Cocaine Toxicity in Emergency Medicine Treatment & Management

Establish the patient's airway, breathing, and circulation (ABCs); provide oxygen; obtain intravenous access; monitor and frequently check vital signs including temperature; monitor glucose levels for patients with altered mental status; carefully use naloxone for patients with altered mental status.

Administer benzodiazepines to manage seizures.

Patients with cocaine toxicity may be combative, aggressive, and disoriented, and have delusions of persecution or hallucinations. Caution is appropriate because the patient may attempt to harm care providers. Physical restraint should be avoided if possible due to risks of rhabdomyolysis and hyperthermia. When required, physical restraint should be used only with caution and adequate personnel.

Data of DAWN-reporting EDs may provide an impression of the degree of physiologic derangement in cocaine-toxic patients presenting to EDs. Past reports indicated that 52.2% of patients presenting to EDs with cocaine toxicity were treated and released, 44.2% were admitted, and 2.2% left against medical advice. The mortality rate was 0.3%.

Patients with cocaine toxicity should receive initial evaluation and stabilization including attention to ABCs, oxygen, intravenous access, and cardiac and pulse oximetry monitoring.

Temperature of a hyperthermic patient may continue to rise secondary to agitation and potentially to fighting of restraints. Temperature may reach critical levels; thus, close monitoring and early intervention is indicated.

Remove residual cocaine from nares.

Monitor for hypoglycemia, which may present as any neuropsychiatric abnormality.

Never base treatment on the results of a drug screen; rely on clinical findings instead.

Provide reassurance.

Avoid physical restraints if possible. Benzodiazepines are an effective and safe pharmacologic restraint if required.

Prevalence of unrecognized pregnancy is up to 6% in ED patients. Perform routine pregnancy testing for appropriate patients as physiologic changes in pregnancy may increase cocaine toxicity. Cocaine may induce miscarriage, premature labor, or fetal toxicity, and modifications may be necessary for acute management.

The effects of cocaine are generally short lived. Monitor patients until they are no longer tachycardic and hypertensive and until they are calm and cooperative.

Medications commonly administered to treat pathophysiologic effects of cocaine may worsen other adverse effects of cocaine. Thus, there is concern primarily about use of epinephrine, lidocaine, and beta-blockers in the setting of acute cocaine toxicity. Conflicting reports and recommendations in the literature compound the controversy.

As an example, the 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care acknowledge that many toxicologic approaches are not based on high quality research, but rather on case reports, small case series, and data extrapolated from animal studies. Therefore, although the American Heart Association (AHA) recommendations for treatment of individuals with poisoning are class IIb (interventions considered within the standard of care), many represent only expert consensus.

Epinephrine and vasopressin

Vasopressin offers considerable theoretical advantage over epinephrine in cardiac arrest secondary to cocaine toxicity.^{[30, 29]} The hyperadrenergic state caused by cocaine increases myocardial oxygen demand. Epinephrine has the same effect. Vasopressin, on the other hand, increases coronary blood flow and myocardial oxygen availability.^[31] Cocaine toxicity frequently causes acidosis: epinephrine loses much of its effectiveness in an acidotic milieu^[31] , whereas vasopressin demonstrates vasoconstricting efficacy even with severe acidosis.^[32]

Epinephrine has been the drug of choice for the treatment of cardiac arrest, primarily for its alpha-adrenergic effects. However, epinephrine and cocaine have many similar cardiovascular effects. Furthermore, cocaine prevents the reuptake of exogenously administered epinephrine. Therefore, if epinephrine is used, AHA Guidelines 2005 and the AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider recommend that high-dose epinephrine be avoided and that the interval for its administration be increased (q5-10min).

If VF or ventricular tachycardia is recurrent or refractory and epinephrine or excessive levels of endogenous catecholamines are the suspected cause, consider withholding further doses of epinephrine. Because of similarity in cardiovascular effects caused by cocaine and epinephrine, administration of epinephrine to a patient who arrests in a hyperadrenergic state has been likened to "pouring gasoline on a fire."^[29]

Lidocaine

Lidocaine is one of the primary drugs used to treat ventricular dysrhythmias. Although some animal data indicate that lidocaine can reverse the ECG effects of cocaine and protect against death, others indicate that lidocaine may lower the seizure threshold and potentiate cocaine toxicity.

