INTRODUCTION — Cocaine, purported to be the most potent stimulant of natural origin, is extracted from the leaves of the coca plant (Erythroxylum coca), which is indigenous to the Andean highlands of South America. Natives in this region chew or brew coca leaves into a tea for refreshment and to relieve fatigue, similar to the customs of chewing tobacco and drinking tea or coffee in other cultures.
Pure cocaine was first isolated in the 1880s and was first used as a local anesthetic in eye surgery. It was particularly useful in surgery of the nose and throat because of its ability to provide anesthesia and constrict blood vessels, thereby limiting bleeding. Cocaine was legal and widely used in the United States during the second half of the 19th century and was a main ingredient of the original Coca-Cola. Despite legislative attempts dating from the early 20th century to eradicate its use, cocaine remains a common and dangerous drug of abuse.
This topic review will discuss the basic pharmacology, clinical presentation, and management of acute cocaine intoxication. Treatment for chronic cocaine abuse, general management of acute drug overdose, and other aspects of drug abuse are discussed elsewhere. A summary table to facilitate emergency management is provided (table 1). (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse" and "Pulmonary complications of cocaine use" and "General approach to drug poisoning in adults".)
EPIDEMIOLOGY — Cocaine remains among one of the most common causes of acute drug-related emergency department visits in the United States. It accounts for more reports to the Drug Abuse Warning Network (DAWN) than marijuana, synthetic marijuana, or hashish the next leading causes . Death from unintentional cocaine overdose and cocaine-related violence occurs throughout the world [2-5]. The epidemiology of cocaine use, including morbidity and mortality, is reviewed in greater detail separately. (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis", section on 'Epidemiology'.)
PHARMACOLOGY — Cocaine is well-absorbed following contact with the oral, nasal, gastrointestinal, rectal, and vaginal mucosa, or via the pulmonary alveoli following inhalation. Cocaine's vasoconstrictive properties prolong the rate of absorption and delay its peak effect when absorbed from mucosal surfaces. The bioavailability of cocaine is approximately 90 percent when smoked and about 80 percent after intranasal use. Bioavailability is decreased when cocaine is ingested, though this is not well studied .
The alkaloidal form of cocaine is extracted from the coca leaf by mechanical degradation in the presence of a hydrocarbon solvent. The resultant product is converted into a hydrochloride salt and extracted into an aqueous phase, from which water is subsequently evaporated to yield a white powder (cocaine hydrochloride).
Smokeable cocaine is formed by dissolving the hydrochloride form of cocaine in water and adding a strong base. A hydrocarbon solvent is then added, the cocaine base is extracted into the organic phase, and the solvent then evaporated. "Free-basing" is a term used to refer to smoking or inhaling cocaine base following extraction and usually done on an individual basis. "Crack" is an analogous compound used in solid form that is produced on a commercial, though illegal, level.
KINETICS — A table summarizing the time of onset, time to peak action, and duration of action for various routes of exposure is provided (table 2). These parameters were determined in volunteers with a history of cocaine use, by administering cocaine via the various routes and measuring serum concentrations. The half-life of cocaine metabolites and their elimination times were noted .
●Metabolites – There are three major metabolites of cocaine: benzoylecgonine (BE) formed from spontaneous hydrolysis (>50 percent), ecgonine methyl ester (EME) formed from metabolism by plasma pseudocholinesterase (32 to 49 percent), and norcocaine formed from metabolism by the p450 system (N-demethylation) (5 percent) .
BE is a potent vasoconstrictor in vitro. BE and EME have poor blood-brain barrier penetration, so central neurologic effects are related to cocaine that enters the central nervous system prior to metabolism. EME is a vasodilator, sedative, and anticonvulsant, and is protective against lethal doses of cocaine [8-10]. In vitro, BE has minimal effect on cardiac sodium and potassium channels and in animal models it is virtually inactive . The metabolite anhydroecgonine methyl ester (AEME), or methylecgonine, is formed by pyrolysis (superheating) of cocaine. It has muscarinic receptor (M2) agonist properties that may contribute to bronchospasm.
A transesterification reaction between ethanol and cocaine produces a unique agent, benzoylmethylecgonine, also called cocaethylene or ethyl cocaine . In healthy volunteers given cocaine and ethanol, cocaethylene accounted for up to 17 percent of the metabolites . Cocaethylene has a long duration of action (up to 13 hours depending on the route of administration ), and like cocaine, is vasoconstrictive, cardiotoxic, dysrhythmogenic, and neurotoxic [15,16]. Cocaethylene is as potent as cocaine at inhibiting dopamine reuptake .
The serum concentration of cocaethylene varies by the route of administration of cocaine. Approximately 24 percent of cocaine is converted to cocaethylene when administration is intravenous (IV), 18 percent when the drug is insufflated and 34 percent when cocaine is used orally. The physiologic effects of cocaethylene typically outlast the effects that would have been observed if cocaine alone was used by any of the common routes of administration .
Cocaine's volume of distribution is about 2.7 L/kg, and it is about 90 percent protein bound. It is unclear whether these values change in overdose states . The serum half-life of cocaine is 0.5 to 1.5 hours. A minor amount is excreted unchanged in the urine . BE and EME are excreted in the urine, and have serum half-lives of 5 to 8 hours and 3.5 to 6 hours, respectively .
PATHOPHYSIOLOGY — Cocaine's effects occur primarily via three mechanisms, which are discussed below.
●Blockade of reuptake of biogenic amines – Cocaine is an indirect sympathomimetic agent, which increases the availability of biogenic amines at adrenergic receptors by blocking their presynaptic reuptake. These effects are described in neurons containing serotonin and catecholamines (ie, dopamine, norepinephrine, and epinephrine) [19,20].
