Shana Kusin
OPIOIDS
EPIDEMIOLOGY
The term opioid refers broadly to all opium-related compounds that possess analgesic and sedative properties. The term narcotic is used by law enforcement to designate a broad variety of controlled substances and is not clinically relevant.
Opioids can be categorized as opiates (naturally occurring compounds), semisynthetic (chemical modifications of natural compounds), or synthetic (completely artificial).
ED visits associated with opioid abuse increased by 43% between 2004 and 2006. The opioids most commonly involved are, in order, heroin, oxycodone, hydrocodone, and methadone.
PATHOPHYSIOLOGY
Opioids modulate nociception in the terminals of afferent nerves in the central nervous system, peripheral nervous system, and the gastrointestinal (GI) tract. They function as agonists at three primary receptors: μ, (mu), κ (kappa), and δ (delta).
Stimulation of μ-receptors results in analgesia, sedation, miosis, respiratory depression, cough suppression, euphoria, and decreased GI motility. Stimulation of κ- and δ-receptors results in some, but generally weaker, analgesia, and κ-receptor stimulation may cause dysphoria or hallucinations. All currently available opioids have some activity at the μ-receptor and cause some degree of respiratory depression.
Standard formulations of opioids are readily absorbed and achieve peak blood levels 30 to 60 minutes after ingestion. Most opioids undergo first-pass hepatic metabolism and have widely varied bioavailability, ranging from 10% to 80%.
The metabolism of codeine, morphine, propoxyphene, oxycodone, meperidine, and methadone is mostly hepatic and is subject to drug interactions and genetic variations.
CLINICAL FEATURES
Opioids cause varying degrees of respiratory and mental status depression, miosis, orthostatic hypotension, nausea, vomiting, histamine release, decreased GI motility, and urinary retention.
Although clasically considered a part of the opioid toxidrome, miosis is not always present. Meperidine, morphine, propoxyphene, pentazocine, and diphenox-ylate have been associated with normal or enlarged pupils, and mydriasis may signal severe cerebral hypoxia or coingestants.
Opioid withdrawal usually manifests in anxiety, insomnia, yawning, lacrimation, diaphoresis, rhinorrhea, myalgia, piloerection, mydriasis, vomiting, diarrhea, and abdominal cramping.
DIAGNOSIS AND DIFFERENTIAL
Opioid intoxication or withdrawal is a clinical diagnosis.
The triad of coma, miosis, and respiratory depression strongly suggests opioid intoxication.
Detection of opioids in the urine may aid in diagnosis; however, many synthetic and semisynthetic opioids are not routinely detected by this modality, and false positives have been associated with poppy seeds and some antibiotics.
An acetaminophen level should be obtained in all cases of opioid-acetaminophen overdoses as well as in any intentional suicidal ingestion.
The differential diagnosis of opioid overdose includes toxicologic exposure to agents producing similar symptoms, such as clonidine, organophosphates and carbamates, phenothiazines, sedative-hypnotic agents, gamma-hydroxybutyrate (GHB), or carbon monoxide; hypoglycemia; central nervous system infection; pos-tictal states; and pontine and intracranial hemorrhage.
The differential diagnosis of opioid withdrawal includes drugs and toxins that promote an adrenergic state, other drug withdrawal, and hyperthyroidism.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Airway protection and ventilatory management are the most important treatment for opioid-intoxicated patients. Bag-valve-mask support may be used to maintain oxygenation while naloxone and/or endotra-cheal intubation are being prepared.
Activated charcoal should be considered at a dose of 1 gram/kg PO if the ingestion occurred within 1 hour.
Naloxone is a pure competitive antagonist at all opioid receptors with particular affinity for the μ-receptor. It can be given by injection (IV, SC, or IM). Onset after IV administration is 1 to 2 minutes and its duration of action is 20 to 90 minutes.
Patients presenting with decreased mental status but minimal respiratory depression should receive a lower naloxone dose of 0.4 milligram IV, repeated until desired effect is reached. Opioid-dependent patients in this scenario should receive an even smaller starting dose of 0.05 milligram IV in order to avoid precipitation of opioid withdrawal.
Patients presenting with significant respiratory depression should receive an initial naloxone dose of 2 milligrams IV, with repeated doses of 2 milligrams IV given every 3 minutes as needed until respiratory depression is reversed or a maximum of 10 milligrams IV has been reached.
Sustained preparations and synthetic opioids such as propoxyphene, fentanyl, pentazocine, and dex-tromethorphan may require larger doses of naloxone.