Derlet, Tseng, and Albertson caution that lidocaine potentiates the CNS toxicity of cocaine.^[33] Noting this small "safety window," Derlet states that lidocaine may be used, but advises precautions, such as double or triple checking the total dose, solution concentration, and any infusion pump.^[34]

Cocaine and lidocaine have similar pharmacologic effects. Therefore, the possibility that lidocaine may increase toxicity by potentiating the effects of cocaine on the cardiovascular system has been a concern.

The AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider cites this similarity for the therapeutic role that lidocaine may play in competing with cocaine at the sodium channel, thereby decreasing the effects of cocaine.

In the setting of cocaine toxicity, the decision as to whether or not to use lidocaine must be carefully considered, weighing its potential benefit on ventricular rhythm disturbances versus the synergistic toxic effects of lidocaine on seizure risk.

Beta-blockers

The Guideline of the American College of Cardiology/American Heart Association on ST-segment Elevation Myocardial Infarction states that beta-blockers should not be administered to patients with STEMI precipitated by cocaine use, because of the risk of exacerbating coronary spasm. A Scientific Statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology, titled "Management of Cocaine-Associated Chest Pain and Myocardial Infarction," expands that caution, stating that beta-adrenergic antagonists should be avoided in the acute setting of cocaine toxicity in patients with cocaine-associated chest pain and/or MI.^[35]

A study by Dattilo and colleagues, however, found a significantly lower incidence of MI in patients who were urine-positive for cocaine and who received beta-blockers compared with those who did not receive beta-blockers (6.1% vs 26%).^[36] It should be emphasized these patients were urine-positive only, and they were not experiencing acute cocaine intoxication (eg, hypertension, tachycardia, seizures).

Although an accompanying editorial by Freeman and Feldman^[37] states that acute myocardial perfusion imaging in patients with cocaine-associated chest pain rarely finds reversible coronary perfusion defects consistent with coronary vasospasm, Holter monitoring has documented cocaine-induced ischemia for several weeks after cocaine use.^[20] Recurrent ischemic chest pain is reported in patients who do and in patients who do not continue to abuse cocaine,^[20] with ischemia persisting for up to 2 weeks after the cessation of cocaine use.

Further research is necessary, with the most appropriate current approach appearing to be that advanced in the Scientific Statement of the AHA; beta-adrenergic antagonists should be avoided in the acute setting of cocaine toxicity in patients with cocaine-associated chest pain and/or MI.^[35]

With regard to nonselective beta-blockers, it should be further noted that echocardiographic data suggest that the antihypertensive effect of propranolol results from depression of cardiac output rather than relief of systemic vascular resistance. Just before death, cocaine toxicity usually results in hypotension, a condition that use of a nonselective beta-blocker further compounds.

Malbrain et al recommended esmolol for "save use" in managing life-threatening hypertension and tachycardia.^[38] Esmolol is a selective beta1-adrenergic blocker with rapid onset and short duration of action (elimination half-life, 9 min). They advise that the coadministration of esmolol and sodium nitroprusside should be reserved for severe hypertension that is unresponsive to other treatment and/or complicated by aortic dissection.

The 2005 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care discusses use of carefully titrated doses of labetalol as a third-line agent for drug-induced hypertensive emergencies.^[39] However, labetalol, a combined alpha- and beta-blocking agent, has an alpha-to-beta blockade ratio of 1:7. Therefore, it may not provide enough protection for cocaine-toxic patients from (relatively) unopposed alpha stimulation. Its risk of exacerbating myocardial ischemia parallels the risk of beta-blockers. Labetalol also increased seizures and mortality in animal models; therefore, its use cannot be promoted.

Cocaine-associated VF

Prolonged resuscitative efforts are recommended in AHA Guidelines 2005 for patients with cardiopulmonary arrest in a setting of drug intoxication.^[39]

Hypotheses about the causes of cocaine-associated VF, if confirmed, have treatment implications. In one study, when the heart rate is held constant, alpha-adrenergic but not beta-adrenergic receptor antagonists prevented cocaine-induced VF. Cocaine activation of myocardial alpha-adrenergic receptors, specifically alpha1A-adrenergic receptors, may substantially contribute to VF during myocardial ischemia. Activation of these receptors elevates cytosolic calcium levels and provokes delayed after-depolarizations. Therefore, calcium overload may be the final common pathway linking enhanced adrenergic activity to cocaine-induced VF.

