratory arrest and deep coma, usually within a few hours. Even when patients are adequately venti¬ lated, serious cardiac toxicity is often caused by IPA and other aliphatic al¬ cohols. Arrhythmias, arterial hy¬ potension, and frank cardiac muscle
necrosis have been described.313 Ingestion of IPA usually causes coma with variable-sized but usually miotic pupils.8 Neurologic signs of subacute intoxication have not been de¬ scribed. The findings of neurologic ex¬ amination in our patient 1 were very unusual: the examination showed dys¬ arthria, nystagmus, and ataxia (find¬ ings common in ethanol intoxication) and prominent corticospinal tract dys¬ function. Although the patient was awake and quite alert, there were se¬ vere cognitive and behavioral abnor¬ malities, with abulia and a very short attention span. The findings mimicked a "subcortical dementia" as has been described in patients with frontal lobe disease, multi-infarct dementia, tha¬ lamic lesions, and various system de¬
generations involving deep gray cere¬ bral nuclei.14 Cerebral, cerebellar, and pyramidal abnormalities improved gradually during 4 days of abstinence. Laboratory findings can separate se¬ rious poisoning with methanol and ethylene glycol from intoxication with ethanol and IPA (Table 2). Patients with methanol and ethylene glycol in¬
toxication present with a severe meta¬ bolic acidosis and a large anion gap. Ethanol and IPA intoxication can cause ketonemia and ketonuria, due to acetoacetic and /3-hydroxybutyric ketone bodies in ethanol overdose and to acetone in IPA toxicity.8 Acetonemia can yield a falsely elevated serum creatinine level when colorimetrie meth-
ods of analysis are used, as in most autoanalyzers. Hypoglycemia is also sometimes present. Elevated cere¬ brospinal fluid protein levels have been reported.15 Assuming that the patient is not starved, the presence of acetonuria varies, and acetonemia with no glycosuria or metabolic acidosis, ie, normal pH, anion gap, and serum bi¬ carbonate levels, strongly suggests IPA intoxication.3 Gas chromatography accurately separates levels of the various alcohol intoxicants. Previously, many widely available methods for measuring se¬ rum alcohol levels used an enzymatic oxidation process employing alcohol dehydrogenase. This method was un¬ able to differentiate among the various alcohols.8·12 Various breath analyzers used by police and emergency depart¬ ment personnel to determine ethanol concentrations will yield false ethanol readings if the patient has consumed methanol, IPA, w-propyl alcohol, eth¬
ylene glycol,
or even
acetaldehyde.16
Some breath analyzer units will read no vapor except ethanol, while others read methanol and IPA, but more slowly than ethanol. Because of the wide range of techniques used, clini¬ cians should become aware of the methods used at their facility and of their accuracy and limitations. Gas chromatography is clearly the method of choice for detecting and quantitating the levels of various alcohol intox¬ icants and their derivatives.2·812 While the management of ethanol intoxication is often routine, the rec¬ ognition and treatment of other alco¬ hol intoxications is more problematic, since, if left unrecognized, methanol, IPA, w-propyl alcohol, and ethylene glycol intoxicants have very high rates of morbidity and mortality.8 Since
methanol and ethylene glycol often pro¬ duce very serious delayed toxicity, hemodialysis is probably imperative. Most patients with IPA toxicity can probably be treated with supportive care. Patients who report with light coma who are not hypotensive usually do well with supportive care only. If the patient is in deep coma, is hypoten¬ sive (the single finding most associated with poor outcome), or has a serum IPA concentration above 67 to 83 mmol/L, hemodialysis should be considered.8 To our knowledge, the se¬ rum level of 89 mmol/L of IPA in our patient 3 is the highest level reported, to date, in a patient who survived. He¬ modialysis dramatically affects the ki¬ netics of IPA. In one patient, 19 g/h of IPA and 7 g/h of acetone were removed using a standard dialyzer; the clear¬ ance of IPA and acetone from this di¬ alysis coil was calculated to be 137 to 165 mL/min.5 The authors calculated that the dialyzer was 52 times more efficient than the kidney in the removal of IPA and 40 times more efficient at removing acetone.5 Other treatments have been pro¬ posed or used to treat IPA intoxica¬ tion. Frequent gastric lavage may be· helpful in removing IPA, since IPA is secreted by the salivary glands of gas¬ tric mucosa into the intestinal tract. Peritoneal dialysis has been success¬ fully used to treat IPA intoxication.17 4-Methylpyrazole, an inhibitor of al¬ cohol dehydrogenase, has been used to treat ethylene glycol poisoning but to our knowledge has not been used to treat patients with IPA intoxication. Since IPA is metabolized to acetone by the enzyme alcohol dehydrogenase, 4methylpyrazole might also be theoret¬ ically useful in the future treatment of IPA intoxication.18·19
References 1. McCord WM, Switzer PK, Brill HH. Isopropyl alcohol intoxication. South Med J. 1948;41:639\x=req-\
642. 2.
