A death from fentanyl overdose

A case of death from self-injection of fentanyl and a method for its detection in autopsy specimens are reported. Fentanyl was measured by extraction of biological samples with ethyl acetate, partitioning into 0.1N HCl, then reextracting into ethyl acetate after alkalinization of the acid phase. After reducing to a residue, the fentanyl was measured by selective ion monitoring gas chromatography/mass spectrometry. Concentrations of 4.8, 6.3, and 4.7 micrograms/L were found in blood, urine, and bile, respectively.     

Rapid death resulting from mesoridazine overdose

A 23-year-old mentally retarded woman was brought to the emergency department 2-2.5 hr after ingesting an unknown quantity of mesoridazine. She was lethargic and somewhat uncooperative, but did answer questions. Her ECG was normal. She was treated with gastric lavage, 50 g activated charcoal, and 10 oz magnesium citrate solution. Her condition continued to decline until, at 2 hr after arrival, she was comatose and becoming increasingly hypotensive. Her ECG showed long runs of markedly widened QRS complexes. The patient was given an iv infusion of dobutamine to maintain blood pressure. She suffered a convulsion, loss of blood pressure, and developed ventricular tachycardia which progressed to ventricular fibrillation unresponsive to electrical cardioversion, pacing, and vigorous prolonged CPR. She was pronounced dead 6-6.5 hr after the ingestion. Antemortem blood level of mesoridazine was 16 micrograms/ml and no other drugs were detected. While sudden deaths have been reported with therapeutic doses of mesoridazine and its parent thioridazine, deaths are uncommon in overdose. Rapid death seen in this case emphasizes the importance of close monitoring and aggressive treatment of phenothiazine overdoses.     

Acute zonisamide overdose: a death revisited

Overdose experience with the anti-epileptic agent zonisamide (Zonegran, ZNS) is limited. We present a case of suspected zonisamide overdose previously reported in abstract form, manifesting as seizures, dysrhythmias and death of an 18-y-o woman after single ingestion of 4.8 g ZNS in a suicide attempt. The patient experienced multiple generalized tonic-clonic seizures and copious airway secretions. En route to the emergency department, she sustained cardiopulmonary arrest from which she was resuscitated. CT scan of the head approximately 24 h after initial presentation revealed massive cerebral edema with tonsillar herniation; brain death was confirmed. Serum ZNS was 44 mg/L, and the case was officially deemed death secondary to ZNS overdose. Subsequently, a comprehensive urine drug screen demonstrated mirtazepine, diphenhydramine metabolites, and caffeine. Due to confounding factors, a definitive causal role for ZNS in this overdose death cannot be made, despite the county coroner's ruling.     

Lamotrigine overdose in an adult

BACKGROUND: Lamotrigine is an antiepileptic agent that has been shown to be an effective adjunctive treatment for refractory partial and generalized seizures. It is now licensed in more than 70 countries for this indication. There is very little published material about the effects of acute overdose with lamotrigine. CASE REPORT: We describe the findings in a patient following the deliberate ingestion of a large amount of lamotrigine (stated 4.5 g, absorbed estimated 2.9 g), in excess of that previously described in the literature. The main clinical features were ataxia and rotary nystagmus. Electrocardiogram was unremarkable. Peak measured concentration of lamotrigine was 35.8 mg/L and half-life 19.5 hours, suggesting linear kinetics in overdose.     

异烟肼在脊柱结核患者不同组织中的分布

目的 研究脊柱结核患者应用异烟肼(INH)化疗时体内不同组织中的药物分布.方法 24例遵循2SHRZ/2.5H2R2Z2化疗方案+手术治疗的患者,按有无病椎骨硬化分为硬化组(15例)和非硬化组(9例),连续服药4周手术.术晨服药后120～130 min和240～250 min两个时点分别取硬化组的病椎硬化骨、硬化壁外"亚正常骨"、硬化壁内病变组织和非硬化组的病椎结核病变组织、病变组织外"亚正常骨"以及两组患者的血浆、髂骨.采用反相高效液相色谱法测定上述样本INH浓度.结果异烟肼的组织分布差异显著,在髂骨及病椎"亚正常骨"可达有效杀菌浓度,而在病椎硬化壁仪为最低抑菌浓度,硬化壁内坏死干酪组织则未检测到INH;非硬化组中的结核坏死病变中INH可达最低杀菌浓度.结论脊柱结核病椎硬化骨为阻碍INH由正常椎骨穿透到椎体病灶内的主要原因.     

