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Toxicity, Acetaminophen: Treatment & Medication
Updated: Aug 25, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Initial appropriate supportive care is essential in acetaminophen poisoning. Immediate assessment of the patient's airway, breathing, and fluid status is critical before treatment for suspected acetaminophen overdose is started. In addition, assessing for other potential life-threatening co-ingestions is important.
- GI decontamination: Consider decontamination with activated charcoal in any patient who presents within 4 hours of ingestion. Consider gastric lavage if ingestion occurred within 1 hour of evaluation. In regard to young children, a small-bore nasogastric (NG) tube may limit the ability to perform effective gastric lavage.
- Oral N-acetylcysteine (Mucomyst)
- The antidote for acetaminophen toxicity is N -acetylcysteine (NAC), which has several mechanisms to prevent hepatotoxicity. The oral formulation is the drug of choice for the treatment of acute, chronic, or late-presenting acetaminophen ingestions.
- NAC is converted to cysteine, which replenishes glutathione stores. NAC also directly detoxifies N -acetyl-benzoquinoneimine (NAPQI) to nontoxic metabolites. NAC provides a substrate for sulfation, increasing the capacity for nontoxic metabolism. NAC can directly conjugate to NAPQI to reduce toxicity.
- The National Multicenter study revealed that oral NAC is safe and effective for as long as 24 hours after a toxic ingestion.5 Treatment with oral NAC effectively prevented hepatotoxicity, regardless of the initial plasma acetaminophen level, if it was started within 8 hours of the ingestion. Its effectiveness did not depend on whether NAC was started 0-4 or 4-8 hours after ingestion.
- Intravenous (IV) NAC (Acetadote)
- In 2004, the US Food and Drug Administration (FDA) approved an IV formulation of NAC for use in adults. In February 2006, this FDA approval was modified to include children (patients <40 kg).
- IV administration of NAC is recommended for use in selected patients, including those with an altered mental status, GI bleeding and/or obstruction or a history of caustic ingestion, potential fetal toxicity from maternal toxicity, or an inability to tolerate oral NAC because of refractory emesis despite proper use of antiemetics.
- Pharmaceutical guidelines for IV NAC administration differ depending on the patient's body weight and/or on whether the ingestion is acute or chronic. Guidelines for IV dosage and administration are discussed in the Medication section.
- Adverse side effects associated with the IV administration include flushing, pruritus, and a rash (seen in about 15% of patients). These side effects are remedied by stopping the infusion, administering an antihistamine, and restarting this antidote at a slower infusion rate. Bronchospasm and hypotension can occur; however these effects are rare (<2% of patients).
Surgical Care
- Surgical evaluation for possible liver transplantation is indicated for patients who have severe hepatotoxicity and potential to progress to hepatic failure.
- Criteria for liver transplantation include metabolic acidosis, renal failure, coagulopathy, and encephalopathy.
Consultations
- A medical toxicologist or a regional poison control center may be helpful in treating patients with possible co-ingestions, complicated histories, or atypical presentations.
- Consultation with a hospital-based pediatric gastroenterologist affiliated with a transplant center is needed for patients who have signs of clinically significant hepatotoxicity.
- If the ingestion is due to an attempt to harm oneself, psychosocial and/or psychiatric evaluation is indicated.
Medication
N -acetylcysteine (NAC), antiemetics, and activated charcoal are helpful in the treatment of acetaminophen toxicity. The American College of Emergency Physicians (ACEP) has recently issued guidelines for acetaminophen overdose.6
Antidotes
NAC, a glutathione precursor, is the antidote of choice to prevent and treat acetaminophen-induced hepatotoxicity. It is indicated for all ingestions above the possible toxicity line on the Rumack-Matthew nomogram. The FDA has approved both oral (Mucomyst) and intravenous (Acetadote) formulations. Three treatment protocols are recognized: 72-hour oral, 21-hour intravenous, and 48-hour intravenous. For maximum hepatoprotective effect, the antidote should be given within 8-10 hours of the acetaminophen ingestion.
N-acetylcysteine (Mucomyst, Acetadote)
PO antidote (Mucomyst) available as a 20% solution (200 mg/mL). Should be diluted to 5% solution (50 mg/mL) with fruit juice or carbonated beverage. Aggressive antiemetic therapy indicated in patients with nausea or vomiting due to acetaminophen-induced hepatic injury or foul smell of the solution. If patient vomits within 60 min of administration, repeat dose. IV formulation (Acetadote) diluted in 5% dextrose in water (D5W) and infused according to protocol for acute (within 8-10 h) or late-presenting or chronic acetaminophen ingestion.
Entire PO or IV regimen should be completed even if acetaminophen plasma levels decrease below toxic range on nomogram.