A continuous naloxone infusion should be considered if the patient has required multiple boluses of naloxone. The IV infusion should be started at an hourly rate that is two-thirds of the total reversal dose required. Patients on naloxone infusions may require additional bolus doses and upward or downward adjustments in the infusion rate.
An ED observation period of 4 to 6 hours is recommended for most cases of opioid exposure.
Patients receiving naloxone in the setting of IV heroin use may be safely discharged 1 to 2 hours following naloxone administration if they meet the following criteria: independently mobile, oxygen saturation >92% on room air, respiratory rate >10 breaths/min, pulse rate >50 beats/min, normal temperature, Glasgow Coma Scale score of 15.
Admit moderate to severely symptomatic patients requiring continued naloxone administration to a monitored setting.
Opioid withdrawal is rarely life threatening. Supportive care with clonidine 2 to 5 micrograms/kg PO, antiemetics, and antidiarrheals may alleviate discomfort.
SPECIAL CONSIDERATIONS
Buprenorphine is a long-acting partial agonist at μ-receptors. It can precipitate an opioid toxidrome in opioid-naive patients or a withdrawal syndrome in opioid-dependent patients. Naloxone may be partially successful in treating intoxication, but prolonged or repeated dosing may be necessary.
Methadone can prolong the QT interval and predispose to cardiac dysrhythmia such as torsades de pointes.
Propoxyphene overdose has been associated with QRS prolongation, heart block, prolonged QT interval, ventricular bigeminy, and seizures. QRS prolongation should be treated with sodium bicarbonate (1 milligram/kg IV). Naloxone may terminate propoxphene-induced seizures but will not reverse ECG changes.
Tramadol overdose is associated with agitation, hypertension, seizures, and death, particularly at doses >500 milligrams in adults. Naloxone is not effective in reversing tramadol-induced seizures.
Serotonin syndrome can result from combining meperidine, dextromethorphan, or tramadol with monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, or linezolid.
Acute lung injury is a rare but serious complication of heroin overdose. It can be delayed up to 24 hours. Treatment includes oxygenation, ventilatory support, and use of positive end-expiratory pressure ventilation. Naloxone, diuretics, and digoxin are not indicated.
COCAINE, AMPHETAMINES, AND OTHER STIMULANTS
EPIDEMIOLOGY
One-third of drug-related ED visits in the United States are related to cocaine use.
Methamphetamine is the second most commonly abused drug worldwide, following cannabis, and is used by 0.6% of the global population.
PATHOPHYSIOLOGY
COCAINE
Cocaine is a water-soluble hydrochloride salt that is rapidly absorbed across all mucous membranes. It can be topically applied, insufflated (snorted), swallowed, or injected IV. Crack cocaine is a free-base form that is stable to pyrolysis and can be smoked.
Insufflation causes a peak effect within 30 minutes and a duration of effect of 1 to 2 hours. Both the IV and inhalational routes produce a rapid onset of action (less than 1 minute) with a duration of 30 to 60 minutes.
Cocaine causes sympathetic nervous system activation via enhanced effects of excitatory amino acids and blockade of presynaptic uptake of norepinephrine, dopamine, and serotonin. This produces its characteristic effects of mydriasis, tachycardia, hypertension, and diaphoresis.
Cocaine is also a local anesthetic and inhibits nerve conduction by blockade of fast sodium channels. It has quinidine-like effects on cardiac conduction, which may widen the QRS complex and prolong the QT interval. In large doses, myocardial toxicity may result in negative inotropy, wide complex dysrhyth-mia, bradycardia, and hypotension.
AMPHETAMINES
Amphetamines comprise a broad class of structurally similar derivatives of phenylethylamine. Modification of the basic amphetamine structure may produce substances with additional psychoactive properties; these drugs comprise the “designer” amphetamines.
Amphetamines enhance release and block reuptake of catecholamines and may directly stimulate catecho-lamine receptors. Some amphetamine metabolites inhibit monoamine oxidase. Some derivatives may also induce serotonin release, causing hallucinogenic effects.
Methamphetamine may be ingested, injected IV, inhaled, or insufflated. As with cocaine, absorption and peak effects occur rapidly via these routes.
Stimulants such as methylphenidate, ephedrine, and phenylpropanolamine produce toxic effects similar to cocaine and amphetamines.
CLINICAL FEATURES
The cocaine- or amphetamine-intoxicated patient may demonstrate tachycardia, tachypnea, hypertension, hyperthermia, and any degree of altered mental status. Common symptoms include chest pain, palpitations, dyspnea, headache, and focal neurologic complaints.