Hackenberger F. Antiseptic drugs. In: Dukes MNG, ed. Meyler's Side Effects of Drugs. 9th ed. Princeton, NJ: Excerpta Medica; 1980:391. 3. Gosselin RE, Smith RP, Hodge HC, eds. Isopropyl alcohol. In: Clinical Toxicology of Commercial Products. 5th ed. Baltimore, Md: Williams & Wilkins; 1984:217-220. 4. Natowicz M, Donahue J, Gorman L, Kane M, McKissick J, Shaw L. Pharmacokinetic analysis of a case of isopropanol intoxication. Clin Chem. 1985;31:326-328. 5. Rosansky SJ. Isopropyl alcohol poisoning treated with hemodialysis: kinetics of isopropyl alcohol and acetone removal. J Toxicol Clin Toxicol. 1982;19:265-271. 6. Daniel DR, McAnalley BH, Garriott JC. Isopropyl alcohol metabolism after acute intoxication in humans. J Anal Toxicol. 1981;5:110-112. 7. Taylor GF, Turrill GH, Carter NG. Blood al-
cohol analysis: a comparison of the gas-chromatographic assay with an enzymatic assay. Pathology.
1984;16:157-159.
8. Lacouture PG, Wason S, Abrams A, Lovejoy FH Jr. Acute isopropyl alcohol intoxication: diagnosis and management. Am J Med. 1983;75:680\x=req-\ 686. 9. Irvine CH. Alcoholic ketoacidosis and isopropyl alcohol intoxication. Arch Intern Med.
1978;138:660.
10. Van de Graff WB. Isopropyl alcohol intoxication. Arch Intern Med. 1978;138:826. 11. Hawley PC, Falko JM. 'Pseudo' renal failure after isopropyl alcohol intoxication. South Med J. 1982;75:630-631. 12. Vasiliades J, Pollock J, Robinson CA. Pitfalls of the alcohol dehydrogenase procedure for the emergency assay of alcohol: a case study of isopropanol overdose. Clin Chem. 1978;24:383-385. 13. Juncos L, Taguchi JT. Isopropyl alcohol intoxication. JAMA. 1968;204:732-734. 14. Cummings JL, Benson DF. Subcortical de-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/19/2015
mentia: review of an emerging concept. Arch Neurol. 1984;41:874-879. 15. Visudhiphyan B, Kauffman H. Increased cerebrospinal fluid protein following isopropyl alcohol intoxication. NY State J Med. 1971;71:887\x=req-\ 888. 16. Jones AW, Goldberg L. Evaluation of breath alcohol instruments, I: in vitro experiments with Alcolmeter pocket model. Forensic Sci. 1978;12:1-9. 17. Mecikalski MB, Depner TA. Peritoneal dialysis for isopropanol poisoning. West J Med.
1982;173:322-325. 18. Galliot M, Astier A,
Bien DV, Gamier R, Likforman J, Bismuth C. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med. 1988;319:97-100. 19. Porter GA. The treatment of ethylene glycol poisoning simplified. N Engl J Med. 1988; 318:109-110.
