Introduction: Rhabdomyolysis and delayed acetaminophen hepatotoxicity may be associated with elevated serum transaminase values. Establishing the cause of elevated transaminases may be especially difficult because of limited or inaccurate histories of acetaminophen ingestion. We hypothesized that the comparative ratios of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) could differentiate acetaminophen hepatotoxicity from rhabdomyolysis.

Methods: We performed a retrospective chart review of patients in four hospitals from 2006 to 2011 with a discharge diagnosis of acetaminophen toxicity or rhabdomyolysis. Subjects were classified into three groups: rhabdomyolysis, acetaminophen overdose (all), and acetaminophen overdose with undetectable serum acetaminophen concentrations (acetaminophen [delayed]). We compared ratios of AST, ALT, and CK using non-parametric statistical methods. 

Results: The AST/ALT ratio for the rhabdomyolysis group was 1.66 (Interquartile range: 1.18- 2.22), for the acetaminophen overdose (all) group was 1.38 (1.08-1.69, statistically lower than the rhabdomyolysis group, p = 0.018), and for the acetaminophen (delayed) group was 1.30 (1.06-1.63, p = 0.037). CK/AST ratios were 21.3 (12.8-42.2), 5.49 (2.52-15.1, p < 0.001 ), and 3.80 (1.43-13.8, p < 0.001) respectively. CK/ALT ratios were 37.1 (16.1-80.0), 5.77 (2.79-25.2, p < 0.001), and 5.03 (2.20-17.4, p < 0.001), respectively. Increasing CK-to-transaminase ratio cutoffs resulted in increasing test sensitivity but lower specificity.  

Conclusion: AST/ALT, CK/AST and CK/ALT ratios are significantly larger in rhabdomyolysis when compared to patients with acetaminophen toxicity. This result suggests that the ratios could be used to identify patients with rhabdomyolysis who otherwise might have been diagnosed as delayed acetaminophen toxicity. Such patients may not require treatment with N-acetylcysteine, resulting in cost savings and improved resource utilization.