This observation raises a question as to the role, if any, of calcium antagonists in cocaine toxicity. Studies supporting the use of calcium channel blockers have been performed only in animal models. Consistent with a local anesthetic mechanism of its toxic effects, calcium channel blockers have not been shown to reduce cocaine toxicity in humans. Furthermore, they increase the lethality of cocaine. This additive lethality may result from the negative inotropic effects shared by these agents.

Cocaine-associated cardiac dysrhythmias

Ventricular ectopy is usually transient and is managed with careful observation and escalating doses of benzodiazepine to blunt the hypersympathetic state by modulating cocaine-induced CNS stimulation. Treat malignant ventricular ectopy and perfusing VT by ensuring good oxygenation, by treating the hyperadrenergic state with escalating doses of benzodiazepine, and by administering appropriate antidysrhythmic medications if ventricular arrhythmias persist. Ensure that a defibrillator is readily available.

Malbrain et al recommend the use of an antidysrhythmic agent, such as bretylium (though now rarely found on code carts).^[38] Another pharmacologic option is magnesium sulfate, though caution is necessary because it may cause hypotension.

Consider sodium bicarbonate for treating dysrhythmias resulting from the direct toxic effects of cocaine,^[41] such as when sodium channel blockade causes a QRS >100 milliseconds. Dual mechanisms of action have been proposed for its therapeutic effects: (1) Alterations in pH may change the conformation of the sodium channel, and (2) increased extracellular sodium concentrations may override sodium channel blockade. Hourly measurements of blood pH are indicated, with appropriate adjustments until the blood pH is properly controlled. End points of bicarbonate therapy are a serum pH of 7.50-7.55.

Paroxysmal SVT (PSVT), atrial flutter, and rapid atrial fibrillation are generally short-lived and do not require immediate treatment. Use escalating doses of benzodiazepine to treat hemodynamically stable patients with persistent supraventricular arrhythmias to blunt the hypersympathetic state by modulating cocaine-induced stimulation of the CNS, taking caution not to depress consciousness and create a need for respiratory assistance. In drug-induced hemodynamically significant tachycardia, the pathophysiologic mechanism responsible may be increased automaticity, triggered activity, or reentry phenomenon. Tachycardia caused by increased automaticity will not be responsive to interventions such as adenosine and synchronized cardioversion. Benzodiazepines are generally safe and effective in drug-induced hemodynamically significant tachycardia (HST).

Cocaine-associated chest pain and MI

Chest pain may result from musculoskeletal, cardiovascular, pulmonary, or other causes. In patients with cocaine-related chest pain, assume that cardiac ischemia is present until this is proven otherwise. Accordingly, the ED approach to such patients, in addition to oxygen, intravenous access, and monitoring, includes the steps outlined below.

Perform 12-lead ECG.

Obtain chest imaging.

Direct the initial pharmacologic approach to suspected cocaine-related myocardial ischemia at increasing coronary blood flow and decreasing sympathetic output.

Nitroglycerin (NTG) is appropriate in managing cocaine-associated infarction or ischemia because it reduces cocaine-induced vasoconstriction in healthy and atherosclerotic segments of the coronary arteries.

Small, incremental doses of benzodiazepines decrease norepinephrine release by the CNS, thereby counteracting the sympathomimetic effects of cocaine on the heart. Similar doses of morphine sulfate (MS) also alter hemodynamics and blood flow dramatically in patients with heightened sympathetic activity. Limiting factors for morphine and benzodiazepines include hypotension, somnolence, and respiratory depression. Kercher cautions that short-acting benzodiazepines (eg, lorazepam) should be prescribed at low doses for patients with hepatic disease, organic brain syndrome, and those taking medications inhibiting the metabolism and clearance of benzodiazepines (eg, those using nicotine or cimetidine [Tagamet]).^[42]

Although benzodiazepines and NTG are first-line agents in drug-induced acute coronary syndromes, cocaine-induced vasoconstriction also is reversed by phentolamine. Therefore, AHA 2005 Guidelines recommends phentolamine as a second-line agent.^[39]

AHA 2005 Guidelines further state that coronary vasodilators administered via the intracoronary route are preferable to peripheral administration, a factor favoring cardiac catheterization, as further addressed below.

