DISPOSITION

..... Admission

Admit all patients who are either suicidal, require hemodialysis, or require ADH inhibition. All patients with abnorSuspected or confirmed toxic

alcohol ingestion

Normal serum pH, osmol

gap, and anion gap

If anion gap unchanged,

toxic alcohol ingestion

ruled-out

Lab studies: Serum pH, electrolytes,

and osmolal ity. Send blood to

reference lab for STAT levels of

ethylene glycol and methanol

Initiate hemodialysis in patients with

ethylene glycol or methanol levels > so

mg/dL, severe acidemia, renal failure,

or visual impairment

• Figure 55-2. Toxic alcohols diagnostic algorithm.

CHAPTER 55

mal vital signs, systemic acidosis, or evidence of end-organ

damage require admission to an intensive care unit setting,

as do patients requiring an ethanol infusion for ADH

inhibition to follow serial ethanol levels and monitor CNS

depression. Patients receiving fomepizole can typically be

admitted to a regular hospital bed.

� Discharge

Unintentional ingestions with no evidence of acidosis or

indications for antidotal treatment or hemodialysis may be

safely discharged after appropriate poison prevention

counseling.

SUGGESTED READING

Brent J. Fomepizole for ethylene glycol and methanol poisoning.

N Engl l Med. 2009;360:2216-23.

Mycyk MB. Toxic alcohols. In: Barton C, Collings J, DeB!ieux P,

et a!., eds. Adams' Emergency Medicine. 2nd ed. Philadelphia,

PA: Elsevier, 2012, pp. 1 292-1298.

Mycyk MB, Aks SE. A visual schematic for clarifying the temporal

relationship between the anion gap and the osmol gap in cases

of toxic alcohol poisoning. Am J Emerg Med. 2003;2 1:333-335.

Smith JC, Quan D. Alcohols. In: Tintinalli JE, Stapczynski JS,

Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds. Tintinalli's

Emergency Medicine: A Comprehensive Study Guide. 7th ed.

New York, NY: McGraw-Hill, 201 1:1222-1230.

Acetaminophen Toxicity

Key Points

• Acetami nophen is the most popular over-the-counter

ana lgesic in the Un ited States and is widely prescribed

in combination form with alternative pain relievers,

resulting in frequent uni ntentional overdose.

• Treatment with N-acetylcysteine detoxifies NAPQI, the

hepatotoxic byproduct of acetaminophen metabolism.

INTRODUCTION

Acetaminophen (APAP) is the most commonly used overthe-counter (OTC) analgesic in the United States. It is

found in more than 100 combination pharmaceuticals

(eg, cold and cough agents, sleep agents) and is present in

multiple prescription opioid analgesics ( eg, Vicodin,

Darvocet). Toxic exposures to analgesics as a class have

increased rapidly over the last decade. According to the

National Poison Data System (NPDS) database of expo ­

sures reported to poison centers nationwide, there were

139,780 exposures to all APAP-containing products in the

year 20 10, with 1 ,142 cases exhibiting "major" effects and

125 fatalities. APAP toxicity is the most common cause of

medication-induced liver failure in the United States and

accounts for a significant portion of liver transplants.

The maximum recommended safe dose is 4 g per day

for adults and 60-90 mg/kg/day for children. Toxicity may

result after an ingestion of 7 g in adults or 140 mg/kg in a

child and is due to the conversion of APAP into toxic

byproducts. APAP is normally metabolized via multiple

pathways in healthy individuals. Sulfonation and

glucuronidation are the two primary mechanisms and

produce nontoxic metabolites that are cleared in the urine.

Approximately 10-1 5%, though, is metabolized via the

Jenny J. Lu, MD

• The Rumack-Matthew nomogram should only be used

in acute overdoses with reliable times of ingestion. Pay

careful attention to all units of measurement.

• Consider early transfer to a liver transplant center for

patients with worsening hepatic function or general

signs of deterioration before they meet criteria for liver

transplantation.

cytochrome P450 system into the toxic metabolite

N -acetyl-p-benzoq uinoneimine (NAPQ I).

After a therapeutic ingestion, endogenous stores of

hepatic glutathione will rapidly detoxify any accumulating

NAPQI. However, in cases of APAP overdose, the sulfonation and glucuronidation pathways are overwhelmed, and a

greater percentage of APAP is metabolized via cytochrome

P450 into NAPQI. Glutathione stores can become rapidly

depleted, resulting in elevated levels of intrahepatic NAPQI

with secondary toxicity. Furthermore, in overdose scenarios, a small percentage of APAP can be metabolized into

NAPQI within the kidneys, resulting in consequent renal

toxicity. Patients with lower glutathione stores (chronically

ill, malnourished, and alcoholics) and those with upregulated cytochrome P450 activity (patients on certain

medications including anticonvulsants and antituberculosis

agents, chronic alcoholics) are more likely to suffer

significant toxicity.

Clinically, APAP poisoning progresses through 4 distinct stages. Although all patients may not progress beyond

the first stage after a toxic exposure, those that do tend to

follow the following timeline. Stage 1 is generally encountered within the first 24 hours postexposure. Symptoms of

gastrointestinal ( GI) irritation predominate, including

abdominal pain and vomiting, although patients may

239

CHAPTER 56

remain asymptomatic. Stage 2 occurs between 24-48 hours

post exposure and is known as the latent stage. GI symptoms resolve, but ongoing hepatotoxicity can lead to significantly elevating serum transaminases. The third stage

occurs within 3-4 days after exposure. Abdominal symptoms return, including pain and vomiting along with jaundice and potential encephalopathy. Laboratory studies may

reveal acidemia, hypoglycemia, renal failure, and coagulopathy. Stage 4 lasts between 4 days and 2 weeks of the

exposure and involves a progression to outright liver failure

and death or complete patient recovery. The hepatic function of those patients who survive APAP poisoning will

also recover completely.