Illicit drug use escalated in the youth population in the mid- 1960s and it remains a major concern for the nation. Smoking, drinking, and drug use are leading causes of morbidity and mortality, both during adolescence and later in life. 1 A pervasive difficulty in dealing with this issue is our societal acceptance of drugs and demand for medications to solve real or perceived health problems. The influence of the media and medication manufacturers to take pills fuels this drive for drugs as problem-solving measures. 2 This article will focus on the most popular drugs of abuse as well as the newer drugs and their clinical presentations and management.
There are many different classification schemes of the various illicit drugs. Some agents have characteristics of more than one class, such as the hallucinogenic amphetamines.
Much of the literature on the topic of substance abuse and overdose consists of review articles and case reports/case series. This is especially true with regards to the discussion of the newer drugs and the effects. Many of the prospective studies are targeted at epidemiologic data. No thorough practice guidelines were found that addressed evaluation and management of the suspected drug overdose patient.
AMS - Altered Mental Status
BZP - N-Benzylpiperazine
CNS - Central Nervous System
DAWN - Drug Abuse Warning Network
DEA - Drug Enforcement Agency
GC-MS - Gas Chromatography-Mass Spectrometry
GHB - Gamma-Hydroxybutyrate
MDMA - Methylenedioxymethamphetaine
MTF - Monitoring the Future Study
NCPE - Noncardiogenic Pulmonary Edema
NIDA - National Institute on Drug Abuse
NMDA - N-methyl-D-aspartate
SAMHSA - Substance Abuse and Mental Health Services Association
TFMPP - 1-(3-Trifluoromethyl)piperazine
The Drug Abuse Warning Network (DAWN) is an organization that has demonstrated which drugs are the most common ones seen in the emergency department (ED) for a patient over 6 years old. 7 DAWN reported that just in the third and fourth quarters of 2003, there were 627,923 visits to an ED with a drug related problem. Half of these visits involved a major substance of abuse with alcohol, cocaine, and marijuana being the most commonly abused substances. 7
The Controlled Substances Act regulates the manufacture, possession, movement, and distribution of drugs in the U.S. It places all drugs in one of five schedules, as listed in Table 4.
Raves feature loud, rapidly pounding music that is accompanied by psychedelic lights, videos, smoke, and even fire. A typical rave club layout often consists of a large dance floor with no air conditioning and a separate "cool down room." The event often lasts all night until well into the morning.
Paraphernalia used at raves includes menthol nasal inhalers, Vicks vapor rub, glow sticks (to enhance the visual effects of Ecstasy), Skittles, M&Ms, or similar candies (to hide drugs), lollipops and pacifiers (to prevent involuntary teeth clenching), and water, juice, and sports drinks (to manage excessive body heat and dehydration). Ecstasy is sold openly at these gatherings. 6
Certain overdose patients may benefit from more extensive pre-hospital interventions.
Opioid intoxication is suggested by pinpoint pupils, hypoventilation, and altered mentation. Naloxone is a mixed opioid agonist-antagonist, whose antagonistic effects may reverse opioid effects. Naloxone can be given intravenously, intramuscularly, subcutaneously, via the endotracheal tube, or intranasally. Intranasal naloxone reduces the risk of blood exposure and is a safe and effective means of managing opioid intoxication. 8-10 Precautions for patients "awakening" with agitation from opioid intoxication should be readied before naloxone administration.
Check a serum glucose level if EMS has not already done so. If glucose was given by EMS, ask if any clinical improvement occurred as a result and recheck the level in the ED. Thiamine has classically been recommended prior to administration of dextrose to prevent Wernicke-Korsakoff syndrome, particularly in malnourished or alcoholic patients. However, there is increasing data that dextrose should not be withheld for administration of thiamine as the consequences of prolonged hypoglycemia can be devastating. 16 In addition, consider a trial of naloxone if there are any clinical clues of opiate overdose. The dose of naloxone varies per patient and ranges from 0.4 to 2.0 mg IV per dose for a child or adult and 0.01 to 0.03 mg/kg IV per dose for a neonate.
