A prospective, randomized, controlled trial of benzodiazepines and nitroglycerine or nitroglycerine alone in the treatment of cocaine-associated acute coronary syndromes

doi:10.1053/ajem.2003.50010

The American Journal of Emergency Medicine

Volume 21, Issue 1, January 2003, Pages 39-42

https://doi.org/10.1053/ajem.2003.50010 Get rights and content

Abstract

The purpose of the present study was to compare the use of lorazepam plus nitroglycerine (NTG) versus NTG alone in the reduction of cocaine induced chest pain in the emergency department. The secondary objective of the study was to help determine the safety of lorazepam in the treatment of cocaine- associated chest pain. The study was a prospective, randomized, single-blinded, controlled trial conducted at an university-affiliated urban emergency department (ED). All patients who presented with cocaine-associated chest pain were enrolled. Exclusion criteria included age greater than 45 years, documented coronary artery disease, chest pain of more than 72 hours duration, or pretreatment with nitroglycerin. Patients were given either sublingual nitroglycerine (SL NTG) (Group 1) or SL NTG plus 1 mg of lorazepam intravenously (Group 2) every 5 minutes for a total of 2 doses. Chest pain was recorded on an ordinal scale of 0 to 10 at baseline, and then at 5 minutes after each dose. Adverse reactions to medication were also recorded. Twenty-seven patients met the inclusion criteria and were enrolled in the study. The average age of these subjects was 34.1 years, and 67% were men. The NTG-only group consisted of 15 patients and the NTG-plus-lorazepam group consisted of 12 patients. Baseline mean chest-pain scores were 6.87 in Group 1 and 6.54 in Group 2, with no differences between groups. Five minutes after initial treatment, mean scores for the two groups were 5.2 and 3.9, respectively, with a difference in means of 1.24 (95% confidence interval [CI] −0.8-3.8). Five minutes after the second treatment, the mean scores were 4.6 and 1.5, respectively, with a difference in means of 3.1 (95% CI 1.2-5). Kruskal-Wallis testing showed a significant difference in pain relief between the two study groups (P =.003), with greater pain relief noted at 5 and 10 minutes in the NTG-plus-lorazepam group (P =.02 and P =.005, respectively). All patients in the study were admitted to the hospital, but no patient in either group had an acute myocardial infarction or cardiac complications in the ED. No adverse side effects were noted for either group. The early use of lorazepam with NTG was more efficacious than NTG alone, and appears to be safe in relieving cocaine-associated chest pain. (Am J Emerg Med 2003;21:39-42. Copyright 2003, Elsevier Science (USA). All rights reserved.)

Section snippets

Methods

A convenience sample of all patients who presented to the ED of our institution with chest pain and self-reported cocaine use in the preceding 72 hours was enrolled between November, 1998 and December, 1999. The institution is a large, urban teaching hospital with an emergency department census of 96,000. Most patients served by this ED are uninsured (39%) or have Medicaid (22%). The ED is staffed by board-certified emergency physicians who supervise emergency medicine residents and physician

Results

A total of 36 patients were enrolled in the study. Nine patients were excluded because they met the study exclusion criteria. These included 5 patients who were older than 44 years, 1 who was 17 years old, 1 who had chest pain for approximately 4 days, 1 who received NTG from emergency medical services personnel, and 1 who took propranolol for hypertension.

Group 1, treated with NTG only, consisted of 15 patients, and group 2, treated with NTG plus lorazepam, consisted of 12 patients. The

Discussion

The results of this study indicate that the early use of lorazepam together with NTG was more efficacious than NTG alone in relieving cocaine-associated chest pain in humans. In this study, lorazepam appeared to be safe in the early management of cocaine- associated chest pain.

Although the exact mechanism of chest pain in the setting of cocaine use is unknown, an increased sympathomimetic response is thought to induce coronary vasoconstriction. This has been shown to be reversible in the

