Subarachnoid and intracerebral hemorrhage in cocaine abusers
Abstract
Background/Aim. Cocaine is an alkaloid extracted from the leaves of the plants Erythroxylum coca and Erythroxylum novogranatense. It can be taken orally, intranasally, intravenously, by inhalation, or intragenitally. Cocaine abuse can cause subarachnoid and intracerebral hemorrhage. The aim of this study was to determine cocaine and benzoylecgonine (BZ) concentrations in various body fluids and organs, the frequency of subarachnoid and intracerebral hemorrhage, and the relationship of concentration of cocaine and BZ in different body fluids with subarachnoid and intracerebral hemorrhage. Methods. The study analyzed a total of 26 autopsies reports from 2005 to 2018 with detected cocaine and/or BZ in the bodies during a forensic autopsy at the Institute of Pathology and Forensic Medicine, Military Medical Academy in Belgrade, Serbia. Brain tissue was taken for histopathological analysis and blood from the femoral vein, while urine, gastric content, brain, kidney, and liver with gallbladder samples were taken for toxicological analyses. Results. There were 26 autopsied patients aged 23 to 56 years (mean age 33.77±8.52); 20 (75.92%) were men and 6 (23.08%) were women. Cocaine was found in the blood of 12 (46.15%), in the urine of 15 (57.69%), and in the brain of 8 (30.77%) autopsied patients. BZ was found in the blood of 20 (76.92%), in the urine of 21 (80.77%), and in the brain of 10 (38.46%) autopsied patients. Subarachnoid hemorrhage was found in 10 (38.46%), intracerebral hemorrhage in 18 (69.23%), and both subarachnoid and intracerebral hemorrhage in 6 (23.07%) autopsied patients. Intracerebral (focal and perivascular) hemorrhage was more frequent. There were statistically significantly higher concentrations of both cocaine and BZ in most of the body fluids and organs of examinees with intracranial hemorrhage compared to examinees without hemorrhage. Conclusion. Subarachnoid and intracerebral hemorrhage were frequent findings in autopsied cocaine abusers. The correlation between subarachnoid and intracerebral hemorrhage and cocaine concentrations in blood was moderate. There were strong correlation between subarachnoid and intracerebral hemorrhage and BZ concentrations in almost all the samples.
References
Karch BS, Drummer HO.Karch's Pathology of drug abuse. 5th ed. Boca Raton (London, NY): CRC Press; 2016. p. 28−32, 38−44.
Coe AM, Jufer Phipps RA, Cone EJ, Walsh SL. Bioavailability and Pharmacokinetics of Oral Cocaine in Humans. J Anal Toxicol 2018; 42(5): 285−92.
Karch BS. Karch's pathology of drug abuse, 3th ed. Boca Raton (London, NY): CRC Press; 2001. p. 35, 52, 157−9.
Dart RC. Medical Toxicology. 3th ed. Philadelphia:Lippincott Williams & Wilkins. 2004.p. 1084.
Kolbrich AE, Barnes JA, Gorelick AD, Boyd JS, Cone JE, Huesfis AM. Major and Minor Metabolites of Cocaine in Human Plasma following Controlled Subcutaneous Cocaine Administration. J Anal Toxicol 2006; 30(8): 501−10.
Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology. 5th ed. Edinburgh: Churchill Livingstone; 2003. p. 41−2.
European Monitoring Centre for Drugs and Drug Addiction. Health and social responses to drug problems: a European guide.Luxembourg:Office of the European Union; 2017.
Chang RT, Kowalski GR, Ricardo Carhuapoma J, Tamargo JR, Naval SN. Cocaine use as an independent predictor of seizures after aneurysmal subarachnoid hemorrhage. J Neurosurg 2016; 124(3): 730−5.
Sang JA, Tae JK, Byung-Woo Y. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke 2017; 19(1): 3−10.
Pilgrim JL, Woodford N, Drummer OH. Forensic Sci Int. Cocaine in sudden and unexpected death: a review of 49 post-mortem cases. Forensic Sci Int 2013; (1−3): 52−9.
Stephens BG, Jentzen JM, Karch S, Mash DC, Wetli CV. 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): 1−10.