If there is an ingestion of a single agent, the physical exam may follow a classic toxidrome. These findings of the toxidromes are summarized in Table 8.
The formation and production of cocaine goes through an intricate process. Once it is derived from the leaves of the coca plant, it is added to hydrochloric acid to form a cocaine hydrochloride salt. This mixture is water soluble and can be injected or snorted. The cocaine hydrochloride salt can also be dissolved in water and mixed with baking soda and heated. This process produces a hard piece of crack cocaine, as its name is derived from the popping noise made by the crystallized cocaine as it is heated and smoked. 20 Snorting is the most popular route of cocaine abuse, followed by smoking cocaine as crack.
Sympathomimetics such as cocaine and amphetamines bind to presynaptic neuronal receptors ultimately preventing the reuptake of dopamine, norepinephrine, and serotonin. 21,22 With the relative increase in dopamine remaining in the synaptic cleft, the postsynaptic neuron is stimulated and causes the euphoric feeling that many abusers seek. 19
The systemic effects of cocaine can be devastating to the body. Many of the reported symptoms of cocaine abuse range from less severe symptoms to those that are life threatening. Anxiety, agitation, psychosis, hyperthermia, vasculitis, vasospasm, seizures, alveolar hemorrhage, pulmonary hypertension, angina, dilated cardiomyopathy, dysrhythmias, hypertension, rhabdomyolysis, myocardial infarction, intracranial hemorrhage, and sudden death have been reported with cocaine use. 23-28 There have also been reported cases of spontaneous intestinal perforation and ischemic bowel in crack abusers, and this has been hypothesized to be due to mesenteric vasoconstriction from norepinephrine. 29
Chest pain is the most common complaint associated with cocaine use. 110 Approximately 40% of patients that use cocaine presenting to the hospital have chest pain as their complaint. 30 In one study of cocaine-associated chest pain patients, 57% were hospitalized; this has reflected an average cost of $83 million annually. 31, 32 There has also been a reported 6% incidence in myocardial infarction in two studies of patients with cocaine-associated chest pain. 31, 33 Cocaine use is associated with myocardial infarction in as many as 25% of patients aged 18 to 45 years who otherwise have no risk factors for coronary artery disease. 34, 110
Aortic dissection is another life threatening event that also must be considered in cocaine-induced chest pain. In one study of 38 reported cases of aortic dissection at San Francisco General Hospital between 1981 to 2001, 14 37% were associated with the use of cocaine. The average time between use of cocaine and the occurrence of chest pain was 12 hours in this group, but the duration ranged between 0 to 24 hours. All 14 of the patients reported having used cocaine within the past 24 hours. 35
Additional causes of chest pain in patients who have insufflated or inhaled cocaine includes pneumothorax, pneumomediastinum, or pneumopericardium. Agitation, anxiety, and hallucinations are common. Amphetamine or cocaine use can cause an acute toxic psychosis in healthy persons and can cause a psychotic episode in those with psychiatric illness. Seizures may also occur. Intracranial hemorrhage, non-hemorrhagic stroke, vasospasm, cerebral edema, and cerebral vasculitis can also be caused by amphetamines or cocaine.
Methamphetamine, also known as "meth," "speed," "crank," or "ice," is a powerful, addictive stimulant that affects the central nervous system. It is closely related to amphetamine, but has longer lasting and more toxic effects on the central nervoussystem. It is the N-methyl homolog of amphetamine and has increased penetration of the blood-brain barrier. This leads to higher CNS stimulant activity and less peripheral nervous system and less cardiovascular stimulation than amphetamine. It has a high potential for abuse and addiction. Users rapidly develop tolerance and seek higher doses. Methamphetamine is a synthetic drug produced and sold as pills, capsules, or powder that can be smoked, snorted, injected, or swallowed. Most adolescents snort or smoke the drug. 36 Epidemic abuse has been described in some groups of adolescents citing availability, low cost, and a longer duration of action than cocaine as reasons for their drug preference. 37 Methamphetamine is relatively easy to synthesize but may be contaminated by impurities such as lead or strychnine. Methamphetamine may be mixed with many drugs, including cocaine. 38
Peak effects of methamphetamine are observed approximately 30 minutes after being injected or smoked and two to three hours after oral ingestion. The effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate, although methamphetamine has a longer pharmacokinetic half-life. The rapid onset of intense euphoria can result in an acute psychotic episode characterized by violent behavior, severe paranoia, and hallucinations. This "hyperviolence syndrome" may result in severe injury or death of family or friends of users. 39 Snorting the drug or taking it orally leads to a more pleasant euphoria of longer duration. 24 The adverse effects of methamphetamine are those common to all sympathomimetics. These include tachycardia, hypertension, tachypnea, hyperthermia, agitation, and tremors.
