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Chapter 68 GENERAL APPROACH TO POISONINGS478

14. Discuss some other useful antidotes for common poisonings.

Naloxone and dextrose are the most common antidotes and should be given routinely to

unconscious overdose patients. Intravenous administration of 2 mg of naloxone that results

in awakening of the patient is diagnostic of acute opiate overdose. Small, incremental doses

of 0.2 mg can be used if it is suspected that the patient is opioid dependent, because the

2-mg dose of naloxone will precipitate withdrawal. Many drugs and chemicals can cause

hypoglycemia, including ethanol, and for this reason dextrose likewise should be given,

unless it can be determined quickly that the blood glucose is normal.

Physostigmine is an antidote for the anticholinergic syndrome. Physostigmine can be used

diagnostically and therapeutically when the diagnosis of the anticholinergic syndrome is

suspected. It should not be used to treat tricyclic antidepressant poisoning (or in patients

with ECG changes suggestive of tricyclic antidepressant poisoning such as QRS widening

or a large R wave in AVR). Seizures and bradydysrhythmias have been reported when used

in this setting. A dose of 1 to 2 mg given slowly intravenously to an adult is usually

sufﬁcient.

Digoxin immune Fab (Digibind, Digitab) is a safe and effective antidote for digitalis

glycoside poisoning and can rapidly reverse dysrhythmias and hyperkalemia, which can be

life-threatening. In contrast to naloxone, Digibind does not work immediately, and a full

response to therapy may not be seen until approximately 20 minutes after administration.

For a life-threatening digitalis overdose when the dose and the serum level are currently

unknown, 10 vials of Digibind should be given.

Atropine and pralidoxime (Protopam) are antidotes used for cholinesterase inhibitor

toxicity. This group of pesticides includes the organophosphates and carbamates, which

commonly are found in household insecticides. Atropine is used to dry up secretions,

primarily pulmonary, and pralidoxime is used primarily to reverse the skeletal muscle

toxicity of these agents, including weakness and fasciculations.

Flumazenil is a benzodiazepine antagonist that has been shown to be useful in cases of

acute benzodiazepine overdose resulting in signiﬁcant toxicity. Its use may precipitate

benzodiazepine withdrawal, including seizures. It should not be used when tricyclic

antidepressants or other pro-convulsants have been coingested with benzodiazepine. The

usual adult dose is 0.2 mg followed in 30 seconds by 0.3 mg, followed in 30 seconds by

0.5 mg, repeated up to a total of 3 mg.

Ethanol and fomepizole are alcohol dehydrogenase blocking agents that are used to treat

methanol and ethylene glycol poisoning. They prevent the metabolism of methanol and

ethylene glycol to their toxic metabolites. Intravenous ethanol is less expensive than

fomepizole but is somewhat more difﬁcult to use. The initial intravenous dose is 8 mL/kg

of 10% ethanol over 30 minutes, followed by an infusion of 0.8 mL/kg/h in a nondrinker,

1.4 mL/kg/h in an average drinker, and 2 mL/kg/h in a heavy drinker. Blood ethanol

concentration should be measured immediately after the loading dose and repeated every

hour initially, and the dose adjusted to maintain a blood ethanol of 100 to 125 mg/dL. The

KEY POINTS: MANAGEMENT OF SUSPECTED TOXIC INGESTION

1. Activated charcoal is sufﬁcient decontamination for most overdose patients.

2. Urine toxicology screens are not indicated in patients with normal mental status and vital

signs.

3. Serum electrolytes and acetaminophen concentration should be obtained in patients with

deliberate overdose.

4. Although there are a few antidotes for speciﬁc toxins, most poisoned patients recover with

supportive care.

Chapter 68 GENERAL APPROACH TO POISONINGS 479

loading dose of fomepizole is 15 mg/kg intravenously over 30 minutes with subsequent

doses of 10 mg/kg every 12 hours. The dose of both agents must be increased in patients

undergoing dialysis.

N-ace tyl cys tei ne is extremely effective in preventing acetaminophen-induced liver

injury. It is most effective if administered within 8 hours of ingestion but reduces

morbidity and mortality even in patients with acetaminophen-induced acute liver failure.

