Postmortem bilirubin measurements can add biochemical context to a death investigation, but a correlated result is not necessarily an interchangeable result. In a 37-case study, cardiac serum missed three of six elevated emergency-department values, while pericardial fluid had lower concentrations and did not significantly distinguish cirrhosis cases from controls. The study did not validate bilirubin as a measure of drug clearance or proof of drug-induced liver injury.
Which earlier results were available?
Takasu, Matsumoto and Sakamoto retrospectively studied forensic autopsies performed at one Japanese center from December 2021 through June 2023. Inclusion required postmortem serum and pericardial-fluid total bilirubin results and emergency-department biochemical data.
The 37 cases included 29 males and eight females, aged 13–87 years, with postmortem intervals of 14–67 hours. All had arrived at the emergency department in cardiopulmonary arrest and received resuscitation. The paper called the emergency-department results “antemortem”; these should not be mistaken for routine healthy outpatient baselines.
Postmortem pericardial fluid was collected through a pericardial incision using a sterile syringe. Serum came from cardiac blood obtained during heart excision, not femoral blood. Specimens were transferred to a laboratory and stored at −80°C; the maximum collection-to-transfer period was three days.
A strong serum correlation still missed individual elevations
Total bilirubin was measured by an oxidation method. Antemortem and postmortem serum concentrations had a Spearman correlation of 0.83, and the paired comparison showed no significant group difference.
However, six cases had emergency-department values above the paper’s living-person reference interval of 0.3–1 mg/dL. Three of those six had postmortem serum results below that interval’s upper boundary. One other case changed from 0.9 mg/dL before death to 1.1 mg/dL afterward.
Thus, a nonsignificant group comparison did not mean that every individual retained the same classification. The discussion once labels the missed elevations “false positives,” but the case table and results identify them as false negatives. That wording inconsistency should not reverse the actual direction of the changes.
Pericardial fluid answered a different specimen question
Pericardial-fluid total bilirubin correlated with the earlier serum result, with Spearman’s coefficient 0.57, but concentrations were significantly lower. The reported fluid-to-earlier-serum ratio was 0.41 ± 0.27 after excluding one case whose earlier value was zero.
The abstract describes this as a median accompanied by a variation term, while the presentation elsewhere does not clearly resolve that summary convention. It is safer to preserve it as the paper’s reported ratio summary rather than invent a uniform conversion.
The investigators also fitted a regression equation. That fit within a small selected dataset was not independent validation of an individual prediction rule, and the report did not provide a validated prediction interval for a new case. Dividing a pericardial result by 0.41 would not create a measured serum concentration.
The cirrhosis comparison had only three affected cases
There were three cirrhosis cases and 34 controls. Serum total bilirubin was significantly higher in cirrhosis both before death and postmortem, with p = 0.0067 and p = 0.037, respectively. Pericardial fluid showed no significant difference, with p = 0.37.
Median pericardial values were 0.10 mg/dL in cirrhosis and 0.20 mg/dL in controls. These results did not establish a diagnostic pericardial threshold. The proposed explanation of dilution was not confirmed: fluid volume also did not differ significantly between groups.
The difference between earlier and postmortem serum bilirubin did not correlate significantly with postmortem interval, with p = 0.65. Within 37 cases and a 14–67-hour interval, that null result cannot establish stability during longer delays or advanced decomposition.
Why this does not measure drug metabolism
The authors acknowledged possible storage effects and did not analyze prescription-related influences because the available medication data were insufficient. The report did not reproduce numerical analytical detection limits, quantitation limits or imprecision estimates for these specimens.
Bilirubin is a biochemical measurement, not identification or quantification of a toxicant. This study cannot establish that a drug impaired liver function, quantify a decedent’s hepatic elimination capacity, or correct an autopsy drug concentration to its antemortem value.
Its practical contribution is to keep specimen, clinical context, individual discordance and diagnostic performance together. A similar distinction between correlation and substitution appears in pericardial diazepam and blood comparisons. Detection of a drug or an abnormal biochemical marker remains separate from an integrated cause-of-death assessment.
Primary source
Takasu S, Matsumoto S, Sakamoto K. A Comparison of Postmortem Serum and Pericardial Fluid Total Bilirubin Levels With Antemortem Data. Cureus. 2025;17(2):e79089. doi:10.7759/cureus.79089.
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