Prehospital Cocaine Toxicity: An Overview

Introduction & Etiology

Cocaine toxicity is a growing problem in the United States, especially with the increase in “lacing” or the addition of other illicit drugs into cocaine. Per NIDA, cocaine was involved in at least 24,486 deaths in 2021. Stimulant abuse in general was a causative factor for a total of 32, 537 deaths in 2021. This does not include hospitalizations that had cocaine as the causative agent or polypharmacy overdoses that do not result in death.

While opioid overdoses are by far the most lethal overdose in the United States, cocaine use remains a threat to public health and is responsible for significant mortality and morbidity. Cocaine was responsible for at least 422,481 hospital admissions in 2018 alone (Gangu et al., 2022).

What is cocaine?

Cocaine is a potent sympathomimetic drug that works by increasing sympathetic nervous system tone and binding to monoamines. Put simply, monoamines are neurotransmitters that are mostly involved in emotional regulation, internal motivation, some muscular functions, and memory. Classic examples of monoamines include dopamine, serotonin, noreadrenaline, and epinephrine. By binding to monoamines, they are blocked from reuptake and thus cannot be removed from circulation. By doing this, cocaine spikes the circulating amount of these neurotransmitters for the duration that the drug has an effect.

The monoamines listed above are involved in the body’s fight or flight response. In addition, they are also the neurotransmitters responsible for the feelings of euphoria, wellbeing, and happiness. Cocaine is commonly known as an “upper” for this reason as patients under the influence will exhibit euphoria/mania signs, erratic and pressured speech, and often a feeling that they’re “on top of the world.” At the same time, the body is physiologically stressed by this abundance of catecholamines.

Cocaine has a rapid onset and lasts for a short duration.

Cocaine is created through the processing of cocoa leaves. Colombia makes up most production of cocaine in the world. It is then shipped north into the US after processing and packaging. Most cocaine in the United States is transported through Mexico before actually being distributed in the mainland.

Common symptoms of cocaine use:

• Hypertension

  • Excessive levels of epinephrine and norepinephrine result in systemic vasoconstriction. In addition, these patients often raise their blood pressure through activity.

• Tachycardia

  • Excessive catecholamines result in positive chronotropic and inotropic effects. Contractility and heart rate are raised, resulting in a higher cardiac output.

• Hyperthermia & Sweating

  • Cocaine prompts the development of a hypermetabolic state - that is, metabolism in excess of a normal person’s. At the same time, cocaine affects the body’s ability to thermoregulate on its own. The body responses by sweating in an attempt to cool down.

• Dilated Pupils

  • An excess of parasympathetic tone (like in opioids) prompts pupillary constriction. An excess of sympathetic nervous tone prompts the opposite and dilates pupils.

    • Think about what humans need in fight or flight mode from an evolutionary standpoint. When we need to be able to run fast and respond to a threat, our pupils also open up to allow the maximal amount of light in to help us see threats in front of us. Cocaine stimulates this.

• Euphoria & Happiness

  • The monoamines play a significant role in mood regulation. By increasing the classic “feel good” neurotransmitters like dopamine and serotonin, these patients may experience a feeling of euphoria and happiness.

  • This is dose and patient-dependent. Rather than feeling euphoria, some patients may feel terror and anxiety instead.

• Anxiety

  • The body maintains a delicate balance of catecholamine neurotransmitters to maintain its normal function and mood. When excessive catecholamines are present, some patients may report feelings of terror, anxiety, and excessive worry. This will contribute to the body’s tachycardia and hypertension response to cocaine.

• Ischemia & Ischemic Symptoms

  • Excessive vasoconstriction can prompt ischemia in almost anywhere in the body. This will be addressed later on in this article.

• Seizures

  • Cocaine lowers the seizure threshold. In high doses, cocaine can prompt cerebral ischemia that then prompts cerebral edema.

• Stroke/CVA & Dissection

  • Cocaine causes severe, systemic vasoconstriction and hypertension. This can result in vascular events such as dissection and ischemic strokes. This will be detailed further below.

Classic Use Cases of Cocaine

Cocaine is commonly thought of as a “party drug” and is often seen in college parties and nightclubs. The Southern US makes up roughly 42 percent of all cocaine use cases resulting in hospitalizations, with the Northeast and Midwest making up the second and third highest use respectively (State Estimates of Past Year Cocaine Use Among Young Adults: 2014 and 2015, n.d.). The Western United States sees the lowest use cases resulting in hospitalization.