It can be administered orally (loading dose 140 mg/kg, subsequent doses 70 mg/kg

every 4 hours) or intravenously (initial dose 150 mg/kg in 200 ml D

W over 15 minutes,

followed by 50 mg/kg in 500 ml D

over 4 hours, followed by 100 mg/kg in 1 L D

infused over 16 hours).

BIBLIOGRAPHY

1. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists:

Position Paper: Gastric lavage. J Toxicol Clin Toxicol 42:933–943, 2004.

2. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists:

Position Paper: Ipecac syrup. J Toxicol Clin Toxicol 42:133–143, 2004.

3. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists:

Position Paper: Single-dose activated charcoal. J Toxicol Clin Toxicol 43:61–87, 2005.

4. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists:

Position Paper: Whole bowel irrigation. J Toxicol Clin Toxicol 43:129–130, 2005.

5. Bronstein AC, Spyker DA, Cantilena JR, et al: 2007. Annual Report of the American Association of Poison

Control Centers’ National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol 46(10):927–1057, 2007.

6. Pond SM, Lewis-Driver DJ, Williams GM, et al: Gastric emptying in acute overdose: a prospective randomised

controlled trial. Med J Aust 163:345–349, 1995.

7. Proudfoot AT, Krenzelok EP, Vale JA: Position paper on urine alkalinization. J Toxicol Clin Toxicol 42:1–26, 2004.

8. Vale JA, Krenzelok EP, Barceloux GD: Position statement and practice guidelines on the use of multi-dose

activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol 37:731–751, 1999.

480

THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL,

METHANOL, AND ISOPROPYL ALCOHOL

CHAPTER 69

Louis J. Ling, MD

1. Is a patient with altered mental status, who smells of alcohol, simply

intoxicated?

In most cases, yes. However intoxicated patients are at increased risk for injury,

immunosuppression, poor nutrition, poor thermal regulation, and many medical conditions.

Every patient assumed to be drunk (only) needs a thoughtful initial evaluation and subsequent

serial evaluations.

2. How should intoxicated patients be evaluated?

Patients who arrive primarily with intoxication and without a history of trauma or injury should

have vital signs taken; a rapid scan for recent trauma; a rapid glucose determination; and

assessment for level of consciousness, responsiveness, and respiratory depression. Examination

should include a look for unequal pupils, ecchymosis, deformity, and palpation everywhere for

abdominal and bony tenderness. If no concerns are identiﬁed, it is important to return and

reexamine the patient every hour or two to ensure that the patient is improving.

3. When should an acutely intoxicated patient be intubated?

Hypopnea and hypoventilation are rarely the issue, but the inability of the patient to protect the

airway is. For patients who are heavily intoxicated but not deemed to require intubation, lateral

decubitus positioning is preferred. Restraining a patient supine or prone can be dangerous

because of the risk of aspiration and airway compromise.

4. Which medications are best for management of alcohol withdrawal?

Benzodiazepines, usually diazepam or lorazepam, can be given orally, intravenously, or in

combination and titrated by clinical response. Patients with mild withdrawal (normal vital

signs, no hallucinosis) may be discharged with a 2- to 3-day course of a single agent (e.g.,

lorazepam, 1–2 mg twice a day). Haloperidol is an appropriate adjunct for hallucinosis.

Theoretical concerns over haloperidol lowering seizure threshold and exacerbating

hemodynamic abnormalities have not been substantiated. More severe withdrawal

syndromes require increasingly aggressive therapy with these same agents while under

observation by medical personnel.

5. What is an appropriate work-up for alcohol withdrawal seizures (AWDs)?

Typically, AWDs occur approximately 6 to 96 hours after the last drink and in clusters of one

to four seizures. The seizures are usually generalized and self-limited. Coincident features of

withdrawal may be lacking, and lateralizing ﬁndings during the seizure, the postictal state, or

both, are often present because of underlying structural pathology.

In a ﬁrst-time evaluation, other causes of or contributors to seizures should be sought.

Laboratory studies (i.e., electrolytes, glucose, magnesium, calcium, toxicologic screen) are

rarely useful unless history or physical examination is suggestive. Noncontrast computed

tomography (CT) shows traumatic, infectious, vascular, or other abnormalities in nearly 10%

of patients Generally, electroencephalography is not integral to the work-up. Lumbar puncture

is indicated when meningitis, meningoencephalitis, or subarachnoid hemorrhage is suspected.