In a study of MI in the setting of cocaine use, Hollander reports on 246 patients enrolled over 46 months at 6 hospitals. Of patients presenting with cocaine-associated chest pain, 5.7% had MI; other studies have reported rates of 19% and 31% for acute MI in patients admitted with chest pain and cocaine use. Route, length, and frequency of use and interval from last use did not differ between patients with MI and those without MI. Of interest, a history of chest pain was less common in patients with MI than in others.^[10]

In patients with prolonged unexplained chest pain, perform serial ECGs and cardiac-marker measurements to rule out MI. However, in one study, Hollander reports that patients with MI were as likely to present with normal or nonspecific ECG findings as with ischemic ECG findings. The sensitivity of the ECG in predicting MI was only 35.7%; therefore, ECG appears to be less sensitive in patients with cocaine-induced myocardial ischemia than in other patients presenting with ischemic chest pain. Interpretation of cardiac markers in patients with cocaine-induced symptoms may be difficult since levels of creatine kinase (CK) and CK MB-isoform (CK-MB) may be elevated in cocaine users who do not have an MI.

Be mindful that as many as 43% of patients with cocaine-related chest pain meet standard ECG criteria for fibrinolysis despite being cardiac marker negative for infarction; a high percentage of such patients have early repolarization.

Of additional importance, an increased incidence of mycotic aneurysms and CNS mass lesions may lead to an increased incidence of hemorrhagic complications in these patients. When evaluating patients for fibrinolytic therapy, remember that a history of intravenous drug use poses a relatively high risk for the possibility of coexisting vascular pathology.^[41] Obtain a detailed history and perform physical and ancillary testing, as appropriate, directed at identifying endocarditis, septic pulmonary emboli, and pseudoaneurysm.

AHA 2005 Guidelines state that intracoronary administration of fibrinolytics is preferred to blind peripheral administration in patients with drug-induced acute coronary syndrome. Fibrinolysis in the presence of hypertension or CNS vasculitis may be dangerous, and percutaneous transluminal coronary angioplasty (PTCA) may be a safer alternative when revascularization is indicated.

In light of the above confounding factors, the AHA Textbook of Advanced Cardiac Life Support for the Experienced Provider indicates that cardiac catheterization is recommended by many experts.

Fibrinolysis should thus be reserved for patients who cannot receive percutaneous coronary intervention within the requisite time and who have low risk for cerebrovascular bleeding and other hemorrhagic complications of fibrinolytic therapy.

Patients may develop chest pain several hours after cocaine use.^[20] Recurrent coronary vasoconstriction associated with increased levels of benzoylecgonine and ethyl-methyl ecgonine may be responsible. Furthermore, patients with cocaine withdrawal may have dopamine depletion, resulting in intermittent coronary spasm.^[27] MI has been attributed to cocaine use several days earlier, and Holter monitoring has documented cocaine-induced ischemia for several weeks after cocaine use.^[20] Recurrent ischemic chest pain is reported in patients who do and in patients who do not continue to abuse cocaine.^[20] Ischemia may persist for up to 2 weeks after the cessation of cocaine use; therefore, avoiding the use of beta-adrenergic blockade for as long as 2 weeks after withdrawal of the toxin may be prudent.

Objective assessment may aid decision-making when the patient's treatment or disposition may be altered in the presence of cocaine.^[17] For example, beta-blockers are relatively contraindicated in cocaine use, but they are commonly given when cocaine is not considered a factor in myocardial injury or ischemia. However, in one study, 28% of patients with chest discomfort who tested positive for cocaine had denied using it. When beta-adrenergic blockade is being considered, even if cocaine toxicity is not suspected, a rapid bedside test for cocaine use may be appropriate because of its prevalence and the substantial rate of false-negative findings in the history of present illness.

Hypertension

Cocaine may precipitate hypertensive emergency due to CNS stimulation and peripheral alpha-agonist effects. Toxicity may be superimposed on preexisting hypertension in patients who have become dependent on elevated BP to maintain cerebral perfusion. Carefully consider the patient's clinical status and history when deciding to treat hypertension.

