Page 1739 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1208 PART 11: Special Problems in Critical Care

no contraindications exist. Activated charcoal reduces the number of solvents. Blue or green fluorescent dye is added to some (eg, antifreeze)
patients reaching toxic serum levels after ingesting more than 10 g of but not all products to identify leaks, allowing for evidence of poison-
acetaminophen and presenting within 24 hours of ingestion, and may ing by urinary fluorescence under a Wood lamp. Methanol is colorless
reduce the need for a full treatment course of NAC and hospital length and odorless but has a bitter taste. It is present in many paint removers,
of stay. 58,105 Reported use of hemodialysis or hemoperfusion for extracor- gas-line antifreeze, windshield washing fluid, and solid canned fuel.
poreal removal of acetaminophen has increased in recent years despite Isopropanol is a colorless and bitter tasting alcohol. It has the smell of
lack of evidence that this is superior to NAC. 106 acetone or alcohol and is found in rubbing alcohol, skin lotions, hair
NAC is available in PO and IV formulations (discussed below). There tonics, aftershave, deicers, and glass cleaners.
are three main mechanisms by which it acts as the antidote for acet- A history of ingestion or inebriation that is not explained by ethanol
aminophen toxicity: (1) it increases glutathione stores (allowing more suggests toxic alcohol poisoning. Methanol and ethylene glycol poison-
detoxification of NAPQI), (2) it binds with NAPQI, and (3) it enhances ing classically present with an elevated anion gap and an elevated osmol
sulfate conjugation. 107 gap, but poisoning can occur without either. 35,42 More specifically, it
All patients with probable or possible hepatic toxicity based on the should be noted that an elevated osmol gap without an anion gap aci-
Rumack-Matthew nomogram (ie, all patients with serum acetamino- dosis would be expected early in methanol or ethylene glycol poisoning,
phen levels above the lower line) should receive NAC. NAC should also and the converse (large anion gap acidosis without osmol gap) would be
be given if there is >5 µg/mL acetaminophen and an unknown time expected in later stages. Isopropanol elevates the osmol gap but does
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of ingestion (but <24 hours), evidence of hepatotoxicity, or if a serum not cause an elevated anion gap metabolic acidosis.
acetaminophen level is not immediately available. In this latter situation, Ethylene glycol is metabolized by alcohol dehydrogenase (ADH) to
the antidote may be discontinued if the acetaminophen level is found to glycoaldehyde and glycolic acid, and then to glyoxylic acid and oxalic acid.
be at a nontoxic level according to the nomogram. Importantly, NAC Accumulation and precipitation of oxalic acid and calcium oxalate in renal
should be considered in all at-risk patients even if levels are nontoxic. tubules produces calcium oxalate crystals that are present in the urine in
The effectiveness of NAC depends on the time of administration. It is 50% of cases. Ingestion of as little as 100 mL can be lethal in adults.
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almost 100% effective when administered within the first 8 to 10 hours. Ethylene glycol poisoning has a triphasic clinical course: stage 1
Efficacy decreases over time, but there is still benefit for up to 24 hours. (30 minutes to 12 hours postingestion) consists of inebriation, ataxia,
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NAC may even improve outcome when it is administered after the onset seizures, variable levels of elevated anion gap metabolic acidosis with
of fulminant hepatic failure. In the setting of liver failure, NAC lowers Kussmaul breathing, elevated osmol gap, crystalluria, and hypocalcemia.
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the incidence of hepatic encephalopathy and improves oxygen transport Cerebral edema causes coma or death. Symptoms may be delayed if there
and consumption. 110-112 is concurrent ethanol consumption, which competes for alcohol dehydro-
The oral loading dose of NAC is 140 mg/kg. This is followed by a dose genase and limits conversion of ethylene glycol to its toxic metabolites.
