Author: Kyle Hughes, MD, Emergency Medicine Resident, PGY-1
Faculty: Alexis Cates, DO, Medical Toxicology/Emergency Medicine Attending

The Case:

A 44-year-old male with unknown past medical history presents to your emergency department reporting constant chest pain that radiates down both of his arms. He is also reporting shortness of breath and nausea.

On quick chart review, you see he’s been to the emergency department multiple times in the past few months for chest pain with a final diagnosis of musculoskeletal pain. His workup during those times have all been negative.

Vitals: HR 125 bpm, BP 178/100, RR 24, SpO2 100% on room air, Temp 38.2C orally

Physical exam shows a moderately disheveled man who appears anxious. He’s diaphoretic and holding onto his chest. Heart sounds are normal with no murmurs, rubs or gallops heard. Lungs are clear. Pupils are dilated to 7mm bilaterally. When you ask if he’s used any recreational drugs he admits to powdered cocaine a few times a week for the past few months, however says he used crack cocaine for the first time about 20 minutes ago. You ask the emergency department tech to immediately get an electrocardiogram on the patient while the nurse is simultaneously drawing a troponin, brain natriuretic peptide, complete metabolic panel, complete blood count, creatinine kinase, urinalysis and urine drug screen. A chest x-ray is also ordered.

Learning Point 1: What patient populations are more likely to use cocaine?

Figure 1: Annual trends in rates of ED visits related to cocaine, psychostimulants (e.g. methamphetamine) or opioid use between 2008-2018.

Over the past two decades, the United States has seen a dramatic rise in recreational drug use. An analysis of the National Hospital Ambulatory Medical Care Survey (NHAMCS), a dataset of ED visits collected by the CDC, between 2008 and 2018 using ICD9-CM/IDC10-CM codes for drug dependence, abuse or poisoning showed a mild but not significant increase in cocaine use related ED visits, increasing from 6.6 to 8.9 ED visits per 10,000 population. Although there was no significant rise in cocaine related visits, there was a significant increase in psychostimulant use such as methamphetamine, rising from 2.2 to 12.9 ED visits per 10,000 population. Patients who presented to the ED with cocaine-related complaints were significantly more likely to be over 40 years-old, identify as black, be experiencing homelessness and presenting to an urban ED (96% of visits).

Learning Point 2: What is the difference between crack and powdered cocaine? Do they share the same risks and/or morbidity?

Powdered cocaine is, ideally, a purified product from the leaves of Erythroxylum coca plants. Crack cocaine is made by dissolving cocaine in water with a strong base such as sodium bicarbonate that you can find in baking soda, then boiling the water until the cocaine is alkalized and forms a solid product. Crack cocaine has a lower melting point than powdered cocaine and therefore can be smoked easier than powdered cocaine. Smoking crack cocaine has a significantly shorter time to peak concentration than snorting powdered cocaine due to its rapid absorption into pulmonary circulation while topical powdered cocaine results in vasoconstriction in the nostrils and delays absorption. No difference is seen in peak concentrations between both forms of cocaine.

There are no well designed prospective trials to assess differences in outcomes associated with powdered versus crack cocaine. Miro et al. performed a retrospective study in Europe assessed the outcomes of those who used powdered versus crack cocaine. The study included 3002 cases from a registry of 22 EDs. Patients who use crack cocaine were significantly more likely to have episodes of hypotension, hypertension and bradypnea while patients who use powdered cocaine were significantly more likely to be tachycardic and have chest pain or palpitations. Patients who use crack cocaine spent significantly more time in the hospital and had fewer deaths than powdered cocaine with no significant difference in mortality between the two. The authors did note patients who use crack cocaine were more likely to co-ingest with opioids, possibly explaining the higher rates of bradypnea. Related to this point, the authors also highlighted the difficulty of estimating accurate mortality risks associated with a specific drug as many patients use multiple drugs at once. 

Another retrospective study performed by Hsue et al. looked at aortic dissections at one San Franciscan hospital between 1981 and 2001. They found of the 38 aortic dissections that presented during that time period, 14 were related to cocaine use. Of these 14, 13 patients reported recent crack cocaine use while only 1 reported powdered cocaine use. Given crack cocaine’s faster time of onset, one could hypothesize worse cardiovascular outcomes with crack cocaine use; however, there is no high quality data to support this theory. Well designed prospective studies are needed to clarify the risks associated with crack and powdered cocaine use.

Learning Point 3: How should patients with acute cocaine intoxication be managed? What important organ systems should be targeted?