\s=b\ Three patients had neurologic signs due to isopropyl alcohol (IPA) intoxication. Over a several-week period, a known alcoholic developed apathy, confusion, ataxia, and hyperreflexia. During this period, there was no ethanol available to him, and he denied use of other intoxicants. He was found stuporous in the hospital after drinking IPA and admitted to IPA abuse during the preceding weeks. Two other men were admitted in a stupor after large ingestions of IPA. Intoxication with IPA has two different presentations: stupor in a known alcoholic and encephalopathy of unknown cause in individuals who hide their addiction. Ethanol, methanol, IPA, and ethylene glycol intoxications are associated with different clinical and labora-
tory findings. (Arch Neurol. 1990;47:322-324)
intoxication is an extremely "p^thanol common social and medical prob¬
lem whose symptoms are well known to laymen. Some alcoholics also abuse cheap substitute intoxicants. The toxic effects of methanol (Sterno) and ethylene glycol (antifreeze) have been well described, but isopropyl al¬ cohol (IPA) (rubbing alcohol, "blue heaven") toxicity is less well known. Patients with IPA intoxication present in two different situations: stupor in a known alcoholic, and as an encephalopathy of unknown cause in individuals who hide their addiction. We describe three patients who pro¬ vide examples of these presentations, and review the scant literature on the clinical and laboratory features and treatment of IPA intoxication. even
Accepted
for publication June 5,1989. From the Department of Neurology, Tufts University, 750 Washington St, Boston, Mass. Reprint requests to Department of Neurology, Tufts University, 750 Washington St, Boston, MA 02111 (Dr Caplan).
REPORT OF CASES
nary acetone
44-year-old black man came department because of epigastric, joint, and muscle pain that had been present for 4 days. He was an alcoholic who had been admitted to another hospital 3 weeks previously after alcohol with¬ drawal seizures. After discharge, he conva¬ lesced at his sister's house; she, along with the patient, insisted that he had had no ac¬ cess to ethanol during the preceding 2 weeks. The sister reported that for a few days he had been uncharacteristically apa¬ thetic, and his speech, walking, and mem¬ ory had deteriorated. The patient also com¬ plained of a constant headache and loss of visual clarity. He vigorously denied re¬ cently drinking alcohol, Sterno, rubbing al¬ Case 1.—A
to the emergency
cohol, or antifreeze. On examination, there
odor of alcohol. The patient was alert but slow and abulie. His speech was dysarthric and terse, with frequent omis¬ sion of words and perseverations during repetition of sentences. His speech compre¬ hension was normal. His short-term mem¬ ory was very poor: he recalled none of three objects after 2 minutes. A short attention span and distractibility made testing of reading, writing, drawing, and copying dif¬ ficult. The patient's cranial nerves were normal, except for sluggish pupils and prominent horizontal nystagmus. His strength was normal, but he had appendicular and gait ataxia. Deep tendon reflexes were exaggerated and plantar responses were extensor. Pin and touch perception were decreased in a stocking distribution. was no
Computed tomographic findings
were
normal. A sample of cerebrospinal fluid was normal except for a protein content of 0.61 g/L. Serum amylase and creatine kinase levels were elevated. After admission, the patient had a grand mal seizure. His think¬ ing, memory, and gait gradually improved, and by day 4, his examination results were nearly normal. The next day, however, he was found wandering around the hospital, confused, with recurrence of dysarthria and ataxia. A nurse alertly noticed that his bedside rubbing alcohol bottle was missing. At that time, admission studies were re¬ ported and showed an acetone level of 41710 Mmol/L and an IPA level of 3 mmol/L. Uri-
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/19/2015
was
absent. Serum electro¬
lyte levels, carbon dioxide content, and anion gap were normal. The patient then admitted to long-term IPA abuse and said that he had drunk rubbing alcohol in his sister's house, as well as in the hospital. Case 2.—A-38-year-old white man was admitted for sudden stupor after a head in¬
