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Toxicity, Acetaminophen: Treatment & Medication
Updated: Sep 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Stabilize immediate life-threatening conditions and initiate supportive care.
Emergency Department Care
- Supportive therapy, including IV fluids, oxygen, and cardiac monitor
- Gastric decontamination
- Oral activated charcoal (AC) avidly adsorbs acetaminophen and should be administered if the patient presents within 1 hour of ingestion.
- Oral AC may be of benefit greater that 1 hour after the ingestion if the ingestion involves an agent that delays gastric emptying or slows GI motility. Oral activated charcoal administered with NAC greater than 4 hours after ingestion has been shown in one case series to be effective in reducing the incidence of transaminitis after toxic acetaminophen ingestion.
- Administer N -acetylcysteine, if indicated. Early administration of NAC, within 8 hours of ingestion, is nearly 100% hepatoprotective. NAC should be administered while awaiting a serum acetaminophen level if the patient presents close to or later than 8 hours postingestion, or if the patient is pregnant.
- Assess for evidence of other life-threatening co-ingestions.
- For further information, see the American College of Emergency Physicians treatment guidelines for acetaminophen poisoning.6
Consultations
- Medical toxicologist, available through consultation with a regional poison control center
- Consultation with a medical toxicologist is recommended for patients who have a complicated or late presentation, hepatic or renal dysfunction, or a history of potentially toxic co-ingestants.
- Hepatologist, in the setting of hepatic dysfunction.
- Transplant surgeon, in the setting of clinical and laboratory indicators that are highly predictive of death unless urgent transplantation is undertaken. The King's College Hospital criteria for the determination of the urgent need for transplantation after acetaminophen-induced fulminant hepatic failure include the following:
- Arterial pH <7.3 (regardless of grade of encephalopathy) OR
- Grade III or IV encephalopathy AND
- PT >100s AND
- Serum creatinine >3.4 mg/dL
Medication
Agents used in the treatment of acetaminophen poisoning include activated charcoal, N -acetylcysteine, and antiemetics.
GI decontaminants
Emergency treatment in poisoning caused by drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
Activated charcoal (Actidose, CharcoAid, Charcodote, Liqui-Char)
Drug of choice for gastric decontamination in patients presenting within 1 h post-ingestion, or in cases where co-ingestants may delay gastric emptying or gut motility.
Adult
1 g/kg PO or 10 times the amount of drug ingested
Pediatric
Administer as in adults
Effectiveness of other medications decreases with coadministration: may inactivate ipecac syrup if used concomitantly; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity to activated charcoal; unprotected airway with absent gag reflex; poisoning or overdose of mineral acids or alkalis; relative contraindication includes ingestion of hydrocarbons
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 very effective in poisonings due to alcohols, lithium, and iron salts; adverse effects include nausea and vomiting; risk of aspiration if the airway is not secure; monitor for bowel sounds to minimize risk of charcoal ileus and potential bowel obstruction (only if multiple doses administered)
Antidote
May provide substrate for conjugation with the toxic metabolite of acetaminophen. Administer all doses, even if acetaminophen level has dropped below toxic range.
N-acetylcysteine (Mucomyst, Acetadote)
Drug of choice for the prevention and treatment of acetaminophen-induced hepatotoxicity. Approved by the FDA for both PO and IV administration. For maximum hepatoprotective effect, administer within 8 h of acetaminophen ingestion. When given PO, dilute in chilled juice or cola to a 5% solution. May be administered via nasogastric tube if severe nausea threatens administration. Repeat dose if vomiting occurs within 1 h of oral administration. When administered IV, dilute in 5% dextrose solution, infuse per recommended IV protocol.
