Cocaine Toxicity


Article Author:
John Richards


Article Editor:
Jacqueline Le


Editors In Chief:
James Beauchamp
Mark Pellegrini
Nicole Hale-Crutch


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
6/8/2019 1:24:46 PM

Introduction

Cocaine abuse is a major worldwide health problem. Patients with acute cocaine toxicity presenting to the emergency department (ED) may require urgent treatment for tachycardia, dysrhythmia, hypertension, and coronary vasospasm, leading to pathological sequelae such as acute coronary syndrome, stroke, and death.[1][2][3]

Etiology

The leaves of the coca plant Erythroxylon coca have been used as a stimulant in South America for over 4000 years. Cocaine was first isolated from the leaves in the mid-1800s. It was considered safe and used in toothache drops, nausea pills, energy tonics, and, of course, the original “Coca-Cola” beverage. Since 1961 the International Single Convention on Narcotic Drugs has made recreational use of cocaine a crime internationally. The resurgence of cocaine’s popularity occurred in the 1970s during the disco era, and then in the 1980s, with the advent of crack cocaine. Cocaine is listed as a DEA Schedule II controlled substance because it has a medical use (see StatPearls chapter “Cocaine”), but also has a high potential for abuse.[4]

Epidemiology

Cocaine abuse remains a major public health problem, with an estimated 20 million users worldwide based on the most recent United Nations World Drug Report. The number of frequent cocaine users, which had been declining since 2006 in North America, has experienced a recent increase, with an estimated 1% of the population reporting use. The Drug Enforcement Agency estimated that in 2012 639,000 persons aged 12 or older had used cocaine for the first time within the previous 12 months in the United States (US), averaging approximately 1,800 initiates per day. In the US, cocaine was the most common drug of abuse resulting in hospital treatment, with 505,224 ED visits (40.3% of drug reported visits) in 2011 based on data from the Substance Abuse and Mental Health Services Administration. This translates to a rate of 162 ED visits per 100,000 population.[5][6]

Pathophysiology

Patients who abuse cocaine risk life-threatening consequences, including tachydysrhythmia, severe hypertension, acute coronary syndrome, stroke, acute myocardial and renal failure, seizure, hyperthermia, cocaine-induced rhabdomyolysis, and fetal/maternal morbidity and mortality.[7]

Toxicokinetics

Cocaine can be snorted, swallowed, injected, or smoked. Its pharmacodynamics involve multiple complex mechanisms although its half-life is short (~ 1 hour). This drug binds and blocks monoamine (dopamine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use.[7] Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation are another deleterious effects, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Similar to local anesthetics such as lidocaine, cocaine blocks sodium channels and interferes with action potential propagation. This Vaughn-Williams Class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.[8]

History and Physical

These patients present to the hospital with agitation, chest pain, anxiety, psychosis, and blunt and penetrating traumatic injuries. They are frequently hypertensive and tachycardic. They may be unwilling to disclose their cocaine use, and clinicians must consider a wide spectrum of diagnoses during the initial evaluation, such as withdrawal syndromes, thyrotoxicosis, acute psychosis, sepsis, pheochromocytoma, anticholinergic toxicity, serotonin and neuroleptic malignant syndromes, and intracranial hemorrhage.

Evaluation

Depending on the patient's presentation, laboratory testing for suspected cocaine toxicity can include complete blood count, comprehensive chemistry panel, troponin, B-type natriuretic peptide, creatinine kinase, urinalysis, urine toxicology screen, and electrocardiogram. Imaging may also include chest x-ray, abdominal x-ray for suspected body packers or stuffers, and head CT if altered mental status suggests intracranial hemorrhage.[9][10]

Treatment / Management

Based on a large systematic review referenced below, cardiovascular toxicity and agitation are best treated first-line with benzodiazepines to decrease CNS sympathetic outflow.[11] However, there is risk of over-sedation and respiratory depression with escalating and numerous doses of benzodiazepines, which is often necessary. Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil have been shown to reliably reduce hypertension, but not tachycardia. Dihydropyridine agents such as nifedipine should be avoided, as reflex tachycardia may occur. The alpha blocker phentolamine has been recommended but only treats alpha-mediated hypertension and not tachycardia. It is a rarely-used drug, and most clinicians are unfamiliar with its use and limited titratability. Nitroglycerin and nitroprusside are effective at lowering blood pressure, but risk of reflex tachycardia should be recognized. The mixed beta/alpha blocker labetalol has been shown to be safe and effective for treating concomitant cocaine-induced hypertension and tachycardia, without any “unopposed alpha-stimulation” adverse events recorded. The use of labetalol is approved by a recent AHA/ACC guideline for cocaine and methamphetamine patients with unstable angina/non-STEMI.[12]