jury. He had a long history of alcoholism complicated by seizures and delirium tremens and took phenytoin sodium and phé¬
nobarbital sodium for seizures. He had been. on a "binge" for 2 weeks. A day before ad¬ mission, he was hit on the forehead, sus¬ taining a laceration that required sutures. On the day of admission, he came to the emergency department because of a nose¬ bleed and frontal headache. On arrival he was alert and walking, but smelled of eth¬ anol. He was dishevelled, unshaven, and unkempt. Findings of the medical resi¬ dent's examination were "nonfocal." Fif¬ teen minutes after the patient was seen us¬ ing the urinal, he was found unresponsive. His temperature was 37.8°C, his pulse rate was 100 beats per minute, and his blood pressure was 120/70 mm Hg. He was unre¬ sponsive to deep pain and did not move his limbs except for two brief witnessed epi¬ sodes of stiffening and trembling of the arms, lasting a few seconds. Pupils, fundi, and oculocephalic responses were normal. Tendon reflexes were normal and plantar responses were flexor. Arterial blood gas analysis showed a pH of 7.25, a Pco2 of 55 mm Hg, and a Po2 of 51 mm Hg. The patient was intubated and mechanically ventilated. A catheterized urine specimen showed blood and 1+ ke¬ tones and bilirubin. Serum urea nitrogen and electrolyte levels were normal. The se¬ rum acetone level was 1650 Mmol/L; etha¬ nol, 74 mmol/L; and IPA, 38 mmol/L. The serum phenytoin level was 15 Mmol/L and phénobarbital was not detectable. A few hours after vigorous hydration and nasogastric lavage, the patient awakened and moved his limbs. On hospital day 2, he was restless and agitated and later reported vi¬ sual hallucinations. After treatment with lorazepam and chlordiazepoxide hydrochlo¬ ride for his delirium tremens, he signed out against medical advice. Case 3.—A 44-year-old man was brought
to the hospital in coma. He was a street person who had had previous admissions
for head injury and other complications of alcoholism. At 9 AM that morning he had visited the emergency department because of a large purulent hand wound, but left, refusing treatment. At 2 pm he was found unconscious in a nearby park amid empty bottles of IPA and mouthwash. He was un¬ responsive. His temperature was 36°C, his blood pressure was 88/62 mm Hg, his pulse rate was 80 beats per minute, and his res¬ piratory rate was 24 breaths per minute. In the emergency department he became more hypotensive; his pulse rate slowed and he had a sinus arrest. Sinus rhythm returned after chest compression and bag ventila¬ tion. After the patient underwent intuba¬ tion and intravenous treatment with saline, thiamine hydrochloride, dextrose, and naloxone hydrochloride, his pulse rate and blood pressure improved and he was admit¬ ted to an intensive care unit. He did not react to painful stimuli. His pupils were initially unreactive but later were 4 mm in diameter and reacted slowly and partially. There was no response to oculocephalic or corneal stimulation. Tone was symmetrically decreased, and the deep tendon reflexes were symmetrically brisk. Plantar responses were extensor. Initial laboratory test results were as follows: se¬ rum sodium, 140 mmol/L; potassium, 3.4 mmol/L; chloride, 105 mmol/L; bicarbon¬ ate, 21 mmol/L; serum urea nitrogen, 3.0 mmol/L; IPA, 89 mmol/L; acetone, 7030 Mmol/L; and ethanol, 16 mmol/L. Hemodialysis was begun at 10 pm. Serum, urinary, and dialysate levels of IPA and acetone are noted in Table 1. At 1:30 am, the patient be¬ gan to awaken and moved all extremities. By 11:30 am he sat up and tried to remove his endotracheal tube. He was extubated the following day and left the hospital against advice early on the fourth hospital day. COMMENT
Alcoholics, like other substance abusers, often have a repertoire of agents they use. Most prefer ethanol, but abuse IPA, methanol, or ethylene access to ethanol is frus¬ trated or when funds run out. A few individuals seem to prefer IPA. The
glycol when
