Original ContributionsBlood cocaine and metabolite concentrations, clinical findings, and outcome of patients presenting to an ED
Abstract
The purpose was to determine if blood cocaine or metabolite concentrations would accurately reflect the severity of clinical findings in patients presenting to the emergency department, identifying those requiring therapeutic intervention or those at risk for poor outcome. Blood for determination of cocaine and metabolite concentrations was drawn from patients and were determined by an extractive alkylation/mass spectrometry procedure. The mean blood concentrations (mg/L) in 111 patients were as follows: cocaine, 0.26 ± 0.5; ecgonine 0.42 ± 0.47; ecgonine methyl ester 0.21 ± 0.37, norcocaine 0.03 ± 0.17; benzoylecgonine 1.28 ± 1.29, cocaethylene 0.02 ± 0.06. Two patients died, 23 required hospital admission, and 88 were discharged from the ED. There was no statistical correlation between cocaine or any metabolite concentration and the severity of clinical symptoms, disposition, need for treatment or outcome. Blood cocaine and metabolite concentrations should be interpreted with caution because they vary widely and do not predict the severity of clinical findings, the incidence of adverse effects, outcome, or need for interventional therapy. (Am J Emerg Med 2000;18:593–598.
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Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations
2021, American Journal of Emergency MedicinePoisonings resulting from the abuse of drugs currently represent a serious problem for public health. Among the main agents involved, cocaine stands out. It became one of the most abused drugs around the world, and one of the main reasons for visits to the emergency department due to the use of illicit substances. The use of cocaine is primarily in combination with alcoholic beverages. There are few studies that correlate cocaine blood concentration and the severity of clinical manifestations in patients evaluated at Emergency Department. The aim of the present study was to verify the possible relationship between the blood concentration of cocaine and cocaethylene (product of the interaction of cocaine with ethanol) with the severity of the clinical manifestations presented by patients with cocaine intoxication.
Blood levels were measured by high-performance liquid chromatography (HPLC) and the severity of clinical manifestations was assessed using the Stimulant Intoxication Score (SIS). To establish this relationship, Pearson's chi-square statistical test (x2) was used for categorical variables and Student's t for continuous variables, with statistical significance of 5% (p < 0.05).
Of the 81 patients included in the study, 77.8% were men with a mean age of 32.5 years ± 8.5 and mean of SIS 3.4 ± 2.5. Considering the toxicological analysis results, 24.7% of the blood samples were positive. The mean of cocaine and cocaethylene concentrations were 0.34 μg/mL ± 0.45 and 0.38 μg/mL ± 0.34, respectively. The blood concentration of cocaine and cocaethylene has not been shown to be useful information for the treatment and prognosis of patients, but blood levels of these substances at the time of treatment, regardless of their concentration, may be an indicator of severity, showing that any concentrations of these substances should be considered as potentially toxic.
The application of the SIS score proved to be an important alternative capable of predicting the severity of the patients due to cocaine intoxication in a fast and simplified way.
Cocaine Use in Adolescents and Young Adults
2019, Pediatric Clinics of North AmericaDeath by rupture of a cocaine packet in the stomach
2019, Toxicologie Analytique et CliniqueBien que rares, les cas de décès chez des passeurs par rupture de sachets de stupéfiants dans le tube digestif sont décrits dans la littérature. Classiquement, il s’agit de la rupture de sachets artisanaux dans l’intestin. Les auteurs présentent un cas inhabituel de décès par intoxication aiguë à la cocaïne chez un transporteur intracorporel de stupéfiants suite à la rupture d’un sachet unique, en latex, localisé dans l’estomac. Les prélèvements autopsiques classiques (sang cardiaque, sang périphérique, contenu gastrique) sont réalisés. Le dosage des alcools effectué par HS-CG-DIF dans le sang périphérique met en évidence une éthanolémie à 0,9 g/L, celui des cocaïniques par CG-SM une concentration de cocaïne à 30 940 μg/L, de benzoylecgonine (BZE) à 58 225 μg/L et d’ecgonine méthylester (EME) à 34 525 μg/L. Le dosage de la méthadone et de l’EDDP par CL-SM/SM montre des concentrations respectives de 780 et 157 μg/L, celui des benzodiazépines des concentrations de diazépam, nordiazépam et témazépam respectivement à 3,7 ; 2,8 μg/L et inférieur à la limite de quantification de la technique analytique. Les concentrations sanguines de cocaïne et de ses métabolites, très élevées, sont très probablement à l’origine du décès.