Adult
Three recognized and acceptable protocols for the administration of NAC are as follows:
PO
Loading dose: 140 mg/kg PO once; follow with maintenance dose
Maintenance dose: (start 4 h after loading dose): 70 mg/kg PO q4h for 17 additional doses (ie, 18 doses totaling 1330 mg/kg administered over 72 h)
Continuous IV administration (total treatment time 21 h)
Acute (8-10 h after ingestion) in patients >40 kg:
Loading dose: 150 mg/kg IV infused over 15 min (dilute in 200 mL D5W) follow with maintenance doses
First maintenance dose: 50 mg/kg IV infused over 4 h (dilute in 500 mL D5W), followed with second maintenance dose
Second maintenance dose: 100 mg/kg IV infused over 16 h (dilute in 1000 mL D5W)
Intermittent IV administration (total treatment time 48 h)
Late presenting or chronic (>10 h after ingestion) in patients >40 kg:
Loading dose: 140 mg/kg IV infused over 1 h (dilute in 500 mL D5W), followed with maintenance dose
Maintenance dose: 70 mg/kg IV q4h for at least 12 doses (dilute each dose in 250 mL of D5W and infuse over minimum 1 h)
Decrease total volume of D5W if fluid restriction required
Shortened courses of NAC (20-48 h) have been shown to be safe and effective in a subset of patients who have undetectable serum acetaminophen levels, and normal AST, ALT, and INR after 20 h of NAC treatment (consult a medical toxicologist or poison control center if considering shortened NAC therapy).7
Pediatric
PO: Administer as in adults
IV (patients <40 kg):
Acute ingestion: Administer as in adults except decrease total volume of D5W with each dose for pediatric patient
NAC decreases carbamazepine levels; NAC enhances hypotension of nitroglycerin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects associated with PO NAC include nausea and vomiting; only 1 case of an anaphylactoid reaction following PO NAC has been reported; IV NAC may cause various degrees of infusion rate-dependent erythema at infusion site or flushing (these are generally self-limited); anaphylactoid reactions, including urticaria, fever, bronchospasm, and hypotension respond to antihistamines and stopping the infusion (they may be limited by slowing infusion rate and may be more common in patients with asthma); adjust total fluid volume for IV in patients <40 kg or fluid restricted patients
Antiemetics
Emesis frequently is associated with acetaminophen toxicity and is a common consequence of activated charcoal and PO NAC administration. For these reasons, antiemetic therapy often is necessary to facilitate the successful administration of PO NAC.
Antiemetics that do not decrease gastric motility or significantly alter mental status are the DOC; anticholinergic drugs, such as prochlorperazine (Compazine) are not considered beneficial, in part because of their propensity to cause both of these effects. Phenothiazines also may add to the toxicity associated with other anticholinergic drugs, which may be in combination with APAP-containing formulations.
Metoclopramide (Reglan)
Functions as an antiemetic by blocking dopamine receptors in the chemoreceptor trigger zone of the CNS. Is generally considered an initial drug of choice due to low cost.
Adult
10-20 mg IV, not to exceed 1 mg/kg; not to exceed 3 mg/kg/d divided prn
Pediatric
1-2 mg/kg IV total dose
Opiate analgesics may increase metoclopramide toxicity in CNS
Documented hypersensitivity to metoclopramide
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with a history of mental illness or Parkinson disease; adverse effects include drowsiness, hypotension, and acute dystonia, especially at high doses; may increase the frequency of seizures in patients with epilepsy
Ondansetron (Zofran)
Selective 5-HT3–receptor antagonist that blocks serotonin both peripherally and centrally. Considered a potentially more effective antiemetic, with less common adverse effects than metoclopramide.
Adult
1 mg, or 0.15 mg/kg, up to 8 mg IV q8h, not to exceed 3 doses in 24 hours
Pediatric
0.15 mg/kg IV q 8h, not to exceed 3 doses in 24 hours
Although cytochrome CYP enzyme inducers (barbiturates, rifampin, carbamazepine, and phenytoin) may potentially change the half-life and clearance of ondansetron, dosage adjustment is not usually required
Documented hypersensitivity to ondansetron
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Medication is to be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting
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References
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US Food and Drug Administration. Organ-specific warnings; internal analgesic, antipyretic, and antirheumatic drug productus for over-the-counter human use. Federal Register. 2009 Apr 29;74(81). Available at http://edocket.access.gpo.gov/2009/pdf/E9-9684.pdf. Accessed August 5, 2009.
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Further Reading
Keywords
acetaminophen toxicity, paracetamol, N-acetyl-p-aminophenol, APAP, analgesic agent, antipyretic agent, N-acetyl-p-benzoquinone-imine, NAPQI, hepatocellular death, hepatocellular necrosis, centrilobular liver necrosis, N -acetylcysteine, NAC, fulminant hepaticfailure, hepatic encephalopathy, renal failure, coagulopathy, diaphoresis, acetaminophen toxicity, acetaminophen overdose, APAP toxicity, APAP overdose, hepatotoxicity, acetaminophen poisoning, APAP poisoning