Caffeine overdose in an adolescent male

A 16 year old male who ingested an estimated 6-8 grams of caffeine is described. Caffeine is commonly thought to be harmless, but its wide availability has promoted abuse. This patient manifested many of the adverse effects seen in acute caffeine ingestion including hypokalemia, elevated blood glucose, tachycardia, bigeminy and agitation. Respiratory alkalosis and chest pain, which have not been previously reported to our knowledge in caffeine overdose, were also noted in this patient. Three serum caffeine levels were analyzed and an abnormally long elimination half-life of approximately 16 hours was calculated from the results.     

An overdose death involving the insufflation of extended-release oxymorphone tablets

Two cases are reported involving the abuse of extended-release oxymorphone hydrochloride tablets (Opana? ER) in combination with alprazolam (Xanax?). Two juvenile females were discovered unresponsive and hypoxic by a male acquaintance. The trio had reportedly crushed and snorted Opana ER tablets and consumed Xanax for recreational purposes. Emergency personnel were able to stabilize one female. The second female was pronounced dead at the scene. Blood and urine samples from the surviving female were collected at the trauma center between 48 and 96 h post incident. Toxicology results showed the presence of oxymorphone, doxylamine, dextromethorphan, alprazolam, α-hydroxyalprazolam, oxazepam, and temazepam in her urine. No drugs were detected in her blood. Toxicology on the deceased female revealed the presence of 0.13 mg/L oxymorphone and 0.04 mg/L alprazolam in her blood. Gastric contents contained 0.25 and 0.93 mg/L of oxymorphone and alprazolam, respectively. Oxymorphone, alprazolam, and α-hydroxyalprazolam were present in her urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the oxime-oxymorphone-trimethylsilyl derivative, alprazolam, and the α-hydroxyalprazolam tert-butyldimethylsilyl derivative. The established linearity ranges for the opiate and benzodiazepine methods were 0.050-3.000 and 0.025-1.000 mg/L, respectively. The cause of death was reported as multiple drug toxicity, and the manner of death was accidental.     

Distribution of prilocaine in body fluids and tissues in lethal overdose

A case of lethal overdose by prilocaine, a local anaesthetic, is presented. The patient died in the dental office during treatment, and the time course of events was documented. The drug concentration in blood, urine, and liver was measured.     

Distribution of temazepam in body fluids and tissues in lethal overdose

Two cases of lethal overdose by temazepam are presented. In both cases, temazepam was the only drug detected, and there was no involvement of alcohol. The drug concentrations in blood, urine, and liver were measured.     

Rhabdomyolysis in isoniazid poisoning.

BACKGROUND: Rhabdomyolysis is one of the reported complications of isoniazid poisoning, but relevant data are limited. METHODS: A retrospective study was conducted on isoniazid poisoning cases seen at the Philippine General Hospital over 5 years (1992-1997). Patients excluded from the study were those who coingested other substances, including hepatotoxic and nephrotoxic drugs, those with underlying medical illnesses, and those without creatine phosphokinase muscle fraction determinations. RESULTS: Out of the 270 cases of isoniazid poisoning, 52 patient records were reviewed. Common clinical manifestations were seizures (100%), depressed sensorium (53%), and vomiting (45%). Laboratory results showed leukocytosis (74.5%), metabolic acidosis (29%), and impaired liver function tests (21%). Creatine phosphokinase muscle fraction was elevated in 59.6% of cases, beginning at a dose of 2.4 g. Values peaked on days 5 and 6 and declined on days 7 and 8. Statistically significant correlations were observed for the elevation of creatine phosphokinase muscle fraction with the duration/amount of drug ingested and the frequency of seizure. No correlation was observed between the frequency of seizures and elevated creatine phosphokinase muscle fraction nor between the time delay in consultation and elevation of creatine phosphokinase muscle fraction. CONCLUSIONS: The incidence of rhabdomyolysis in isoniazid poisoning was 3/100 cases a year. The findings suggesting its direct toxic effect on the muscles may not be clinically relevant.     

Acute quetiapine overdose in an eleven-year-old girl

We present a case of acute Quetiapine (SeroQuel) overdose in an 11-y-old girl who ingested 1,300 mg (22.2 mg/kg bw). Initial lethargy developed within I h followed by an episode of agitation and combativeness 3 h after ingestion. After treatment with lorazepam the patient experienced extended somnolence followed by return to normal mental status 16 h after ingestion. No cardiotoxic or laboratory abnormalities were found. This is the first report of acute Quetiapine overdose in an adolescent and suggests a relatively benign clinical course.     