Cocaine stimulates alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors through increased levels of norepinephrine, and to a lesser extent epinephrine. Cocaine has preferential alpha-receptor activity on the cardiac and peripheral vasculature and additional cardiac effects through beta-adrenergic agonism. The alpha-adrenergic agonist effects of norepinephrine cause vasoconstriction in both cardiac and peripheral vasculature.
The euphoric properties of cocaine derive from the inhibition of neuronal serotonin reuptake in the central nervous system, while addiction has been linked to effects on dopamine reuptake. In animal studies, effects on the dopamine-containing neuronal systems traveling from the limbic region to the frontal cortex are strongly associated with cocaine addiction .
●Sodium (Na+) channel blockade – Cocaine slows or blocks nerve conduction and acts as a local anesthetic by altering the recovery of the neuronal Na+ channels. Local anesthetics block conduction by decreasing or preventing the large transient increase in the permeability of excitable membranes to Na+ that normally is produced by a slight depolarization of the membrane. Cocaine has similar effects on cardiac Na+ channels and is able to slow Na+ current in cardiac myocytes. With severe overdose, these cardiac Na+ channel effects manifest on an electrocardiogram as prolongation of the QRS complex, and clinically as negative inotropy.
●Excitatory amino acid stimulation – Cocaine increases the concentration of the excitatory amino acids glutamate and aspartate in the brain, particularly in the nucleus accumbens . Glutamate is the main excitatory neurotransmitter of the central nervous system . Aspartate has similar actions, although its exact role as a neurotransmitter is not as well defined; it is only active at certain subtypes of glutamate receptors . Aspartate also serves as a precursor for glutamate.
CLINICAL MANIFESTATIONS — Cocaine produces a dose-dependent increase in heart rate and blood pressure accompanied by increased arousal, improved performance on tasks of vigilance and alertness, and a sense of self-confidence, euphoria, and well-being. Use is typically followed by a craving for more of the drug. Cocaine produces end-organ toxicity in virtually every organ system in the body, primarily through its hemodynamic effects.
Cardiovascular — Acute cocaine use is associated with arterial vasoconstriction and enhanced thrombus formation [25-27]. It causes tachycardia, hypertension, increased myocardial oxygen demand, and increased vascular shearing forces. Cocaine causes coronary vasoconstriction in a dose-dependent fashion and is associated with cardiac ischemia in 5 to 6 percent of patients with cocaine-related visits to the emergency department (ED) . At high blood concentrations, cocaine's negative inotropic effects may cause acute depression of left ventricular function and heart failure . Cocaine can cause supraventricular and ventricular dysrhythmias through direct actions at myocardial receptors or as a complication of myocardial ischemia. Aortic dissection and rupture occur rarely after cocaine use . (See 'Pathophysiology' above.)
Chronic cocaine use can cause accelerated atherogenesis [31,32] and left ventricular hypertrophy, which increase the risk of myocardial ischemia or infarction, and can lead to dilated cardiomyopathy. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
Central nervous system — Cocaine can cause a variety of central nervous system (CNS) complications including psychomotor agitation, seizures, coma, headache, intracranial hemorrhage, and focal neurologic symptoms . Cocaine-induced psychomotor agitation can cause hyperthermia when peripheral vasoconstriction prevents the body from dissipating the heat being generated from persistent agitation. Mortality can be as high as 33 percent when hyperthermia develops in the setting of cocaine intoxication .
Psychomotor agitation occurs via several mechanisms. Cocaine causes an increase in the CNS excitatory amino acids glutamate and aspartate, and release of the excitatory neurotransmitters norepinephrine, serotonin, and dopamine. The hyperthermia seen in cocaine-intoxicated patients is directly related to the extent of their psychomotor agitation and the ambient temperature . (See 'Pathophysiology' above.)
Seizures occur in approximately 3 to 4 percent of cocaine-related ED visits following acute or chronic use [29,34]. Seizures may occur after large doses in patients without an underlying seizure focus .
Cocaine is associated with both focal neurologic deficits and coma. Possible etiologies include vasoconstriction (ie, transient ischemic attack or ischemic stroke) and intracerebral hemorrhage. Numerous reports describe patients with subarachnoid, intraventricular, and intraparenchymal bleeding associated with cocaine use [35-38]. Other neurologic complications, such as paralysis from vasospasm-induced anterior spinal cord syndrome, occur rarely .
Headaches occur often and are likely due to neurotransmitter dysregulation or hemodynamic alterations [15,39]. Occipital or bilateral headaches that begin immediately after use and persist up to 48 hours can develop in individuals who use cocaine intravenously (IV), while throbbing frontal headaches can develop in individuals who use cocaine intranasally. Individuals who smoke crack cocaine can develop either type. Headaches are often accompanied by nausea and vomiting.
Cocaine may cause psychotic symptoms, possibly including paranoia, delusions, or hallucinations, which may resemble the positive symptoms of schizophrenia. Cocaine-related psychosis is discussed separately. (See "Cocaine use disorder: Epidemiology, clinical features, and diagnosis", section on 'Psychiatric effects'.)
Pulmonary — Crack cocaine requires high temperatures to be vaporized and smoked. Angioedema and pharyngeal burns can occur when crack cocaine is smoked. Injury to the upper and lower airway occurs primarily from inhalation of heated fumes and is not a direct toxic effect of the drug. Alveolar hemorrhage can result. The pulmonary complications of cocaine use are reviewed in greater detail separately. (See "Pulmonary complications of cocaine use".)
