CORK Bibliography: Sudden Unexpected Death

18 citations. January 2003 to present

Prepared: March 2012

Adabag AS; Peterson G; Apple FS; Titus J; King R; Luepker RV. Etiology of sudden death in the community: Results of anatomical, metabolic, and genetic evaluation. American Heart Journal 159(1): 33-39, 2010. (43 refs.)

Background: Identifying persons at risk for sudden cardiac death (SCD) is challenging. A comprehensive evaluation may reveal clues about the clinical, anatomical, genetic, and metabolic risk factors for SCD. Methods: Seventy-one patients who had SCD (25-60 years old) without an initially apparent cause of death were evaluated at the Hennepin County Medical Examiner's office (Minneapolis, MN) from August 2001 to July 2004. We reviewed their clinic records conducted next-of-kin interviews and performed autopsy, laboratory testing, and genetic analysis for mutations in genes associated with the long QT syndrome. Results: Mean age was 49.5 +/- 7 years, 86% were male, and 2 subjects had history of coronary heart disease (CHD). Coronary risk factors were highly prevalent in comparison to individuals of the same age group in this community (eg, smoking 61%, hypertension 27%, hyperlipidemia 25%) but inadequately treated. On autopsy, 80% of the subjects had high-grade coronary stenoses. Acute coronary lesions and previous silent myocardial infarction (MI) were found in 27% and 34%, respectively. Furthermore, 32% of the subjects had recently smoked cigarettes, and 50% had ingested analgesics. Possible deleterious mutations of the ion channel genes were detected in 5 subjects (7%). Of these, 4 were in the sodium channel gene SCN5A. Conclusions: Most of the persons who had SCD in the community had severe subclinical CHD, including undetected previous MI. Traditional coronary risk factors were prevalent and undertreated. Mutations in the long QT syndrome genes were detected in a few subjects. These findings imply that improvements in the detection and treatment of subclinical CHD in the community are needed to prevent SCD.

Antai-Otong D. Medical complications of cocaine addiction: Clinical implications for nursing practice. Journal of Addictions Nursing 17(4): 215-225, 2006. (51 refs.)

Cocaine abuse is an important public health problem, with almost two million users in the United States alone. Cocaine abuse kills thousands annually. According to medical examiners, cocaine is the most frequent cause of drug-related deaths. As the use of cocaine remains pervasive so have cocaine-related medical problems. The most serious medical consequences of cocaine abuse are associated with the drug's potent vasoconstrictor properties that can cause life-threatening cocaine-related medical problems such as myocardial ischemia, cardiomyopathies, strokes, renal failure, respiratory arrest, neuronal destruction, and sudden death. Addiction nurses are challenged to not only understand the complexity of cocaine addiction and its potential and actual deleterious effects on major body systems but also implement interventions that reduce health risks and facilitate recovery. This article focuses on cocaine-related medical complications, medical stabilization, and drug rehabilitation. The role of the nurse is discussed along with strategies and evidence-based approaches to treating patients presenting with cocaine related medical and psychiatric consequences.

2006, Taylor & Francis

Benowitz NL. Cigarette smoking and cardiovascular disease: Pathophysiology and implications for treatment. (review). Progress in Cardiovascular Disease 46(1): 91-111, 2003. (125 refs.)

These 3 issues of Progress in Cardiovascular Diseases provide a comprehensive review of cigarette smoking and cardiovascular disease. The pathophysiology of smoking as a cause of cardiovascular disease is complex and is not fully understood. However, the available information provides important insight not only into smoking but also into general mechanisms of atherogenesis and acute cardiovascular events, and how chemical factors may contribute. Even if smoking disappears, the research described in these issues will help elucidate workplace and other environmental factors that might be contributing to cardiovascular disease. Acute myocardial infarction and sudden death in smokers have a somewhat different pathophysiology from that seen in nonsmokers. The role of thrombosis is greater, and the presence of thrombosis may provide guidance in selecting the optimal approaches to revascularization and to preventive pharmacotherapy. Smoking cessation has been recognized for many years as perhaps the most important intervention in preventive cardiology. Disappointingly, smoking cessation is not part of the routine practice for many physicians, including cardiologists -- who see the direct consequences of this behavioral disorder.

Bents RT; Tokish JM; Goldberg L. Ephedrine, pseudoephedrine, and amphetamine prevalence in college hockey players: Most report performance-enhancing use. Physician and Sportsmedicine 32(9): 30-34, 2004. (20 refs.)

