Methamphetamine use and the risk of diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is a life-threatening condition arising in individuals with insulin-dependent diabetes mellitus, associated with hyperglycaemia and hyperketonaemia. While drugs such as methadone, cocaine and certain prescription medications may precipitate DKA, the potential effect of methamphetamine is unclear. Analysis of autopsy and toxicology case files at Forensic Science SA, Adelaide, South Australia, was therefore undertaken from 1 January to 31 December 2019 of all cases where methamphetamine was detected in post-mortem blood samples. There were 94 cases with 11 diabetics (n = 6 type 1 and n = 5 type 2). Four of the six decedents with type 1 diabetes had lethal DKA (66.7%; age range 30-54 years; average age 44.6 ± 10.5 years; M:F ratio 1:1). This incidence of DKA was higher than that of the general insulin-dependent diabetic population (6%) and also significantly higher than in medico-legal cases (13%; p < 0.05). The clinical and autopsy assessment of insulin-dependent diabetics presenting with DKA should therefore include specific screening for methamphetamine. The increase in both insulin-dependent diabetes and methamphetamine abuse in the community may lead to increases in such cases in medico-legal and health contexts.

Recent trends in barbiturate detection in medicolegal deaths.

A study was undertaken of 51 cases where barbiturates were detected in post-mortem blood samples from 2000 to 2019 at Forensic Science South Australia, Adelaide, Australia. The cause of death was drug toxicity in only 27 (53%) (M:F = 19:8; age range 19-74yrs, mean 46yrs). In 17 cases, barbiturate toxicity was the primary cause of death, 14 due to pentobarbitone and 3 to phenobarbitone. All were suicides. Barbiturates were obtained by online purchase from overseas sources in 9 cases (33%), and through veterinary practice in 2 cases (7%). Drug toxicity deaths where barbiturates were detected rose from 1 in 2000-2004 to 11 in 2015-2019, and those where deaths were primarily due to barbiturate toxicity rose from 1 in 2000-2004 to 9 in 2015-2019. However, the mere detection of barbiturates in post mortem samples did not equate with illicit use, as 23 of the deaths (45%) were due to natural causes in individuals prescribed barbiturates for epilepsy. The usefulness of examining subset populations separate from accrued national data is also demonstrated in the significantly younger age of decedents in South Australia dying from deliberately administered barbiturates (46 yrs) compared to the national average of 57.9 yrs. The reasons for this difference will require further investigation as this may impact upon local suicide prevention strategies.

Increasing age and methamphetamine use.

ANALYSIS: of autopsy files at Forensic Science SA was undertaken over a 20-year period (2000-2019) in five representative time periods to determine the average ages for all adults (≥18 years) where methamphetamine was detected. There were 239 cases with statistically significant increased mean ages over the time of the study ranging from 32.6yrs in 2000 to 42.2yrs in 2019 (p < 0.0001). Although methamphetamine use may be considered predominantly a feature of younger individuals this does not appear to be the case. Whether this apparent increase in the age of methamphetamine users was due to natural aging of methamphetamine users, an increase in use of methamphetamine by older individuals, or to an increased capture of older cases due to wider toxicological screening is uncertain. However, the importance of these results is to alert practitioners to the presence of methamphetamine use in older individuals which may predispose to death given the increased incidence of underlying cardiovascular diseases with age. In addition, in clinical settings there exists a cohort of older individuals who may be at risk of exacerbating their heart disease and precipitating cardiac events by using methamphetamine.

Methamphetamine deaths: Changing trends and diagnostic issues.

The term 'amphetamine' refers to a class of synthetic drugs which includes methamphetamine. The latter is a globally popular drug of abuse which induces euphoria, affecting cognitive/psychomotor performance and sleep. It also provokes risk taking and violent behaviour. The central effects of methamphetamine are due to the overproduction of neurotransmitters, resulting in high levels of dopamine. In recent years, there have been significant increases in cases of methamphetamine abuse in North and South America, Australia and Asia due to its ready availability and low cost. The following review examines changing trends in methamphetamine use and problems that arise diagnostically in medico-legal cases in determining the significance of post-mortem blood levels, the relationship of these to ante-mortem levels, the possible effects on physical and psychological behaviours and the possible contribution of the drug to a lethal episode.

