What are the vital sign derangements associated with acetaminophen (Tylenol) overdose?

From the Guidelines

Tylenol (acetaminophen) overdose typically causes minimal vital sign derangements in the early stages, which can create a false sense of security, but as hepatotoxicity develops, vital sign abnormalities become more pronounced, including tachycardia, hypotension, tachypnea, and fever, and treatment should focus on N-acetylcysteine (NAC) administration, ideally within 8 hours of ingestion, as recommended by the Annals of Emergency Medicine 1.

Initial Presentation

Initially, patients may present with normal vital signs or mild tachycardia, but as the condition progresses, vital sign abnormalities become more pronounced.

• Tachycardia
• Hypotension
• Tachypnea
• Fever These changes reflect the progression from initial minimal symptoms to hepatic injury, metabolic acidosis, coagulopathy, and potentially multi-organ failure.

Treatment and Monitoring

The standard regimen for NAC administration is a 21-hour IV protocol: 150 mg/kg loading dose over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours, as supported by the study published in the Annals of Emergency Medicine 1.

• Vital signs should be closely monitored throughout treatment, as NAC itself can occasionally cause anaphylactoid reactions with hypotension and bronchospasm, particularly during the loading dose.
• The Rumack-Matthew nomogram allows for risk stratification for hepatotoxicity of patients who present with a single known time of an acetaminophen overdose within 24 hours of ingestion, as discussed in the study by Keays et al. 1.

Severe Cases

In severe cases progressing to liver failure, patients may develop significant hypotension requiring vasopressor support, respiratory distress requiring ventilatory support, and hypothermia.

• The potential for benefit of NAC administration in these cases suggests that it should be considered, as demonstrated by the studies showing a reduction in mortality and disease progression in patients with hepatic failure due to acetaminophen toxicity 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY (Antidotal) Acetaminophen is rapidly absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Oral administration of acetylcysteine, especially in the large doses needed to treat acetaminophen overdose, may result in nausea, vomiting and other gastrointestinal symptoms.

The vital sign derangements with Tylenol overdose include nausea and vomiting. Other gastrointestinal symptoms may also occur. 2, 2, 2

From the Research

Vital Sign Derangements with Tylenol Overdose

• The typical clinical course of acetaminophen toxicity involves peak serum transaminase activities usually occurring 48-96 hours after acute ingestion 3.
• Patients who have chronically ingested excessive acetaminophen doses and develop hepatotoxicity usually present with such, and renal failure is more common in this population 3.
• Vital sign derangements may include signs of liver failure, such as coagulopathy, jaundice, and encephalopathy, as well as signs of renal failure, such as oliguria and electrolyte imbalances.
• The treatment of acetaminophen overdose centers on administration of N-acetylcysteine (NAC) to prevent hepatotoxicity, though NAC also improves outcomes in patients who present with acute liver failure 3.

N-Acetylcysteine Treatment

• NAC is generally well-tolerated when given intravenously, with the main concern being anaphylactoid reactions, which usually occur during loading doses and are easily treated with discontinuation of the NAC infusion, administration of antihistamines, and then restarting the loading dose at a slower infusion rate 3.
• The optimal route and duration of administration for N-acetyl-cysteine in the management of acetaminophen poisoning are controversial, with some studies suggesting that oral NAC is superior to intravenous NAC in presentations later than 15 hours 4.
• Other studies have found that the oral NAC protocol preserves more hepatocytes than the 21-h intravenous protocol for patients presenting within 24 hours of ingestion 5.

Prevention of Acetaminophen Toxicity

• Co-administration of N-acetylcysteine and acetaminophen has been shown to efficiently block acetaminophen toxicity in a mouse model, suggesting that concomitant oral dosing with APAP and NAC can provide a convenient and effective way of preventing toxicity associated with large dosage of APAP 6.
• This approach may be a viable over-the-counter (OTC) alternative to the current practice of providing APAP OTC and treating APAP toxicity if/when it occurs 6.