Hypertension secondary to cocaine is commonly responsive to intravenous benzodiazepines because benzodiazepines minimize the stimulant effects of cocaine on the CNS.

A vasodilator, such as nitroglycerine (NTG) or nitroprusside, may be titrated to effect if further therapy is indicated. NTG is the drug of choice in patients with chest pain. The use of nitroprusside to control hypertension has the additional advantage of aiding heat loss by peripheral vasodilatation.

Hypotension

Hypotension may be treated with parenteral fluids and, if refractory to fluids, norepinephrine, a direct-acting pressor, is preferred over indirect agents like epinephrine.

Aortic dissection

Include type A aortic dissection in the differential diagnosis of cocaine abuse with chest pain. ED care entails close cardiac and hemodynamic monitoring, treatment to reduce the progression of dissection, and administration of narcotics as needed for pain. Sodium nitroprusside should be used to control BP, but it may cause tachycardia, for which esmolol may be considered. Although the goals of therapy are to decrease the heart rate to 60-80 bpm and BP to 100-120 mm Hg, the therapeutic endpoint is the lowest level that permits continued end-organ perfusion.

Cocaine affects pulmonary dynamics and may cause pulmonary edema. Other causes of pulmonary edema in the setting of cocaine use include CHF (with or without MI) and subarachnoid hemorrhage or concomitant use of other drugs (eg, heroin). Most patients with cocaine-associated pulmonary edema respond to standard medical treatment.

For resistant hypoxemia, positive-pressure ventilation with continuous positive airway pressure (CPAP) or intubation supplemented with positive end-expiratory pressure (PEEP) is usually effective. For patients with respiratory depression intubation may be indicated, as it is for those with apnea.

Administration of naloxone to a patient who has been speedballing may negate the sedative effect of the opioid and leave the stimulant effect of the cocaine unopposed, precipitating or worsening cocaine toxicity. Naloxone is still indicated in respiratory depression but should be used with caution (ie, slowed rate of administration, lowered doses).

Administration of flumazenil to patients with benzodiazepine use (eg, to blunt the effects of cocaine) may be dangerous. Cocaine is a gamma-aminobutyric acid (GABA) antagonist that may be blocked by benzodiazepines and potentiated by flumazenil. Use of flumazenil in the cocaine-intoxicated patient may induce seizures.

Seizures are a concern. Cocaine is one of the most common causes of drug- and toxin-associated seizures. Seizures may be a dire sign of toxicity that heralds life-threatening physiologic instability. Cocaine-associated seizures are usually generalized, but they may be partial. They may result directly from toxicity of the CNS or indirectly from hypoxemia, stroke, or other conditions. They may occur after recreational use, long-term abuse, or cocaine overdose. Seizures also occur in people who pack or stuff cocaine in their body, affecting 4% of patients who are body stuffers, with seizures expected in the first 2 hours.

Seizures occurring from cocaine toxicity are managed as part of comprehensive patient treatment. Seizures and severe agitation require prompt attention to protect the airway and prevent hyperthermia. Although patients with serious compromise may require paralysis and mechanical ventilation, benzodiazepines are first-line therapy. Benzodiazepines directly enhance GABA-mediated neuronal inhibition, affecting the clinical and electrical manifestations. Their overall effectiveness in terminating cocaine-induced seizures is 75-90%.

Although Perrone and Hoffman recommend head CT in all cases of cocaine-associated seizures because of the risk of associated intracranial lesions,^[27] Renzi believes that a brief seizure, clearly temporally related to cocaine use, requires no further workup if the patient is otherwise healthy, alert, coherent, without headache, and neurologically intact.^[28] If patients are not admitted, monitor them in the ED for several hours.

Emotional distress can exacerbate dystonic reactions, whereas relaxation may reduce the intensity of such attacks. Using a calm reasoned approach in a quiet room markedly complements the effectiveness of pharmacologic interventions.