of IPA is rubbing alcohol, which contains a 70% solution of IPA. Rubbing alcohol is used widely in hospitals and medical facilities and is readily available in many stores. In hospitals, IPA is often colored with blue dye to distinguish it visually from many other clear and colorless liquids; this practice has led to the designation blue heaven by abusers. Two of our pa¬ tients ingested IPA in hospital facili¬ ties, one in the emergency department, and the other in his room, from his bedside rubbing alcohol bottle. The other patient drank IPA in a nearby park. One of us (L.R.C.), during an in¬ ternship at the Boston (Mass) City most common
source
Hospital, observed
many alcoholics
Table 1.—Levels of
Isopropyl Alcohol (IPA)
and Acetone
IPA, mmol/L Serum
Urine
(Patient 3)
Acetone, Mmol/L Serum
Dialysate
Urine
Dialysate
Day 1, before dialysis Day 2, after dialysis 28
1 AM
4:30
17 460
am
5800
15
2
31980
PM
Day 3, Day 4,
4
am
840
4 am
Table 2.—Differential Characteristics of Alcohol Intoxications*
Isopropyl Methanol Characteristic
Ethanol
Ethylene Glycol
Alcohol
Yes
Yes
Yes
No
Onset
Rapid (30-60 min)
Rapid (30-60 min)
Rapid (30-60 min)
Late effects Metabolic
Severe (24 h) Severe (lactate
Mild to moderate
Absent
Rapid (30-60 min) Severe (48 h) Severe (lactate,
odor
acidosis
formate)
(lactic)
or
slight
(lactic)
oxalate,
glycolate) Ketones
Ketobutyric
Acetoacetic
Anion gap >12 mmol/L
Large
Moderate
Serum
Each 80 mg/dL adds 27 mOsm
Each 350
Acetone
hydroxybutyrate
osmolarity
mg/dL
adds 80 mOsm
Slight
Large
Each 340 mg/dL adds 60 mOsm, and each 55
Each 21 mg/dL adds 3.5 mOsm
mg/dL
of acetone adds 10
mOsm Serum
Amylase increased Hypoglycemia
Hypoglycemia
Hypocalcemia
Other
Dilated nonreactive
Gastritis,
Oxalic acid
findings
pupils, retinal
hematemesis
crystalluria
edema, blindness Modified from chart in LaCoutre et al."
drinking blue thermometer fluid (IPA) in the emergency department when they believed themselves to be unob¬
served. Since the first case of IPA intoxica¬ tion was reported in 1948 by McCord et al,1 much has been learned about the pharmacologie effects of this agent. The acute potency of IPA as a central nervous system depressant is about twice that of ethanol. The fatal inges¬ tion dose is about 250 mL in a nonalco¬ holic patient, but alcoholics clearly have a higher tolerance to its toxic effects.24 Essentially, all of an ingested dose is absorbed within 30 minutes, but massive doses may take somewhat longer to absorb. Isopropyl alcohol is eliminated from the body by firstorder kinetics; ie, its half-life is not dependent on the size of the dose.4"7 It has a volume of distribution of 0.6 to 0.7 L/kg.8 The primary metabolite of IPA is acetone. In one study that ex¬ amined the kinetics of IPA and acetone in a nonalcoholic patient, the serum
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/19/2015
half-lives of IPA and acetone in the were similar to those in the serum.4 Alcoholics metab¬ olize IPA more quickly than do nonalcoholics, showing a half-life of 3 to 4 hours6-8; this rapid clearance probably at least partially accounts for toler¬
cerebrospinal fluid
ance.
Ingestion of IPA can cause severe pain, with gastritis and frequent nausea and vomiting, occa¬ sionally with hematemesis.2·8"" Our pa¬ tient 1 had prominent intestinal symp¬ toms mimicking or associated with pancreatitis. Early nervous system abdominal
symptoms of IPA intoxication
are
qualitatively similar to those of etha¬ nol intoxication, but the initial phase
of exhilaration often described after ethanol use is conspicuously absent after IPA use. Dizziness, ataxia, head¬ ache, and confusion are reported. Iso¬ propyl alcohol can rapidly produce coma (as in patients 2 and 3). Coma rarely persists for more than 12 hours in nonfatal cases.812 Death after a
large ingestion of IPA is usually pre¬ ceded by respiratory arrest and deep coma, usually within a few hours. Even when patients are adequately venti¬ lated, serious cardiac toxicity is often caused by IPA and other aliphatic al¬ cohols. Arrhythmias, arterial hy¬ potension, and frank cardiac muscle
necrosis have been described.313 Ingestion of IPA usually causes coma with variable-sized but usually miotic pupils.8 Neurologic signs of subacute intoxication have not been de¬ scribed. The findings of neurologic ex¬ amination in our patient 1 were very unusual: the examination showed dys¬ arthria, nystagmus, and ataxia (find¬ ings common in ethanol intoxication) and prominent corticospinal tract dys¬ function. Although the patient was awake and quite alert, there were se¬ vere cognitive and behavioral abnor¬ malities, with abulia and a very short attention span. The findings mimicked a "subcortical dementia" as has been described in patients with frontal lobe disease, multi-infarct dementia, tha¬ lamic lesions, and various system de¬
