Brain tissue can help assess whether postmortem gamma-hydroxybutyrate (GHB) findings are compatible with intake before death, but a proposed brain threshold of 10 mg/kg is not a universal test for exposure. In a 221-autopsy study, its usefulness depended on the degree of decomposition, and only three cases had reported GHB intake.
What specimens did the study compare?
Thomsen and colleagues collected femoral venous blood and frontal-lobe cortical gray matter in 221 consecutive autopsies during an eight-month period in 2015–2016. GHB intake was not suspected in 218 cases; intake was reported in three. The absence of a reported history did not independently establish that those 218 people had never taken GHB.
Bodies were held at 5°C after arrival, with autopsy one to four days after arrival. That interval is not necessarily the time since death. Blood was collected at the start of autopsy and stored at −20°C with 1% sodium fluoride and 0.2% potassium oxalate by weight. Brain tissue was also stored at −20°C.
The investigators quantified GHB by UHPLC–MS/MS after protein precipitation. The quantification range was 2–200 mg/kg in both matrices, with dilution above the upper limit. Blood imprecision was below 14.8% CV and accuracy was 94–104%. At a brain quality-control concentration of 200 mg/kg, the reported CV was 7.3% and accuracy was 89.4%. Those high-concentration brain control results do not, by themselves, establish classification accuracy around a 10 mg/kg interpretive threshold.
Decomposition changed the comparison
Among 189 cases without suspected intake and with no or minor decomposition, femoral blood GHB ranged from 4.8 to 45.4 mg/kg, with a median of 15.3 mg/kg. Brain values ranged from not detected to 9.8 mg/kg, with a median of 4.8 mg/kg. All concentrations here, including blood concentrations, are reported in mg/kg.
In 29 cases without suspected intake but with advanced decomposition, blood ranged from 11.7 to 162 mg/kg, with a median of 21.6 mg/kg. Brain ranged from 2.2 to 49.6 mg/kg, with a median of 6.7 mg/kg. The decomposition-group differences were statistically significant in blood and brain, with p values of 9.4 × 10−6 and 4.4 × 10−6, respectively.
Thus, advanced decomposition produced brain results well above the proposed 10 mg/kg threshold in cases without a reported intake history. Brain-to-blood ratios also overlapped between decomposition groups; their medians were approximately 0.30 and 0.29. A ratio did not solve the origin question.
What did the three reported-intake cases show?
The reported-intake cases had blood/brain concentrations of 199/166, 142/78.4 and 40.3/12.7 mg/kg. The third case is especially instructive: brain exceeded 10 mg/kg although blood was within the range observed among the 189 cases without suspected intake and with limited decomposition. The detailed account attributed that death to morphine poisoning, with possible contributions from other substances including GHB.
These cases support investigating brain as an additional matrix. Three reported-intake cases cannot establish robust diagnostic sensitivity, specificity or a fatal-concentration threshold. The authors accordingly described 10 mg/kg as a tentative brain cutoff for limited decomposition.
How to apply the finding in a case review
A report should identify the sampled brain region, decomposition category, blood collection site, preservation, analytical range and the evidence supporting an intake history. Quantitative detection establishes the measured concentration in the submitted specimen; it does not establish dose, impairment or cause of death. A classification threshold is also different from an analytical detection or quantification limit.
For a separate question about changes after collection, see GHB formation in stored postmortem blood. Storage-related formation and decomposition at autopsy require their own assessment.
Primary source
Thomsen R, Rasmussen BS, Johansen SS, Linnet K. Postmortem concentrations of gamma-hydroxybutyrate (GHB) in peripheral blood and brain tissue—Differentiating between postmortem formation and antemortem intake. Forensic Science International. 2017;272:154–158. doi:10.1016/j.forsciint.2016.12.038.
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