Subsequent visits for suspected AWDs demand scrupulous history and physical examination

to ensure that other pathologic causes have not developed in the interim. If the presentation

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL 481

matches prior episodes and the ﬁndings on current neurologic examination are baseline, no

other work-up, including CT, is necessary. Lingering postictal confusion warrants a check of

glucose and electrolytes. If the history or examination has changed signiﬁcantly or is worrisome,

the clinician should start from scratch.

6. How should AWDs be managed?

Acute: As with all seizures, ensure a patent airway and administer 50% dextrose (D

) and

benzodiazepines intravenously (as needed). An observation period of 6 hours is optimal

because recurrent seizures are common within this period. Benzodiazepines in the

immediate and 2-day postseizure period decrease the incidence of additional seizures

during this time.

Chronic: Patients whose seizures have an epileptogenic focus (e.g., old subdural) should

have an anticonvulsant, such as phenytoin, administered. However, compliance is typically

poor. In the patient with pure AWDs, long-term anticonvulsant therapy is contraindicated.

Physicians must resist the imperative to prescribe something unless there is clear

justiﬁcation.

7. Can AWDs be prevented?

Benzodiazepines in the acute withdrawal period, particularly in patients with a history of

AWDs, can decrease seizures.

8. Who is at risk for alcohol-induced hypoglycemia (AIH)? What is the clinical

presentation?

AIH results from:

a. Insufﬁcient glycogen stores

b. Alcohol-induced impairment of gluconeogenesis

The three groups vulnerable to AIH are:

a. Chronic alcoholics

b. Binge drinkers

c. Young children

AIH may occur during intoxication or up to 20 hours after the last drink. Manifestations of

neuroglycopenia (e.g., headache, depressed mental status, seizure, or coma) predominate.

Evidence of catecholamine excess, typical of insulin-induced hypoglycemia (tremulousness,

diaphoresis, anxiety), is unusual. Seizures are a frequent presentation in children. Localized

central nervous system signs, including a stroke-like picture (alcohol-induced hypoglycemic

hemiplegia), often occur in adults.

9. What causes alcoholic ketoacidosis (AKA)?

This common metabolic disturbance occurs early after heavy binge drinking and is heralded

by starvation and vomiting and occasionally shortness of breath (Kussmaul respirations) and

abdominal pain. Ketoacidosis results from accumulation of acetoacetate and, particularly,

b-hydroxybutyrate. Because the latter is not measurable on routine blood and urine tests, the

patient may have trace or absent ketones at presentation. Similarly, as the patient improves

and b-hydroxybutyrate is metabolized to acetoacetate, there may be a paradoxical spike in

urine and serum ketones.

At presentation, serum pH and bicarbonate average 7.1 and 10, respectively. These values

vary widely because of the frequently overlapping ketoacidosis (metabolic acidosis),

withdrawal-related hyperventilation (respiratory alkalosis) and protracted emesis (metabolic

alkalosis). When all three are coincident, the result is a triple acid-base disturbance. This

allows you to interpret arterial blood gases and electrolytes pretty much any way you wish

and be at least partially correct. Decreased body stores of potassium and phosphate are

typical. In AKA, serum glucose is usually normal or low, a distinguishing feature from diabetic

ketoacidosis.

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL482

10. How should AKA be managed?

Treatment consists of rehydration with dextrose-containing crystalloid, antiemetics if needed,

benzodiazepines for withdrawal, and multivitamins, potassium, and phosphate as indicated.

Bicarbonate is rarely required, and insulin therapy is proscribed. Metabolic abnormalities

usually resolve with 12 to 16 hours of therapy.

11. What is the relationship between alcohol and metabolic acidosis?

Ethanol: Acute ethanol ingestion results in a mild increase in the lactate-to-pyruvate ratio.

Clinically signiﬁcant metabolic acidosis does not ensue.

AKA: This ethanol abstinence syndrome produces marked elevations in acetoacetate and

b-hydroxybutyrate with resultant and occasionally profound increased anion gap metabolic

acidosis. During the correction phase, a non-anion gap, hyperchloremic picture often

develops (because some of the bicarbonate-bound ketoacids are excreted in the urine) on

the road to normalization.