Intranasal and inhalational cocaine use is associated with pneumothorax, pneumomediastinum, and pneumopericardium [40-42]. These complications result from the Valsalva maneuver applied by the user to avoid exhaling the drug.
Cocaine is associated with exacerbations of reversible airway disease and bronchospasm [43-45]. Crack lung can also cause shortness of breath.
Cocaine use is associated with vasoconstriction , vasospasm, and enhanced thrombus formation . This predisposes patients who use cocaine to pulmonary infarction. Patients with this complication usually present with shortness of breath and pleuritic chest pain, as well as the other findings that may be confused with pulmonary embolism [46,47]. It is not known whether the risk of pulmonary embolism is increased among cocaine abusers.
Gastrointestinal and renal — Cocaine users have a disproportionate incidence of perforated ulcers. Possible mechanisms include increased sympathetic tone causing increased gastric acid production or local ischemia in the gastrointestinal tract [48-50]. Cocaine is also implicated in cases of ischemic colitis, intestinal infarction, and metabolic acidosis. Patients presenting with signs and symptoms of bowel obstruction may be engaged in body packing . (See 'Body packers and stuffers' below.)
Although less common, infarction of the spleen or kidney can occur from cocaine use [51,52]. In cocaine users, minor abnormalities of liver enzymes are common and rarely associated with symptoms . More severe hepatic failure can be seen following hyperthermia due to psychomotor agitation. (See 'Central nervous system' above.)
Other organ systems and complications
●Musculoskeletal – Patients with cocaine toxicity can present with a spectrum of musculoskeletal concerns. Signs can range from mild creatine phosphokinase and myoglobin elevation to electrolyte alterations (hyperkalemia, hypocalcemia) seen with rhabdomyolysis. Patients can demonstrate a range of complications from localized or diffuse muscle pain to frank compartment syndrome [15,54]. Patients with severe rhabdomyolysis may have a lactic acidosis, life-threatening hyperkalemia, and acute kidney injury. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)", section on 'Treatment'.)
●Ophthalmologic – Sympathetic stimulation causes mydriasis through activation of the dilator fibers of the iris. The pupil usually maintains its ability to constrict to light. Cocaine, like other mydriatic agents, can cause acute angle-closure glaucoma, and vasospasm of the retinal vessels can produce unilateral or bilateral vision loss [55,56]. Patients who smoke crack cocaine may develop mydriasis (unilateral or bilateral), suffer corneal epithelial destruction, or singe their eyebrows and lashes (madarosis) due to heat or direct topical effects [15,57].
●Pregnancy (pre and postnatal exposure) – Chronic cocaine use during pregnancy is associated with problems in fetal development . Acute cocaine exposure in pregnancy is associated with abruptio placentae . The effects of in-utero cocaine exposure are discussed more extensively elsewhere. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Opioids' and "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Clinical features and diagnosis", section on 'Cocaine'.)
●Passive cocaine exposure – Children and elderly patients can present with signs and symptoms of cocaine intoxication and/or complications of cocaine exposure by proximity to users of inhalational cocaine. Cocaine exposure can also occur via ingestion of cocaine or crack, typically when cocaine is left within a child's reach. The incidence of unintentional cocaine exposure may be as high as 5 percent among all children presenting to urban EDs . (See 'Pediatric considerations' below.)
●Hematologic and other effects of adulterants ‒ Levamisole, an immunomodulator, has been found in cocaine and can cause agranulocytosis, leukoencephalopathy, and cutaneous vasculitis, possible leading to cutaneous necrosis. Clenbuterol, another adulterant, can cause tachycardia, hyperglycemia, palpitations, and hypokalemia. (See 'Adulterants and their effects' below.)
ADULTERANTS AND THEIR EFFECTS
Levamisole — Levamisole is a common adulterant of cocaine that can cause agranulocytosis, leukoencephalopathy, or cutaneous vasculitis, possibly leading to cutaneous necrosis [61-67]. (See "Drug-induced neutropenia and agranulocytosis", section on 'Cocaine and heroin' and "Approach to the patient with retiform (angulated) purpura", section on 'Other'.)
A review of published cases of levamisole-related toxicity noted that 52 percent of these patients presented with oropharyngeal complaints, while 27 percent presented with soft tissue infections or purpura [68-70]. Exposure to cocaine adulterated with levamisole should be suspected in patients with these entities or complaints. Levamisole was used as an adjuvant treatment for colon cancer and an immunomodulator for various conditions and is now used primarily in veterinary practice as an anthelminthic agent . A small case series describes an association between levamisole and hyponatremia, but this phenomenon has yet to be formally studied .
The United States Drug Enforcement Agency first noted levamisole mixed with cocaine in 2003 and beginning in 2008 investigators in New Mexico reported that some patients who had been exposed to cocaine were developing agranulocytosis (confirmed by bone marrow histopathology). In 2008, levamisole was found in about 44 percent of seized cocaine, and by 2009, this amount rose to 69 to 73 percent . In 2010, investigators in Colorado found that 78 percent of patients with a urine drug screen positive for cocaine also tested positive for levamisole . In Europe and around the world, levamisole is widely used as a cutting agent for cocaine [73,74].
Clenbuterol — Clenbuterol, a beta adrenergic agonist, has been found as an adulterant in cocaine and heroin. It can cause hyperglycemia and hypokalemia.