Environmental Methamphetamine Exposures and Health Effects in 25 Case Studies.

The clandestine manufacture and use of methamphetamine can result in contamination of residential properties. It is understood that this contamination remains in homes for a significant period, however there are a lack of data available to understand the health effects of exposure to environmental methamphetamine contamination (third-hand exposure). Our study collected information from 63 individuals in 25 separate case studies where the subjects had unwittingly suffered third-hand exposure to methamphetamine from former manufacture, use, or both. Data included environmental contamination data, information on subjects' health effects, and evidence of exposure using hair analysis. This study identified a range of health effects that occur from residing in these properties, including behavioural effects or issues, sleep issues, respiratory effects, skin and eye effects, and headaches. Methamphetamine was detected in hair samples from some individuals, including children. The exposures and concomitant reported health effects covered a wide range of environmental methamphetamine levels in the properties, including low levels close to the current Australian guideline of 0.5 µg methamphetamine/100 cm2. There were no discernible differences between health effects from living in properties contaminated from former manufacture or use. This study demonstrates that residing in these properties can represent a serious public health risk.

Increasing Methamphetamine Detection in Cases of Early Childhood Fatalities.

Age and organ maturity can influence drug toxicity in children; however, most clinical data and literature are based on drug concentrations in adults. Therefore, the interpretation of drugs detected in children is often difficult or not possible. Retrospective reviewing of pathology and toxicology information from postmortem cases may assist in future interpretations or identify drug trends. A search of the Forensic Science SA case files was undertaken over 15 years from January 2002 to December 2016 for all children (<13 years). Of the 412 pediatric coronial cases, toxicological information was available on 373. At least one drug was detected in 94 cases with paracetamol, ibuprofen, codeine and hospital-administrated lignocaine and morphine among the most commonly detected agents. Methamphetamine, one of the most commonly abused illicit drugs in Australia, was found in seven cases. In the methamphetamine cases, deaths were associated with shared sleeping in three, pneumonia in one, and stillbirth in one. Methamphetamine was considered potentially contributory to death in two cases. The causes of death in the remaining two cases were undetermined. As six of the seven positive cases occurred in the 2012-2016 (n = 106) timeframe, an increase has occurred over recent years in the number of infants and young children presenting to forensic autopsy in South Australia who have detectable concentrations of methamphetamine. If this is an indication of a more generalized increased childhood exposure in the community there may be significant long-term physical and psychological effects.

Driving Simulator Performance After Administration of Analgesic Doses of Ketamine With Dexmedetomidine or Fentanyl.

PURPOSE/BACKGROUND: As a sole agent, ketamine acutely compromises driving ability; however, performance after coadministration with the adjuvant sedating agents dexmedetomidine or fentanyl is unclear. METHODS/PROCEDURES: Using a randomized within-subject design, 39 participants (mean ± SD age, 28.4 ± 5.8 years) received 0.3 mg/kg bolus followed by 0.15 mg kg h infusion of ketamine (3-hour duration), in addition to either (i) 0.7 µg kg h infusion of dexmedetomidine for 1.5 hours (n = 19; KET/DEX) or (ii) three 25 µg fentanyl injections for 1.5 hours (n = 20; KET/FENT). Whole blood drug concentrations were determined during ketamine only, at coadministration (KET/DEX or KET/FENT) and at 2 hours after treatment. Subjective effects were determined using a standardized visual analog scale. Driving performance was assessed at baseline and at posttreatment using a validated computerized driving simulator. Primary outcomes included SD of lateral position (SDLP) and steering variability (SV). FINDINGS/RESULTS: Administration of ketamine with dexmedetomidine but not fentanyl significantly increased SDLP (F1,18 = 22.60, P < 0.001) and reduced SV (F1,18 = 164.42, P < 0.001) 2 hours after treatment. These deficits were comparatively greater for the KET/DEX group than for the KET/FENT group (t37 = -5.21 [P < 0.001] and t37 = 5.22 [P < 0.001], (respectively). For the KET/DEX group, vehicle control (SV) and self-rated performance (visual analog scale), but not SDLP, was inversely associated with ketamine and norketamine blood concentrations (in nanograms per milliliter). Greater subjective effects were moderately associated with driving deficits. IMPLICATIONS/CONCLUSIONS: Driving simulator performance is significantly compromised after coadministration of analgesic range doses of ketamine with dexmedetomidine but not fentanyl. An extended period of supervised driver abstinence is recommended after treatment, with completion of additional assessments to evaluate home readiness.