Ibuprofen overdose in adults.

A prospective study of 63 ibuprofen overdose cases in adults (14 years or older) reported to the Rocky Mountain Poison and Drug Center between March 1987 and February 1988 was done to determine the incidence of renal injury and utility of timed plasma levels. No serious toxicity was noted. No CNS or other significant toxicity was seen with ingestion of less than 3 g. Two patients with normal serum creatinines had minor elevations of the blood urea nitrogen after ingesting 4 and 4.8 g. Timed plasma levels (125 total) from patients without coingestants from this study (48) and previously published reports (77) were compared with a previously described nomogram. The resulting nomogram revision may be useful in determining which initially asymptomatic patients are likely to remain so. Renal function tests are not routinely required for patients ingesting less than 6 g. Four h of observation is sufficient for asymptomatic patients not requiring psychiatric admission. Plasma ibuprofen levels are not required for proper patient management.     

Distribution of GHB in tissues and fluids following a fatal overdose

Gamma-hydroxybutyrate (GHB) is encountered in biological specimens as an endogenous neuromodulator, recreational drug, or therapeutic agent. Clinically, the drug is useful for the treatment of cataplexy. Illicit doses are typically 2-4 g, and the onset of action is rapid, occurring 15-30 min following oral ingestion. Dose-dependent effects include drowsiness, euphoria, dizziness, vomiting, respiratory depression, coma, and death. GHB was isolated from biological samples using a simple liquid-liquid extraction. The trimethylsilyl derivative (GHB-di-TMS) was analyzed using gas chromatography-mass spectrometry with positive chemical ionization. Deuterated internal standard and selective ion monitoring were used throughout. We report a GHB fatality involving a 35-year-old male who was partying with friends. Subjects at the party ingested unknown quantities of wine and GHB. A female companion at the party reported seeing the male alive before she herself passed out. She awoke to find the decedent cold and stiff. Postmortem specimens were submitted for comprehensive toxicology testing. No alcohol or common drugs of abuse were detected. A targeted analysis revealed GHB in urine, brain, vitreous fluid, femoral blood, heart blood, and liver at concentrations of 1665 mg/L, 102 mg/kg, 48 mg/L, 461 mg/L, 276 mg/L, and 52 mg/kg, respectively. Concentrations of the drug in urine and vitreous fluid are important in death investigations because of significant postmortem production of GHB in blood specimens. The cause of death was attributed to GHB intoxication, and the manner of death was accidental.     

Changes in characteristics of drug overdose death trends during the COVID-19 pandemic

BackgroundReports analyzing drug overdose (OD) mortality data during the COVID-19 pandemic are limited. Outcomes across states are heterogenous, necessitating assessments of associations between COVID-19 and OD deaths on a state-by-state level. This report aims to analyze trends in OD deaths in Massachusetts during COVID-19.MethodsAnalyzing 3,924 death records, we characterize opioid-, cocaine-, and amphetamine-involved OD mortality and substance co-presence trends from March 24-November 8 in 2020 as compared to 2018 and 2019.ResultsOD deaths involving amphetamines increased by 85% from 2019 to 2020 (61 vs. 113; P<0.001) but were steady from 2018 to 2019. Heroin's presence continued to decrease (341 in 2018, 247 in 2019, 157 in 2020; P<0.001); however, fentanyl was present in more than 85% of all OD deaths across all periods. Among OD deaths, alcohol involvement consistently increased, present in 250 deaths in 2018, 299 in 2019 (P=0.02), and 350 in 2020 (P=0.04). In 2019, 78% of OD decedents were White and 7% were Black, versus 73% and 10% in 2020 (P=0.02).ConclusionIncreased deaths involving stimulants, alcohol, and fentanyl reflect concerning trends in the era of COVID-19. Rising OD death rates among Black residents underscore that interventions focused on racial equity are necessary.     

Clozapine tissue concentrations following an apparent suicidal overdose of Clozaril.

Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical" antipsychotic drug. A 25-year-old male was brought to a hospital emergency room following the ingestion of an estimated 20 100-mg tablets of clozapine. After several hours in the hospital, the patient died. The cause of death was listed as acute clozapine intoxication. It was also noted upon autopsy that the patient had an unusual eosinophilic myocarditis. The toxicological and pathological findings are presented in this report.