Dopamine and acetylcholine have mutually antagonistic functions in the nigrostriatal system. Although diphenhydramine, with its anticholinergic properties, is the drug of choice for most dystonic reactions, it should be used with caution in cocaine toxicity. Antihistamines cause hyperthermia by central (eg, hypothalamic) and peripheral (inhibition of sweating and muscular rigidity) effects; cocaine also causes hyperthermia. Antihistamines and cocaine are sodium channel blockers. Therefore, coadministration of an antihistamine in the setting of cocaine use may potentiate a molecular pathophysiological cascade that exacerbates end-organ dysfunction.

Benzodiazepines, with their anxiolytic and muscle relaxant properties, are alternative drugs for the treatment of dystonia. Although they only treat the manifestations of dystonias and not the pathophysiology underlying their development; the advantage of using benzodiazepines lies in their safety.

Hypoglycemia may present as any neuropsychiatric syndrome and is always a consideration in patients who present with altered mental status or convulsions. Rapid diagnosis by meter or Dextrostix prevents the deleterious effects reported for the administration of dextrose in the absence of hypoglycemia. If the adult patient is hypoglycemic, administer thiamine 100 mg followed by 50 mL of 50% dextrose (D50W).

Acidosis has a profoundly adverse effect on myocardial contractility and may potentiate the effect of catecholamines. The correction of arterial pH, through ventilatory assistance and appropriate use of sodium bicarbonate, may be effective in terminating cocaine-induced dysrhythmias with resulting improvement of hemodynamics.

Recognize and treat hyperthermia as a distinct entity. If psychostimulant-intoxicated patients do not die as a result of cardiac or cerebrovascular complications, the next most important steps in preventing further morbidity are control of hyperthermia and treatment of rhabdomyolysis. Assess the patient's core body temperature and maintain a high index of suspicion for hyperthermia. In the setting of serious hyperthermia, continuously monitor the core body temperature.

Hyperthermia may be treated with convection cooling, which involves spraying the patient's exposed body with tepid water as fans circulate air. Tepid water prevents maladaptive shivering that may be induced by conduction cooling methods, although ice packs, ice water gastric lavage, or cooling blankets may also be used. Direct efforts at reducing body temperature to 101 º F in 30-45 minutes.

Do not use restraints (physical or pharmacologic) that interfere with dissolution of heat. If necessary, use light hand and foot restraints. Ensure adequacy of hydration and electrolytes. Benzodiazepines are an effective and safe pharmacologic restraint in these patients. Given parenterally, with the usual precautions, they rapidly calm hyperactive patients.

Do not administer phenothiazines. Goldfrank, Flomenbaum, Lewin, and Weisman apply this injunction to butyrophenones as well.^[43] Contrary views are, however, expressed in the literature. Callaway and Clark maintain that concerns about the potentiation of drug-induced seizures by butyrophenone neuroleptics (eg, haloperidol) may be exaggerated because such drugs have less effect on human seizure threshold than phenothiazines, and they interfere less with sweat-mediated evaporative cooling in drug-induced hyperthermia.^[13] Although Callaway and Clark believe that further studies are necessary to assess the efficacy of butyrophenones in the treatment of psychostimulant overdose,^[13] Colucciello and Tomaszewski indicate that haloperidol is effective in treating cocaine-related agitation and that no clinical data proscribe its use, theoretic concerns notwithstanding.^[44]

Monitor patients with hyperthermia in the ED for several hours if they are not being admitted.

The reported incidence of rhabdomyolysis in ED patients who use cocaine is 5-30%. Pathophysiologic hypotheses include placement of excessive demands on healthy muscle cells that cannot be met by available energy supplies, direct toxicity of cocaine upon the muscle membrane, cocaine-induced seizures, and the potential concomitant use of other drugs (eg, PCP, amphetamines) that are known to cause this syndrome.

Risk factors for rhabdomyolysis include altered mental status, hyperactivity, fever, seizures, hypotension, dysrhythmias, and cardiac arrest. Rhabdomyolysis may be associated with hyperphosphatemia, myoglobinuria, nephrotoxicity, hyperkalemia, hypocalcemia, compartment syndromes, or disseminated intravascular coagulation (DIC). The most critical sequelae of rhabdomyolysis are shock and renal failure.

Rapid fluid resuscitation promotes urine output and alleviates the effect of myoglobin on the kidneys. Generous amounts of intravenous fluids with close monitoring of urine output and pH are indicated for rhabdomyolysis associated with severe psychostimulant toxicity. Fluid resuscitation should maintain urine output of 1-3 mL/kg/h to minimize renal damage from rhabdomyolysis. Patients with rhabdomyolysis may require up to 20 L of fluid in the first 24 hours to achieve these urinary flow rates, and close monitoring of cardiac status and electrolytes is necessary.