In early 2005, cases were reported in the northeastern and southern United States describing a number of patients with atypical presentations following heroin or cocaine use . The most common findings were tachycardia (89 percent), hyperglycemia (78 percent), palpitations (78 percent), and hypokalemia (78 percent). In one case series, 67 percent of the patients had all four findings. Other common findings included nausea, hypotension, chest pain, venous hyperoxia, lactic acidosis, agitation, and anxiety. Investigators attributed these symptoms to the heroin and cocaine supply being adulterated with clenbuterol.
Fentanyl — Fentanyl is increasingly found as an adulterant of cocaine [76,77] and crack cocaine [78,79], leading to life-threatening opioid poisoning in many cases. In a recent cluster, 18 patients, primarily middle-aged men without a history of prior opioid use, presented with an opioid toxidrome (ie, lethargy, respiratory depression, and pinpoint pupils) following cocaine use . Most patients responded to naloxone; three patients died. Testing confirmed cocaine use in 16 patients and fentanyl exposure in 15. Investigation could not determine whether fentanyl adulteration was intentional or incidental. (See "Acute opioid intoxication in adults", section on 'Fentanyl and fentanyl analogs'.)
DIFFERENTIAL DIAGNOSIS — Psychomotor agitation is a common, important feature of many overdose and disease states, including:
●Synthetic cathinone abuse
●Synthetic cannabinoid abuse
●Hypoxia (see "Measures of oxygenation and mechanisms of hypoxemia")
●Alcohol and sedative-hypnotic withdrawal syndromes (see "Management of moderate and severe alcohol withdrawal syndromes")
●Serotonin syndrome (see "Serotonin syndrome (serotonin toxicity)")
●Neuroleptic malignant syndrome (see "Neuroleptic malignant syndrome")
●Heat-related illness (see "Severe nonexertional hyperthermia (classic heat stroke) in adults")
●Thyroid storm (see "Thyroid storm")
●Subarachnoid hemorrhage (see "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis")
●Infections of the central nervous system (ie, meningitis and encephalitis) (see "Clinical features and diagnosis of acute bacterial meningitis in adults")
●Seizures (see "Overview of the management of epilepsy in adults").
●Several psychiatric diseases
The majority of these diagnoses are determined from the patient's medical history. A review of the patient's medications and a detailed account of their substance abuse preferences through family, friends, and first responders, may provide valuable clues. Diagnostic testing may include computed tomography (CT) scan of the head and lumbar puncture as appropriate. We discourage indiscriminate drug testing as a means to differentiate diagnostic possibilities because of the high rate of clinically false positive results and adulterants that may be misleading. (See "General approach to drug poisoning in adults" and "Testing for drugs of abuse (DOAs)".)
Other diagnostic possibilities include cardiopulmonary disease, such as acute coronary syndrome, pulmonary embolus, aortic dissection, and pneumothorax. These diagnoses are generally identified through standard tests such as an electrocardiogram, chest radiograph, echocardiography, chest CT, or cardiac biomarkers. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Overview of acute pulmonary embolism in adults" and "Clinical features and diagnosis of acute aortic dissection" and "Pneumothorax in adults: Epidemiology and etiology".)
In most situations, general supportive care with sedation, cooling, and intravenous (IV) fluids is appropriate while diagnostic testing is performed.
LABORATORY AND RADIOGRAPHIC EVALUATION
●General testing – Routine laboratory evaluation in the potentially poisoned patient should include the following:
•Fingerstick glucose, to rule out hypoglycemia as the cause of any alteration in mental status
•Acetaminophen and salicylate levels, to rule out these common coingestants if the circumstances suggest self-harm
•Electrocardiogram (ECG), to rule out conduction system poisoning by drugs that effect the QRS or QTc intervals; cocaine can cause ECG changes due to its sodium channel effects or from ischemia
•Pregnancy test in women of childbearing age
●Specific testing – Benzoylecgonine (BE), the major urinary metabolite of cocaine, is the analyte usually tested for in blood, urine, saliva, hair, and meconium. Cocaine is rapidly metabolized and detectable in blood and urine only briefly (ie, several hours) after use. BE can be detected in the urine for several days following intermittent use and up to 10 days or more after heavy use.
Although the assay for BE is highly accurate, false negatives may occur, albeit rarely. A drug assay "positive for cocaine" does not necessarily connote acute cocaine use due to BE's prolonged presence. BE is not a psychostimulant and can cause a clinical false positive result (ie, patient's symptoms are mistakenly attributed to acute cocaine intoxication). Analytical false positives are rare, as xenobiotics are not inappropriately detected by the BE immunoassay. Should test results and clinical findings be inconsistent, clinicians should discuss the matter with their laboratory director to determine what xenobiotics may have caused false results. Gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry is the gold standard for testing for cocaine and its metabolites. This usually requires that the specimen be sent to a specialized laboratory.
Radiographs can play a role in the detection of body stuffing and packing. (See 'Body packers and stuffers' below.)
Additional laboratory and radiographic testing can be helpful depending on the clinical setting. As examples, a troponin, creatine kinase, ECG, and chest radiograph are obtained in a patient with chest pain, creatine kinase and urine myoglobin are obtained in a patient at risk for rhabdomyolysis, and a CT of the head, followed by cerebrospinal fluid analysis if the CT is nondiagnostic, is obtained in a patient with symptoms concerning for intracranial hemorrhage.
