Circumstantial and toxicological features of deaths from self-administered intravenous anesthetic/narcotic agents.

For a better understanding of circumstantial and toxicological findings of fatalities resulting from self-administration of intravenous anesthetic/narcotic agents, medico-legal autopsy files of the State Institute of Legal and Social Medicine Berlin from 1998 to 2011 were reviewed retrospectively. Of a total of 15,300 autopsies, 9 cases of such deaths were identified, and all were health care professionals. Medical supplies for injection were found still on, or near, the body at the scene. Anesthetic/narcotic agents detected were classified into 3 categories, and administered solely or in combination. Propofol was the most common agent, being detected in 6 cases. In 2 out of 6 cases, propofol was detected substantially above therapeutic levels and was considered the cause of death. In the remaining 4 cases, propofol levels were within the therapeutic range, but propofol intoxication was considered as lethal due to it being administered by rapid continuous injection. In 5 cases, injection of opioid narcotics was fatal. Alongside the 2 propofol-detected cases, there was one case where a higher-than-therapeutic level of piritramide and a therapeutic level of alfentanil was identified. Despite suspected usage, remifentanil was not detected due to its rapid metabolism by elastases in one case, and sufentanil was undetectable due to putrefaction in another, but death was attributed to their potent respiratory depressant effects without respiratory assistance. Benzodiazepines were detected in 4 cases. All of them were used together with propofol or opioids, and contributed to death by inhibiting respiration. It is essential to consider means of administration as well as additive or synergistic effects of combined agents when interpreting toxicological results in such cases.

[Determination of propofol in human blood by GC-MS].

OBJECTIVE: To establish a gas chromatography-mass spectrometry (GC-MS) method for determination of propofol in human blood. METHODS: Propofol and 2-(tert-Butyl)-4,6-dimethylphenol (internal standard) were isolated from human blood samples with liquid-liquid ether extraction. The organic layer was collected after centrifugation and dried using the water bath. The extracted residue was analyzed by GC-MS. RESULTS: Propofol and the internal standard showed a good separation with a good linear concentration ranged from 0.02 to 10 microg/mL in blood. The linear function was y = 0.313 6 x-0.006 8 with the correlation coefficient of 0.9997. The precision of intra-day and inter-day were less than 4.8% and the lower limit of detection of propofol was 0.005 microg/mL. Propofol concentration of blood was 0.14 microg/mL using this method in the practice work. CONCLUSION: The GC-MS method is rapid, sensitive, reliable and suitable for qualitative and quantitative analysis propofol of blood in forensic toxicological analysis and clinical drug monitoring.

Determination of propofol in human blood by GC-MS / 法医学杂志

OBJECTIVE@#To establish a gas chromatography-mass spectrometry (GC-MS) method for determination of propofol in human blood.@*METHODS@#Propofol and 2-(tert-Butyl)-4,6-dimethylphenol (internal standard) were isolated from human blood samples with liquid-liquid ether extraction. The organic layer was collected after centrifugation and dried using the water bath. The extracted residue was analyzed by GC-MS.@*RESULTS@#Propofol and the internal standard showed a good separation with a good linear concentration ranged from 0.02 to 10 microg/mL in blood. The linear function was y = 0.313 6 x-0.006 8 with the correlation coefficient of 0.9997. The precision of intra-day and inter-day were less than 4.8% and the lower limit of detection of propofol was 0.005 microg/mL. Propofol concentration of blood was 0.14 microg/mL using this method in the practice work.@*CONCLUSION@#The GC-MS method is rapid, sensitive, reliable and suitable for qualitative and quantitative analysis propofol of blood in forensic toxicological analysis and clinical drug monitoring.

Prevention of local anesthetic systemic toxicity.

Although new drugs and techniques may improve outcomes when unintended high blood levels of local anesthetics occur, the primary focus of daily practice should remain the prevention of such events. Although adoption of no single "safety step" will reliably prevent systemic toxicity, the combination of several procedures seems to have reduced the frequency of systemic toxicity since 1981. These include the use of minimum effective doses, careful aspiration, and incremental injection, coupled with the use of intravascular markers when large doses are used. Epinephrine remains the most widely used and studied marker, but its reliability is impaired in the face of beta-blockade, anesthesia, advanced age, and active labor. As an alternative, the use of subtoxic doses of local anesthetics themselves can produce subjective symptoms in unpremedicated patients. Fentanyl has also been confirmed to produce sedation in pregnant women when used as an alternative. The use of ultrasound observation of needle placement and injection may be useful, but has also been reported as not completely reliable. Constant vigilance and suspicion are still needed along with a combination of as many of these safety steps as practical.

Concentration-time profiles of gamma-hydroxybutyrate in blood after recreational doses are best described by zero-order rather than first-order kinetics.