Cocaine can be insufflated/snorted, smoked, ingested, or injected. Snorting is the most common way to use cocaine. For injection, users often mix cocaine in water before injecting it intravenously. Intravenous and snorting typically result in the most morbidity and mortality. Effects are felt within seconds to minutes of use by all non-enteric routes and usually last up to 90 minutes. Oral cocaine use affords both the slowest onset of symptoms and the longest amount of symptomatic time with up to 90 minutes of effect (American Addiction Centers, 2022). Cocaine users will often use cocaine repeatedly throughout one use session to maintain their high, and often will use until they are interrupted by an external factor or run out of cocaine.

Patients using cocaine often have difficulty self-regulating the amount of cocaine that they actually do. The risk of overdose increases with each dose as the patient loses their inhibitions.

Cocaine is one of the most expensive street drugs available and is most commonly used by those with higher socioeconomic statuses. Young females are prone to trafficking by criminals who purposely get them addicted and then use their continued access to the drug as leverage.

Cocaine does have some legitimate medical use during anesthesia by ENT surgeons.

Trafficking - A Note

Most drugs in the United States come in via the land border with Mexico. Traffickers use a variety of methods to transport drugs into the mainland, but one of the most clinically concerning methods is the use of balloons entered into the GI system. Traffickers will have “mules” transport various amounts of drugs through airports and land borders by having the drugs contained in tied-off balloons. These “mules” will pass through security and then defecate these balloons once they are in the mainland US.

These balloons can prompt bowel ischemia, constipation, and mechanical damage to the digestive tract. If they burst, they will release their contents into the body to be systemically absorbed. Many of these mules will carry several balloons at once; putting them at risk for overdose. Several balloons bursting can easily result in a fatal overdose.

It is critically important to maintain a high index of suspicion for this if you are in a jurisdiction near a port of entry. Patients who exhibit sudden onset GI upset, agitation, general symptoms of increased sympathetic nervous tone, or delirium should all be closely assessed for the possibility of trafficking-related injury.

An example of cocaine trafficking balloons. Image sourced from BBC News..

Speedballing

Speedballing is a street term for combining fentanyl or another opioid drug with cocaine. These two drugs will act synergistically to one another and boost the other’s effects. Patients that “speedball” will often present with symptoms of both opioid and stimulant drugs. Symptoms will also be dependent on the exact ratio of cocaine to opioids involved.

For instance, patients that use a relatively small amount of cocaine combined with a larger dose of heroin may still exhibit the classic opioid overdose effects of respiratory depression, CNS depression, altered mental status, and hypotension. However, providing naloxone to these patients will only reverse the effects of the opioid involved. Naloxone will not have any effect on cocaine use. On the other hand, patients that use a comparatively small amount of opioid combined with a larger dose of cocaine may still exhibit the classic cocaine use signs of hypertension, euphoria/mania, delirium, pressured speech, and heightened motor activity. Once the cocaine wears off, the longer-lasting opioid may still have effects and could even prompt respiratory depression depending on what medication was used.

Cocaine & Alcohol - A Warning

Because it is such a prevalent party drug, cocaine is often ingested with other substances - most notably alcohol. Many cocaine users will ingest alcohol simultaneously with cocaine during their use session, or afterwards as a means to self-soothe from the effects of cocaine.

Cocaine combines with alcohol ethanol to form a substance called cocaethylene (Pergolizzi et al., 2022). This is an extremely cardiotoxic compound that can prolong the timeframe that symptoms are felt, produce significant altered mental status and agitation, and worsen patient outcomes. Rather than a mere mix of cocaine and ethanol, this is an entirely new byproduct within the body (Pergolizzi et al., 2022).

Cocaine works jointly on both serotonin and dopamine receptors while cocaethylene derives most of its effect through dopamine reuptake blockade. As mentioned above, it spikes the circulating amount of dopamine in the body by preventing its removal from circulation. It enhances the typical euphoria of cocaine through this mechanism.