Ethylene glycol and methanol: Toxic metabolites of these compounds produce increased

anion-gap metabolic acidosis. In the suspected alcoholic patient who presents with

signiﬁcant metabolic acidosis, a quick method of distinguishing the presence of ethylene

glycol or methanol from AKA is the osmolal gap. If this exceeds 25 mOsm/Kg, it is 88%

speciﬁc for the presence of ethylene glycol or methanol.

Isopropyl alcohol: A signiﬁcant portion of isopropyl alcohol is metabolized to acetone.

This is a ketone but not a ketoacid, causing ketosis and ketonuria but not acidosis.

12. How is coagulation affected in a chronic alcoholic?

Bone marrow depression from ethanol, folate deﬁciency, and hypersplenism secondary to

portal hypertension all cause thrombocytopenia. Platelet counts less than 30,000/mL,

resulting from alcohol usage alone, are unlikely. Qualitative platelet defects also occur.

Hepatocyte loss from chronic alcohol abuse depletes all coagulation factors except VIII,

particularly II, VII, IX, and X. Alcoholics often have inadequate vitamin K, a requisite cofactor

for the production of factors II, VII, IX, and X because of hepatobiliary dysfunction and poor

diet. When faced with gastrointestinal hemorrhage in a chronic alcoholic, an intravenous

vitamin K supplementation trial is warranted. The far more likely culprit is hepatocellular

destruction, however, for which vitamin K would not be helpful. Vitamin K does not begin to

restore factor levels for 2 to 6 hours, so for emergent scenarios, fresh frozen plasma provides

immediate factor supplementation.

13. How should the combative alcoholic patient be managed?

When the patient or staff is in jeopardy, the ﬁrst step is physical restraint of the patient.

A sufﬁcient number of competent personnel and restraint devices are necessary. Closed

head injury, hypoxia, or a full bladder may be the source of distress and should be excluded,

managed, or relieved.

For chemical sedation, haloperidol (5–10 mg intravenous push) has rapid onset of

sedation (5 minutes), but repeat doses may be required. This agent is not detrimental to

airway patency, ventilation, or hemodynamics. There is a 5% to 10% incidence of

extrapyramidal reactions, usually within 12 to 24 hours. Droperidol (2.5–5 mg

intramuscularly) is another effective butyrophenone, but it received a black-box warning

in 2004 due to reports of QT prolongation and torsades de pointes. In any case, haloperidol

and droperidol have been shown to be relatively comparable in efﬁcacy and side effects.

14. When is an intoxicated patient safe to discharge from the ED?

From a management perspective, there are two fundamental concerns:

Acute intoxication obfuscates the veriﬁcation of certain diagnoses and the exclusion of

others.

A physician who discharges an acutely intoxicated (i.e., incompetent) patient may be

held accountable for the actions of that patient subsequent and proximate to discharge

from the ED.

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL 483

The degree of clinical intoxication at a speciﬁc serum alcohol level is variable in accordance

with the patient’s chronicity and severity of drinking. A veteran drinker with a level in excess of

500 mg/dL can look less drunk than a teenager at 100 mg/dL. Documentation of the discharge

examination includes mental status, gait, and the fact that the patient is clinically sober.

Particular attention should be paid to potential abdominal or closed head trauma. The patient

should be discharged to an appropriate environment. Serum or breath alcohol determinations

sometimes can be helpful at the outset of care but unneeded at discharge.

KEY POINTS: ALCOHOL-RELATED DISORDERS

1. Airway protection: Clinical judgment is the key factor in determining whether an acutely

intoxicated patient requires intubation for airway protection.

2. Phenytoin should only be given to patients with clear indication of an epileptogenic focus.

Otherwise, its use for prevention of alcohol withdrawal seizures is strictly proscribed.

3. Discharge documentation: The critical determination in the discharge of the patient is the

progression to and documentation of clinically sober.