Even at low doses, cocaine can produce coronary artery vasoconstriction resulting in chest pain. This effect is potentiated by cigarette smoking.
Cocaine induces a variety of cardiotoxic effects, including dysrhythmias, myocarditis, cardiomyopathy, myocardial ischemia and infarction, aortic rupture, aortic and coronary artery dissection, and acelerated or increased atherogenesis.
The increased adrenergic tone associated with cocaine and amphetamine can lead to seizures, intracranial hemorrhage, and cerebral infarction as well as other neurologic sequelae.
Crack cocaine use has been associated with pulmonary hemorrhage, pneumonitis, asthma, pulmonary edema, pneumomediastinum, pneumothorax, and pneumopericardium.
Cocaine-induced mesenteric vasospasm can cause intestinal ischemia, bowel necrosis, ischemic colitis, GI bleeding, bowel perforation, and splenic infarction.
Rhabdomyolysis may occur with cocaine or amphetamine use and can lead to renal failure.
Cocaine abuse during pregnancy increases the risk of spontaneous abortion, abruptio placentae, fetal prematurity, and intrauterine growth retardation. Methamphetamine abuse also has detrimental effects on fetal growth.
Mortality is most commonly the result of severe hyperthermia, dysrhythmias, intractable seizures, or hypertension leading to intracranial infarction, hemorrhage, or encephalopathy.
DIAGNOSIS AND DIFFERENTIAL
Diagnosis of cocaine, amphetamine, and stimulant intoxication is usually made clinically by recognition of the sympathomimetic toxidrome in the correct clinical context.
Concomitant use of substances such as alcohol or opioids may significantly alter the presentation.
The differential diagnosis includes intoxication with other sympathomimetic substances, withdrawal syndromes, and infection. Occult trauma and hypoglycemia should be considered.
Patients with hyperthermia or significant agitation should be evaluated for acidosis, renal failure, and rhabdomyolysis with a basic chemistry panel and creatine kinase (CK).
An ECG, chest radiograph, and cardiac enzymes should be considered in cocaine- or amphetamine-intoxicated patients presenting with chest pain or dyspnea.
Urine drug screening for cocaine is fairly specific and exhibits little cross reactivity. It is usually positive for up to 72 hours following exposure.
Urine drug screens for amphetamines are not specific and have high false-negative and false-positive results.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The mainstay of treatment of cocaine and amphetamine toxicity involves adequate sedation and monitoring of vital signs. Benzodiazepines, such as lorazepam 2 milligrams IV or diazepam 5 milligrams IV, will often improve tachycardia, hypertension, and agitation.
Antipsychotics should be avoided due to the risk of lowering the seizure threshold and contributing to hyperthermia or dysrhythmias.
Active cooling with mist spray and fanning is used to treat moderate or severe hyperthermia.
Seizures should be treated with benzodiazepines; for refractory seizures, phenobarbital or neuromuscu-lar blockade should be considered. CT of the brain should be performed to assess for a structural central nervous system (CNS) lesion such as hemorrhage or infarction.
Cardiac ischemia or infarction should be treated with aspirin, nitrates, morphine, and benzodiazepines. ß-Blockers are contraindicated. Fibrinolytic therapy should be used with caution since cocaine-associated intracranial hemorrhage and aortic or coronary artery dissection is a contraindication to thrombolysis.
Treat cocaine-induced wide complex tachydysrhyth-mias and QRS interval prolongation by alkalinizing the serum to a pH of 7.45 to 7.5 with sodium bicarbonate.
Treat hypertensive emergencies with nitroprusside or phentolamine.
Asymptomatic “body packers” (individuals who ingest prepared packets of cocaine with the intent to transport it) may be treated with whole-bowel irrigation using polyethylene glycol electrolyte solution. If these patients exhibit any signs of intoxication, then administer benzodiazepines and have immediate surgical consultation for laparotomy and packet removal.
Acidification of the urine for amphetamine intoxication is not recommended.
Many amphetamines have a longer duration of effect than cocaine, and intoxicated patients may require longer periods of observation or hospital admission.
Patients with significant laboratory or vital sign abnormalities, ECG changes consistent with myocar-dial ischemia, or concern for CNS injury should be hospitalized in an intensive care unit setting.
HALLUCINOGENS
EPIDEMIOLOGY
After ethanol, marijuana (cannabis) is currently the most prevalent psychoactive substance abused by young people.
PATHOPHYSIOLOGY
The term “hallucinogen” has clasically referred to indole alkylamines such as lysergic acid diethyla-mide (LSD) and psilocybin and phenylethylamines such as methylenedioxymethamphetamine (MDMA, “ecstasy”) and mescaline. Other drugs such as phencyclidine (PCP) and marijuana are also frequently abused for the purpose of alteration of sensory perception.