BACKGROUND: Performance-enhancing drugs are used by some athletes, even though the substances may be potentially dangerous and some are banned. OBJECTIVE: To assess the use of metabolic stimulants among collegiate hockey players. METHODS: Surveys were administered to college hockey players on five teams. Participation was voluntary, and respondents remained anonymous. The survey included questions regarding use of specific stimulants (eg, ephedrine, amphetamines, pseudoephedrine), awareness of potential side effects, and knowledge of National Collegiate Athletic Association (NCAA) rules. RESULTS: More than half (58%) of the 122 college hockey players who completed the survey reported past or present use of the specific stimulants. Almost half (46%) reported pseudoephedrine use to enhance performance, including 24% who indicated current use, and 38% reported ephedrine use, including 11% who admitted current use. Stimulant users had good knowledge about the potential side effects of ephedrine, including sudden death, hypertension, and insomnia. Nearly all (92%) stimulant users were aware of the current NCAA ban of ephedrine. Over 33% stated they would use a banned substance if it would help them get to the National Hockey League. CONCLUSION: A large number of collegiate hockey players admit to using metabolic stimulants despite knowledge of side effects and the NCAA ban on two of these substances. More effective educational interventions, perhaps coupled with a stronger testing policy, may be necessary to curb this potentially dangerous practice.

Chugh SS; Socoteanu C; Reinier K; Waltz J; Jui J; Gunson K. A community-based evaluation of sudden death associated with therapeutic levels of methadone. American Journal of Medicine 121(1): 66-71, 2008. (33 refs.)

BACKGROUND: Published case reports have associated the therapeutic use of methadone with the occasional occurrence of sudden cardiac death. Because of the established utility of this drug and with the eventual goal of enhancing safety of use, we performed a community- based study to evaluate this association. METHODS: During a 4-year period, we prospectively evaluated all patients who consecutively had sudden cardiac death and underwent investigation by the medical examiner in the metropolitan area of Portland, Ore. Case subjects of interest were those with a therapeutic blood level of methadone (< 1 mg/L), and case comparison subjects were those with no methadone identified. Patients with recreational drug use or any drug overdose were excluded from either group. Detailed autopsies were conducted, including the detection and quantification of all substances in the blood. RESULTS: A total of 22 sudden cardiac death cases with therapeutic levels of methadone ( mean 0.48 +/- 0.22 mg/L; range 0.1-0.9 mg/L) were identified (mean age 37.0 +/- 10 years, 68% were male) and compared with 106 consecutive sudden cardiac death cases without evidence of methadone ( mean age 42 +/- 13 years, 69% were male). The most common indication for methadone use was pain control (n = 12, 55%). Among cases receiving methadone therapy, sudden death-associated cardiac abnormalities were identified in only 23% (n = 5), with no clear cause of sudden cardiac death in the remaining 77% (n = 17). Among cases with no methadone, sudden death-associated cardiac abnormalities were identified in 60% (n = 64, P = .002). CONCLUSION: The significantly lower prevalence of cardiac disease in the case group implicates methadone, even at therapeutic levels, as a likely cause of sudden death. These findings point toward an association between methadone and occurrence of sudden death in the community. Clinical safeguards and further prospective studies specifically designed to enhance safety of methadone use are warranted.

Cox RD; Koelliker DE; Bradley KG. Association between droperidol use and sudden death in two patients intoxicated with illicit stimulant drugs. Veterinary and Human Toxicology 46(1): 21-23, 2004. (16 refs.)

Illicit drug intoxication is often a cause of extreme agitation in the emergency department and prehospital settings. Chemical restraint is often required to protect patient as well as health-care providers. Droperidol has commons been used to sedate extremely agitated patients in the emergency department and psychiatric settings. Its safety has been demonstrated in these settings and in patients who's agitation has been attributed to amphetamine toxicity. We present 2 cases of sudden death following the use of droperidol to sedate I patient who was extremely agitated secondary to cocaine intoxication and another secondary to phencyclidine intoxication.

Fugelstad A; Ahlner J; Brandt L; Ceder G; Eksborg S; Rajs J et al. Use of morphine and 6-monoacetylmorphine in blood for the evaluation of possible risk factors for sudden death in 192 heroin users. Addiction 98(4): 463-470, 2003. (37 refs.)