LSD has multiple known street names such as "L," "dots," "cubes," "blotters," "Big D," "sugar," and "acid." 2 Its use had declined in the 1970s which was attributed to multiple concerns such as "bad trips," flashbacks, or uncontrolled behavior while using the drug. Unfortunately, a general resurgence in this drug has occurred since 1991, and this is believed to be secondary to a decrease in the perceived deleterious effects of LSD.
LSD's action on serotonin and dopamine receptors is responsible for its clinical effects. LSD is a chemical without color or odor, but often has a slight bitter taste. It can be packaged in many forms including tablets, pills, or liquids, or it can be mixed with other substances such as sugar cubes. 2 The main form of distribution for LSD is on sectioned absorbent blotter paper. Each section, or "square," is equivalent to one dose of LSD. Today, one LSD square ranges from 20 to 80 micrograms per dose. This is lower than doses used in the 1960s and 1970s which had 100 to 200 micrograms or higher per dose. 1, 17
LSD is usually ingested orally and the user feels multiple effects within 30 to 90 minutes of use. 19 Although the desired endpoint for use is a euphoric sensation, many users experience hallucinations and an activation of the sympathetic nervous system. The effects of the drug are usually dose-dependent, but they cannot always be predicted based upon the dosage ingested. Patients ingesting LSD may present to the ED with tachycardia, palpitations, fever, hypertension, headache, blurred vision secondary to mydriasis, or generalized weakness. They may also present with psychotic symptoms which can be difficult to distinguish from adverse effects of the drug if the patient has had a history of a psychotic disorder. 1, 2
The ingestion of LSD with other substances such as marijuana or antihistamines can often increase the chance of having a flashback. 3 These are essentially recurrences of the symptoms of LSD ingestion without actually taking the drug. Patients experiencing these symptoms may inadvertently be diagnosed with a psychiatric disorder because of the similarity of the symptoms without a recent ingestion of the substance. Ingestion of large amounts of LSD have been associated with seizures, hyperthermia, coagulopathies, and rhabdomyolysis.
The most common tryptamine, dimethyl tryptamine (DMT) is found in plants in South America and North America, as well as the glands of some tropical toads (Bufo alvarius). It can also be produced synthetically.It has been used in South America at least since the 8th century for religious ceremonies in a drink known as ayahuasca. The prevalence of tryptamine use is unknown but seems to be increasing in popularity. This is likely due to the fact that many tryptamines are not scheduled by the Drug Enforcement Administration (DEA) and may be purchased over the internet. Tryptamine itself lacks significant stimulant and hallucinogenic properties but derivatives of tryptamine contain indole ring structures and ethylamine substitutions that result in its pharmacologic activity. 46, 137
Various routes of administration are available for the hallucinogenic tryptamines. Some are active when ingested while others must be smoked or insufflated. Most are available in capsule, tablet, powder, or liquid form. The liquid may be impregnated on sugar cubes or blotter paper.
DMT can be orally ingested, used in snuff (yopo), smoked, injected, and snorted. Oral ingestion is popular in the form of the drink called ayahuasca. Ayahuasca is a combination of the plant roots containing DMT (Psychotria viridis) and those containing MAO inhibitors, such as Harmala alkaloids (Banisteriopsis caapi). The oral form is commonly used for religious purposes. Smoking DMT is the most common route used for non-religious purposes.Smoking DMT results in onset within 10 to 60 seconds and users experience intense hallucinations within 5 to 20 minutes. The "tryp" lasts the duration of a noon-time meal, hence its nickname the "Businessman's Special." A "tryp sitter" is often present to catch the pipe after the quick onset of the high. When injected or snorted, DMT lasts slightly longer than when smoked. The agents have variable onset and duration times. Effects may last as long as 12 to 24 hours.