Table 107-1 summarizes the classification, mechanism, typical dose, duration of action, features, complications, and specific treatments of commonly abused hallucinogens.
There are a number of “natural” hallucinogens being encountered with increased frequency, partly due to dissemination of information on and ease of procurement via the Internet.
TABLE 107-1 Commonly Abused Hallucinogens
CLINICAL FEATURES
LSD is rapidly absorbed with onset of symptoms within 30 minutes. Sympathomimetic symptoms usually precede psychedelic effects. Acute adverse psychological effects can lead to dangerous behavior or potential trauma. Massive overdoses may produce coma, respiratory arrest, hyperthermia, and coagulopathy.
Psilocybin causes symptoms similar to, but less severe than, LSD. Serious medical side effects are rare, but seizures and hyperthermia have been reported.
Mescaline causes hallucinogenic effects similar to, but weaker than, LSD. These effects are usually preceded by GI symptoms, dizziness, and headache, are delayed in onset, and persist for 6 to 12 hours. Significant morbidity and mortality is rare.
MDMA or “ecstasy” is structurally related to both amphetamines and mescaline. Effects include intensification of sensory stimuli and mood as well as hallucinations. Physical manifestations include sympathomimetic effects such as mydriasis and elevations of pulse and blood pressure. Nausea, bruxism, myalgias, and ataxia also occur.
Death associated with MDMA use has been attributed to severe hypertension, intracranial hemorrhage, hyponatremia, hyperthermia, and arrhythmias.
PCP is a piperidine derivative that is structurally related to ketamine. It has dissociative properties and causes clouding, rather than heightening, of the sensorium. It has been used as an adulterant in other drugs, and patients may be unwittingly exposed.
The clinical presentation of PCP is variable and can include CNS stimulation or depression, violent behavior, catatonia, and a combination of choliner-gic, anticholinergic, and sympathomimetic effects. Nystagmus and hypertension are frequent findings.
Rhabdomyolysis, renal failure, seizure, ataxia, muscle rigidity, hypoglycemia, and elevated CPK levels are common complications of PCP abuse.
Marijuana use most commonly causes drowsiness, euphoria, heightened sensory awareness, paranoia, and distortions of time and space. Significant medical complications are rare.
DIAGNOSIS AND DIFFERENTIAL
The differential diagnosis of hallucinogen intoxication includes alcohol and benzodiazepine withdrawal, hypoglycemia, anticholinergic poisoning, thyrotoxi-cosis, CNS infections, structural CNS lesions, and acute psychosis.
Routine drug screens will not detect psilocybin or mescaline.
Urine drug screens for MDMA, like other amphetamine drug screens, have low specificity and frequent false positives for a number of pharmaceutical agents.
Urine tests for PCP and marijuana may be positive for days to weeks after use and are not useful for diagnosing acute intoxication. The PCP screen also has a high rate of false positives.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Initial management of patients with hallucinogen intoxication is support of airway, breathing, and circulation. Hypoxia and hypoglycemia must be diagnosed and treated immediately.
Most hallucinogens are rapidly absorbed, but activated charcoal may be considered for ingestions within the previous hour.
Calm reassurance is often sufficient to soothe the agitated patient. Benzodiazepines are the mainstay of pharmacologic treatment. Haloperidol may be considered as a second-line agent but should be used with caution because it has anticholinergic properties and can lower the seizure threshold. Physical restraints should be avoided if possible as they can exacerbate agitation and contribute to rhabdomyolysis and hyperthermia.
Tachycardia and hypertension often respond to sedation with benzodiazepines. Severe hypertension can be treated with nitroprusside.
MDMA-associated hyponatremia can be significant. Administration of 3% saline to prevent brain stem herni-ation and death may be necessary in severe cases (serum sodium concentration <115 mEq/L, seizure, or coma).
Hyperthermia should be treated with rapid cooling. Severe cases may require neuromuscular paralysis and intubation.
Seizures are treated with benzodiazepines. Refractory seizures may require propofol or barbiturates.
Most patients with hallucinogen intoxication can be safely discharged from the ED after a period of observation. Patients with medical complications should be admitted to the hospital.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 180, “Opioids,” by Suzanne Doyon; Chapter 181, “Cocaine, Methamphetamine, and Other Amphetamines,” by Jane M. Prosser and Jeanmarie Perrone; and Chapter 182, “Hallucinogens,” by Katherine M. Prybys and Karen N. Hansen.