Approach Considerations
Obtain an electrocardiogram in order to exclude the presence of cardioactive substances/co-ingestants.
In females of childbearing age, obtain levels of human chorionic gonadotropin (HCG).[7] Acetaminophen crosses the placenta, and the fetal liver is able to elaborate NAPQI by 14 weeks of gestation. A delay in treating pregnant patients with antidotal therapy is associated with fetal demise. Obtain a type and cross-match in the event of coagulopathy and active bleeding.
Perform a urinalysis to assess the presence of proteinuria and hematuria, which may be seen with acute tubular necrosis, sometimes occurring in conjunction with hepatic failure.
Obtain an arterial blood gas evaluation. A pH of less than 7.3 is one laboratory indicator predictive of mortality.
Consider computed tomography (CT) scanning of the brain in patients with altered mental status. This study may reveal cerebral edema in patients with late presentation and encephalopathy. If clinically indicated, abdominal ultrasonography may reveal mild hepatic enlargement in late-presenting patients.
Gastric lavage has no proven efficacy in isolated acetaminophen (APAP) overdose.
Serum Acetaminophen Levels
A serum acetaminophen (APAP) concentration drawn 4 or more hours after a single ingestion should be plotted on the Rumack-Matthew nomogram as a guide to predicting the likelihood of potential hepatotoxicity and the indication for N -acetylcysteine (NAC) therapy. The nomogram is not applicable in the cases of multiple ingestions or chronic APAP overuse. In addition, it may be less reliable in cases of APAP ingestions associated with anticholinergic agents or opioids or in the case of extended-release APAP formulations. (See Treatment for information regarding extended-relief APAP.)
A serum APAP concentration should be measured after any intentional overdose, because the history of APAP ingestion may not be elicited and the onset of clinical toxicity is delayed after overdose. Delay in the initiation of NAC therapy is associated with an increased risk of morbidity.
Liver Function Studies
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels begin to rise within 24 hours after an acute ingestion and peak at about 72 hours. Toxicity is defined as serum AST or ALT levels greater than 1000 IU/L.
A serum glucose level should be obtained. Prothrombin time (PT) and international normalized ratio (INR) should be measured and followed if hepatic dysfunction and liver failure develop, as they indicate impaired hepatic synthetic function. Abnormalities in these laboratory components are predictive of mortality.
Serum concentrations of NAPQI-protein adducts have been measured as evidence of acetaminophen (APAP)–induced hepatotoxicity.[8] The peak serum concentrations of NAPQI adducts correlate with peak AST and ALT concentrations, and they may be diagnostic of APAP-induced hepatotoxicity in late-presenting patients with acute liver failure of unknown etiology.
However, the measurement of NAPQI-protein adducts is not available in real-time clinical practice and requires the resources of specialized laboratories. These laboratory measurements should not guide treatment decisions.
Electrolyte and Creatinine Levels
A high anion gap may be found in the setting of early, sick acetaminophen (APAP) ingestions; the etiology is hypothesized to be an elevated serum lactate level.{Ref6} In critically ill patients, an elevated serum lactate value is a laboratory component predictive of mortality. However, this laboratory finding is not predictive of clinical course or outcome if patients are treated with standard treatment.
Acute tubular necrosis and renal failure have been shown to coexist with or, rarely, occur independent of hepatotoxicity in APAP overdose. One study indicated that this is more likely to occur in persons with a history of ethanol abuse. Renal failure, when it occurs, usually occurs within 2-3 days of an acute overdose.
Elevated serum creatinine level is a laboratory component predictive of mortality.
It has been suggested that serum phosphate values can be used as an early predictor of outcome in severe APAP-induced hepatotoxicity.[9] Again, as a prognostic indicator, this finding has not been used to guide antidotal treatment.
US Food and Drug Administration. June 29-30, 2009: Joint meeting of the Drug Safety and Risk Management Advisory Committee with the Anesthetic and Life Support Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee: meeting announcement. Available at http://www.fda.gov/AdvisoryCommittees/Calendar/ucm143083.htm. Accessed August 5, 2009.
US Food and Drug Administration. Organ-specific warnings: internal analgesic, antipyretic, and antirheumatic drug products 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.
US Food and Drug Administration. Acetaminophen information. Available at http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm. Accessed August 18, 2011.
Mitchell I, Bihari D, Chang R, Wendon J, Williams R. Earlier identification of patients at risk from acetaminophen-induced acute liver failure. Crit Care Med. Feb 1998;26(2):279-84. [Medline].
Schmidt LE, Dalhoff K. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity. Hepatology. Sep 2002;36(3):659-65. [Medline].
Bernal W, Donaldson N, Wyncoll D, Wendon J. Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet. Feb 16 2002;359(9306):558-63. [Medline].
Crowell C, Lyew RV, Givens M, Deering SH. Caring for the mother, concentrating on the fetus: intravenous N-acetylcysteine in pregnancy. Am J Emerg Med. Jul 2008;26(6):735.e1-2. [Medline].
James LP, Capparelli EV, Simpson PM, Letzig L, Roberts D, Hinson JA, et al. Acetaminophen-associated hepatic injury: evaluation of acetaminophen protein adducts in children and adolescents with acetaminophen overdose. Clin Pharmacol Ther. Dec 2008;84(6):684-90. [Medline].
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[Guideline] Wolf SJ, Heard K, Sloan EP, Jagoda AS. Clinical policy: critical issues in the management of patients presenting to the emergency department with acetaminophen overdose. Ann Emerg Med. Sep 2007;50(3):292-313. [Medline]. [Full Text].
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Betten DP, Cantrell FL, Thomas SC, Williams SR, Clark RF. A prospective evaluation of shortened course oral N-acetylcysteine for the treatment of acute acetaminophen poisoning. Ann Emerg Med. Sep 2007;50(3):272-9. [Medline].
Whyte IM, Francis B, Dawson AH. Safety and efficacy of intravenous N-acetylcysteine for acetaminophen overdose: analysis of the Hunter Area Toxicology Service (HATS) database. Curr Med Res Opin. Oct 2007;23(10):2359-68. [Medline].
Spiller HA, Winter ML, Klein-Schwartz W, Bangh SA. Efficacy of activated charcoal administered more than four hours after acetaminophen overdose. J Emerg Med. Jan 2006;30(1):1-5. [Medline].
Tsai CL, Chang WT, Weng TI, Fang CC, Walson PD. A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication. Clin Ther. Mar 2005;27(3):336-41. [Medline].
Zein JG, Wallace DJ, Kinasewitz G, Toubia N, Kakoulas C. Early anion gap metabolic acidosis in acetaminophen overdose. Am J Emerg Med. Sep 2010;28(7):798-802. [Medline].
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