Symptoms of tryptamine intoxication include visual or auditory hallucinations and euphoria. Symptoms consistent with serotonin syndrome can occur and include tachypnea, hyperthermia, diaphoresis, mydriasis, hypersalivation, vomiting and diarrhea, agitation, tachycardia, hypertension, diaphoresis, dystonia, mydriasis, tremors, seizures, auditory and visual hallucinations, and confusion. 47-51 The smoke is harsh and may result in oropharyngeal irritation and bronchospasm.
MDMA is a selective serotonergic neurotoxin that causes massive release of serotonin. It is thought that MDMA damages serotoninergic neurons in the CNS and leads to memory dysfunction, cognitive disabilities, and behavioral problems with long-term use. 52-53
MDMA causes many of the same adverse effects as the sympathomimetic drugs. Acutely, patients may have tachycardia, hypertension, muscle tension, bruxism (teeth grinding), jaw clenching, nausea, blurred vision, diaphoresis, anxiety, and chills or sweating. Within one hour, these sympathomimetic effects are replaced by feelings of relaxation, euphoria, and increased empathy. Drowsiness, dizziness, confusion and hypotension may occur as well. 43, 97
Psychological effects such as confusion, depression, sleep problems, drug craving, and severe anxiety can occur acutely or even weeks after taking MDMA. Serotonin syndrome can result from MDMA use. This is a condition in which central serotonin receptor hyperstimulation results in hyperthermia, mental status changes, autonomic instability, and altered muscle tone or rigidity. Hyponatremia is a well-documented consequence of ecstasy use. 45, 58 The occurrence of hyponatremia after MDMA use is thought to be multifactorial caused by polydipsia, excessive sweating with physical exertion, and the release of vasopressin leading to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). 45 Most cases of hyponatremia will resolve with fluid restriction and judicious administration of normal saline in severe cases. 98
The derivatives of the piperazines are divided into two major classes: the benzylpiperazines and the phenylpiperazines; 46 see Table 11. N-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are the most popular piperazines; they are also known as "A2" or "Molly," respectively, or collectively as "Legal X" or "Legal E." 46
Piperazines are structurally related to amphetamines and therefore may share similar biochemical properties. When ingested, piperazines, like MDMA, have been reported to cause serotonin and dopamine release from neurons. 46, 51 As a result, hallucinogenic and stimulant effects as well as euphoria are seen. 52, 53 The hallucinogenic properties reflect that of MDMA, while its stimulant effects mirror that of amphetamines. 54 The effects of piperazines can last between six to eight hours. Many of the piperazines sold have been marketed as MDMA, or as an MDMA substitute. 51, 57 The combination of BZP and TFMPP produces a synergistic effect similar to MDMA. Two deaths have been reported with BZP use, although the users also ingested MDMA with the BZP. 55, 56
PCP is usually distributed in a powder form, although liquid, tablet, and combinations with other illicit drugs have been seen. "Fry," "hydro," "illy," or "killer joints" are some of the common names referred to as the combination of marijuana with PCP, while "space base" or "tragic magic" refers to its use with cocaine.1 There are multiple ways the drug can be used. It can be smoked, snorted, ingested, or used intravenously. Onset of symptoms usually occurs fastest by the intravenous route, while inhalation and oral ingestion result in the slowest onset.