INITIAL MANAGEMENT — General management of the overdose patient is discussed elsewhere (see "General approach to drug poisoning in adults"). Specific management strategies for cocaine overdose are discussed below. A summary table to facilitate emergency management is provided (table 1). The management of myocardial infarction diagnosed in the setting of cocaine intoxication is reviewed elsewhere. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
Airway and breathing — Supplemental oxygen should be administered only as needed. If rapid sequence tracheal intubation is necessary, we suggest that succinylcholine not be used. Plasma cholinesterase (PChE) metabolizes both succinylcholine and cocaine, and coadministration of succinylcholine can prolong the effects of cocaine and the paralysis from succinylcholine . In the setting of rhabdomyolysis and hyperthermia, succinylcholine may worsen hyperkalemia and cause life-threatening arrhythmias .
We suggest using a nondepolarizing neuromuscular blocker, such as rocuronium, if paralysis is indicated. Acceptable induction agents in cocaine-intoxicated patients include: benzodiazepines, etomidate, or propofol. (See "Rapid sequence intubation in adults for emergency medicine and critical care" and "Rapid sequence intubation (RSI) in children for emergency medicine: Approach".)
Approach to management — Most cardiovascular stimulation from cocaine is centrally mediated via the sympathetic nervous system. As such, sedation with a benzodiazepine, using an appropriate dose and route of administration, is first-line therapy for cardiovascular complications stemming from acute cocaine intoxication. Benzodiazepine therapy is generally sufficient to alleviate cardiovascular symptoms and signs. The dosing of benzodiazepines used for psychomotor agitation is described below, and such dosing is appropriate for the treatment of cardiovascular symptoms and signs. (See 'Psychomotor agitation' below.)
In patients with refractory or symptomatic cocaine-induced hypertension, phentolamine can be used to counteract the alpha-adrenergic vasoconstrictive effects of cocaine (caused by norepinephrine release). However, the use of alpha-adrenoceptor blocking agents, such as phentolamine, may cause an increase in heart rate . Suitable alternative medications for the management of refractory hypertension include vasodilators without beta blocking effects, such as nitroglycerin or nitroprusside. Phentolamine is given as an intravenous (IV) bolus. The usual dose is 5 to 15 mg IV every 5 to 15 minutes as necessary. We prefer to start with lower doses and titrate to the desired blood pressure.
We recommend that beta-adrenergic antagonists (ie, beta-blockers), including mixed alpha/beta blockers such as labetalol and carvedilol, not be used for cardiovascular complications associated with acute cocaine intoxication. The use of beta blockers and chest pain associated with cocaine intoxication are discussed further below. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse" and 'Use of beta adrenergic antagonists (beta blockers)' below and 'Chest pain' below.)
Hypertensive emergencies can be seen in the setting of acute cocaine intoxication and are usually defined as an elevated blood pressure associated with end-organ damage. There are no treatment goals specifically defined for cocaine-related hypertensive emergencies, but the initial aim of treatment in general hypertensive crises is to lower the diastolic pressure rapidly to about 100 to 105 mmHg; this goal should be achieved within 2 to 6 hours, with the maximum initial fall in mean arterial blood pressure not exceeding 25 percent of the presenting value. Cocaine-related hypertension should be treated judiciously given its usually self-limited nature (hypertension generally resolves when cocaine is metabolized) and the importance of avoiding hypotension. Treatment with benzodiazepines, possibly in conjunction with the medications discussed above (phentolamine, nitroglycerin, or nitroprusside), is sufficient in most cases. Hypertensive emergencies are discussed separately. (See "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults", section on 'Goal of therapy' and "Evaluation and treatment of hypertensive emergencies in adults".)
If a patient no longer appears acutely agitated and other signs of sympathetic excess (eg, tachycardia, diaphoresis) have resolved, but significant hypertension persists, acute cocaine exposure is unlikely to be the cause. In such cases, hypertension should be managed based upon the patient’s medical comorbidities and clinical status.
Cocaine toxicity usually causes hypertension, but massive toxicity may result in hypotension due to myocardial sodium-channel blockade, cardiac dysrhythmias, or cardiac ischemia. Patients with hypotension should be treated with IV isotonic saline. If hypotension persists after 2 to 3 L of rapidly infused isotonic saline, direct-acting vasopressors such as norepinephrine or phenylephrine can be given and titrated to effect. An electrocardiogram (ECG) should be obtained, and if there are signs of QRS widening (suggesting sodium channel blockade), hypertonic sodium bicarbonate should be administered at a dose of 1 to 2 mEq/kg by bolus via a large bore IV. A repeat ECG should be obtained to evaluate whether QRS narrowing has occurred in response to treatment. (See "Tricyclic antidepressant poisoning", section on 'Sodium bicarbonate for cardiac toxicity'.)
Management of patients suspected to be body packers or stuffers is discussed briefly below and in detail separately. (See 'Body packers and stuffers' below and "Internal concealment of drugs of abuse (body packing)".)
Use of beta adrenergic antagonists (beta blockers) — We recommend that beta-blockers not be used to treat cardiovascular complications, particularly myocardial ischemia, in patients with acute cocaine intoxication. This proscription in the acute setting is based principally upon concerns of coronary artery vasoconstriction and systemic hypertension, which can result from unopposed alpha-adrenergic stimulation. Details pertaining specifically to the issue of beta blockers therapy in the setting of cocaine use, and more generally to the diagnosis and management of the cardiovascular complications of cocaine use, are reviewed separately. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
Note that labetolol (a mixed alpha/beta antagonist with predominantly beta-blocking effects) is included among the medications proscribed, although several articles suggest that mixed alpha/beta blockers, including labetalol and carvedilol, may be safe and effective in these patients [81-83]. We acknowledge that available evidence pertaining directly to this clinical scenario is weak [80,84,85]. The data are even less clear for patients with cocaine-related chest pain or acute coronary syndrome who are not manifesting signs of acute cocaine toxicity.