Agitated patients are best treated with benzodiazepines, but antipsychotics such as haloperidol and olanzapine may also be useful. Combination treatment with benzodiazepines and antipsychotics has been shown to be more efficacious than monotherapy.[13]  Diphenhydramine is often added to enhance sedation and as prophylaxis against dystonia and akathisia. A common example of this is the “B-52” with its combination of haloperidol (5 mg), diphenhydramine (50 mg), and lorazepam (2 mg). Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachydysrhythmia in several case reports. Hyperthermia from cocaine toxicity is best treated with external cooling measures. Tepid water misting with convection cooling from a fan is the easiest and safest method to accomplish this in the field and in all emergency departments.[11]

Complications

  • Thrombophlebitis
  • HIV
  • Cellulitis
  • Hepatitis
  • Endocarditis
  • Pulmonary emboli
  • Aneurysms

Pearls and Other Issues

The phenomenon of “unopposed alpha-stimulation,” in which blood pressure increases or coronary artery vasoconstriction worsens after blockade of beta-2 vasodilation in cocaine-abusing patients, is controversial. This rarely-encountered adverse effect has resulted in some clinicians advocating for an absolute contraindication to the use of all beta-blockers, including specific, non-specific, and mixed. Many clinicians disregard this dogma and administer beta-blockers for cocaine-related chest pain and acute coronary syndrome, especially when there is demand ischemia from uncontrolled tachycardia.[8] Of the 1,744 total patients identified in the systematic review, only seven adverse events were from putative cases of “unopposed alpha-stimulation” due to propranolol (n=3), esmolol (n=3), and metoprolol (n=1). The authors of the original “unopposed alpha-stimulation” articles dating back to the 1980s concluded in a 2017 review that the phenomenon might actually be the from effects of cocaine alone, with or without beta-blockers.[11]

Enhancing Healthcare Team Outcomes

Over the past three decades, the rates of overdose from cocaine have gradually increased. In the US, deaths involving cocaine range from 0.9-1.6 per 100,000 population. Only in the last five years have the rates started to decrease to 0.78 per 100,000 population. People who inject cocaine into the neck veins have been known to develop a pneumothorax, thrombophlebitis, hemothorax, and myositis. In addition, there are reports that intravenous injections can be associated with aneurysms of vessels, resulting in rupture, obstruction and fistula formation. When cocaine is combined with other illicit and prescription drugs, the mortality rates are also high. More important, cocaine and alcohol have been associated with a 16 fold increase in the risk of suicide than either agent alone. Individuals who use cocaine often select a violent method for self-harm. Finally, cocaine use during pregnancy is also associated with adverse perinatal outcomes.[14][15](Level V) 

To date, there is no drug to prevent or cure cocaine addiction. The key is to educate the patient when he or she presents to the emergency department. Patients should be urged to seek drug counseling. Those who intended to commit suicide should be referred to a mental health counselor prior to discharge.


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Cocaine Toxicity - Questions

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A 24-year-old male unconscious patient is brought to the emergency department due to wide-complex tachydysrhythmia after smoking a white powdery substance in an attempt to get high. Even after the most appropriate initial resuscitation, he expires in the emergency department. Based on the description of the drig and patient' clinical presentation, which of the following agent is most likely to cause fatal cardiac tachydysrhythmias?



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A 33-year-old male presents to the emergency department after using an unknown amount of cocaine. He has ataxia, rotary nystagmus, slurred speech, and does not react to painful stimuli. His heart rate is 140b/min, and blood pressure is 190/110mmHg. Which of the following adulterants is the most likely cause of the patient's presentation?



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A 42-year-old male patient is seen in the emergency department with a presumed diagnosis of a cocaine overdose. The patient is agitated, and his vitals reveal a blood pressure of 180/95mmHg, respiratory rate of 22/min, and a pulse rate of 120b/min. Which of the following drugs is most likely to be useful for the treatment of BOTH tachycardia and hypertension?



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What is the most important fact about cocaine abuse?



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A 42-year-old male presents to the emergency department complaining of acute onset of severe chest pain. He additionally tells the physician that he developed chest pain after he snorted cocaine. During this recent emergency department visit, his ECG shows ST-depression in the anterior leads. Also, his vital signs are a heart rate of 120b/min, blood pressure of 160/100 mmHg, respiratory rate of 20/min, and temperature of 36C. Which of the following medication should be given first in cocaine-associated myocardial ischemia and infarction?



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A 33-year-old agitated male patient with cocaine overdose presents to the emergency depatment. What objective vital sign finding would be expected in the setting of cocaine toxicity?



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A 21-year-old female patient is admitted to the hospital for a cocaine overdose. She starts having short episodes of ventricular tachycardia that become longer in duration (> 30 seconds). Vital signs are blood pressure 110/50 mmHg, heart rate 140b/min, respiratory rate 20/min, and temperature 37C. Administration of which one of the following drugs would be indicated for treating this wide-complex tachydysrhythmia?