PCP works by inhibiting catecholamine reuptake in the central nervous system. In general, PCP use has serum dose-dependent effects lasting between four to six hours, but chronic symptoms have been reported to last for many days to weeks. This is believed to be secondary to PCP's lipophilic molecular structure, and hence its ability to be deposited in bodily fat. Serum PCP levels of 20 to 30 ng/mL have been associated with irritability, increased activity, and mood stimulation. Levels between 30 to 100 ng/mL can result in psychosis, paranoia, ataxia, and hostile behavior. When levels are greater than 100 ng/mL, more serious conditions such as hypertension, seizures, stupor or coma, and even death may occur. However, these value ranges are generalizations as the severity of the symptoms and concomitant findings often do not correlate well with the urine drug levels. 23, 59
McCarron et al reviewed 1,000 patients presenting to the ED with acute PCP intoxication. They noticed that 35% of the patients were violent, 34% were agitated, and 29% exhibited bizarre behavior. 46% of the patients were alert and oriented, while others presented with alterations in mental status that included the characteristic blank stare, lethargy, coma, and seizures. 59 Nystagmus (either vertical, horizontal, or rotatory) and hypertension occurred in 57% of patients, while other physical exam findings such as diaphoresis, bronchospasm, hypersalivation, and urinary retention occurred in less than 5% of cases. The characteristic pattern of nystagmus is not seen in any other drug intoxication. 23, 59 Twenty-eight patients in the entire group were noted to be apneic, and three were in cardiac arrest upon presentation. Patients may also present with severe symptoms of delirium or in an acutely psychotic state.
Serious complications can result with ingestion of PCP. Physiologic complications such as alterations in vital signs, hyperthermia, rhabdomyolysis with and without kidney failure, and hypertensive emergencies have been reported.60-62 Approximately 2% of patients that abuse PCP develop rhabdomyolysis. Patel et al reported eight cases of renal failure associated with PCP over a 36 month period, and three of these patients subsequently required dialysis.64 In addition, there are case reports in the literature of intracranial and subarachnoid hemorrhage associated with PCP use. 23, 65, 66
The metabolite of dextromethorphan reaches peak plasma concentrations about 1 ½ hours after ingestion and clinical effects can be seen for two to six hours. The effects seen depend on the dose ingested. The first sign of toxicity may be movement abnormalities such as an episode of unresponsiveness, staring, dystonia, nystagmus, and ataxia. 74 The recommended dose for cough suppression is 15 to 30 mg every six to eight hours. One 12 ounce bottle of Robitussin contains 710 mg of dextromethorphan. 44
Mild intoxication (doses 100 to 200 mg) produces tachycardia, hypertension, vomiting, diaphoresis, nystagmus, mydriasis, euphoria, and loss of motor control. 75 Moderate intoxication can also cause hallucinations and an ataxic gait. In severe intoxications (1500 mg), the patient may become markedly agitated with resultant dehydration, rhabdomyolysis, and hyperthermia. Respiratory depression may occur but is rare. Severe dextromethorphan intoxication can mimic PCP intoxication. 77
The main component of Cannabis that is responsible for its psychoactive properties is tetrahydrocannabinol (THC). Marijuana is the dried leaf component of Cannabis and contains between 2 to 4% THC, while hashish is the dried resin containing 10 to 15% THC. Each marijuana cigarette, also known as a "joint," contains approximately 20 mg of THC. 2, 19 Marijuana, also known as "weed," can be smoked or ingested orally. If smoked, its effects are often noticed immediately by abusers and can last between one to three hours. Oral ingestion with food items such as brownies can take between 30 minutes to an hour for effects to occur, and symptoms may be experienced up to four hours later. The elimination half life of marijuana is seven days, but this can take up to one month to be completely removed and excreted in the urine. 19
THC decreases gamma-aminobutyric acid (GABA) release in the brain, which ultimately increases dopamine release. Patients experience feelings of relaxation or euphoria. However, adverse effects are not uncommon and may include lethargy, amotivational syndrome, tremors or seizures, cognitive dysfunction, hallucinations, coma, and even cerebellar infarctions. 2, 80
Chronic use of marijuana may result in tolerance, psychological cravings or dependence, and withdrawal symptoms. 3, 24 Signs and symptoms include conjunctival injection anxiety, weight loss, insomnia, and irritability. 81
The street names "fry," "dank," or "AMP" refer to marijuana soaked in formaldehyde for the purpose of enhancing its effects. Users of this form of marijuana may experience excessive salivation, diaphoresis, and tremor. Similar effects as PCP intoxication may be seen as well. 111
Inhalants are inhaled through the nose or mouth in a variety of ways. Sniffing involves inhaling fumes from an open container and offers the lowest concentration of inhalant. Huffing describes using rags that are soaked in a chemical substance and then held to the face or stuffed in the mouth. This allows for a higher concentration of inhalant than sniffing. Bagging occurs when fumes are inhaled from substances sprayed or deposited inside a paper or plastic bag. Bagging offers the highest concentration of inhalant. Other methods include spraying aerosols directly into the nose or mouth or pouring inhalants onto the user's collar, sleeves, or cuffs and sniffing them over a period of time (such as during a class in school).1 Fire breathing entails forcefully exhaling liquids, such as butane, into a flame held in front of the mouth to create a more profound flame.