We believe, based on the available evidence and our clinical experience, that optimal therapy for patients experiencing cardiovascular complications in the setting of acute cocaine intoxication begins with reduction in central nervous system catecholamine release, rather than peripheral antagonism of released catecholamines, and that benzodiazepines have a proven role in this regard [86,87]. (See 'Psychomotor agitation' below.)
Nevertheless, due to increasing evidence of safety , some clinicians may choose to give beta blockers as part of their management of acute cocaine-related cardiovascular complications. Should beta blockade be performed in this setting, it should be done cautiously, ideally in combination with an alpha antagonist or some other vasodilator without beta blocking effects (eg, nitroglycerin or nitroprusside), and under close observation, including frequent measurements of vital signs and serial ECGs. The general use of beta blockers in the settings of acute coronary syndrome and coronary heart disease is reviewed separately, as is the detailed management of cardiovascular complications from cocaine abuse. (See "Acute myocardial infarction: Role of beta blocker therapy" and "Beta blockers in the management of chronic coronary syndrome" and "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
Psychomotor agitation — Agitated patients are sedated as needed with benzodiazepines, after ensuring they are not hypoglycemic or hypoxic. We suggest diazepam be given in an initial dose of 10 mg IV, then 5 to 10 mg IV every 3 to 5 minutes until agitation is controlled. Monitor patients for respiratory depression and hypotension. Intramuscular lorazepam or midazolam can be used if IV access is unavailable, but their peak effect is typically delayed (10 to 20 minutes).
Hyperthermic patients should be cooled rapidly, optimally in 30 minutes or less, to a goal core body temperature of <102°F. Immersion in ice or ice water is the most rapid cooling method for severely hyperthermic patients; cooling via evaporative spray may be sufficient in moderately hyperthermic patients [89-91]. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)
Gastrointestinal decontamination — Since the popular methods of cocaine use are nonenteral (ie, inhalational, IV, and intranasal), the majority of patients who present with cocaine intoxication will not require gastrointestinal decontamination . Decontamination should be performed, if required, by removing any cocaine powder from nares, mouth, or oropharynx. Gentle nasal irrigation with 0.9 percent (isotonic) saline could be used if the patient presents with a visible white powder presumed to be cocaine . Activated charcoal reduces the lethality of oral cocaine . The dose of activated charcoal is 1 g per kg body weight (up to 50 g) and should be administered by mouth every 4 hours for several doses. Body packing and stuffing is discussed elsewhere. (See "Internal concealment of drugs of abuse (body packing)".)
Chest pain — Cocaine-associated chest pain (CACP) accounts for a sizeable portion of cocaine-related visits to the emergency department. Acutely, cocaine causes vasoconstriction and enhances thrombus formation, increasing the risk of myocardial ischemia. Up to 6 percent of patients presenting with CACP manifest elevations in biomarkers or other signs (eg, electrocardiogram [ECG] findings) consistent with myocardial injury. The epidemiology, presentation, and management of myocardial ischemia and other cardiovascular complications diagnosed in the setting of cocaine intoxication is reviewed in detail separately. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse".)
Although acute coronary syndrome remains an important concern, ED clinicians should avoid prematurely discounting alternative diagnoses in patients with CACP but no clear evidence of myocardial infarction. Pneumothorax and crack lung can present as chest pain following cocaine use. Other potential complications include aortic dissection, myocarditis, and arrhythmia. Complications can develop regardless of the form of cocaine use (eg, smoking, intravenous [IV], intranasal). (See 'Crack lung and other pulmonary complications' below and "Clinical features and diagnosis of acute aortic dissection" and "Clinical manifestations and diagnosis of myocarditis in adults".)
Symptoms associated with myocardial ischemia from acute cocaine use are indistinguishable from those associated with other cases. According to one retrospective cohort study, patients with CACP most commonly complain of: substernal chest pain (76 percent), shortness of breath (62 percent), tightness/pressure/squeezing (55 percent), and diaphoresis (48 percent) .
Evaluation of patients with CACP pain includes serial ECGs, plain chest radiograph, and biomarkers to exclude myocardial infarction. Two prospective observational studies suggest the ECG has limited accuracy in the setting of CACP, and ECG evidence of ischemia or infarction may not correlate with myocardial infarction, as diagnosed by an elevation in cardiac biomarkers [28,94]. According to these studies, the sensitivity and specificity of the ECG are approximately 36 and 90 percent respectively. However, the number of patients diagnosed with myocardial infarction in each study was small so the accuracy of the ECG in CACP remains unclear.
Early management of patients with CACP includes the administration of oxygen as necessary to maintain SpO2 ≥93 and reduction of sympathetic outflow using benzodiazepines given IV. We suggest benzodiazepines be given to patients who are anxious, agitated, hypertensive, or tachycardic; we suggest nitroglycerin be given in addition to patients with hypertension. We give diazepam (5 mg IV every 3 to 5 minutes) or lorazepam (1 mg IV every 5 to 10 minutes) until sedation is achieved. We give nitroglycerin 0.4 mg sublingual every 5 minutes as needed for a maximum of three doses. If additional nitroglycerin is needed, an infusion can be started with the dose titrated to effect.
The pharmacologic treatment of patients with CACP differs in several important ways from the standard treatment of myocardial ischemia from atherosclerotic coronary artery disease. Beta blockers are generally not recommended in patients who have recently used cocaine (<24 hours), and in patients with CACP, although evidence is limited. Beta blockers may lead to unopposed alpha adrenergic stimulation, which can cause coronary arterial vasoconstriction, ischemia, and infarction. The use of beta blockers and other treatments for acute coronary syndrome in the setting of cocaine use is discussed separately. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse", section on 'Treatment of cocaine-related myocardial ischemia/infarction'.)