Although rare, cases of death by rupture of packets in the digestive tract are described in the literature classically by the breaking of small bags in the intestine. The authors present an unusual case of death by acute cocaine intoxication in an intracorporeal drug carrier following the rupture of a single packet made of thermoformed latex, located in the stomach. Classical autopsy samples (cardiac blood, peripheral blood, gastric contents) are made. The determination of alcohols carried out by HS-GC-FID shows an ethanolemia at 0.9 g/L, the determination of cocaine by GC-MS in the peripheral blood shows a concentration of cocaine at 30 940 μg/L, a concentration of benzoylecgonine (BZE) at 58 225 μg/L and a concentration of ecgonine methyl ester (EME) at 34 525 μg/L. The dosage of methadone and EDDP by LC-MS/MS shows respective concentrations of 780 and 157 μg/L, benzodiazepine concentrations of diazepam, nordiazepam and temazepam respectively at 3.7 μg/L, 2.8 μg/L and below the limit of quantification. High blood levels of cocaine and its metabolites are most likely the cause of death.
Pharmacogenomics of drugs of abuse
2019, Critical Issues in Alcohol and Drugs of Abuse TestingIndividual variability in response to drugs of abuse, risk for drug addiction, and success of addiction therapy is mediated in part by hereditary factors. Although some studies suggest that genetic influences on these processes comprise a large part of the inter-individual variability, to date there are few genes and variants definitively associated with drug use and addiction. This chapter will highlight the current understanding of pharmacogenetic variants relevant to drugs of abuse, including genes encoding drug-metabolizing enzymes, receptors, transporters, and neurotransmitters.
Interest of toxicological data in medical management of intracorporeal drugs carriers: Two case reports
2018, Toxicologie Analytique et CliniqueLa cause de complications et de décès la plus fréquente chez les transporteurs de drogues intracorporels est la toxicité par rupture des boulettes ou paquets ingérés. La prise en charge du patient peut être adaptée en fonction de l’état clinique, des résultats de la radiologie et du bilan toxicologique. Nous rapportons deux cas dans une même affaire, illustrant l’intérêt de l’analyse toxicologique. Une étude rétrospective entre janvier 2010 et juin 2018 décrit quelques données actuelles sur des transporteurs intracorporels nécessitant une hospitalisation dans un service de réanimation. Deux jeunes hommes ayant ingéré a priori des petits ballots d’aspect identique pour dissimulation pendant leur interpellation par la police, ont nécessité des hospitalisations séparées. Monsieur LR (20 ans) est pris en charge pour arrêt cardio-respiratoire par un service de réanimation. Sur les 50 petits ballots estimés ingérés, 30 sont recrachés immédiatement. Il élimine les autres par voies orale et rectale pendant l’hospitalisation. Des prélèvements urinaires et sanguins ainsi que trois ballots sont analysés par le laboratoire. Il décède à J14 des suites d’une encéphalopathie post-anoxique. Monsieur NC (13 ans) sans antécédents médicaux est hospitalisé dans un service médico-chirurgical pédiatrique suite à l’ingestion de 20 ballots similaires. Il est asymptomatique à l’entrée et 11 sachets sont visualisés et retirés par endoscopie gastrique en urgence. Seuls des échantillons urinaires et deux ballots sont analysés. Il est hospitalisé pendant 5 jours avant d’être remis aux autorités de police. Le bilan d’entrée toxicologique de Monsieur LR (screenings urinaire immunologique et plasmatique par LC-MS/DAD) est négatif. Pour Monsieur NC, seule la cocaïne urinaire est dépistée par bandelette (SureStep™ Multi-Drug) jusqu’à J3. L’analyse des ballots expulsés permet de confirmer la présence de cocaïne dans les deux cas en présence d’un ou plusieurs produits de coupe : phénacétine dans le cas de Monsieur LR et phénacétine, caféine et lévamisole dans le cas de Monsieur NC. Le suivi de l’élimination de la cocaïne pour Monsieur LR n’a mis en évidence à aucun moment la présence de son métabolite, la benzoylecgonine (BZE) dans les prélèvements biologiques. Ces résultats contribuent à orienter rapidement les cliniciens vers une cause d’arrêt cardiaque non toxique. Pour Monsieur NC, l’absence de conséquences cliniques et la négativation de la présence de BZE dans les urines au bout de 72 h ont permis une sortie du patient après 5 jours d’hospitalisation. L’analyse toxicologique montrait également que dans une même affaire, des boulettes visuellement identiques n’étaient pas constituées par les mêmes produits de coupe et étaient donc vraisemblablement d’origine différente. L’étude rétrospective décrit 44 patients hospitalisés en réanimation dans le cadre d’une prise en charge en tant que transporteurs intracorporels. Environ 20 % étaient des consommateurs habituels (cannabis et/ou cocaïne). En somme, 63,6 % avaient été interpellés dans les aéroports parisiens et l’hospitalisation avait alors duré 3 jours (valeur médiane) avec un suivi toxicologique toutes les 12 h. Environ 46 boulettes (valeur médiane avec un maximum de 129 boulettes) contenant de la cocaïne dans 77,3 % des cas, ont été récupérées chez les porteurs hospitalisés. Dans 75 % des cas, la récupération a été faite par voie basse. Le bilan toxicologique d’entrée montrait que 43,2 % des patients étaient positifs en cocaïne et 20,4 % en cannabis.