Cocaethylene has a significantly longer half-life than cocaine alone (2 hours versus 1 hour with cocaine alone) and thus yields a risk for more erratic, health-endangering behavior while someone is under its influence (Pergolizzi et al., 2022). Cocaethylene additionally has a more profound effect on both blood pressure and heart rate than cocaine use alone (Pergolizzi et al., 2022). Patients that have used both alcohol and cocaine may need more aggressive resuscitation efforts than cocaine alone. Due to the dehydrating effects of alcohol, patients may also need more fluid resuscitation with cocaethylene than if they used cocaine alone.

Prehospital Medical Emergencies & Cocaine

Prehospital management of cocaine toxicity is based on timely recognition of symptoms and supportive care. There is no specific antidote, especially prehospital, to cocaine use and toxicity. In addition, it is important to note that specifically treating cocaine-induced hypertension is not always necessary, and it is especially not necessary to do so in the absence of neurologic symptoms suggesting hypertensive encephalopathy. Be aggressive with your interventions when necessary while also recognizing that most instances of cocaine use will self-resolve without the need for prolonged medical intervention.

Cocaine users will often not call for help themselves unless they are experiencing an adverse reaction. A common reason for EMS to encounter a victim of cocaine toxicity is when the police call for assistance when someone has an altered mental status. Second and third party callers for cocaine users are also common.

When encountering someone who you believe may have used cocaine, take a calm and nonjudgmental approach. These patients are often prone to overstimulation and could be experiencing significant anxiety. By approaching these patients in a calm manner and appearing as a friend trying to help them, you may be able to elicit cooperation from an otherwise combative patient.

Remember: these patients are experiencing a general amplification of every feeling that they have - including doom, anxiety, euphoria, trust, and mistrust. They may exhibit significant emotional lability. Gentle reassurance and the removal of environmental stimuli are some of the best routes to ensure that the patient remains cooperative.

It is also important to remember that many cocaine users do not necessarily use recreational drugs on a regular basis. For many EMS providers, the most common instances we see these patients will be after parties or at clubs when someone is offered something, takes it, and then feels an adverse reaction to the drug. These patients may have no tolerance to these drugs and may be unfamiliar with managing their own feelings regarding recreational drugs. These patients may feel judged or shame for their actions. This makes maintaining a nonjudgmental attitude even more important.

Many of these patients will also be dishonest if in the presence of law enforcement for fear of their own prosecution. Interviewing these patients in a safe but isolated location may yield more honest interview findings. Emphasize to these patients that you are not the police, are not involved with the police, and only wish to obtain information about what substance they used so that you can better treat them.

Some interventions for reducing stimulation include:

• Turning down the ambulance lights, and turning off the emergency lights when unnecessary.

• Offering a blanket or something for them to fidget with. Occupying their hands may provide a channel for their anxiety.

• Speaking in a moderately low, slow tone of voice. Avoid using phrases or words with potentially ambiguous meanings. Be clear, honest, and straightforward with these patients.

• Provide instructions sequentially, and avoid giving multiple directions at once. Providing excessive or multi-step instructions to these patients may overstimulate them.

Managing Agitation

These patients may unfortunately present in an agitated and inconsolable way. It may be necessary to chemically sedate these patients for the safety of the patient, the crew, and the public at large. It is important to consider sedation anytime a patient is generally inconsolable to the point of self-harm or severe anxiety, is violent towards themselves or others, or exhibits dangerous behaviors such as running into traffic.

Benzodiazepines are the medication class of choice for sedating these patients. Benzodiazepines work by prompting the release of GABA, an inhibitory neurotransmitter for the brain. GABA works against the sympathetic effects of cocaine and helps prompt relaxation and sedation in acutely agitated patients.

A 2021 study out of Florida Atlantic University authored by Joshua J. Solano, MD found that patients who had used cocaine and then received ketamine for sedation purposes had a significantly increased risk of intubation requirement upon arrival at the emergency room (Solano, 2021). No specific mechanism for this interaction is known, but is important to carefully weigh your sedation options for the best outcome for the patient.

It is important to remember that ketamine has some stimulating effects on the CNS and can increase sympathetic nervous tone in an already overstimulated patient (Lippmann & Kakazu, 2007). Patients who have used cocaine have little risk for catecholamine depletion. Ketamine use simultaneously can potentiate the effects of cocaine.