Patients who present with acute cocaine intoxication are at high risk of neurological and cardiovascular adverse events. Cocaine works by blocking the reuptake of excitatory amines such as serotonin, dopamine, norepinephrine and epinephrine. These can directly lead to blockage of GABA and thus precipitate seizures. This autonomic instability also leads to a downstream effect of hypertension and tachycardia. From a cardiac standpoint, cocaine increases a patient’s risk for myocardial infarction by inducing vasospasms of the coronary arteries, inducing a hypercoagulable state and activating platelets. Cocaine can also block cardiac sodium channels, leading to delayed depolarization of the cardiac action potential, widening of the QRS and dysrhythmias. 

Unfortunately there have been no well designed placebo randomized control trials to validate the efficacy of specific treatment regimens for the cardiovascular instability associated with cocaine intoxication. Richards et al. performed a systematic review assessing the treatment of cocaine cardiovascular toxicity and found data favoring the use of nitroglycerin and benzodiazepines. Of the 80 patients treated with nitroglycerin amongst the collective studies, 49% reported improvement to their chest pain; of those who reported improvement they were significantly more likely to have ischemic findings on their echocardiograms or discharged with a diagnosis of ischemic heart disease. Benzodiazepines had mixed results with some studies showing improvement in chest pain while others showing limited benefit; however, authors concluded benzodiazepines were likely safe to use in the setting of cocaine intoxication. Calcium channel blockers were shown to effectively treat hypertension; however, they had a high risk of reflex tachycardia. As for beta blockers, Lange et al. showed cocaine introduced into patient’s coronary arteries, followed by propranolol, lead to worsening coronary vascular resistance and blood flow with one patient suffering from a STEMI (relieved by nitroglycerin). The fear of possible unopposed alpha stimulation after using beta blockers to manage the cardiovascular toxicity from cocaine became widespread and was cited in multiple AHA/ACC guidelines for the reason why beta blockers should not be used. However, in Richards et al.’s systematic review, of 1744 patients who received beta blockers, only seven had adverse events and none of these adverse events were in patients who received labetalol or carvedilol, which have alpha-1 blocking properties. A retrospective study by Dattilo et al. looked at 348 patients who tested positive for cocaine and were admitted to either telemetry units or the ICU. They found patients who were given a beta-blocker during their admission were significantly less likely to have an acute myocardial infarction and had a lower mortality rate. 

Current AHA/ACC guidelines still do not recommend giving beta-blockers during cocaine intoxication; however, do state benzodiazepines with or without nitroglycerin are reasonable for the management of hypertension and tachycardia in patients with NSTEMIs. AHA/ACC guidelines for the management of STEMIs do not include any recommendations for cocaine-induced myocardial infarctions.

Learning Point 4: Are there any treatments for Cocaine Use Disorder (CUD)?

Unlike opioid use disorder, CUD has limited treatment options. Classically, topiramate has been used to manage CUD. Singh et al. performed a systematic review of topiramate for CUD which included five studies and 518 patients. The authors found topiramate significantly improved abstinence rates, however did not improve retention rates in substance misuse programs. Only one of the five studies they included showed a significant reduction in cravings with topiramate use. However, possibly on the horizon, ketamine infusions may prove to be another pharmacologic agent to treat CUD. Dakwar et al. performed a placebo and blinded randomized controlled trial to see if a one-time ketamine infusion could improve retention and abstinence rates in patients with CUD. 55 patients in this study were admitted to the hospital for five days of mindfulness sessions. On day two, they received either an infusion of ketamine or a placebo that consisted of midazolam. Patients were discharged on day five and followed up twice a week for four weeks with urine drug screens and physician visits. Six months later, patients were followed up with a telephone interview. Patients who received a one-time ketamine infusion were significantly more likely to stay in the program and be abstinent from cocaine. Six months later, 44% of the patients who received ketamine were still abstinent from cocaine, while none of the patients who received midazolam were abstinent from cocaine. Dakwar et al. provides strong evidence that Ketamine may be another therapeutic option to treat CUD. More randomized control trials should be conducted to validate these results.

Figure 2: Time to first use or dropout (survival probability), by treatment group, in a randomized controlled trial of ketamine and a mindfulness-based behavioral modification for cocaine dependence

The Case Concluded…

The patient’s EKG shows ST depressions in the anterior leads with an elevated troponin of 0.32. Other significant laboratory findings were CK of 450, BNP of 300, and urine drug screen positive for cocaine and marijuana. You administer 2mg of lorazepam and one 400µg sublingual nitroglycerin tablet. When you reassess the patient 20 minutes later, the patient reports moderate improvement to his chest pain. His vital signs are now HR 102 bpm, BP 155/82, RR 18, SpO2 100% on room air, Temp 37.2C. Repeat electrocardiogram shows normal sinus rhythm and you admit the patient to telemetry for further monitoring.

References:

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