of 70 mg/kg every 4 hours for 17 doses. There are limited data supporting Stage 2 (12-24 hours) is dominated by myocardial dysfunction with
shorter treatment courses in selected patients. Woo and colleagues con- high- or low-pressure pulmonary edema. Myocardial dysfunction or
ducted a retrospective, observational case study of short-course treatment respiratory failure causes death in this stage. Stage 3 (2-3 days) is domi-
in acute overdose with acetaminophen levels in the toxic range. Patients nated by acute renal failure due to acute tubular necrosis with an element
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received an oral loading dose of 140 mg/kg NAC followed by 70 mg/kg of tubular obstruction from calcium oxalate precipitation. 121-123 Late
every 4 hours until the serum acetaminophen level was undetectable. Of (6-18 days) neurologic sequelae have been described in survivors. 121,124,125
the 75 patients, 25 (33.3%) were treated for less than 24 hours. The mean Methanol is metabolized by ADH to formaldehyde, which is metabo-
duration of therapy was 31 ± 16 hours. The incidence of hepatotoxicity lized to formic acid by aldehyde dehydrogenase. Formic acid is the
was low and comparable to patients treated in the standard way. If vomit- primary toxin responsible for metabolic derangements and ocular dis-
ing interferes with oral NAC use, the dose should be repeated along with turbances. Intoxication can occur orally, by inhalation, or by absorption
an antiemetic such as metoclopramide or ondansetron. Occasionally, a through skin. As little as 30 mL causes significant morbidity, and 150 to
nasogastric tube is necessary, or patients can be considered for IV therapy. 240 mL of 40% solution can be lethal. Methanol initially results in
Protocols using a 21-hour IV course and a 48-hour IV course have headache, inebriation, dizziness, ataxia, and confusion. As formic acid
also been shown to be safe and effective. 114,115 The most commonly used accumulates (6-72 hours), the anion gap elevates and the optic nerve
21-hour scheduling of IV NAC includes a loading dose of 150 mg/kg swells. Decreased visual acuity and blindness are classic features.
over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over Pancreatitis also occurs. 126,127 As in ethylene glycol poisoning, symptoms
16 hours. Use of an IV protocol over an oral protocol has been the of methanol poisoning may be delayed by concurrent ethanol.
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source of recent debate. The two have been shown to be equally effec- Treatment of ethylene glycol and methanol poisoning is similar. 128,129
tive in treatment and prevention of hepatic failure. In addition, the IV Inhibiting the formation of toxic metabolites by ADH and/or urgent dia-
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protocol has been shown to be more cost-effective than the oral protocol lytic removal of these alcohols and their metabolites are the cornerstones
and decreases hospital length of stay. 116 of therapy. Bicarbonate infusion may be necessary to improve metabolic
Fatal outcomes in acetaminophen overdose are associated with late acidosis. Hypocalcemia and hypoglycemia should be corrected. In
presentation, high coma grade, prothrombin time >100 seconds, pH methanol intoxication, folate is important in the metabolism of formic
<7.30, creatinine >300 µmol/L, cerebral edema, and sepsis. 117,118 When acid to CO and water; in ethylene glycol poisoning, pyridoxine and
2
poor prognostic features are present, liver transplantation may be thiamine are important in the metabolism of glycolic acid. It should be
considered, but whether to perform liver transplantation is a difficult noted that bicarbonate, folic acid, pyridoxine, and thiamine have not
decision. An accurate assessment of prognosis at the time of admission been proven to improve outcomes.
to the ICU would help apply this therapy to the appropriate patient Fomepizole (4-methylpyrazole) inhibits ADH; ethanol prolongs
population. To this end, investigators from King’s College Hospital the half-life of methanol and ethylene glycol by competing for ADH.
Liver Unit demonstrated that an Acute Physiology and Chronic Health Of the two, fomepizole is preferred because it does not exacerbate the
Evaluation (APACHE) II score >15 provided an accurate assessment of inebriated state, does not require blood monitoring, and is not itself
hospital mortality and identified patients with acetaminophen-induced toxic. 130,131 The protocol consists of a 15 mg/kg IV loading dose followed
liver failure in need of transplantation. 119 by a 10 mg/kg IV bolus every 12 hours. After 48 hours, the bolus dose
should be increased to 15 mg/kg every 12 hours to account for enhanced
Alcohols: Clinical features of ethylene glycol, methanol, and isopropanol fomepizole metabolism. 132,133 For both ethylene glycol and methanol,
poisoning are listed in Table 124-22. Ethylene glycol is an odorless and patients are treated until serum levels fall below 20 mg/dL and the
sweet tasting fluid that is found in antifreeze, deicers, and industrial patient is asymptomatic with a normal pH.

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