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Unexplained Sudden Death in Drug Abusers

Unexplained Sudden Death in Drug Abusers. Blake Hutchinson, MS-4 Faculty Representative Gregory Davis, MD Department of Pathology. Key Points. Cocaine causes deleterious effects on the heart Clinical toxicity from cocaine use does not correlate with blood or urine levels

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Unexplained Sudden Death in Drug Abusers

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  1. Unexplained Sudden Death in Drug Abusers Blake Hutchinson, MS-4 Faculty Representative Gregory Davis, MD Department of Pathology

  2. Key Points Cocaine causes deleterious effects on the heart Clinical toxicity from cocaine use does not correlate with blood or urine levels Even in the absence of acute cocaine intoxication, abusers are at higher risk for sudden death

  3. Cocaine Cardiovascular ToxicityCoronary Artery Disease Coronary artery spasm 10% decrease in vessel caliber Preexisting coronary disease Accelerated atherosclerosis Supported by lab studies

  4. Cocaine Cardiovascular ToxicityCoronary Artery Disease Coronary artery dissection Left anterior descending Hematoma compresses true lumen Intimal proliferation Resembles chronic rejection Entire length of vessel; angiography

  5. Cocaine Cardiovascular ToxicityMyocardial Hypertrophy Clinical and autopsy studies ECG Heart weights Mechanism Cocaine induced hypertension Direct oxidant effect

  6. Cocaine Cardiovascular ToxicityMyocardial Hypertrophy Angiogenesis lags hypertrophy Underperfusion and ischemia Ischemia disrupts repolarization Reentry arrhythmias

  7. Cocaine Cardiovascular ToxicityCatecholamine Toxicity Norepinephrine “myocarditis” Microfocal fibrosis Contraction band necrosis Result Favors reentry arrhythmias

  8. Cocaine Cardiovascular ToxicityMicrovascular disease Microangiopathy Cocaine induced apoptosis Thickening of small intramyocardial arteries Treatment implications Therapeutic anti-apoptotic drugs

  9. Cocaine Cardiovascular ToxicityQT abnormalites QT interval dispersion QT in max lead – QT in min lead Increased dispersion increases chance of SCD Increased QTd in cocaine users occurs in absence of hypertrophy

  10. Cocaine Cardiovascular ToxicityQT abnormalities Torsade de pointes Cocaine modulates ion channels Cocaine induced LQTS increases TdP risk Greater risk in partially expressed congenital LQTS and drug induced LQTS

  11. Cocaine Clinical ToxicityDose- response relationship Hypothesis: The severity of symptoms in patients presenting to an ED do not correlate with either blood cocaine or metabolite concentrations Blood cocaine and metabolite concentrations, and outcome of patients presenting to an ED. Blaho, et al. Am J Emerg Med 2000.

  12. Cocaine Clinical ToxicityDose- response relationship Methods Stimulant Intoxication Scale HR, BP, Orientation, MS, Temp Cocaine equivalents Sum of cocaine and metabolite concentration (mM)

  13. Cocaine Clinical ToxicityDose- response relationship Stimulant Intoxication Scale Admitted 7.9 +/- 3.5 Discharged 5.3 +/- 2.2 Significant difference (P = 0.008)

  14. Cocaine Clinical ToxicityDose- response relationship Blood cocaine levels Admitted 0.33 +/- 0.64 Discharged 0.29 +/- 0.50 No significant difference

  15. Cocaine Clinical ToxicityDose- response relationship Stimulant Intoxication Scale Survivor 5.7+/- 2.5 Decedent 12

  16. Cocaine Clinical ToxicityDose- response relationship Blood cocaine concentration Survivor 0.27 +/- 0.51 Decedent 0.20 +/- 0.25 No significant difference

  17. Cocaine Clinical ToxicityDose- response relationship Summary Neither cocaine nor metabolite concentrations were different among patients who were admitted vs discharged or who lived vs died No statistical correlation was noted between cocaine and metabolite blood concentration and SIS (r = 0.120)

  18. Myocardial IschemiaIn absence of Cocaine Hypothesis: Cocaine abusers have increased prevalence of myocardial ischemia even in the absence of cocaine on urine drug screen Myocardial Ischemia during Cocaine Withdrawal. Nademanee, et al. Annals of Internal Medicine. 1989.

  19. Myocardial IschemiaIn absence of Cocaine Methods Patient population Male chronic cocaine abusers No history of heart disease Study Protocol Urine drug screen, Holter monitor, Treadmill

  20. Myocardial IschemiaIn absence of Cocaine

  21. Myocardial IschemiaIn absence of Cocaine Cocaine abusers were at higher risk for ST changes than healthy volunteers (P = 0.0004, RR = 16) despite the absence of cocaine from the body and negative treadmill tests Mechanism for these changes remains unknown but coronary vasospasm is suspected

  22. Unexplained Sudden DeathAbsence of established pathology Hypothesis: Deaths where neither toxicological or anatomical cause is found at autopsy share a common history of drug abuse Unexplained Sudden Death and the Likelihood of Drug Abuse. Gruszecki et al. J Forensic Sci 2005.

  23. Unexplained Sudden DeathAbsence of established pathology Methods Retrospective case-control study Control group killed in MVC Study group undetermined death Matched for age and date of death Social trends Toxicological methods

  24. Unexplained Sudden DeathAbsence of established pathology Methods All patients were evaluated for compelling evidence of drug abuse Decedents lacked sufficient disease to explain death, including autopsy and toxicological findings

  25. Unexplained Sudden DeathAbsence of established pathology History of drug abuse Study group 17 Control group 1

  26. Unexplained Sudden DeathAbsence of established pathology Evidence of drug abuse Study group 21 Control group 5 Significant difference (P = 0.0017)

  27. Unexplained Sudden DeathAbsence of established pathology Decedents in study group were 4.2 times (95% CI 1.6 – 11.1) more likely to have evidence of drug abuse than the control group A history of drug abuse was also present in a statistically disproportionate number of study group cases

  28. Conclusions • Evidence indicates that blood and urine concentrations of cocaine and cocaine metabolites do not correlate with severity of clinical symptoms or clinical outcomes • Evidence indicates that, in cases of unexplained sudden death, cocaine use plays a major role despite the lack of acute intoxication with cocaine

  29. Conclusions • Evidence suggests that cocaine use induces chronic biochemical and physiologic changes that persist beyond the presence of cocaine in the blood • Evidence suggests that these changes increase the likelihood of sudden death; further research will better characterize these changes

  30. References 1. Gruszecki A, McGwin G, Robinson C, Davis G. Unexplained Sudden Death and the Likelihood of Drug Abuse 2. Karch, SB: Cocaine cardiovascular toxicity. TheSouthern Medical Journal 2005; 98; 794-799 3. Nademanee K, Gorelick DA, Josephson MA, Ryan MA, Wilkins JN, Robertson HA, Mody FV, Intarachot V. Myocardial ischemia during cocaine withdrawal. Ann Intern Med 1989;111:876–80. 4. Blaho K, Logan B, Winbery S, Park L, Schwilke E. Blood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED. Am J Emerg Med 2000;18:593–8. 5. Stephens B, Jentzen J, Karch S, Mash D, Wetli C. Criteria for the Interpretation of Cocaine Levels in Human Biological Samples and Their Relation to the Cause of Death. Am J Forensic Med Pathol 2004;25:1-10

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