Adult
PO
Loading dose: 140 mg/kg PO once
Maintenance dosage (start 4 h after loading dose): 70 mg/kg PO q4h for 17 doses; total 18 doses administered equaling 1330 mg/kg over 72 h
IV (patients >40 kg)
Acute (8-10 h after ingestion)
Loading dose: 150 mg/kg IV infused over 1 h; dilute in 250 mL D5W
First maintenance dose: 50 mg/kg IV infused over 4 h; dilute in 500 mL D5W
Second maintenance dose: 100 mg/kg IV infused over 16 h; dilute in 1000 mL D5W
Each infusion immediately follows the previous; total treatment time 21 h
Late presenting or chronic (>10 h after ingestion)
Loading dose: 140 mg/kg IV infused over 1 h; dilute in 500 mL D5W
Maintenance doses: 70 mg/kg IV q4h for at least 12 doses; dilute each dose in 250 mL of D5W and infuse over minimum 1 h; total treatment time 48 h
Decrease total volume of D5W if fluid restriction required
Pediatric
PO: Administer as in adults
IV (patients <40 kg)
Acute ingestion: Administer as in adults except decrease volume of D5W with each dose for pediatric patient
May decrease carbamazepine serum levels; coadministration with nitroglycerin increases risk of hypotension
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
PO commonly causes nausea and vomiting; anaphylactoid reaction reported in patient starting PO therapy; IV can cause various infusion rate-dependent erythema at infusion site and/or generalized flushing; other adverse effects include diarrhea, headache, and anaphylactoid reactions with bronchospasm, hypotension, tachycardia, flushing, angioedema, or rash; adverse reactions respond well to antihistamines and to slowing or stopping infusion; patients with history of asthma or bronchospasm at increased risk for reactions; adverse reactions occur in about 3-9% and thought to be due to histamine release
Antiemetic agents
Nausea and vomiting in acetaminophen-induced hepatotoxicity may due to acetaminophen, activated charcoal, or oral NAC. Antiemetic therapy is indicated in patients with these symptoms to enable successful treatment with oral NAC.
Metoclopramide (Reglan)
Antiemetic effect appears to be due to ability to block dopamine receptors in chemoreceptor trigger zone (CTZ) of CNS. Also enhances GI motility and accelerates gastric emptying time.
Adult
10-20 mg/dose IV; not to exceed 1 mg/kg/dose or 3 mg/kg/d in divided doses as needed
Pediatric
1-2 mg/kg/d IV in divided doses
Anticholinergics may antagonize effects; opiate analgesics may increase toxicity and cause CNS depression
Documented hypersensitivity; pheochromocytoma or GI hemorrhage; obstruction or perforation
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse reactions include drowsiness, diarrhea, and hypotension; acute dystonic reactions most common at high doses; caution in epilepsy (may increase seizure activity), mental illness, and Parkinson disease
Ondansetron (Zofran)
Selective 5-hydroxytryptamine (5HT3) receptor antagonist. Blocks serotonin by acting on vagus nerve peripherally and at CTZ in CNS. Considered more effective than metoclopramide with fewer adverse effects. More expensive antiemetic than metoclopramide.
Adult
8 mg IV q8h, not to exceed 3 doses/d
Pediatric
0.15 mg/kg IV q8h, not to exceed 3 doses/d
CYP inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) can potentially change half-life and clearance, but dosage adjustment not usually required
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Headache common
Decontamination agents
Consider decontamination with activated charcoal in any patient who presents within 4 hours after the ingestion. Activated charcoal may be helpful more than 4 hours postingestion if a co-ingestion with an agent that slows gut motility occurred or if a sustained-release preparation was ingested. Activated charcoal adsorbs acetaminophen, but its use has been controversial because activated charcoal may absorb oral NAC. Although activated charcoal significantly reduces the bioavailability of NAC, the small decrease in the NAC bioavailability is unlikely to reduce the effectiveness of oral NAC as an antidote.
Activated charcoal (Actidose-Aqua, Liqui-Char)
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores absorbs 100-1000 mg of drug per gram of charcoal. Prevents absorption by adsorbing drug in the intestine. Multidose charcoal may interrupt enterohepatic recirculation and enhance elimination by enterocapillary exsorption. In theory, by constantly bathing GI tract with charcoal, intestinal lumen serves as dialysis membrane for reverse absorption of drug from intestinal villous capillary blood into intestine. Does not dissolve in water.
For maximum effect, administer within 30 min after ingestion or poison.
Adult
50-100 g, 1 g/kg, or 10 times the weight of ingested poison given PO as suspension in 4-8 oz. of water.
Pediatric
<1 year: Not recommended
>1 year: Administer as in adults
Effectiveness of other medications decrease with coadministration; do not mix with sherbet, milk, or ice cream (decreases absorptive properties)
Documented hypersensitivity; poisoning or overdosage of mineral acids and alkalies
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Not effective in poisonings of ethanol, methanol, or iron salts; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns black
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| Differential Diagnoses & Workup: Toxicity, Acetaminophen |
 Treatment & Medication: Toxicity, Acetaminophen |
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References
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Further Reading
Keywords
acetaminophen overdose, acetaminophen toxicity, acetaminophen toxicity nomogram, acetaminophen-induced hepatotoxicity, alanine aminotransferase, ALT, aspartate aminotransferase, AST, APAP, APAP toxicity, N -acetylcysteine, NAC, N -acetyl-p -aminophenol, analgesics, activated charcoal, AC, hepatic centrilobular necrosis, hepatic cytochrome P450 system, CYP system, hepatotoxicity, N -acetyl-benzoquinoneimine, NAPQI, acetaminophen-induced hepatic failure, liver transaminases, paracetamol, Rumack-Matthew nomogram, hypoglycemia, coagulopathy, renal failure, malnutrition, gastroenteritis, alcoholism, HIV, hepatic failure, liver transplantation, hepatomegaly, acute tubular necrosis, proteinuria, hematuria
