Acute Fatal Acetaminophen Overdose Without Liver Necrosis

Abstract

Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the usual extensive centrilobular necrosis of the liver are reported. Both cases were subjected to comprehensive drug screening by immunoassay, and a combination of gas chromatography with mass spectrometry, nitrogen detection, and electron capture detection. Acetaminophen was detected in both cases. No other drugs were detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was detected in case #2. No anatomical cause of death was identified in either case. If untreated, the normal outcome of a large acetaminophen overdose would be massive hepatic necrosis with delayed death and low blood and tissue acetaminophen concentrations. In contrast, particularly high postmortem acetaminophen concentrations were measured in both our cases with little hepatic tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878 mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779 mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured using high performance liquid chromatography with UV detection (254 nm) using 3-hydroxyacetanilide as the internal standard. The very high concentrations of acetaminophen is these cases but relatively little hepatic damage suggests an alternative, possibly cardiac, mechanism of death.

Simple and rapid analysis of acetaminophen in human autopsy samples by vortex‐assisted dispersive liquid–liquid microextraction‐thin layer chromatography‐image analysis

“…Under the optimized and validated conditions, VA‐DLLME‐TLC‐image analysis method was applied for the quantitative determination of APAP in blood and tissue samples from above case. Results obtained by TLC‐image analysis were in closed agreement with the results obtained by GC–MS analysis and previous case reports [40,41]. The amount of APAP detected in blood and stomach content by TLC‐image processing and GC–MS are shown in Table 2.…”

The importance of scene photography in routine coronial practice: Results of an audit with an illustrative case of suspected suicidal fatal air embolism

“…The blood paracetamol concentration (221mg/L) was high and indicated that an excess of the analgesic had been taken and was sufficiently elevated, to have potentially induced liver necrosis if the drug had been ingested several days earlier. However, the concentration was well below that potentially associated with the exceptionally rare instances of fatal acute toxicity [1][2][3] .…”

Simultaneous quantification of acetaminophen and structurally related compounds in human serum and plasma

“…[19][20][21][22][23][24][25] Various other analytical methods have also been applied to detect APAP and its metabolites, such as high performance liquid chromatography (HPLC) in combination with accelerator mass spectrometry (AMS), [26] diode-array detection (DAD), [8] chemical reaction interface for mass spectrometry (CRIMS), [27] UV, [9] as well as capillary electrophoresis (CE) with UV detection. [19][20][21][22][23][24][25] Various other analytical methods have also been applied to detect APAP and its metabolites, such as high performance liquid chromatography (HPLC) in combination with accelerator mass spectrometry (AMS), [26] diode-array detection (DAD), [8] chemical reaction interface for mass spectrometry (CRIMS), [27] UV, [9] as well as capillary electrophoresis (CE) with UV detection.…”

“…Usually APAP is quantified by immunoassay techniques, either as part of a general screen or as specific target. [19][20][21][22][23][24][25] Various other analytical methods have also been applied to detect APAP and its metabolites, such as high performance liquid chromatography (HPLC) in combination with accelerator mass spectrometry (AMS), [26] diode-array detection (DAD), [8] chemical reaction interface for mass spectrometry (CRIMS), [27] UV, [9] as well as capillary electrophoresis (CE) with UV detection. [28] In particular, hyphenated HPLC-mass spectrometry (LC-MS) has shown great potential, because of its specificity and its ability to identify structurally-related substances that could bias the result of immunoassay analysis.…”