The recreational drug gamma-hydroxybutyrate (GHB) has a short plasma elimination half-life (t(1/2)) reported to be about 30-50 min. However, this represents a terminal half-life and therefore might not necessarily apply after large (abuse) doses are taken. Clinical studies with sodium oxybate (sodium salt of GHB) suggest that zero-order rather than first-order kinetics are more appropriate to describe post-peak concentration-time (C-T) profiles. We report the case of a 23-year-old male found unconscious by the police and a blood sample contained 100 mg/L GHB and 0.14 g% ethanol. On regaining consciousness the man admitted drinking alcohol about 6 h earlier but claimed that his drink must have been spiked with GHB. The police wanted to know how much GHB had been administered to account for the man's clinical condition. A back-calculation for 6 h, assuming a GHB half-life of 40 min, gives a very high concentration in blood of approximately 900 mg/L, which would probably have proven fatal. Back-calculating using zero-order kinetics and a proposed elimination rate of 18 mg/L per hour leads to a GHB concentration of 208 mg/L, which is much more realistic. Toxicologists should not arbitrarily apply the principles of first-order kinetics after abuse doses of drugs, when zero-order or saturation kinetics (Michaelis-Menten) are more appropriate.

Brugada-like EKG pattern and myocardial effects in a chronic propofol abuser.

INTRODUCTION: Cases of death are reported due to medical use of propofol, whereas deaths due to recreational purpose are unusual. CASE REPORT: A 26-year-old Caucasian man, physician trainee in anesthesiology, was referred to an intensive care unit. The man was found unconscious in his bed with a butterfly-needle canalized into the vein of the left forearm and connected to an empty syringe. Transferred to the local hospital, the patient was monitored, and EKG showed typical Brugada features in V1-V3. Profound hypotension and metabolic acidosis were registered. Half an hour after admission, the patient developed prolonged QT interval, idioventricular rhythm, and ventricular fibrillation. Strong positive reaction for tumor necrosis factor alpha in cardiac myocytes and a diffuse apoptotic process in the heart specimens were observed. The multiple needle marks on the hands and forearms, and the propofol concentration in the hair examined (0.73 microg/g), led us to believe that the young man was a long-term propofol abuser. DISCUSSION: Development of the EKG pattern of ST-segment elevation in leads V1-V3 may be the first indicator of electrical instability and high risk for imminent sudden death. Whether this finding applies to other patients poisoned with propofol is unclear, but the association of sudden death and the acquired EKG pattern has been observed in other disease states. CONCLUSION: This article describes a fatal propofol-related death case because of recreational purpose; the EKG pattern, the cardiac morphology, and the expression of tumor necrosis factor alpha and apoptosis in cardiac tissue specimens are discussed to elucidate the mechanism of death.

Death from propofol: accident, suicide, or murder?

A 24-yr-old woman was found dead in her home from apparent propofol "toxicity." Her blood level of propofol was 4.3 microg/mL. She had no history of drug abuse and no evidence of such behavior at autopsy. The medical examiner and police investigators felt that she died from probable homicide. Attention was focused on a male registered nurse acquaintance, who had acquired propofol and other drugs in the course of his regular duties in a surgical intensive care unit. This is the first reported case of murder with propofol.

High mortality rates among GHB abusers in Western Sweden.

BACKGROUND: GHB is a drug of abuse and acute poisonings have been an increasing medical problem over the last decade in Sweden. OBJECTIVES: To document all cases of GHB poisonings in Gothenburg during 1995-2004 and to record drug-related deaths to compare the toxicity of GHB with other illicit drugs, such as heroin and amphetamine. METHODS: The number of GHB-poisoned patients treated at the Sahlgrenska University Hospital has been recorded with the help of an in-house database. The number of deaths by illicit drugs was recorded during 2004. Seizures of the drugs GHB, 1,4-butanediol, and GBL were registered between 1996 and 2004. RESULTS: The number of poisoned patients was 259. The number of seizures with GHB was 743, GBL 343, and 1,4-butanediol 236. In 2004 the number of deaths was 6 with heroin, 7 with GHB, 32 with amphetamine, 6 with cocaine, and one with methadone. One patient with GHB poisoning died during hospital care. CONCLUSIONS: Intoxication by GHB has substantial morbidity and abuse of GHB has substantial mortality. The acute prognosis is good but long-term prognosis is insecure with an increased risk for drug dependency and an early death.

Lethal self administration of propofol (Diprivan). A case report and review of the literature.