In acid urine, myoglobin is essentially a toxin, and uric acid tends to crystallize at low pH; sodium bicarbonate may be used to alkalinize the urine of patents with rhabdomyolysis. However, without prospective randomized studies to differentiate the role played by volume versus alkalinization, it is possible that volume alone represents maximally effective therapy. This is important because cocaine metabolites are best excreted in acid urine, and it calls into question the role of urinary alkalinization.

When cocaine has been ingested (not as part of body packing or body stuffing), the patient without altered mental status may be treated by administration of activated aqueous charcoal. Gastric lavage and induction of vomiting via ipecac syrup is not recommended because of the risk of seizure, with the potential for airway compromise and aspiration of vomitus.

In body packers, although a risk for toxicity exists, the drugs are often carefully packaged to prevent rupture or leakage. Carriers often purge the GI tract with a laxative before they ingest the drug packages and then consume only clear liquids until the drugs are delivered. If a constipating agent was used, they ingest a laxative to enhance evacuation when arriving at their destination.

Conversely, body stuffers quickly ingest drug packages to avoid arrest. Therefore, body stuffers are at increased risk for aspiration because of the rapidity with which they attempt to remove the evidence from police accessibility. Bronchoscopy has been used to successfully remove a drug packet aspirated into the lung.

Body stuffers have other risks as well. Because they were not planning to ingest the packet (as opposed to the body packer) and because they took no precautions selecting the drug container, the wrapping material often acts as a semipermeable membrane. The hypertonic content of the drug packet attracts water, making the ingested packages especially prone to rupture or leakage resulting in toxicity.

Potent polypharmaceutic overdose is also common, resulting from an attempt to swallow all of the illegal drugs on site.

The administration of activated charcoal has been recommended to adsorb any toxins from leaking bags, from ruptured bags, or that were liberated during enhancement of bowel transit (eg, whole-bowel irrigation). Treatment of asymptomatic patients should include laxatives (eg, sodium sulfate, magnesium sulfate, magnesium citrate, psyllium hydrophilic mucilage) or whole-bowel irrigation, several doses of activated charcoal, and close observation.

If a polyethylene glycol electrolyte lavage solution (eg, GoLYTELY, Colyte) is to be used for whole-bowel irrigation, Malbrain cautions that it must follow the administration of activated charcoal because the maximal adsorptive capacity of activated charcoal is at pH 7 and the polyethylene glycol electrolyte lavage solution has a pH of 8.^[38] Do not use paraffin-containing laxatives (eg, Lansoyl) because they degrade latex. Avoid endoscopic manipulation and enemas because the drug packet may be ruptured. Contraindications to whole-bowel irrigation include ileus, GI hemorrhage, or bowel perforation.

Monitor body stuffers for several hours. Body packers may require hours to days of hospitalization until all the packets have been passed. Surgical intervention is needed if patients present with serious signs or symptoms or intestinal obstruction.

Individuals using cocaine expect to become euphoric, energetic, and confident. However, with large doses or prolonged use, they may become agitated, anxious, or panicky. A wild, combative patient intoxicated with cocaine may be sedated with lorazepam or midazolam, both of which can be adequately absorbed via the intramuscular route if intravenous access is unobtainable.

Given the contradictory literature about butyrophenones that was previously addressed, attempt to avoid use of antipsychotics because they may confuse the clinical picture, exacerbate anticholinergic crisis, lower the seizure threshold, or cause a dystonic reaction.

When treating a traveler who presents with fever, bizarre mental state, or coma, especially if the person has come from West Africa or South America, consider cerebral malaria, treated with intravenous quinine.

Test patients who inject drugs for HIV and hepatitis (with their permission, if required by state law).

If a patient with cocaine toxicity is being considered as an organ donor, remember that cocaine preferentially accumulates in the liver and kidney. Therefore, use of these organs may result in the transplantation of a substantial reservoir of the toxin.

Consultation with a regional poison control center or a medical toxicologist may be appropriate in complicated cases.