Aims To detect risk factors for sudden death from heroin injection. Design Evaluation of data from forensic investigations of all fatal cases of suspected heroin death in a metropolitan area. Only cases with detectable morphine and 6-monoacetylmorphine (6-MAM) in blood were included in order to select heroin intoxication cases. Setting: Stockholm, Sweden. Measurements: Autopsy investigation and toxicological analysis of blood and urine; and police reports. Findings: In two-thirds of the 192 cases, death occurred in public places, and mostly without any time delay. Blood concentrations of morphine ranged from 50 to 1200 ng/g, and of 6-MAM from 1 to 80 ng/g. Codeine was detected in 96% of the subjects. In the majority of cases the forensic investigation indicated polydrug use, the most common additional findings being alcohol and benzodiazepines. However, in one-quarter of the cases other drug combinations were found. Previous abstinence from heroin and use of alcohol were identified as risk factors. For 6-MAM there was also a correlation with the presence of THC and benzodiazepines. Despite a high frequency of heart abnormalities (e.g. myocarditis and focal myocardial fibrosis), these conditions did not correlate with morphine or 6-MAM blood concentrations. Conclusions: We confirm that alcohol intake and loss of tolerance are risk factors for death from heroin use, whereas no connection to heart pathology was observed. Further, prospective, studies should focus on other possible risk factors.

Gould MS; Walsh BT; Munfakh JL; Kleinman M; Duan NH; Olfson M et al. Sudden death and use of stimulant medications in youths. American Journal of Psychiatry 166(9): 992-1001, 2009. (40 refs.)

Objective: The authors sought to determine whether a significant association exists between the use of stimulants and the rare event of sudden unexplained death in children and adolescents. Method: A matched case-control design was performed. Mortality data from 1985-1996 state vital statistics were used to identify 564 cases of sudden death occurring at ages 7 through 19 years across the United States along with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents. The primary exposure measure was the presence of amphetamine, dextroamphetamine, methamphetamine, or methylphenidate according to informant reports or as noted in medical examiner records, toxicology results, or death certificates. Results: In 10 (1.8%) of the sudden unexplained deaths it was determined that the youths were taking stimulants, specifically methylphenidate; in contrast, use of stimulants was found in only two subjects in the motor vehicle accident comparison group (0.4%), with only one involving methylphenidate use. A significant association of stimulant use with sudden unexplained death emerged from the primary analysis, which was based on exact conditional logistic regression (odds ratio=7.4, 95% CI=1.4 to 74.9). A comprehensive series of sensitivity analyses yielded qualitatively similar findings. Conclusions: This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents. Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment.

Gruszecki AC; McGwin G; Robinson CA; Davis GG. Unexplained sudden death and the likelihood of drug abuse. Journal of Forensic Sciences 50(2): 419-422, 2005. (9 refs.)

The common history of drug abuse in adults with an undetermined cause of death has led us to hypothesize that chronic drug abuse increases the risk of sudden death. To begin evaluating this hypothesis, we conducted a retrospective case-control study of 61 decedents whose cause of death remained undetermined following autopsy matched one to one to a control group of pedestrians or passengers killed in motor vehicle collisions. In 21 pairs, the case subject had evidence of drug abuse but the control did not, and in 5 cases the reverse was true. Analysis showed that individuals with an undetermined cause of death are 4.2 times more likely to have evidence of drug abuse than are victims of a motor vehicle collision.

Krantz MJ; Mehler PS. QTc prolongation: Methadone's efficacy-safety paradox. (commentary). Lancet 368(9535): 556-557, 2006. (11 refs.)

For decades, methadone has been the most widely prescribed treatment for heroin addiction worldwide. In 1973, clinicians in New York sought an explanation for a perceived increase in the risk of sudden death in heroin addicts, even in those successfully treated with methadone. The rate-corrected QT interval (QTc) was found to be prolonged in many patients, which was attributed to illicit polysubstance abuse. Careful inspection of that dataset, however, suggests a striking alternative: QTc prolongation occurred in 34% of methadone-treated individuals compared with only 3% of heroin addicts who were not treated with methadone. This difference did not pique further consideration because at the time there was no evidence that methadone possessed any cardiac-repolarisation activity. Indeed, the notion that methadone might independently alter cardiac repolarisation was not widely appreciated until nearly 30 years later, when torsade de pointes, a form of ventricular tachycardia associated with QTc prolongation, was reported in a small series of US and Canadian patients receiving very high doses of oral methadone. We believe that this dose-dependent effect of methadone on the QTc interval represents an increasingly important issue facing clinicians who prescribe methadone for either chronic pain or opioid dependence. The authors conclude that although QTc prolongation associated with higher doses of methadone is an important safety concern, we do not believe that routine ECG screening is warranted for heroin addicts entering treatment. However, individuals with structural heart disease (eg, left ventricular dysfunction) and those with additional risk factors for QTc prolongation (eg, hypokalaemia, cytochrome P450 inhibitors, other QT-prolonging drugs) may benefit from ECG screening.