The death of a female anaesthesiologist is reported. Although the situation at the scene indicated propofol overdose-related death, self-administration of such high doses of propofol was unlikely, given the pharmacological properties of this drug. The analysis of the situation at the scene and the toxicological analysis in which the blood and liver propofol concentrations were 2.40microg/ml and 0.56microg/g, respectively, supported the conclusion that the death was a consequence of propofol self-administration at therapeutic doses from a person who used the drug on chronic basis seeking to its euphoric effects. However, because the toxic concentrations of propofol in non-intubated patients may be different from those intubated and fully supported in the operating room or in the intensive care unit, a mere interpretation of the blood and tissue concentrations of propofol in the toxicological analysis can confirm the drug intake but it may be of limited diagnostic significance without taking into account this difference.

[Lethal mixed intoxication with propofol in a medical layman]. / Letale Propofol-Mischintoxikation bei einem medizinischen Laien.

The authors report on a drug fatality of a 21-year-old man with a propofol (2,6-di-isopropylphenol) dependency. Propofol was detected in tissues and body fluids using SPME-GC/MS methods. The postmortem concentrations of propofol were 364 ng/ml in urine, 71 ng/ml in heart blood and 79 ng/ml in femoral blood. The drug addict had only an autodidactic medical knowledge, but had inserted himself a permanent cannula for intravenous injection of propofol several times a day. The injection material was bought via online auctions from eBay. The case illustrates how job-related drug dependencies become indistinct due to the free access to information and goods via the Internet.

The insulin pump as murder weapon: a case report.

Microprocessor-controlled insulin pumps designed for continuous delivery of short-acting insulin analogs into subcutaneous tissues offer several important potential benefits for diabetic patients. The delivery of other substances using these systems is technically feasible. We present a case of homicide involving lethal doses of etomidate and atracurium injected via the victim's insulin pump. This unique situation could be encountered by homicide investigators more frequently as the popularity of these systems continues to grow.

The prevalence and correlates of gamma-hydroxybutyrate (GHB) overdose among Australian users.

AIM: The aim of this study was to examine the correlates, context and risk perceptions regarding gamma-hydroxybutyrate (GHB) overdose among a sample of recreational GHB users in Australia. DESIGN: A cross-sectional survey of 76 GHB users who were administered a structured interview on GHB use. They were asked a series of questions regarding whether they had ever experienced a GHB overdose, the context of their most recent GHB overdose, and about their perceptions of the risks of GHB overdose. FINDINGS: This sample of GHB users had not had a long or extensive experience with GHB use; despite this, half (53%) had experienced a GHB overdose. This sample of GHB users appeared to be well-educated, employed and a history of either drug treatment or incarceration was uncommon. There were no differences between those who had or had not overdosed in terms of socio-demographic characteristics, extent of other drug use or typical patterns of other drug use when using GHB. However, those who had overdosed on GHB had used it more times during their life-time, and had been using it for a longer period of time. CONCLUSIONS: GHB-related overdoses were common among a sample of GHB users who had only recently begun using the drug. The only apparent distinguishing factor between those who had and had not overdosed on GHB was the amount of experience with GHB use.

Death after excessive propofol abuse.

Abuse of the anaesthetic agent propofol (2,6-diisopropylphenol) is rare, but we report a case of a 26-year-old male nurse in which the autopsy showed unspecific signs of intoxication and criminological evidence pointed towards propofol abuse and/or overdose. Intravenously administered propofol is a fast and short-acting narcotic agent, therefore it seemed questionable whether the deceased would have been able to self-administer a lethal overdose before losing consciousness. The blood and brain concentrations corresponded to those found 1-2 min after bolus administration of a narcotic standard dose of 2.5 mg propofol/kg body weight. Extremely high propofol concentrations were found in the urine indicating excessive abuse before death. However, due to the short half-life of propofol, the cumulative effects of repeated injections should not be relevant for toxicity, since this would result in a blood level increase of only 1-2 micrograms/ml. Furthermore, the detection and quantitation of propofol in three different hair segments indicated chronic propofol abuse by the deceased. The results of the investigation suggest that death was not caused by a propofol overdose but by respiratory depression resulting from overly rapid injection.

Blood, brain, and hair GHB concentrations following fatal ingestion.

Despite the increasing incidence of illicit use of gamma-hydroxybutyrate (GHB), little information is available documenting levels of the drug in GHB fatalities. We measured GHB levels in postmortem blood, brain and hair specimens from a suspected overdose case by gas chromatography/mass spectrometry (GC/MS) following solid phase extraction (SPE) and derivatization with bis(trimethyl-silyl) trifluoroacetamide (BSTFA). Examination found 330 microg/mL GHB in femoral blood and 221 ng/mg GHB in frontal cortex brain tissue, values higher than those typically reported in the literature. The hair shaft was negative for GHB whereas the plucked root bulbs with outer root sheath attached (2,221 ng/mg) and root bulbs after washing and removal of the outer root sheath (47 ng/mg) contained the drug. Our results are consistent with an acute single dose of GHB and, as the toxicology screen was negative for other drugs of abuse, emphasize the significant danger of this drug.