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Citation Excerpt :
Benzodiazepines are included as first-line therapy in patients with cocaine-associated chest pain, specifically in those patients manifesting features of increased sympathetic tone, including anxiousness, hypertension, and tachycardia.89,104 Nitroglycerin has been shown to decrease chest pain in patients presenting with cocaine-associated symptoms.55,66 Cardiac catheterisation studies have demonstrated the ability of nitroglycerin to reverse the coronary artery vasoconstriction caused by cocaine.15
Cocaine is one of the most commonly abused drugs and represents a major public health concern. Cocaine users frequently present to the emergency department, with chest pain being the most common presenting complaint. The incidence of acute myocardial infarction in patients with cocaine-associated chest pain is often quoted as 6%, but it is highly variable depending on the included population. Risk assessment can be challenging in these patients; serial assessment of electrocardiograms and troponins is often required. This review focuses on the assessment and management of patients presenting with cocaine-associated chest pain and cardiotoxicity. Specific treatments are discussed, including benzodiazepines, nitroglycerin, calcium channel blockers, and phentolamine, and how treatment priorities differ from patients with noncocaine presentations. The use of beta-blockers in this population remains controversial, and the literature around its use is reviewed. The most recent literature and recommendations for the use of percutaneous coronary intervention and fibrinolytics in cocaine-associated myocardial infarction is discussed as well. Cocaine-associated dysrhythmias are suggested to be the cause of sudden cardiac death in some users. The pathophysiology and evidence-based treatments for dysrhythmias are reviewed. This review provides evidence-based recommendations for the assessment and management of patients presenting with cocaine-associated cardiovascular toxicity.
La cocaïne, l’une des substances addictives les plus répandues, constitue une préoccupation majeure en santé publique. Les consommateurs de cocaïne se présentent fréquemment aux urgences généralement pour des douleurs thoraciques. L’incidence de l’infarctus aigu du myocarde chez les patients souffrant de douleurs thoraciques associées à la cocaïne serait de 6 % selon des estimations souvent citées, mais elle est très variable selon la population. L’évaluation des risques peut se révéler difficile chez ces patients; elle nécessite souvent une série d’électrocardiogrammes et de dosages de la troponine. Le présent article de synthèse porte sur l’évaluation et la prise en charge des patients qui éprouvent des douleurs thoraciques et des manifestations de cardiotoxicité associées à la cocaïne. Nous y abordons certains traitements, comme les benzodiazépines, la nitroglycérine, les inhibiteurs calciques et la phentolamine, ainsi que les priorités thérapeutiques, qui diffèrent de celles appliquées pour les non-consommateurs de cocaïne. L’utilisation de bêtabloquants chez les patients cocaïnomanes demeure controversée et nous passons en revue la littérature à ce sujet. Nous examinons aussi les publications et les recommandations les plus récentes concernant le recours à une intervention coronarienne percutanée et aux fibrinolytiques dans les cas d’infarctus du myocarde associé à la cocaïne. D’aucuns ont avancé l’hypothèse que les dysrythmies associées à la cocaïne causeraient la mort subite par arrêt cardiaque de certains consommateurs. Dans ce contexte, nous nous penchons sur la physiopathologie des dysrythmies ainsi que sur les modalités de traitement à la lumière des données probantes. Le lecteur trouvera dans notre article des recommandations fondées sur des données probantes pour l’évaluation et la prise en charge des patients présentant des manifestations de toxicité cardiovasculaire associée à la cocaïne.
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These European Resuscitation Council (ERC) Cardiac Arrest in Special Circumstances guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required to basic and advanced life support for the prevention and treatment of cardiac arrest in special circumstances; specifically special causes (hypoxia, trauma, anaphylaxis, sepsis, hypo/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), special settings (operating room, cardiac surgery, catheter laboratory, dialysis unit, dental clinics, transportation (in-flight, cruise ships), sport, drowning, mass casualty incidents), and special patient groups (asthma and COPD, neurological disease, obesity, pregnancy).
Drugs of Abuse and Cardiotoxicity
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European Resuscitation Council Guidelines for Resuscitation 2015. Section 4. Cardiac arrest in special circumstances
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Treatment of toxicity from amphetamines, related derivatives, and analogues: A systematic clinical review
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Citation Excerpt :
There were no high-quality studies of benzodiazepines for treatment of ARDA-associated hyperadrenergic state. Two level I studies of cocaine-induced chest pain compared benzodiazepines to nitroglycerin, with dual therapy having advantage over single therapy in one study (Honderick et al., 2003). In the other trial there was no difference between dual versus single agent therapy (Baumann et al., 2000).
Overdose of amphetamine, related derivatives, and analogues (ARDA) continues to be a serious worldwide health problem. Patients frequently present to the hospital and require treatment for agitation, psychosis, and hyperadrenegic symptoms leading to pathologic sequelae and mortality.
To review the pharmacologic treatment of agitation, psychosis, and the hyperadrenergic state resulting from ARDA toxicity.
MEDLINE, PsycINFO, and the Cochrane Library were searched from inception to September 2014. Articles on pharmacologic treatment of ARDA-induced agitation, psychosis, and hyperadrenergic symptoms were selected. Evidence was graded using Oxford CEBM. Treatment recommendations were compared to current ACCF/AHA guidelines.
The search resulted in 6082 articles with 81 eligible treatment involving 835 human subjects. There were 6 high-quality studies supporting the use of antipsychotics and benzodiazepines for control of agitation and psychosis. There were several case reports detailing the successful use of dexmedetomidine for this indication. There were 9 high-quality studies reporting the overall safety and efficacy of β-blockers for control of hypertension and tachycardia associated with ARDA. There were 3 high-quality studies of calcium channel blockers. There were 2 level I studies of α-blockers and a small number of case reports for nitric oxide-mediated vasodilators.
High-quality evidence for pharmacologic treatment of overdose from ARDA is limited but can help guide management of acute agitation, psychosis, tachycardia, and hypertension. The use of butyrophenone and later-generation antipsychotics, benzodiazepines, and β-blockers is recommended based on existing evidence. Future randomized prospective trials are needed to evaluate new agents and further define treatment of these patients.
Intravenous methylphenidate: An unusual way to provoke ST-elevation myocardial infarction
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^☆: Address reprint requests to David C. Seaberg, MD, Department of Emergency Medicine, University of Florida Health Science Center, PO Box 100186, Gainesville, FL 32610-0186. E-mail: [email protected]

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Brief ReportsA prospective, randomized, controlled trial of benzodiazepines and nitroglycerine or nitroglycerine alone in the treatment of cocaine-associated acute coronary syndromes☆,☆☆

Abstract

Section snippets

Methods

Results

Discussion

Am Heart J

Ann Emerg Med

Am J Cardiol

Chest

The management of cocaine induced myocardial ischemia

N Engl J Med

Prospective multicenter evaluation of cocaine associated chest pain. Cocaine associated chest pain (COCHPA) study group

Acad Emerg Med.

Cocaine induced coronary vasoconstriction

N Engl J Med

Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both

N Engl J Med

Platelet responsiveness and biosynthesis of thromboxane and prostacyclin in response to in vitro cocaine treatment

Hemostasis

Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade

Ann Intern Med

Second American Heart Association International Evidence Evaluation Conference; Part 6: Advanced Cardiovascular Life Support; Section 1: Introduction to ACLS 2000: Overview of Recommended Changes in ACLS From the Guidelines 2000 Conference

Circulation

Brief Reports
A prospective, randomized, controlled trial of benzodiazepines and nitroglycerine or nitroglycerine alone in the treatment of cocaine-associated acute coronary syndromes☆,☆☆