Jenkins JA, Keenan MR, Henningfield EJ, Edward J. Correlation Between Pharmacological Effects and Plasma Cocaine Concentrations after Smoked Administration. J Anal Toxicol 2002; 26(7): 382−92.
Kurth CD, Monitto C, Albuquerque ML, Feuer P, Anday E, Shaw L. Cocaine and its metabolites constrict cerebral arterioles in newborn pigs. J Pharmacol Exp Ther 1993; 265(2): 587−91.
Levine SR, Brust JC, Futrell N, Brass LM, Blake D, Fayad P, et al. A comparative study of the cerebrovascular complications of cocaine: alkaloidal versus hydrochloride-a review. Neurology 1991; 41(8): 1173−7.
Demaerschalk BM, Kleindorfer DO, Adeoye OM, Demchuk AM, Fugate JE, Grotta JC, et al. American heart association stroke council and council on epidemiology and prevention. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the american heart association/american stroke association. Stroke 2016; 47(2): 581−641.
. Si X, Luo JJ. Acute Cocaine Exposure and Cerebrovascular Diseases: A Retrospective Clinical Study and Literature Review. J Neurol Exp Neurosci 2018; 4(1): 1−6.
Cheng YC, Ryan AK, Qadwai AS, Shah J, Sparks JM, Wozniak AM, et al. Cocaine Use and Risk of Ischemic Stroke in Young Adults. Stroke 2016; 47(4): 918−22.
Siniscalchi A, Bonci A, Mercuri NB, De Siena A, De Sarro G, Malferrari G, et al. Cocaine dependence and stroke: Pathogenesis and management. Curr Neurovasc Res 2015; 12(2): 163−72.
Bajwa AA, Silliman S, Cury JD, Seeram V, Shujaat A, Usman F, et al. Characteristics and Outcomes of Cocaine-Related Spontaneous Intracerebral Hemorrhages. ISRN Neurology 2013; 2013: 124390.
Martin-Schild S, Albright KC, Hallevi H, Barreto AD, Philip M, Misra V, et al. Intracerebral hemorrhage in cocaine users. Stroke 2010; 41(4): 680−4.
Aggarwal SK, Williams V, Levine SR, Cassin BJ, Garcia JH. Cocaine-associated intracranial hemorrhage: absence of vasculitis in 14 cases. Neurology 1996; 46(6): 1741−3.
Sordo L, Indave BI, Barrio G, Degenhardt L, de la Fuente L, Bravo MJ. Cocaine use and risk of stroke: A systematic review. Drug Alcohol Depend 2014; 142: 1−13.
Conway BS, Tamargo RJ. Cocaine Use Is an Independent Risk Factor for Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage. Stroke 2001; 32(10): 2338−43.
Bachi K, Mani V, Jeychandran D, Fayad AZ, Goldstein ZR, Klein NA. Vascular disease in cocaine addiction. Atherosclerosis 2017; 262: 154−62.
Esse K, Fossati-Bellani M, Traylor A, Martin-Schild S. Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Brain Behav 2011; 1(1): 44−54.
Green RM, Kelly KM, Gabrielsen T, Levine S, Vanderzant C. Multiple intracerebral hemorrhages uner smoking "crack" cocaine. Stroke 1990; 21(6): 957−62.
Kibayushi K, Mastri AR, Hirsch CS. Cocaine induced intracerebral hemorrhage: Analysis of predisposing factors and mechanisms causing hemorrhagic strokes. Hum Pathol 1995; 26(6): 659−63.
Salas-Esindola Y, Peniche-Castellanos A, López-Gehrke I, Mercadillo-Pérez P..Leukocystoclastic vasculitis related to cocaine use. Actas Dermosifiliogr 2011; 102(10): 825−7.
Melzer R, Schmid L. Cocaine-induced periostitis and vasculopathy. Rheumatology (Oxford) 2018; 57(39): 450.
Marquez J, Aguirre L, Muñoz C, Echeverri A, Restrepo M, Pinto LF. Cocaine-Levamisole-Induced Vasculitis/Vasculopathy Syndrome. Curr Rheumatol Rep 2017; 19(6): 36.
Brajković G, Kilibarda V, Rančić D, Tomašević G, Krstić N, Babić G. Case report. Determination of levamisole as an adulterant in street. MD-Medical Data 2013; 5(1): 99−103. (Serbian)