Lucena J; Blanco M; Jurado C; Rico A; Salguero M; Vazquez R et al. Cocaine-related sudden death: A prospective investigation in south-west Spain. European Heart Journal 31(3): 318-329, 2010. (62 refs.)

With an estimated 12 million consumers in Europe, cocaine (COC) is the illicit drug leading to the most emergency department visits. The aim of this study was to examine a consecutive series of sudden deaths (SDs) to focus on the prevalence, the toxicological characteristics, and the causes of death in COC-related fatalities. Prospective case-control study of forensic autopsies was carried out in the time interval November 2003 to June 2006 at the Institute of Legal Medicine, Seville, south-west Spain, with a reference population of 1,875,462 inhabitants. Toxicology included blood ethanol analysis and blood and urine investigation for drugs of abuse and medical drugs. Autopsy was performed according to the European standardized protocol. Ten age- and sex-matched patients who died of violent causes with no antecedents of COC consumption and negative toxicology served as controls. During the study period, 2477 forensic autopsies were performed, including 1114 natural deaths. Among the latter, 668 fulfilled the criteria of SD and 21 (all males, mean age 34.6 +/- 7.3 years) resulted to be COC-related (3.1%). Cocaine was detected in 67.1% of the blood (median 0.17 mg/L, interquartile range 0.08-0.42) and in 83.0% of the urine samples (median 1.15 mg/L, interquartile range 0.37-17.34). A concomitant use of ethanol was found in 76.0% and cigarette smoking in 81.0%. Causes of SD were cardiovascular in 62.0%, cerebrovascular in 14.0%, excited delirium in 14.0%, respiratory and metabolic in 5.0% each. Left ventricular hypertrophy was observed in 57.0%, small vessels disease in 42.9%, severe atherosclerotic coronary artery disease in 28.6%, and coronary thrombosis in 14.3%. Systematic toxicology investigation indicates that 3.1% of SDs are COC-related and are mainly due to cardio-cerebrovascular causes. Left ventricular hypertrophy, small vessel disease, and premature coronary artery atherosclerosis, with or without lumen thrombosis, are frequent findings that may account for myocardial ischaemia at risk of cardiac arrest in COC addicts.

Opeskin K; Berkovic SF. Risk factors for sudden unexpected death in epilepsy: A controlled prospective study based on coroners cases. Seizure 12(7): 456-464, 2003. (75 refs.)

We performed a controlled prospective study of pathologically verified sudden unexpected death in epilepsy (SUDEP) in a coronial setting, to identify risk factors. We prospectively studied coronial deaths of people with epilepsy in Vic., Australia, during a 21-month period. Fifty SUDEP and 50 subjects with epilepsy who died of other causes (controls) were collected sequentially. Clinical data was obtained shortly after death from questionnaires completed by treating doctors, discussion with family members and coronial files, including police reports of death, autopsy and toxicology reports. Factors assessed were age, sex, duration of epilepsy, type of seizure(s), seizure frequency, symptomatic epilepsy, including post-traumatic epilepsy, presence of structural brain lesion, idiopathic epilepsy, mental retardation, psychiatric illness, including dementia, recent stressful life event, particular antiepileptic drugs (AEDs) and AED polytherapy, compliance with AED treatment, psychotropic drug prescription, alcohol and other substance abuse, place of death and evidence of terminal seizure. The SUDEP group was characterised by younger age and higher proportion found dead in bed and with evidence of terminal seizure compared to controls. The profile of patients at risk for SUDEP are young people with epilepsy. They are most likely to die in sleep and our data support the view that SUDEP is a seizure-related event. This, taken in conjunction with the finding that there was no increased risk associated with a particular AED in monotherapy or multiple AEDs suggests that attempts to better treat patients' epilepsy with AEDs might decrease the risk of SUDEP. Although the literature suggests that SUDEP is more frequent in patients with severe epilepsy, we did not find a correlation with seizure frequency suggesting that other clinical indices may be more important.

Pestaner JP; Southall PE. Sudden death during arrest and phencyclidine intoxication. American Journal of Forensic Medicine and Pathology 24(2): 119-122, 2003. (34 refs.)

Deaths of individuals being arrested are important and complex medicolegal cases. Conclusions regarding the cause and manner of death for such cases must take into account multiple factors that may have played a role, as well as anticipate the forensic issues that will arise. In this article, we review the deaths of 2 individuals in which phencyclidine intoxication was a factor that contributed to death during arrest. Most cases of sudden death during arrest have involved cocaine intoxication; because phencyclidine's pharmacologic properties are quite different from those of cocaine, these cases allow for comparisons to those factors that may have greater importance.

