CLINICAL PRESENTATION

..... History

Always attempt to identify the exact formulation, amount,

and timing of the ingestion. Ask about any coingestants

(eg, ethanol) that might impact the metabolism of APAP

and clarify the number and frequency of ingestions to rule

out chronic toxicity. Ask about risk factors for increased

toxicity, including chronically ill and alcoholic patients and

those taking medications that activate the cytochrome

P450 system (eg, anticonvulsants, antituberculosis).

The majority of symptoms are abdominal and

neurologic in nature. Ask about the presence of any

abdominal pain, nausea, and vomiting. Inquire about any

symptoms of altered mental status and decreased levels of

consciousness, as these portent a more serious clinical

course.

..... Physical Examination

Pay careful attention to the patient's vital signs.

Hemodynamic instability suggests a significant poisoning.

Significant tachypnea may indicate an attempt to

compensate for an ongoing metabolic acidosis.

Coingestions or combination products ( eg, APAP + opioid

or APAP + diphenhydramine) may cause marked

abnormalities due to concurrent opioid or anticholinergic

toxidromes.

Note the patient's general appearance, mental status,

and level of consciousness. Carefully examine the abdomen.

Diffuse abdominal tenderness is common after significant

overdose, and tender hepatomegaly may be evident

beginning in the latent stage. Finally, examine the skin and

sclera, looking for signs of jaundice.

DIAGNOSTIC STUDIES

..... Laboratory

Obtain an immediate serum APAP level in all patients and

follow with serial testing to establish an upward or

downtrending value. In patients with clearly timed acute

ingestions, order a second level at the 4-hour mark

postexposure. These values can be plotted on the RumackMatthew nomogram to help determine treatment

(Figure 56-1). Check a full panel of liver studies (aspartate

aminotransferase, alanine aminotransferase, albumin,

bilirubin) in all patients and follow serially, looking for

evidence of worsening hepatotoxicity. Order a coagulation

profile (prothrombin time [PT] , international normalized

ratio and partial thromboplastin time) to determine the

degree of liver synthetic dysfunction.

Check a baseline complete blood count and follow

serial hemoglobin levels in patients who develop

coagulopathies. Order a metabolic panel to assess for

electrolyte abnormalities and to calculate the anion gap, as

a significantly elevated anion gap metabolic acidosis may

be present. Confirm the degree of acidosis with blood gas

sampling. Finally, check the renal function in all patients,

as acute kidney injury is common secondary to intra-renal

NAPQI production.

..... Imaging

Consider a head computed tomography (CT) in patients

whose mental status does not correlate with an isolated

ingestion. Cerebral edema secondary to hyperammonemia

may occur in hepatic failure. Abdominal CT imaging is

usually of limited utility in APAP poisoning but should be

considered in patients with signs of peritonitis.

MEDICAL DECISION MAKING

Many exposures and overdoses have the potential for

significant hepatotoxicity. In most cases, a thorough history

will be sufficient to identify APAP as the culprit. In patients

presenting with elevated transaminases or signs of hepatic

failure and no obvious source, there is usually little

downside in empirically starting therapy with

N -acetylcysteine (NAC) until more information is o btained.

Draw baseline APAP and liver function tests and follow

serially to determine whether the levels are rising or falling.

In patients with acute ingestions of reliable timing,

plot their 4-hour APAP level on the Rumack-Matthew

nomogram to determine treatment. Of note, the

nomogram cannot be used if either the time of ingestion is

unknown or the ingestion is chronic (occurring over

hours/days). The nomogram may also be unreliable in

cases of coingestions with products that alter APAP

absorption and pharmacokinetics.

Use the King's College liver transplant criteria early to

estimate the severity of exposure and identify which

patients may require transfer for specialty care. Patients

with either a pH <7.3 after fluid resuscitation or a combination of PT > 100, creatinine >3.3 mg!dL, and grade 3 or

4 encephalopathy are considered to meet these criteria.

Consult your regional poison control center for all patients

with significant hepatotoxicity to help determine the ideal

treatment (Figure 56-2).

TREATMENT

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Figure 56-1 . Rumack-Matthew nomogram. Reprinted with permission from

Tintinalli JE, Stapczynski JS, Ma OJ, Cline OM, Cydulka RK, Meckler GO. Chapter 1 84.

Acetaminophen. In: Tintinalli JE, Stapczynski JS, Ma OJ, Cline OM, Cydulka RK,

Meckler GO, eds. Tintinolli's Emergency Medicine: A Comprehensive Study Guide.

7th ed. New York: McGraw-Hill, 201 1.

26

As with all cases of acute poisoning, address the patient's

airway, breathing, and circulation. Gastric decontamination

is occasionally indicated and generally performed with

activated charcoal (AC). AC readily absorbs APAP and

should be given in cases with recent ingestions (within

8-12 hours of exposure) or those with evidence of ongoing

absorption, provided there are no contraindications. Give

a starting dose of 1 g/kg and consider repeated dosing in

patients with significantly large ingestions. Beware AC

products containing sorbitol with repeated dosing to

avoid significant fluid and electrolyte abnormalities.

Gastric lavage and whole-bowel irrigation are rarely

CHAPTER 56

.A. Figure 56-2. Acetaminophen toxicity diagnostic algorithm. ABCs, airway, breathing, and circulation; AC, activated

charcoal; ALT, alanine aminotransferase; APA� acetaminophen; AST, aspartate aminotransferase; CM� comprehensive

metabolic panel; ICU, intensive care un it; NAC, N-acetylcysteine.

utilized due to the effective binding qualities of AC and

the ready availability of an effective antidote.

NAC detoxifies NAPQI via multiple pathways, including

functioning as a glutathione precursor. It is given orally in

a loading dose of 140 mg/kg and subsequent doses of

70 mg/kg every 4 hours. NAC is adsorbed by charcoal, but

there is no evidence that there is less effectiveness when

NAC and charcoal are given together orally. Of note, oral

NAC can be given by the intravenous (N) route if passed

through a 0.22-micron filter, and multiple protocols exist

taking advantage of this. There is also a Food and Drug

Administration-approved IV NAC formulation, Acetadote,

that doesn't require the use of a filter and has a lower

likelihood of anaphylactoid reaction compared with giving

the oral compound intravenously. N NAC can be used in

all patients (including pregnancy) and is particularly

useful in patients who cannot tolerate anything by mouth

due to vomiting or altered mental status. Regardless of

route, current guidelines recommend to continue NAC

treatment until the liver function has normalized and

APAP levels are undetectable.