15. Must thiamine be administered before glucose in the alcoholic patient?

Wernicke-Korsakoff syndrome develops over hours to days. The precipitous initiation of

Wernicke-Korsakoff syndrome by dextrose has not been substantiated. The consequences

of neuroglycopenia begin within 30 minutes and are easily prevented. In alcoholic patients

with known or suspected hypoglycemia, promptly administer glucose and deliver thiamine

empirically as soon afterward as possible. Because magnesium is a cofactor of thiamine

and because alcoholics are frequently hypomagnesemic, 2 g of IV magnesium should be

administered when there is suspicion of Wernicke-Korsakoff syndrome.

16. Is it dangerous to administer thiamine intravenously?

Orally administered thiamine is often absorbed poorly in the alcoholic patient. The

intramuscular route is painful and can result in hematomas or abscesses, particularly in

patients with impaired coagulation status. The experience with intravenous thiamine is

extensive. Thiamine may be given as part of ﬂuid hydration with multivitamin preparations

or by bolus infusion.

17. Is there a cure for a hangover?

Probably not, at least not one with solid scientiﬁc credentials. There is no shortage of

remedies, however, from the well-worn “hair of the dog that bit you” (i.e., start drinking again)

to a more recently acclaimed concoction of vitamin B

, nonsteroidal anti-inﬂammatories, and

hydration. The only sure-ﬁre measure is the avoidance of drinking in the ﬁrst place.

18. Are there speciﬁc criteria for the diagnosis of Wernicke-Korsakoff syndrome?

Criteria require two of the following four signs to be present:

a. Dietary deﬁciencies

b. Oculomotor abnormalities

c. Cerebellar dysfunction

d. Either an altered mental state or mild memory impairment.

19. Why is it important to understand the metabolism of methanol?

The metabolites of methanol are the toxins and depend on alcohol dehydrogenase (ADH) for

their conversion from the non-toxic parent methanol. Ethanol and fomepizole both saturate

ADH and greatly slow the metabolism of methanol to the toxic metabolite. Folate is a cofactor

in the breakdown of formic acid, and in monkeys (and other primates) folate supplementation

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL484

maximizes its metabolism and decreases injury. Knowledge of the metabolism directs the

treatment.

ADH Folate

Methanol → Formaldehyde → Formic Acid → CO

1 H

(toxic) (toxic) (nontoxic)

20. List the signs and symptoms of methanol poisoning.

Gastrointestinal toxicity

Nausea and vomiting

Abdominal pain

Central nervous system toxicity

Headache

Decreased level of consciousness

Confusion

Ocular toxicity

Retinal edema

Hyperemia of the disc

Decreased visual acuity

Other toxicity

Metabolic acidosis

KEY POINTS: METHANOL

1. Symptoms and acidosis are delayed.

2. Osmolal gap is often absent.

3. Persistent acidosis correlates with a poor prognosis.

4. Fomepizole, ethanol, and dialysis can all be used to treat the poisoned patient.

21. Why is it important to understand the metabolism of ethylene glycol?

As with methanol, ethanol and fomepizole saturate ADH, inhibiting conversion of ethylene glycol

into its harmful metabolites. Pyridoxine (vitamin B

) and thiamine are cofactors in the ﬁnal steps

to form nonharmful end products and should be given to ensure maximal metabolism. Oxalate

crystals may not appear until late in the course of the poisoning (Fig. 69-1).

22. Why are the symptoms of ethylene glycol and methanol overdose often

delayed?

It may take 6 to 12 hours for sufﬁcient quantities of the toxic metabolites to accumulate and

cause symptoms. The delay in symptoms is even greater with concurrent ethanol intoxication

because the ethanol slows down the rate of methanol and ethylene glycol metabolism and

delays the appearance of the toxic metabolites.

KEY POINTS: ETHYLENE GLYCOL

1. Symptoms and acidosis are often delayed.

2. Urinary oxalate crystals, ﬂuorescence, early osmolal gap, and metabolic acidosis all suggest

ethylene glycol poisoning.

3. Fomepizole, ethanol, and dialysis can all be used to treat the poisoned patient.

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL 485

23. How are methanol and ethylene glycol poisonings similar?

Methanol and ethylene glycol are metabolized initially by ADH. Methanol is metabolized further to

formic acid, and ethylene glycol is metabolized to glycolic acid, glyoxylic acid, oxalate, and several

nontoxic metabolites. Because of these end products, both poisons result in metabolic acidosis

with an anion gap. Because of their low molecular weight, both increase the osmolar gap.