Pileggi P; Teatino A; La Marca A; Barbaro A. About a cocaine-associated sudden death casework. Forensic Science International 146(Supplement S): S77-S78, 2004. (0 refs.)

A man 24-year-old died suddenly while he was doing shopping. It was supposed that the death was caused by ictus or by cardiac pathology. During the autopsy, some biological samples were taken (hair, urine, blood and lachrymal liquid) for the toxicological analysis and also the heart, some fragments from the liver, lungs, spleen, and kidneys for the histo-pathological analysis.

Pilgrim JL; Gerostamoulos D; Drummer OH; Bollmann M. Involvement of amphetamines in sudden and unexpected death. Journal of Forensic Sciences 54(2): 478-485, 2009. (34 refs.)

In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.

Stanistreet D; Gabbay M; Jeffrey V; Taylor S. Are deaths due to drug use among young men underestimated in official statistics? Drugs: Education, Prevention and Policy 11(3): 229-242, 2004. (31 refs.)

We explored the impact of drug misuse on sudden, unexpected, violent or unnatural male deaths, checking the association between official mortality statistics, health records, and coroner evidence and verdicts. We searched health and coroner records for all Merseyside and Cheshire coroner cases for men aged 15-39 in 1995, comparing our data with government mortality statistics. We explored the relationship between accidental/undetermined and suicide verdicts, and post-mortem drug and alcohol toxicity. Our survey included 238 cases; 221 had toxicological data and formed our final sample. There was post-mortem evidence of drugs in 90 cases, alcohol in 102, and both in 46. Overdose verdicts were given for 74 cases. We found evidence of significant alcohol problems in 18 cases and drug misuse in 74. The presence of drugs at post-mortem was significantly related to a verdict of accident/undetermined rather than suicide (p = 0.03). Post-mortem Class A drug toxicity was significantly related to accidental/undetermined verdicts compared to Class B/C drugs. There was no significant relationship between the number of drugs found and the verdict. While coroners determined drugs to be related to death in 90 cases, official classifications would have recorded this figure as 60 (ONS standard) or 40 (EMCDDA-European Union recommended classification). Our findings support the recommendations of the recent ACMD report into the reduction of drug-related deaths.

Sugie H; Sasaki C; Hashimoto C; Takeshita H; Nagai T; Nakamura S et al. Three cases of sudden death due to butane or propane gas inhalation: analysis of tissues for gas components. Forensic Science International 143(2-3): 211-214, 2004. (6 refs.)

We report three cases of sudden death due to inhalation of portable cooking stove fuel (case 1), cigarette lighter fuel (case 2), and liquefied petroleum gas (LPG) (case 3). Specimens of blood, urine, stomach contents, brain, heart, lung, liver, kidney, and fat were collected and analyzed for propylene, propane, isobutane, and n-butane by headspace gas chromatography. n-Butane was the major substance among the volatiles found in the tissues of cases 1 and 2, and propane was the major substance in case 3. A combination of the autopsy findings and the gas analysis results revealed that the cause of death was ventricular fibrillation induced by hard muscle exercise after gas inhalation in cases 1 and 2, and that the cause of death in case 3 might be hypoxia. It is possible that the victim in case 3 was under anesthetic toxicity of accumulated isobutane which is a minor component of liquefied petroleum gas.

Taylor D; Parish D; Thompson L; Cavaliere M. Cocaine induced prolongation of the QT interval. Emergency Medicine Journal 21(2): 252-253, 2004. (12 refs.)

Prolongation of the QT interval is a serious electrocardiogram finding because of its association with torsandes de pointes and sudden cardiac death. Both congenital and acquired factors can lead to abnormal lengthening of the QT interval. While there are multiple congenital bases, there are also acquired causes, such as hypomagnesisum, HIV infection, and myocardial ischemia. Cocaine use has been associated with many cardia complications including ventricular arrhythmias and sudden death, and cocaine induced torsades de points in patients have been reported in case reports. In 1997, the first case of cocaine induced QT prolongation is the absence of congenital long QT syndrome was reported. The authors provide a case report of a 37 year old man with a history of chest pain after a three day crack cocaine binge. The medical history, physical examination findings are summarized. This case reinforces the need for close cardiac monitoring and the potential for electrophysiological effects that are not necessarily related to the drug's inducement of a hyperadrenergic or cardioischaemic state. It highlights the caution needed in prescribing QT prolonging drugs to those who have recently used cocaine or have a history of cocaine use.