injuries poisoning
Acetaminophen Poisoning
AcuteAcetaminophenPoisoning
To cause toxicity, an acute oral overdose must total≥150 mg/kg (about 7.5 g in adults) within 24 hours. 2 years of age has been associated with several hundred reports of overdoses, including several dozen fatalities, several in children. Most of these adverse events were the result of dosing errors because the drug is dosed in milligrams but dispensed in milliliters. Because these overdoses are iatrogenic, reliable information regarding time and total dose is available. The has thus been used with success to predict toxicity. Overdoses 48 hours after ingestion. Symptoms, which occur in 4 stages (see table Stages of Acute Acetaminophen Poisoning ), include anorexia, nausea, vomiting, and right upper quadrant abdominal pain. Renal failure and pancreatitis may occur, occasionally without liver failure. After Serumacetaminophenlevels Rumack-Matthew nomogram Acetaminophenoverdose should be considered in all patients with nonaccidental ingestions that may be suicide attempts and in children with ingestions because formulations containingacetaminophenare frequently ingested in such overdoses and are not reported. Also, becauseacetaminophenoften causes minimal symptoms during the early stages and is potentially lethal but treatable, ingestion should be considered in all patients with accidental ingestions as well. Consider occultacetaminophentoxicity in all patients who have ingestions. level. If the time of acute ingestion is known, the is used to estimate likelihood of hepatotoxicity; if the time of acute ingestion is unknown, the nomogram cannot be used. For a single acute overdose of traditional If the exact time of a single ingestion cannot be confirmed, the worst case is assumed for risk determination. That is, the earliest possible time of ingestion is estimated and then plotted on the Rumack-Matthew nomogram. For example, if a patient states the overdose was taken between 6 and 9 PM, then 6 PM is used as the time of ingestion (worst case). Similarly, if a child lived in a home that had noacetaminophenproducts but for the previous 24 hours was visiting a relative whose home did have such products, then anacetaminophenlevel drawn at presentation would be interpreted as a 24-hour level. In practice, worst-case estimates are often difficult to make. Semilogarithmic plot of plasmaacetaminophenlevels vs time.Cautions for use of this nomogram: The time coordinates refer to time after ingestion. Serum levels drawn before 4 hours may not represent peak levels. The graph should be used only in relation to a single acute ingestion. The lower solid line 25% below the standard nomogram is included to allow for possible errors inacetaminophenplasma assays and estimated time from ingestion of an overdose. Adapted from Rumack BH, Matthew H:Acetaminophenpoisoning and toxicity.Pediatrics55(6): 871–876, 1975; reproduced by permission ofPediatrics. If poisoning is confirmed or strongly suspected or if the time of ingestion is unclear or unknown, additional testing is indicated. Liver tests are done and, in suspected severe poisoning, prothrombin time is measured. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) results correlate with the stage of poisoning (see table ). AST levels Low-level transaminase elevations (eg, up to 2 or 3 times the upper limit of normal) may occur in adults taking therapeutic doses ofacetaminophenfor days or weeks. These elevations appear to be transient, usually resolve or decrease within a few days (even with continuedacetaminophenuse), are usually clinically asymptomatic, and are probably insignificant. Acetaminophen/cysteineprotein adducts are new biomarkers developed and marketed as indicators ofacetaminophen-induced hepatotoxicity. Although the biomarkers may indicate exposure toacetaminophen, they do not conclusively indicateacetaminophen-induced hepatotoxicity. Other biomarkers such as microRNA, high-mobility group box-1 (HMGB-1), and keratin-18 are under investigation but are not standard diagnostic tools. With appropriate treatment, mortality is uncommon. Poor prognostic indicatorsat 24 to 48 hours postingestion include all of the following: pH<7.3 after adequate resuscitation International normalized ratio (INR)>3 Serum creatinine>2.6 Hepatic encephalopathy grade III (confusion and somnolence) or grade IV (stupor and coma) Hypoglycemia Thrombocytopenia Acuteacetaminophentoxicity does not predispose patients to cirrhosis. Oral or IVN-acetylcysteine Possibly activatedcharcoal Activatedcharcoalmay be given ifacetaminophenis likely to still remain in the gastrointestinal (GI) tract. N-Acetylcysteineis an antidote foracetaminophenpoisoning. This drug is a glutathione precursor that decreasesacetaminophentoxicity by increasing hepatic glutathione stores and possibly via other mechanisms. It helps prevent hepatic toxicity by inactivating the toxicacetaminophenmetabolite NAPQI (N-acetyl-p-benzoquinone imine) before it can injure liver cells. However, it does not reverse damage to liver cells that has already occurred. For acute poisoning,N-acetylcysteineis given if hepatotoxicity is likely based onacetaminophendose or serum level. The drug is most effective if given within 8 hours ofacetaminopheningestion. After 24 hours, the benefit of the antidote is questionable, but it should still be given. If degree of toxicity is uncertain,-acetylcysteineshould be given until toxicity is ruled out. N-Acetylcysteineis equally effective given IV or orally. IV therapy is given as a continuous infusion. A loading dose of 150 mg/kg in 200 mL of 5% D/W given over 15 minutes is followed by maintenance doses of 50 mg/kg in 500 mL of 5% D/W given over 4 hours, then 100 mg/kg in 1000 mL of 5% D/W given over 16 hours. For children, dosing may need to be adjusted to decrease the total volume of fluid delivered; consultation with a poison control center is recommended. The oral loading dose ofN-acetylcysteineis 140 mg/kg. This dose is followed by 17 additional doses of 70 mg/kg every 4 hours. Oralacetylcysteineis unpalatable; it is given diluted 1:4 in a carbonated beverage or fruit juice and may still cause vomiting. If vomiting occurs, an antiemetic can be used; if vomiting occurs within 1 hour of a dose, the dose is repeated. However, vomiting may be protracted and may limit oral use. Allergic reactions are unusual but have occurred with oral and IV use. Liver failure is treated supportively. Patients with Acute Liver Failure may require has been reported with Hemodialysis and continuous venovenous hemodialysis. Consultation with a poison control center or toxicologist is recommended. Becauseacetaminophenis ubiquitous and initially asymptomatic and treatable in overdose, consider toxicity in all possibly poisoned patients. Use the Rumack-Matthew nomogram when time of ingestion is known to predict risk of hepatotoxicity based on serumacetaminophenlevels. If hepatotoxicity is likely, give oral or IVN-acetylcysteine. Ifacetaminophenis still probably in the gastrointestinal tract, give activatedcharcoal. If degree of toxicity is uncertain, begin IV or oral-acetylcysteineuntil more conclusive definitive information is available. 