24. What is an anion gap?

A normal anion gap is the difference between measured and unmeasured anions (e.g., various

proteins, organic acids, phosphates) and measured and unmeasured cations (e.g., potassium,

calcium, and magnesium). The anion gap can be calculated from the formula:

Anion gap 5 (Na

) 2 (HCO

1 Cl

)

25. What causes an increased anion gap?

When metabolic acidosis results from an ingestion of nonvolatile acids, there are increased

hydrogen ions with positive charges. Because there is an equal increase in unmeasured

negatively charged anions but no increase in chloride, the difference between the measured

cations and measured anions is increased, causing an increased anion gap. The normal anion

gap is about 6 to 10 mEq/L. The causes of increased anion gap can be remembered by the

mnemonic A MUD PILES.

A 5 Alcohol, M 5 Methanol, U 5 Uremia, D 5 Diabetic ketoacidosis, P 5 Paraldehyde,

I 5 Iron, Isoniazid (INH), L 5 Lactate, E 5 Ethylene glycol, S 5 Salicylate

26. What is an osmolal gap?

Small atoms and molecules in solution are osmotically active, and this activity can be

measured by a depression in the freezing point or an elevation in the boiling point of the

solution. If there is an increase in low-molecular-weight molecules, such as acetone,

methanol, ethanol, mannitol, isopropyl alcohol, or ethylene glycol, the osmolality is greater

than what is calculated from the usual serum molecules. The difference between the actual

measured osmolality and the calculated osmolality is the osmolal gap, and a gap greater than

about 10 mOsm is considered abnormal.

Figure 69-1. Metabolism of methanol and ethylene glycol.

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL486

27. How is an osmolal gap calculated?

One formula is 2 3 Na

(mEq/L) 1 glucose (mg/dL)/18 1 blood urea nitrogen (BUN)

(mg/dL)/2.8 1 ethanol (mg/dL)/4.3. The inclusion of the ethanol level excludes patients who

have an elevated osmolal gap from ethanol ingestion alone. Using International System (SI)

units, the calculated osmolality 5 2 3 Na (mEq/L) 1 glucose (mmol/L) 1 BUN (mmol/L) 1

ethanol (mmol/L). The calculated osmolality is 285 6 5 mOsm/L. A toxic ethylene glycol level

of 25 mg/dL can be predicted to increase the osmolal gap 5 mOsm/L. Because of the small

effects on the osmolality and the imprecision of the measurement, this test is not precise

enough to be deﬁnitive so a normal osmolal gap does not exclude toxic levels of methanol

or ethylene glycol. The laboratory must use the method of freezing-point depression so that

volatile alcohols contributing to an osmolal gap are not boiled away during a boiling point

elevation procedure.

28. What comes ﬁrst, the anion gap or the osmolal gap?

With initial absorption, the small parent molecules cause an early osmolal gap, but with

metabolism, acidic metabolites are formed causing a late metabolic anion-gap acidosis.

29. How toxic are methanol and ethylene glycol?

Death is reported after 15 to 30 mL (1–2 tablespoons) of methanol. Others have

survived larger ingestions, however. A minimal lethal dose for ethylene glycol is

approximately 1–2 mL/kg.

30. What is the toxicity of ethylene glycol?

Initially, there is central nervous system intoxication and gastrointestinal irritation, followed by

metabolic acidosis. Renal failure occurs frequently and typically is delayed in presentation.

Cranial nerve deﬁcits are a rare complication.

31. Why is ethylene glycol so dangerous to animals?

Ethylene glycol is a frequent cause of death in animals who ingest antifreeze (especially dogs,

who drink almost anything). The taste is sweet and a small volume is deadly. The cause of

death for these animals may not be apparent because toxicity is delayed, and death occurs

long after the animal has left the scene.

32. Why does antifreeze have such a bright color?

Antifreeze is a bright color that ﬂuoresces with ultraviolet (UV) light so that leaks from

auto radiators can be detected more easily. If the mouth and the urine are examined with a

UV light, ﬂuorescein can be detected in about 30% of patients after ingestion. A positive

test should encourage immediate treatment, but a negative test misses two thirds of

ingestions.

33. How should patients with methanol and ethylene glycol poisoning be

treated?