Neurocognitive performance under combined regimens of ketamine-dexmedetomidine and ketamine-fentanyl in healthy adults: A randomised trial.

Analgesic doses of ketamine affects neurocognition; however, deficits under co-administration regimens are unknown. This study evaluated the effects of ketamine, alone and in combination with dexmedetomidine or fentanyl on neurocognition. Using a randomised, within-subjects gender stratified design, 39 participants (mean age = 28.4, SD ±â€¯5.8) received a ketamine bolus of 0.3 mg/kg followed by 0.15 mg/kg/h infusion of ketamine (3 h duration). At 1.5 h post-ketamine infusion commencement, participants received either: i) 0.7 µg/kg/h infusion of dexmedetomidine (n = 19) (KET/DEX) or (ii) three 25 µg fentanyl injections over 1.5 h (n = 20) (KET/FENT). Reaction and Movement time (RTI, Simple and 5Choice), Visuospatial Working Memory (SWM) and Verbal Recognition Memory (VRM) were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Whole blood drug concentrations were determined during ketamine-only infusion, at co-administration (KET/DEX or KET/FENT) and at 2-h post-treatment. Ketamine-only administration impaired psychomotor response speed (Simple and 5Choice) and impaired memory (all p < .001), however did not alter executive function abilities. Independent of sedation, co-administration of dexmedetomidine produced synergistic performance and memory deficits which persisted at post-treatment (KET/DEX) (all p < .001), and were comparatively greater than for KET/FENT (all p < .05). Ketamine, norketamine and dexmedetomidine concentrations were modestly associated with reduced psychomotor speed and accuracy (all p < .05), and an inverse relationship was found between blood concentrations of ketamine, norketamine and dexmedetomidine and performance on memory tasks. Co-administration of ketamine with dexmedetomidine but not with fentanyl exerts synergistic effects on psychomotor performance and memory without executive dysfunction. Assessment of these effects in clinical groups is warranted.

Body pushing, prescription drugs and hospital admission.

A 39-year-old man died of multi-organ failure complicating mixed drug toxicity that included methadone, oxazepam, oxycodone and nitrazepam. His past medical history involved alcohol and poly-substance abuse with chronic self-harm and suicidal ideation. There had been multiple hospital admissions for drug overdoses. At autopsy the most unusual finding was of two packages of 10 tablets each, wrapped in thin plastic film within the rectum. The insertion of drugs into body orifices and cavities has been termed body pushing to distinguish it from body packing where illicit drugs are wrapped and swallowed for transport and smuggling, and body stuffing where small amounts of loosely wrapped or unwrapped drugs are swallowed to conceal evidence from police. This case demonstrates that body pushing may not always involve illicit drugs or attempted concealment from police or customs officials. It appears that the drugs had been hidden to ensure an additional supply during the time of residence in hospital. The extent to which body pushing is currently being used by patients to smuggle drugs into secure medical facilities is yet to be determined.

Adverse Health Effects Associated with Living in a Former Methamphetamine Drug Laboratory - Victoria, Australia, 2015.

The manufacture of methamphetamine in clandestine drug laboratories occurs in various locations, including residential houses and apartments. Unlike the controlled manufacture of chemicals and drugs, clandestine manufacture results in the uncontrolled storage, use, generation, and disposal of a wide range of chemicals and the deposit of methamphetamine drug residues on indoor surfaces (1). These residues have been found at high levels on porous and nonporous surfaces and have been shown to persist for months to years (1). Persons exposed to these environments often have poorly defined exposures and health effects. It is commonly assumed that these levels of exposure are low compared with those related to illicit drug use or therapeutic use of amphetamine-based drugs for managing behavioral issues such as attention deficit hyperactivity disorder (2). In 2015, a family that was unknowingly exposed to methamphetamine residues in a house in Australia was found to have adverse health effects and elevated methamphetamine levels in hair samples, highlighting the potential for public health risks for persons who might live in methamphetamine-contaminated dwellings. This case study highlights the importance of the identification and effective decontamination of former clandestine drug laboratories.