Recreational ketamine-related deaths notified to the National Programme on Substance Abuse Deaths, England, 1997-2019.

BACKGROUND: Ketamine is a phencyclidine derivative with dissociative anaesthetic properties. Increasing numbers of individuals in England take ketamine recreationally. Information on deaths arising from such use in England is presented. METHODS: Cases were extracted on 31 January 2020 from the National Programme on Substance Abuse Deaths database, based on text searches of the cause of death, coroner's verdict and positive toxicology results for the terms 'ketamine' or 'norketamine'. FINDINGS: During 1997-2005, there were <5 deaths p.a. in which ketamine was implicated. Numbers increased until 2009 (21), plateauing until 2016; thereafter, deaths have risen to about 30 p.a. Decedents' characteristics (N = 283): male 84.1%, mean age 31.2 (SD 10.0) years, employed 56.5%, drug use history 79.6% and living with others 60.3%. Ketamine was detected with other substances in most cases. Main (74.6%) underlying cause of death was accidental poisoning. Ketamine may have impaired judgement in other cases. CONCLUSIONS: Although controlled, recreational ketamine use and related fatalities continue to increase. Consumers need to be more aware of the potentially fatal risks they face.

Violence against women and drug-facilitated sexual assault (DFSA): A review of the main drugs.

Sexual violence is a universal phenomenon without restriction to sex, age, ethnicity or social class that causes devastating effects in the physical and mental health spheres, in the short-term and long-term, such as pregnancy, sexually transmitted infections (STI) and greater susceptibility to psychiatric symptoms, especially depression. Some cases of sexual assault and rape are based on the use of so-called drug-facilitated sexual assault (DFSA), which cause victims' loss of consciousness and inability to defend, making them vulnerable to violence. Thus, this article aimed to review the literature on gender violence and the drugs used to facilitate sexual assault, addressing their mechanism of action and pharmacokinetics, as well as drug detection times in human body and types of forensic identification. It is understood that the knowledge of these drugs and their pharmacological and diagnostic mechanisms should be widely disseminated, especially about sensitivity tests and the time the drug remains in the body, which would validate the promotion of evidence to prove abuse, and, thus, being able to give a promising outcome to cases of aggression, which is extremely beneficial for women.

First reported fatalities associated with the 'research chemical' 2-methoxydiphenidine.

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework.

Prolonged sedation and airway complications after administration of an inadvertent ketamine overdose in emergency department.

The use of ketamine for pediatric sedation in the Emergency Department for painful procedures has become increasingly popular. Ketamine is a safe and effective sedative for diagnostic or therapeutic procedures in the Emergency Department. Sedation with this dissociative agent produces a rapid onset action, potent analgesia, adequate sedation, amnesia and minimal side effects. We report a case of prolonged sedation and airway complications after administration of an inadvertent intramuscular ketamine overdose in a healthy child.

A fatal chronic ketamine poisoning.

A few papers in the literature reported incident deaths by acute ketamine poisoning. In this paper, we report an unusual homicide caused by chronic ketamine poisoning. The victim was a 34-year old married woman with no previous medical history (except as reported herein) who died in her own home. The court investigation revealed that she was chronically poisoned by her husband over a period of about one year in an act of homicide. Determination of ketamine concentrations in autopsy specimens was carried out with gas-chromatography/mass spectrometry (GC-MS). The results showed that ketamine concentration was 21 microg/mL in gastric contents, 3.8 microg/mL in blood and 1.2 microg/mL in urine. The most striking forensic findings were cardiac muscle fibrosis and hyaline degeneration of small arteries in victim's heart, the pathological features of ketamine poisoning previous reported only in animal studies.

Postmortem blood ketamine distribution in two fatalities.

Despite the reported increased use of ketamine as a recreational drug, relatively few fatalities attributed to ketamine poisoning have been documented. Two recent fatalities in which ketamine was detected are described and compared with cases previously reported in the scientific literature. Concentrations of ketamine were measured in the heart and femoral blood samples using gas chromatography with nitrogen phosphorus detection. Ketamine concentrations in a 26-year-old man whose death was attributed to ketamine intoxication were 6.9 and 1.8 mg/L in heart and femoral blood, respectively. In this case, the ketamine concentration detected in the heart blood is in agreement with the lowest concentration reported in the literature, in which ketamine intoxication was ruled as the cause of death and no other drugs were present. Ketamine concentrations in a 20-year-old man, whose death was attributed to asthma and ketamine was considered an incidental finding, were 1.6 and 0.6 mg/L in heart and femoral blood, respectively. Marked differences between heart and femoral blood ketamine concentrations were observed in both of the reported cases. This may be indicative of incomplete distribution prior to death and/or postmortem redistribution of ketamine.