Airway protection is paramount in patients with decreased level of consciousness or

respiratory depression. Small volumes and rapid absorption limit the effectiveness of gastric

lavage and charcoal. Acidosis (pH ,7.2) should be treated aggressively with sodium

bicarbonate. Ethanol and 4-methylpyrazole (4-MP) are antidotes that competitively block the

conversion of methanol and ethylene glycol to their toxic metabolites, allowing for elimination

of the unchanged poison without injury.

34. What are the indications for ethanol or 4-MP therapy?

They should be used if ethylene glycol or methanol levels exceed 20 mg/dL; if acidosis is

present, regardless of drug level; and if there is a history of a toxic ingestion while awaiting

conﬁrmatory blood methanol or ethylene glycol levels.

Chapter 69 THE ALCOHOLS: ETHANOL, ETHYLENE GLYCOL, METHANOL, AND ISOPROPYL ALCOHOL 487

35. How do you choose between fomepizole (4-MP) and ethanol?

Ethanol is difﬁcult to give consistently; ethanol blood levels are required to adjust the dose

and infusion can cause pain, resulting in the use of a central catheter. Ethanol may cause

hypoglycemia and respiratory depression, especially in children. These patients usually require

the close monitoring of an intensive care unit (ICU). 4-MP is replacing ethanol because it does

not cause sedation, does not require blood testing, is easily given as a bolus, and does not

require ICU management.

36. How do you use 4-MP?

The dose is 15 mg/kg every 12 hours and is increased to every 4 hours during dialysis.

Typical treatment is for 48 hours.

37. What are the indications for hemodialysis?

Dialysis used to be the primary treatment for these poisons and should be done in patients

with blood levels greater than 50 mg/dL, when the metabolic acidosis is not correctable, with

pending renal failure, or with visual symptoms in a methanol overdose. Many clinicians

recommend dialysis when blood levels exceed 25 mg/dL, if dialysis is readily available.

Hemodialysis can be avoided with prolonged fomepizole treatment.

38. What if dialysis is unavailable?

Patients with ethylene glycol poisoning can be treated successfully with 4-MP alone without

dialysis if there is no acidosis or renal failure. Because the half-life of ethylene glycol is

prolonged to 17 hours, the treatment may be extended but avoids invasive treatment of

dialysis. In methanol poisoning, 4-MP slows the metabolism and increases the half-life of

methanol to 30-52 hours. The use of 4-MP alone would not sufﬁce for these patients.

39. How is isopropyl alcohol poisoning different from methanol and ethylene

glycol poisoning?

Isopropyl or rubbing alcohol is metabolized in the liver to acetone, which results in

measurable ketonemia in the serum. Acetone is excreted by the kidney, resulting in ketonuria,

and is exhaled through the lungs, giving patients an acetone aroma on their breath. Because

these metabolites are not acidic, isopropyl alcohol poisoning does not result in metabolic

acidosis and is far less toxic than either methanol or ethylene glycol.

40. What are the symptoms of isopropyl alcohol ingestion?

Isopropyl alcohol has a three-carbon chain rather than the two-carbon chain of ethanol.

Because of this, it crosses the blood-brain barrier faster and is about twice as intoxicating as

ethanol. Because it is commonly found in concentrated solutions and is more potent, the

central nervous system depression can occur rapidly and can continue from residual poison in

the stomach. Isopropyl alcohol is much more irritating than ethanol to the gastric mucosa and

often causes abdominal pain, vomiting, and hematemesis.

41. Why is isopropanol so frequently abused?

Isopropanol is easy and legal to obtain; rubbing alcohol is 70% isopropanol. Unlike

consumable beer, wine, and liquor, it is not taxed and is very inexpensive.

42. What treatment is advisable for isopropyl alcohol poisoning?

Patients need observation to watch for respiratory depression similar to patients

intoxicated with ethanol. An isopropyl alcohol level is roughly equivalent to an ethanol level

twice as high. An isopropyl level usually does not add greatly to clinical observation. In

the rare instance of coma or hypertension corresponding to isopropyl levels greater than

500 mg/dL, intubation and ventilation may be necessary, and hemodialysis can greatly

enhance removal of isopropyl alcohol from the body. An antidote is not available for

isopropyl alcohol (nor is one needed).