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A 24-year-old male is brought to the emergency department for cocaine use and headache. On presentation to the emergency department, his vital signs recorded included a blood pressure of 180/100 mmHg and a heart rate of 140 b/min. Physical examinations revealed agitation, restlessness, sweating, and dilated eyes. Additionally, a head CT scan was also performed, which showed no abnormalities. Based on the patient history and physical examination, which of the following is the best drug to manage the patient's current condition?



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A 52-year-old male has a blood pressure of 245/132 after cocaine use and is unresponsive to anything except painful stimuli. He is intubated and on a ventilator. The patient has dense left hemiparesis but intact gag, cough, and corneal reflexes. CT shows a large intracranial bleed in the right frontoparietal area. The patient deteriorates, his right pupil dilates, and his blood pressure drops to 192/98. Which of the following interventions is least appropriate?



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What is the lowest dose of cocaine that can cause severe adverse effects in an adult?



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A 24-year-old male presents to the emergency department with agitation, tachycardia, and hypertension directly after injecting cocaine. His vital signs include a heart rate of 140b/min, blood pressure 200/100mmHg, respiratory rate 20/min, and temperature of 38C. What should be the first-line treatment of cocaine central nervous system and/or cardiovascular toxicity?



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A 30-year-old female presents to the emergency department with acute psychosis, tachycardia, and hypertension after smoking crack cocaine. The patient does not respond to multiple escalating doses of intravenous (IV) benzodiazepines. Which of the following is the second-line treatment of the concomitant refractory tachycardia and hypertension?



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Cocaine Toxicity - References

References

Hantson P, Mechanisms of toxic cardiomyopathy. Clinical toxicology (Philadelphia, Pa.). 2018 Sep 27     [PubMed]
Mikhail A,Tanoli O,Légaré G,Dubé PA,Habel Y,Lesage A,Low NCP,Lamarre S,Singh S,Rahme E, Over-the-Counter Drugs and Other Substances Used in Attempted Suicide Presented to Emergency Departments in Montreal, Canada. Crisis. 2018 Sep 14     [PubMed]
Narula N,Siddiqui F,Katyal N,Krishnan N,Chalhoub M, Cracking the Crack Dance: A Case Report on Cocaine-induced Choreoathetosis. Cureus. 2017 Dec 22     [PubMed]
Mladěnka P,Applová L,Patočka J,Costa VM,Remiao F,Pourová J,Mladěnka A,Karlíčková J,Jahodář L,Vopršalová M,Varner KJ,Štěrba M, Comprehensive review of cardiovascular toxicity of drugs and related agents. Medicinal research reviews. 2018 Jul     [PubMed]
Paulozzi LJ, Opioid analgesic involvement in drug abuse deaths in American metropolitan areas. American journal of public health. 2006 Oct     [PubMed]
Turner C,Chandrakumar D,Rowe C,Santos GM,Riley ED,Coffin PO, Cross-sectional cause of death comparisons for stimulant and opioid mortality in San Francisco, 2005-2015. Drug and alcohol dependence. 2018 Apr 1     [PubMed]
Agrawal PR,Scarabelli TM,Saravolatz L,Kini A,Jalota A,Chen-Scarabelli C,Fuster V,Halperin JL, Current strategies in the evaluation and management of cocaine-induced chest pain. Cardiology in review. 2015 Nov-Dec     [PubMed]
Maraj S,Figueredo VM,Lynn Morris D, Cocaine and the heart. Clinical cardiology. 2010 May     [PubMed]
Richards JR,Gould JB,Laurin EG,Albertson TE, Metoprolol treatment of dual cocaine and bupropion cardiovascular and central nervous system toxicity. Clinical and experimental emergency medicine. 2018 Jan 31     [PubMed]
Richards JR,Garber D,Laurin EG,Albertson TE,Derlet RW,Amsterdam EA,Olson KR,Ramoska EA,Lange RA, Treatment of cocaine cardiovascular toxicity: a systematic review. Clinical toxicology (Philadelphia, Pa.). 2016 Jun     [PubMed]
Modisett KL,Walsh SJ,Heffner AC,Pearson DA,Kerns W 2nd, Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2016 Sep     [PubMed]
Alfa-Wali M,Atinga A,Tanham M,Iqbal Q,Meng AY,Mohsen Y, Assessment of the management outcomes of body packers. ANZ journal of surgery. 2016 Oct     [PubMed]
Zimmerman JL, Cocaine intoxication. Critical care clinics. 2012 Oct;     [PubMed]
Richards JR,Hollander JE,Ramoska EA,Fareed FN,Sand IC,Izquierdo Gómez MM,Lange RA, β-Blockers, Cocaine, and the Unopposed α-Stimulation Phenomenon. Journal of cardiovascular pharmacology and therapeutics. 2017 May;     [PubMed]
Zun LS, Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy. The Journal of emergency medicine. 2018 Mar;     [PubMed]

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