Autoerotic accident associated with self-applied ketamine.

We present a rare case of an autoerotic accident involving a fatal combination of asphyxia by suffocation and intoxication with self-administered intravenous ketamine. Of note in this case is the fact that the victim was an emergency medical technician. Ketamine causes complete analgesia with superficial unconciousness and amnesia called "dissociative anasthesia". Futhermore low anaesthetic doses of ketamine induce alterations in mood, cognition and body image and the substance is an emerging drug of abuse. We discuss the death scene investigation, findings at autopsy and the toxicological report.

Ketamine in non-hospital and hospital deaths in New York City.

We reviewed all ketamine-positive deaths (87) examined at the New York City Office of Chief Medical Examiner over a two-year period (1997 to 1999). There were 15 non-hospital deaths with 12 due to acute multidrug intoxications, one due to sarcoidosis, and two due to physical injury (blunt and thermal). In no instance was a fatal intoxication caused exclusively by ketamine. Opiates (10/15), followed by amphetamines (7/15) and cocaine (6/15), were the most frequent co-intoxicants. Ethanol was found in only one death. The race of all decedents was white and the majority were men (11/15) between the ages of 18 and 30 years. The remaining 72 instances of positive ketamine findings were hospital deaths following surgical procedures or burns.

A fatality due to injection of tiletamine and zolazepam.

A 22-year-old male with more than 28 needle marks on his right arm was found dead. First, he was suspected as a drug abuser. Blood, urine, spleen, and injection-site tissue was collected during autopsy. The blood and urine specimens were screened for drugs. Immunoassay studies did not show any illegal drugs. However, two unidentified peaks were isolated in both of these biological fluids by routine gas chromatography-flame-ionization detection (GC-FID) and thermionic specific detection. Additional gas chromatography-mass spectrometry analysis determined these two peaks to be tiletamine and zolazepam. These two agents are used in combination as veterinary anesthesia. The concentrations of these drugs in blood were quantitated by GC-FID and found to be 0.85 mg/L of tiletamine and 3.3 mg/L of zolazepam. In urine, tiletamine and its metabolite, 2-(ethylamino)-2-(2-thionyl) cyclohexanol, were identified to be present along with zolazepam. The concentrations of tiletamine and zolazepam in spleen were revealed to be 0.92 and 3.5 mg/kg, respectively. Injection-site tissue concentrations were determined to be 25.1 mg/kg tiletamine and 23.3 mg/kg for zolazepam. The cause of death in this case was determined to be due to the multiple drug intoxication of tiletamine and zolazepam.

Acute ketamine intoxication treated by haloperidol: a preliminary study.

In an open, double-blind study of phencyclidine intoxication, 21 white male subjects were later found to have instead ingested ketamine. These subjects were divided into two cohorts, one treated with 5 mg intramuscular haloperidol and the second with an active placebo. Assessment with the Brief Psychiatric Rating Scale revealed significant reduction in symptoms with haloperidol.

Tissue distribution of ketamine in a mixed drug fatality.

While reports of ketamine abuse are increasing, reports of ketamine deaths and tissue concentrations associated with fatalities are rare. We report here a case of a mixed drug fatality involving ketamine and ethanol. Ketamine analysis was carried out by gas chromatography with a nitrogen-phosphorus detector (NPD). We found the following tissue concentrations: blood 1.8 mg/L; urine 2.0 mg/L; brain 4.3 mg/kg; spleen 6.1 mg/kg; liver 4.9 mg/kg, and kidney 3.6 mg/kg. The blood ethanol concentration was 170 mg/dL. Because an empty nalbuphine ampule was found in the possession of the deceased, the blood was assayed for this opioid compound using a gas chromatography/mass spectrometry (GC/MS) method. None was detected at a limit of detection of 0.02 mg/L.