Aspirin is contraindicated in patients suspected of having an aortic dissection, but can be given at standard doses to patients with CACP when myocardial ischemia is the suspected cause.
Phentolamine, an alpha-adrenergic antagonist, can be used to reduce cocaine-induced coronary artery vasoconstriction when managing CACP or hypertension that is unresponsive to benzodiazepines and nitroglycerin [25,95-98]. Phentolamine is given as an IV bolus of 1 to 2.5 mg every 5 to 15 minutes as necessary. (See 'Cardiovascular complications' above and 'Psychomotor agitation' above.)
In one prospective observational study, adult patients with no history of cocaine use were given a low dose (2 mg/kg) of intranasal cocaine while undergoing cardiac catheterization . Cocaine caused an increase in heart rate, blood pressure, and coronary vascular resistance, and narrowing of the coronary artery diameter by 13 percent. Coronary artery diameter returned to baseline with the administration of phentolamine.
Crack lung and other pulmonary complications — Several potentially severe pulmonary complications can occur from cocaine use, primarily smoking, including crack lung, eosinophilic pneumonia, pneumothorax and pneumomediastinum, alveolar hemorrhage, and chronic lung disease. The pulmonary complications of cocaine use are reviewed in detail separately. (See "Pulmonary complications of cocaine use".)
Crack lung is a syndrome of hemorrhagic alveolitis from inhalational cocaine use. Cough and shortness of breath are common presenting symptoms. Additional signs and symptoms may include: acute lung injury, hypoxia, chest pain, hemoptysis, fever, focal infiltrates, and bronchospasm. A chest radiograph and a history of cocaine use provide the basis for diagnosis.
Initial management includes maintenance of oxygenation, ventilation, and symptomatic care. Patients with airway compromise may require endotracheal intubation. Succinylcholine should not be used. (See 'Airway and breathing' above.)
Body packers and stuffers — The term "body packer" is used to refer to persons who swallow large quantities of prepackaged drugs with the intention of smuggling these drugs across international borders. Body packers have been called swallowers, internal carriers, couriers, or mules. Body stuffers are persons who swallow relatively small quantities of drugs in poorly constructed packets (usually in haste) to avoid repercussions from law enforcement agents. The presentation and management of body packers and body stuffers are discussed in detail separately. (See "Internal concealment of drugs of abuse (body packing)" and "Acute ingestion of illicit drugs (body stuffing)".)
Body packers with symptoms of acute cocaine intoxication (eg, tachycardia, hypertension, hyperthermia, agitation, seizures, or cardiac dysrhythmias) often develop life-threatening complications. The majority who sustain adverse outcomes have symptoms at presentation or within the first few hours. Management begins with stabilization of the airway, breathing, and circulation, and may involve gastrointestinal decontamination with either activated charcoal or whole bowel irrigation or both. Immediate surgical intervention to remove drug packets can be required. (See "Internal concealment of drugs of abuse (body packing)", section on 'Sympathomimetic (cocaine or amphetamine) toxicity'.)
Presentation — Children can present with signs and symptoms of cocaine intoxication or complications of cocaine exposure from being around adults who use cocaine [60,99-101]. Unintentional cocaine exposure in children may occur from passive inhalation of free-base cocaine vapors or ingestion. The incidence of unintentional cocaine exposure among all children treated in the emergency department may be as high as 6 percent, particularly in urban settings [60,100,102].
Observational data suggests that passive exposure to cocaine may manifest as more frequent respiratory symptoms in infants, with and without fever , and more frequent generalized and focal seizures in children below eight years [99,101,103]. Clinical findings in older children are similar to adults.
Fetal exposure to cocaine is discussed separately. (See "Substance use during pregnancy: Overview of selected drugs", section on 'Cocaine' and "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Clinical features and diagnosis", section on 'Cocaine'.)
Specific management — There are no special decontamination procedures in children who are exposed to cocaine. Management of children exposed to crack cocaine fumes or cocaine residue is symptomatic. In rare circumstances, children have been used to smuggle drugs from foreign countries by making them swallow packets of cocaine. (See 'Body packers and stuffers' above.)
Cocaine-exposed children may need to be admitted to the hospital. Social work and/or child protective services must be notified. The involvement of local law enforcement authorities follows local practices.
Decontamination — Gastrointestinal decontamination is rarely needed for patients with cocaine intoxication. Should it be needed, dosing and other information is provided separately. (See "Gastrointestinal decontamination of the poisoned patient".)
DISPOSITION — Patients with severe complications of cocaine abuse are managed as described above and admitted to the hospital at the appropriate level of care. (See 'Initial management' above.)
In general, patients who present with acute findings from cocaine toxicity that resolve are observed for 6 to 8 hours. Patients who have returned to their baseline level of function can generally be discharged after this period with appropriate referrals.
Patients who present with cocaine-associated chest pain (CACP) are observed for 8 to 12 hours while cardiac biomarkers and serial electrocardiograms (ECGs) are obtained. This assumes the patient is pain-free, or rapidly made pain-free, and has a normal initial ECG. Cardiac biomarkers are typically performed 8 to 12 hours apart. Although this is not the standard approach to the management of patients with suspected acute coronary syndromes (ACS) unrelated to cocaine, the incidence of myocardial infarction in patients with CACP is extremely low (approximately 6 percent in one study) [28,104-107]. For patients with CACP at low risk for ACS, observation in a chest pain unit is reasonable.