Managing Myocardial Infarction, Rhythm Changes, & Ischemic Chest Pain

Cocaine is a potent vasoconstrictor and works on almost every blood vessel in the body.- with the coronary arteries being no exception. Considering the possibility of polypharmacy use and a general substance abuse disorder in many cocaine-using patients, these patients are often not in the best health to start.

One of the most lethal presentations of acute cocaine toxicity is new-onset myocardial infarction. Cocaine prompts vasoconstriction in addition to an overall increase in platelet count, production, and aggregability (McCord et al., 2008). Cocaine can induce a prothrombotic environment and increase the incidence of dangerous thrombus formation that can occlude blood flow in the coronary vessels. Albeit dated, a 2007 study found that cocaine use precipitated an MI in 1 percent of studied cases (Rezkalla & Kloner, 2007). Cocaine use has the highest risk of MI in the first hour of use (Rezkalla & Kloner, 2007).

Secondary to an actual MI, cocaine can also prompt coronary vessel vasospasm and result in widespread cardiac ischemia. This ischemia can cause patients to develop otherwise unexplained cardiogenic shock and be a significant life threat. Vasospasm can also result in potentially fatal dysrhythmias.

The most common rhythm associated with cocaine use is sinus tachycardia (Dominic et al., 2022). In most instances, cardiac rhythms do not need acute management and are merely a side effect of cocaine use. However, patients experiencing hemodynamic changes due to vasospasm or an actual MI are at risk of ventricular rhythms such as ventricular fibrillation and ventricular tachycardia. For these instances, treat the patient as you would any other patient experiencing such dysrhythmias under current ACLS guidelines and your local protocols.

An example of Bruguda morphology (V1, V2) in a patient suffering from cocaine toxicity. Sourced from Dr Smith’s ECG Blog.

An EKG from a case study for a 41yom post cocaine use resulting in inferolateral STEMI/ischemia. (Patel et al., 2023)

The standard STEMI treatments of adequate oxygenation, aspirin administration, and analgesia through nitroglycerin + fentanyl/morphine remain in use for cocaine-induced MIs.

Be careful when providing fluid resuscitation, as these patients may have a reduced ejection fraction as a result of their ischemia or underlying health comorbidities. Provide fluid resuscitation as necessary to correct dehydration and promote a healthy volume status while avoiding volume overload.

Vasculopathies in Cocaine Use

Image sourced from UPMC.

Beyond MI and myocardial ischemia, cocaine use also presents a lethal risk of arterial dissection - most notably aortic dissection. CVA - both ischemic and hemorrhagic- is also a significant risk of cocaine use.

A 2020 retrospective study found that a concerning amount of young men with a median age of 40 were suffering from acute aortic dissection following cocaine ingestion (Greve et al., 2020). Many of the studied patients did have some form of significant comorbidity including nicotine use, prolonged cocaine use, or hyperlipidemia (Greve et al., 2020). Nicotine abuse was one of the strongest risk factors correlated with cocaine-induced aortic dissection (Greve et al., 2020).

As mentioned above, cocaine works by inhibiting the reuptake of catecholamines and thus prompting hypertension, tachycardia, and an overall increase in sympathetic tone. In patients with pre-existing vascular atherosclerosis or damage, this can exacerbate weaknesses in the arterial wall and prompt rupture.

Management of an aortic dissection in the prehospital realm focuses on maintaining a normotensive state, if possible, and prompt recognition. It is important to select a destination that can offer prompt surgical intervention for this condition while avoiding delays in transfer to tertiary care. These patients are, of course, not appropriate for a freestanding ER or a community hospital without significant surgical capability if a greater hospital is available.

Circle of Willis image. Sourced from Medline Encyclopedia.

The vascular system of the brain is also inherently fragile with little room for hemodynamic extremes. Both soaring hypertension and hypotension can prompt cerebral vasospasm and prompt cerebral ischemia. Cocaine can prompt hypertensive encephalopathy and vasospasm that can lead to a hemorrhagic stroke when a weakened vessel ruptures or an ischemic stroke through the same mechanisms that causes an MI. By inducing a hypertensive and hypercoagulable state, cocaine is a significant risk factor for CVA incidence.

