Characteristics and dose-effect relationship of clinical gamma-hydroxybutyrate intoxication: A case series

Gamma-Hydroxybutyrate (GHB) overdoses cause respiratory depression, coma, or even death. Symptoms and severity of poisoning depend on blood-concentrations and individual factors such as tolerance. A retrospective case study was conducted, evaluating GHB intoxication cases. GHB-concentrations in blood and urine were determined by gas chromatography-mass spectrometry (GC-MS) along with, in part, via enzymatic assay. GHB-concentrations, demographic data, and additional drug use, as well as specific clinical information, were evaluated. The correlation between GHB-levels in blood and associated symptoms were examined. In total, 75 cases originating from the Emergency Departments (EDs) of Hamburg and surrounding hospitals were included. Fifty-four of the patients (72%) were male. The mean GHB-concentration in blood was 248 mg/L (range 21.5–1418 mg/L). Out of the group with detailed clinical information (n = 18), the comatose group (n = 10/18) showed a mean of 244 mg/L (range 136–403 mg/L), which was higher than that of the somnolent and awake patients. Of the comatose collective, 70% (n = 7) showed co-use of one or more substances, with the additional use of cocaine being the most frequently detected (n = 5). In conclusion, a moderate dose-effect relationship was observed, although, there was some overlap in dosage concentration levels of GHB in awake and comatose patients. In GHB-intoxication cases, co-use was common as were clinical effects such as acidosis, hypotension, and impact on the heart rate. Timely analytical determination of the GHB-concentration in blood could support correct diagnosis of the cause of unconsciousness.     

A Census of Medicolegal Death Investigation in the United States: A Need to Determine the State of our Nation’s Toxicology Laboratories and Their Preparedness for the Current Drug Overdose Epidemic

In 2007, the Bureau of Justice Statistics reported on 2004 data collected from the Census of Medical Examiner and Coroner Offices (CMEC). The CMEC was one of the first comprehensive reports on the state of the medicolegal death investigation system in the United States and included information on administration, expenditure, workload, specialized death investigations, records and evidence retention, and resources. However, the report did not include responses on questions that were related to toxicology such as specimen retention and type of testing. The purpose of this publication is to provide the community with toxicology laboratory-specific responses from nearly 2000 medical examiner and coroner (MEC) offices. Data obtained from a BJS CMEC public use dataset for any remaining information that was not reported in the 2007 BJS report were evaluated specific to the operation of toxicology laboratories within a MEC office or specific to toxicology testing. The CMEC includes information on average operating budget for MEC offices with internal or external toxicology services, budget for toxicology/microbiology services, respondents’ routine uses of toxicology analysis, toxicology specimen retention time, average turnaround times, use of computerized information management systems, and participation in federal data collections. These historical data begin to address the present state of our nation’s toxicology laboratories within the medicolegal death investigation system and their preparedness for the current drug overdose epidemic.     

Medical examiner response to the drug overdose epidemic in King County Washington: “Real-time” surveillance,data science,and applied forensic epidemiology

As the overdose epidemic overwhelmed medicolegal death investigation offices and toxicology laboratories, the King County Medical Examiner's Office responded with “real-time” fatal overdose surveillance to expedite death certification and information dissemination through assembling a team including a dedicated medicolegal death investigator, an information coordinator, and student interns. In-house testing of blood, urine, and drug evidence from scenes was performed using equipment and supplies purchased for surveillance. Collaboration with state laboratories allowed validation. Applied forensic epidemiology accelerated data dissemination. From 2010 to 2022, the epidemic claimed 5815 lives in King County; the last 4 years accounted for 47% of those deaths. After initiating the surveillance project, in-house testing was performed on blood from 2836 decedents, urine from 2807, and 4238 drug evidence items from 1775 death scenes. Time to complete death certificates decreased from weeks to months to hours to days. Overdose-specific information was distributed weekly to a network of law enforcement and public health agencies. As the surveillance project tracked the epidemic, fentanyl and methamphetamine became dominant and were associated with other indicators of social deterioration. In 2022, fentanyl was involved in 68% of 1021 overdose deaths. Homeless deaths increased sixfold; in 2022, 67% of 311 homeless deaths were due to overdose; fentanyl was involved in 49% and methamphetamine in 44%. Homicides increased 250%; in 2021, methamphetamine was positive in 35% of 149 homicides. The results are relevant to the value of rapid surveillance, its impact on standard operations, selection of cases requiring autopsy, and collaboration with other agencies in overdose prevention.     

The Prevalence of Paraphernalia Found at the Scene of Drug‐Related Deaths

Many illicit drugs involve the use of paraphernalia, and the presence of paraphernalia found at the scene of death may suggest that the death is drug‐related. Few sources of objective data are available regarding the prevalence of drug paraphernalia found at the scene of drug‐related deaths or the likelihood of a death with drug paraphernalia found at the scene to be drug‐related. This study reviews the deaths which were investigated by the Bexar County Medical Examiner's Office in an attempt to provide objective data. Over 4000 deaths with scene investigations were reviewed, and the presence of paraphernalia was found to be strongly associated with the death being drug‐related, heroin‐related, or cocaine‐related with the relative risk for each being 5.0, 15.4, and 6.6, respectively. This confirms that the presence of drug paraphernalia at the scene of death strongly suggests the death to be drug‐related and in particular heroin‐related.     

Suicide by gabapentin overdose

Gabapentin is an antiepileptic drug that is prescribed for both FDA-approved and multiple off-label conditions, and has a relatively safe side-effect profile. Rare cases of overdose-related adverse effects have been reported in the literature. Described herein are the circumstances and autopsy findings of a 62-year-old woman with a history of depression, whose death was caused by intentional ingestion of excess gabapentin. The postmortem peripheral blood gabapentin concentration as determined by high-performance liquid chromatography/tandem mass spectroscopy was 88 μg/mL. Previously reported cases of individuals surviving gabapentin overdoses are discussed and compared with this case. Based on a review of the available literature, this appears to be the first published report of a death due solely to gabapentin toxicity.     

Fatal Overdose of Gamma‐hydroxybutyrate Acid After Ingestion of 1,4‐Butanediol

We report a case of fatal intoxication from 1,4‐butanediol (1,4‐BD), which was ingested by a young and “naïve” gamma‐hydroxybutyrate (GHB) consumer during a party with the co‐ingestion of alcohol, cannabis, and methylene‐dioxy‐methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4‐BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri‐ and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.     

Importance and Approach to Manner of Death Opinions in Opioid-Related Deaths

The majority of opioid-related deaths are accidental. However, the number of opioid-related suicidal deaths is likely under recognized. Presented here is a case of suicide by heroin overdose. The manner of death would have likely been deemed accidental if not for critical information shared by the decedent’s family during follow-up telephone interviews between the forensic pathologist and the decedent’s family, which included text messages that were sent by the decedent just before his death that were not known at the time of the initial medicolegal death scene investigation. This case highlights that when a forensic pathologist establishes an engaged relationship with the decedent’s family, the information elucidated can prove to be invaluable in reaching an informed opinion about the manner of death. For overdose cases, identifying an accurate manner of death allows the design of public health efforts that adequately address the health risks in the community. For aid in the determination of the manner of death for overdose cases, we propose a five-step checklist that may assist forensic pathologists and medicolegal death investigators when approaching similar cases.