The results of an observational study of 59 patients with CACP at low risk for ACS suggest that such patients can be discharged safely after nonischemic ECGs, normal cardiac biomarkers, and a negative coronary computerized tomography angiography (CTA) study . However, further research is needed before such an approach can be recommended.
Patients in whom cocaine use is not the sole risk factor for ACS or who have a moderate or high score on a validated cardiac risk assessment (eg, HEART or TIMI risk score) should be evaluated like any patient presenting to the emergency department with a possible ACS. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
Patients who present with psychomotor agitation, hyperthermia, or other neurological complications of cocaine toxicity may require admission for monitoring and management of sequelae. If after 6 to 8 hours of observation their symptoms are completely resolved, they are awake, alert, and ambulate without difficulty, and their reexamination reveals no concerning findings, they may discharged.
Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Stimulant use disorder and withdrawal" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use" and "Society guideline links: Cocaine use and cocaine use disorder".)
SUMMARY AND RECOMMENDATIONS
●Clinical manifestations – Cocaine can produce end-organ toxicity in virtually every organ system primarily through hemodynamic effects. Potential effects include hypertension, arterial vasoconstriction (eg, coronary arteries), thrombus formation, psychomotor agitation (neurologic effects range from agitation to seizures to intracranial hemorrhage), severe hyperthermia, dyspnea (from pneumothorax, pulmonary infarction, or other pulmonary injury), and ischemic bowel. (See 'Clinical manifestations' above.)
●Differential diagnosis – Numerous drugs and disease states can mimic the cardiovascular effects and/or psychomotor agitation of acute cocaine overdose. A thorough history, including medications and preferred drugs of abuse, is often the key to diagnosis. (See 'Differential diagnosis' above.)
●Drug testing – Benzoylecgonine (BE), the major urinary metabolite of cocaine, is the analyte usually tested for. Cocaine is rapidly metabolized and detectable in blood and urine only briefly (ie, several hours). BE can be detected in the urine for several days following intermittent use and up to 10 days or more after heavy use. Therefore, a drug assay "positive for cocaine" does not necessarily connote acute use. (See 'Laboratory and radiographic evaluation' above.)
●Emergency management – A summary table to facilitate emergency management is provided (table 1). If rapid sequence tracheal intubation (RSI) is necessary, we suggest that succinylcholine not be used because it can prolong the effects of cocaine and cause other complications (Grade 2C). A nondepolarizing neuromuscular blocker (eg, rocuronium) is preferred. Acceptable induction agents include benzodiazepines, etomidate, or propofol. (See 'Airway and breathing' above.)
●Cardiovascular effects – Most cardiovascular stimulation from cocaine is centrally mediated via the sympathetic nervous system. We suggest initial treatment with a benzodiazepine, using an appropriate dose and route to alleviate cardiovascular symptoms (Grade 2C). Suitable dosing is described above (see 'Psychomotor agitation' above).
In patients with severe, refractory, or symptomatic cocaine-induced hypertension, we suggest phentolamine be used to counteract the alpha-adrenergic effects of cocaine (Grade 2C). Phentolamine is given as an intravenous (IV) bolus. The usual dose is 5 to 15 mg every 5 to 15 minutes as necessary; we prefer to start with low doses and titrate to effect.
We recommend that beta blockers, including labetalol, not be used in patients with acute cocaine toxicity because of the risk of cardiovascular complications from unopposed alpha-adrenergic stimulation (Grade 1C). (See 'Cardiovascular complications' above.)
●Agitation – It is important to rule out hypoglycemia and hypoxia as the causes of psychomotor agitation. For cocaine-induced agitation, we suggest treatment with benzodiazepines (eg, diazepam 5 to 10 mg IV every 3 to 5 minutes until agitation is controlled) (Grade 2C). (See 'Psychomotor agitation' above.)
●Cocaine-associated chest pain – Chest pain is a common presentation of acute cocaine intoxication, but myocardial infarction is uncommon. Early management includes the administration of oxygen and reduction of sympathetic outflow using benzodiazepines. We suggest benzodiazepines be given to patients who are anxious, agitated, hypertensive, or tachycardic (Grade 2C). We give diazepam 5 mg every 3 to 5 minutes or lorazepam 1 mg every 5 to 10 minutes as an IV dose until sedation is achieved. We suggest nitroglycerin be given (in addition to a benzodiazepine) to patients with chest pain and hypertension (Grade 2C). Beta blockers are contraindicated in the setting of acute cocaine intoxication. (See 'Chest pain' above and 'Cardiovascular complications' above and 'Use of beta adrenergic antagonists (beta blockers)' above.)
●Crack lung – Crack lung is a syndrome of hemorrhagic alveolitis from inhalational cocaine use. Cough and shortness of breath are common presenting symptoms. Patients with airway compromise may require tracheal intubation. (See 'Crack lung and other pulmonary complications' above.)
●Pediatric considerations – Passive exposure to cocaine may cause more frequent respiratory symptoms in infants, with and without fever, and more frequent generalized and focal seizures in children below eight years. Clinical findings in older children are similar to adults. There are no special decontamination procedures in children. Fetal exposure to cocaine is discussed separately. (See 'Pediatric considerations' above and "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Clinical features and diagnosis", section on 'Cocaine'.)
●Disposition – Disposition strategies are discussed above. Body packers and stuffers are discussed in detail separately. (See 'Disposition' above and "Internal concealment of drugs of abuse (body packing)".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stephen J Traub, MD, former section editor of the toxicology program, for 20 years of dedicated service.
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