Intracorporeal drug carriage may lead to potential life-threatening complications with acute overdose syndromes and death due to ruptured package and intestinal obstruction. Patient management may be adjusted based on clinical symptoms, radiological examination and toxicological data. We describe two case reports of body stuffers in the same arrest by the police that highlights the value of toxicological analysis for the medical management of the patients. A retrospective study, between January 2010 and June 2018 brings additional data related to intracorporeal drug carriers requiring intensive care. To avoid an encounter with the police, two men have ingested some similar small-sized packages and were hospitalized in two different ICU. Mr LR (20-year-old) was admitted into an intensive care unit following cardiopulmonary arrest after ingestion. Of the 50 ingested estimated packages, 30 were immediately spit out and the others were removed through oral and rectal ways. Toxicological analyses were performed on plasma, urine and on three packages. The patient died 14 days after his hospitalization due to a hypoxic encephalopathy. Mr NC (13-year-old) was admitted in a pediatric ICU following ingestion of 20 similar packages. He was asymptomatic and 11 packages were visualized and removed by gastric endoscopy. Only urine and two packages were investigated for toxicological analysis. He had been hospitalized for 5 days before being handed over to the police. For Mr LR, analytical screening procedure with LC-MS/DAD (plasma) and immunological tests (urine) were negative. For Mr NC, positive results for cocaine were observed during three days with immunochromatography analysis (SureStep™ Multi-Drug). In both cases, toxicological analysis of little packages has identified cocaine with phenacetine for Mr LR and cocaine with phenacetine, caffeine and levamisole for Mr NC. Negative results obtained with the monitoring of urinary cocaine elimination for Mr LR oriented medical diagnosis of cardiopulmonary arrest with non-toxic etiology. These results can be explained by the quality of the little packages. For Mr NC, the absence of clinical symptoms and the negative results after 72 h of monitoring, allow discharge of the patient. Toxicological analysis revealed different composition for similar packages and provided further information about manufacturing methods. In a retrospective study, a total of 44 patients suspected of body packing or body stuffing were admitted to reanimation medical unit in Lariboisière hospital. 20% were regular drug users (cannabis and/or cocaine). In total, 63.6% of the intracorporeal drug carriers were arrested in Paris airports and medical management in reanimation unit was necessary during 3 days (median value) with toxicological monitoring every 12 hours. The median number of packages ingested was 46 (maximum 129) and the main illegal carried substance was cocaine (77.3%). 75% of them were evacuated spontaneously. Toxicological results in plasma or urine were mainly positive for cocaine (43.2%) and for cannabinoids (20.4%).
Concentrations of Cocaine in Blood Samples From Impaired Drivers and Drug-Related Deaths
2017, The Neuroscience of Cocaine: Mechanisms and TreatmentCocaine acts as a powerful stimulant of the central nervous system and is a major recreational drug of abuse in most nations. In forensic and legal medicine cocaine is encountered in blood samples from impaired drivers and in drug-related deaths. Highly sensitive and specific analytical methods (GC-MS and LC-MS) are available for determination of cocaine and its metabolites in biological specimens. The plasma elimination half-life (t½) of cocaine is relatively short (30–90 minutes), although its main metabolite benzoylecgonine (BZE) is measurable in blood and urine for much longer (t½ =4–6 hours). The concentrations of cocaine and BZE in blood samples from impaired drivers and cocaine-related deaths showed large interindividual variations and the frequency distributions overlap. The clinical manifestations of cocaine abuse and drug toxicity cannot be predicted from the concentration of the stimulant in blood. Much depends on the types of coingested drugs, e.g., heroin and/or ethanol, the person’s state of health, previous experience with central stimulants, and the development of central nervous tolerance.