Prehospital management of a CVA induced by cocaine focuses on supportive care and is not inherently different from any other CVA. Prompt recognition and management of complications such as ICP changes are the best ways to ensure a good outcome for your patient in the prehospital realm.

Hospital Management

Hospital management for most instances of cocaine overdose or toxicity is largely conservative. Patients will be provided fluid resuscitation as needed, have a drug test performed in some instances, and be provided general supportive care. Benzodiazepines will be used for general anxiolysis and, for lack of a better word, simmering the patient down. Beta-blockers and antidysrhythmic agents will also be used to control heart rate and reduce the excessive beta-2 stimulation that cocaine provides.

Conclusion

Managing patients suffering from cocaine toxicity is an evolving challenge in both the prehospital and in-hospital realms. A combination of soft social skills to calm patients in addition to keen assessment skills is necessary to ensure that life threatening conditions are adequately recognized, avoided, and treated as they arise.

Did this article help you be a better provider or teach you something that you did not know before? Please let me know in the comments below and feel free to email with any questions you may have.

References

American Addiction Centers. (2022, December 16). How long does cocaine stay in your system? https://americanaddictioncenters.org/cocaine-treatment/how-long-in-system

Dominic, P., Ahmad, J., Awwab, H., Bhuiyan, M. S., Kevil, C. G., Goeders, N. E., Murnane, K. S., Patterson, J. C., Sandau, K. E., Gopinathannair, R., & Olshansky, B. (2022). Stimulant drugs of abuse and cardiac arrhythmias. Circulation: Arrhythmia and Electrophysiology, 15(1). https://doi.org/10.1161/circep.121.010273

Drug overdose death rates | National Institute on Drug Abuse. (2023, September 25). National Institute on Drug Abuse. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates#:~:text=The%20number%20of%20deaths%20involving%20cocaine%20has%20also%20increased%20steadily,in%202021%20(Figure%208).

Gangu, K., Bobba, A., Basida, S., Avula, S., Chela, H. K., & Singh, S. (2022). Trends of Cocaine use and Manifestations in Hospitalized Patients: A Cross-Sectional study. Cureus. https://doi.org/10.7759/cureus.22090

Greve, D., Funke, J., Khairi, T., Montagner, M., Starck, C., Falk, V., Sá, M. P. B. O., & Kurz, S. (2020). Cocaine-Related Aortic Dissection: what do we know? Brazilian Journal of Cardiovascular Surgery, 35(5). https://doi.org/10.21470/1678-9741-2020-0333

Lippmann, M., & Kakazu, C. (2007). Intubating ICU patients with ketamine. Chest, 132(6), 2054. https://doi.org/10.1378/chest.07-1113

McCord, J., Jneid, H., Hollander, J. E., De Lemos, J. A., Cercek, B., Hsue, P. Y., Gibler, W. B., Ohman, E. M., Drew, B. J., Philippides, G. J., & Newby, L. K. (2008). Management of Cocaine-Associated chest pain and myocardial infarction. Circulation, 117(14), 1897–1907. https://doi.org/10.1161/circulationaha.107.188950

Miller, J. (2024, March 8). Cocaine Statistics - Trusted stats for cocaine abuse and addiction. AddictionHelp.com. https://www.addictionhelp.com/cocaine/statistics/#:~:text=In%202011%2C%20there%20were%20505%2C224,are%20dangerous%20and%20potentially%20deadly.

Patel, N., Bhanushali, K., & Asnani, H. K. (2023). A sniff away from death: a rare case of Cocaine-Induced triple vessel coronary artery disease in a 41-Year-Old male patient. Cureus. https://doi.org/10.7759/cureus.40707

Pergolizzi, J. V., Breve, F., Magnusson, P., LeQuang, J. A., & Varrassi, G. (2022). Cocaethylene: when cocaine and alcohol are taken together. Cureus. https://doi.org/10.7759/cureus.22498

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Solano, J. (2021, September 21). EMS ketamine use on agitated patients on cocaine increases intubation 5.75-fold, study finds. ScienceDaily. https://www.sciencedaily.com/releases/2021/09/210929092628.htm

State Estimates of Past Year Cocaine Use among Young Adults: 2014 and 2015. (n.d.). https://www.samhsa.gov/data/sites/default/files/report_2736/ShortReport-2736.html