generations involving deep gray cere¬ bral nuclei.14 Cerebral, cerebellar, and pyramidal abnormalities improved gradually during 4 days of abstinence. Laboratory findings can separate se¬ rious poisoning with methanol and ethylene glycol from intoxication with ethanol and IPA (Table 2). Patients with methanol and ethylene glycol in¬
toxication present with a severe meta¬ bolic acidosis and a large anion gap. Ethanol and IPA intoxication can cause ketonemia and ketonuria, due to acetoacetic and /3-hydroxybutyric ketone bodies in ethanol overdose and to acetone in IPA toxicity.8 Acetonemia can yield a falsely elevated serum creatinine level when colorimetrie meth-
ods of analysis are used, as in most autoanalyzers. Hypoglycemia is also sometimes present. Elevated cere¬ brospinal fluid protein levels have been reported.15 Assuming that the patient is not starved, the presence of acetonuria varies, and acetonemia with no glycosuria or metabolic acidosis, ie, normal pH, anion gap, and serum bi¬ carbonate levels, strongly suggests IPA intoxication.3 Gas chromatography accurately separates levels of the various alcohol intoxicants. Previously, many widely available methods for measuring se¬ rum alcohol levels used an enzymatic oxidation process employing alcohol dehydrogenase. This method was un¬ able to differentiate among the various alcohols.8·12 Various breath analyzers used by police and emergency depart¬ ment personnel to determine ethanol concentrations will yield false ethanol readings if the patient has consumed methanol, IPA, w-propyl alcohol, eth¬
ylene glycol,
or even
acetaldehyde.16
Some breath analyzer units will read no vapor except ethanol, while others read methanol and IPA, but more slowly than ethanol. Because of the wide range of techniques used, clini¬ cians should become aware of the methods used at their facility and of their accuracy and limitations. Gas chromatography is clearly the method of choice for detecting and quantitating the levels of various alcohol intox¬ icants and their derivatives.2·812 While the management of ethanol intoxication is often routine, the rec¬ ognition and treatment of other alco¬ hol intoxications is more problematic, since, if left unrecognized, methanol, IPA, w-propyl alcohol, and ethylene glycol intoxicants have very high rates of morbidity and mortality.8 Since
methanol and ethylene glycol often pro¬ duce very serious delayed toxicity, hemodialysis is probably imperative. Most patients with IPA toxicity can probably be treated with supportive care. Patients who report with light coma who are not hypotensive usually do well with supportive care only. If the patient is in deep coma, is hypoten¬ sive (the single finding most associated with poor outcome), or has a serum IPA concentration above 67 to 83 mmol/L, hemodialysis should be considered.8 To our knowledge, the se¬ rum level of 89 mmol/L of IPA in our patient 3 is the highest level reported, to date, in a patient who survived. He¬ modialysis dramatically affects the ki¬ netics of IPA. In one patient, 19 g/h of IPA and 7 g/h of acetone were removed using a standard dialyzer; the clear¬ ance of IPA and acetone from this di¬ alysis coil was calculated to be 137 to 165 mL/min.5 The authors calculated that the dialyzer was 52 times more efficient than the kidney in the removal of IPA and 40 times more efficient at removing acetone.5 Other treatments have been pro¬ posed or used to treat IPA intoxica¬ tion. Frequent gastric lavage may be· helpful in removing IPA, since IPA is secreted by the salivary glands of gas¬ tric mucosa into the intestinal tract. Peritoneal dialysis has been success¬ fully used to treat IPA intoxication.17 4-Methylpyrazole, an inhibitor of al¬ cohol dehydrogenase, has been used to treat ethylene glycol poisoning but to our knowledge has not been used to treat patients with IPA intoxication. Since IPA is metabolized to acetone by the enzyme alcohol dehydrogenase, 4methylpyrazole might also be theoret¬ ically useful in the future treatment of IPA intoxication.18·19
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