Chapter 106. Analgesics

Over-the-counter analgesics, such as salicylates (ASA) and acetaminophen, can result in fatal overdose, but early identification of toxicity and initiation of appropriate treatment can significantly reduce mortality from these exposures. Nonsteroidal anti-inflammatory drug (NSAID) overdoses are rarely fatal and typically require only supportive care.

Clinical Features

The features of aspirin (ASA) toxicity are summarized in Table 106-1. Clinical symptoms of acute toxicity include hyperthermia, tachypnea, and altered mental status. Chronic or “therapeutic” (repeated dose) poisonings are generally more serious and associated with higher mortality than acute overdoses, and are typically encountered in elderly patients with multiple medical problems. Chronic toxicity develops at lower drug levels compared to acute overdoses. The duration of symptoms is often prolonged and there may be a delay in diagnosis because the clinical picture is similar to that of infection. Consider chronic salicylism in any patient with unexplained nonfocal neurologic and behavioral abnormalities, especially with coexisting acid-base disturbance, tachypnea, dyspnea, or noncardiogenic pulmonary edema. Patients taking carbonic anhydrase inhibitors to treat glaucoma are at increased risk for chronic salicylism.

In children, acute ASA overdoses generally present within hours of ingestion. Children younger than 4 years of age tend to develop early metabolic acidosis (pH <7.38), whereas children older than 4 years usually manifest a mixed acid-base disturbance as seen in adults.

Diagnosis and Differential

ASA toxicity is a clinical diagnosis made in conjunction with the patient's acid-base status. Respiratory alkalosis with an anion-gap metabolic acidosis, and hypokalemia are the classic features of this poisoning. ASA blood concentrations correlate poorly with toxicity, and relying on drug levels as a measure of toxicity is the most common pitfall in the management of ASA overdose.

Check bedside glucose determination in all patients with altered mental status. Additional laboratory studies include electrolytes, blood urea nitrogen (BUN), creatinine, complete blood count (CBC), prothrombin time (PT), ASA level, acetaminophen level (to exclude coingestion), and venous blood gas. Hypoglycemia or hyperglycemia may be seen with severe or chronic toxicity.

The differential diagnosis of ASA toxicity includes diabetic ketoacidosis, sepsis, meningitis, acute iron poisoning, caffeine overdose, theophylline toxicity, and Reye syndrome.

Emergency Department Care and Disposition

1. Institute cardiac monitoring and support the ABCs. Establish intravenous (IV) or intraosseous (IO) access early. Careful airway management is critical in ASA-poisoned patients: a sudden drop in serum pH due to respiratory failure can precipitously worsen ASA toxicity, and careful ventilation guided by acid-base status is essential in the intubated patient. Respiratory acidosis frequently occurs shortly after a mechanical ventilator is set to a “normal” rate and volume parameters, and is typically a premorbid event.

2. Administer activated charcoal 1 gram/kilogram po. Whole-bowel irrigation may effectively decontaminate the GI tract in the setting of large overdoses, enteric-coated, or sustained-release preparations.

3. Administer IV normal saline (NS) to patients with evidence of volume depletion. During initial resuscitation, monitor urine pH, ASA level, electrolytes, glucose, and acid-base status hourly. Add dextrose to parenteral fluids after initial NS resuscitation. Consider 10% dextrose in the setting of hypoglycemia or neurologic symptoms. Add potassium 40 mEq/L after establishing adequate urine output (1 to 2 mL/kg/h), if not contraindicated by initial electrolytes and renal function.

4. Alkalinize the serum and urine to enhance ASA protein binding and urinary elimination: administer a bolus of 1 to 2 mEq/kg of sodium bicarbonate, then add 150 mEq (3 ampules) of sodium bicarbonate to 1 L 5% dextrose in water and infuse at 1.5 to 2.0 times the patient's maintenance rate; adjust the infusion to maintain urine pH >7.5 if possible. Bicarbonate may worsen hypokalemia and precipitate arrhythmias.

5. Consider hemodialysis for all cases with ASA levels in excess of 100 milligrams/dL. Indications for hemodialysis may be significantly lower in the setting of chronic toxicity (60 to 80 milligrams/dL). Also consider hemodialysis for clinical deterioration despite supportive care and alkalinization, renal insufficiency or failure, severe acid-base disturbance, altered mental status, or adult respiratory distress syndrome. Check serial ASA levels every 2 hours until they begin to fall, then every 4 to 6 hours until the level is nontoxic.

6. Enteric-coated and sustained-release preparations result in delayed peak serum levels (0 to 60 hours postingestion) and their ingestion requires admission for at least 24 hours to ensure declining serial ASA levels and improving clinical status.

7. Discharge a patient from the ED if there is progressive clinical improvement, no significant acid-base abnormality, and a decline in serial ASA levels toward the therapeutic range. In deliberate overdoses, obtain a psychiatric consultation before discharge.

Clinical Features

Acute acetaminophen toxicity can present in 4 classic stages outlined in Table 106-2. Massive acetaminophen ingestions (4-hour acetaminophen level >800 micrograms/mL) may cause coma or agitation and lactic acidosis early, as opposed to delayed symptom onset seen in smaller overdoses.

Diagnosis and Differential

Toxic exposure to acetaminophen is likely when an adult ingests >10 grams or 200 milligrams/kilogram in a single ingestion or over a 24-hour period, or >6 grams or 150 milligrams/kilogram/day for 2 consecutive days. Confirm toxicity with a serum acetaminophen concentration and determining the time of ingestion. Plot the serum acetaminophen level on the Rumack-Matthew nomogram (Fig. 106-1); this nomogram applies only to the setting of a single acute exposure and a window between 4 hours and 24 hours postingestion. Obtain additional laboratory studies, including electrolytes, glucose, BUN, creatinine, transaminases, CBC, and PT, ASA, urine toxicology screen, and ECG as clinically indicated (eg, potential coingestion in the suicidal patient).

Emergency Department Care and Disposition

1. N-acetylcysteine (NAC) is the antidote for acetaminophen poisoning. Dosing of NAC is outlined in Table 106-3, and the treatment algorithm is depicted in Fig. 106-2.

2. If acetaminophen is still detectable after the dosing regimens described in Table 106-3 are complete, continue NAC until acetaminophen is undetectable in serum.

3. Treat abnormalities related to fulminant hepatic failure by correcting coagulopathy and acidosis, managing cerebral edema, and supporting multiorgan failure, and refer early to a transplant center.

4. Patients with nontoxic acetaminophen levels based on the Rumack-Matthew nomogram may be medically cleared from the ED if there is no evidence of other drug ingestion. Admit all patients receiving NAC therapy.

Clinical Features

Clinical features of NSAID toxicity after acute overdose are outlined in Table 106-4, though toxicity is more commonly associated with chronic therapeutic use of NSAIDs than acute ingestion.

Diagnosis and Differential

The manifestations of NSAID toxicity are nonspecific. NSAID levels are not readily available or clinically useful in assessing toxicity. Laboratory evaluation should include electrolytes, glucose, renal and hepatic function tests, and acetaminophen level (if indicated). Bedside glucose determination is indicated for altered mental status or seizures.

Emergency Department Care and Disposition

A general algorithm for acute NSAID overdoses is outlined in Fig. 106-3.