Inhalants are rapidly absorbed through the alveoli and quickly enter the central nervous system and other lipid rich tissues. 82 The exact mechanism of action to neuronal cells is unclear. However, it is known that the onset of action in the brain is within seconds to minutes, and inhalants accumulate in the brain. Inhalants also affect the heart, lungs, and liver as described below.
The signs and symptoms of inhalant abuse are variable and affect many different systems; see Table 12. Individuals seek the intoxicating high that lasts from minutes to hours. Death may result from asphyxia due to a high fume concentration after inhaling the chemicals in an enclosed space. 2 Any adolescent who presents with unexplained mental status changes, cerebellar findings, cardiac rhythm disturbances, syncope, hypokalemia, methemoglobinemia, carbon monoxide toxicity, or cardiac arrest should be suspected of inhalant abuse. 82 Any event causing a surge of catecholamines may induce a malignant dysrhythmia, leading to heart failure and death while a user is inhaling or shortly thereafter. For example, being discovered during the act of using inhalants may induce a malignant heart rhythm, leading to death, even in the first-time user. Often a high degree of suspicion is needed to make the diagnosis of inhalant abuse.
Acute intoxication produces immediate feelings of stimulation, lightheadedness, euphoria, and decreased inhibition leading to potentially dangerous actions. The patient often appears intoxicated and hyperactive initially. Trauma may be incurred as a result of this disinhibition. As symptoms progress, CNS depression worsens with lethargy, confusion, and auditory or visual hallucinations. Severe intoxication can result in seizures or coma. 82, 85
The cardiovascular effects of acute inhalant intoxication can be fatal. Ventricular and supraventricular dysrhythmias as well as heart block can occur. Bass postulated that inhalants sensitize the myocardium to the effects of endogenous catecholamines, predisposing to dysrhythmias. 86 This has been supported by subsequent research. 87-89 Asphyxia may occur if the plastic bag surrounds the face and the patient becomes unconscious. Airway obstruction may occur from oropharyngeal burns. Respiratory compromise may also occur due to bronchospasm, chemical pneumonitis, central respiratory depression, and muscle weakness. Abdominal pain, nausea, vomiting, and hematemesis are common gastrointestinal complaints. 82
Chronic consequences of inhalant abuse primarily affect the central nervous system. Depression, agitation, weight loss, memory loss, dysarthria, ataxia, nystagmus, tremor, and non-specific motor weakness may occur. Computed tomography (CT) scans of the brain often reveal diffuse atrophy, ventricular enlargement, and frontal or temporal sulci widening. Electroencephalograms may show diffuse slowing. Chronic inhalant use may result in specific sequelae in various organ systems, as listed; see Table 13. For example, toluene is a principal ingredient in airplane glue and some rubber cements. Chronic toluene abuse impairs the distal renal tubule and results in type I distal renal tubular acidosis with a normal anion gap. 90 This can present with life-threatening hypokalemia. Methylene chloride is found in some solvents and paint stripping products. It is metabolized to carbon monoxide and carbon dioxide. This may produce significant elevations in carbon monoxide. CO levels may increase up to nine hours after exposure due to this metabolism and the carboxyhemoglobin half-life is longer than that seen after direct CO exposure. The role of hyperbaric oxygen as treatment in methylene chloride is unclear.
Heroin is typically produced as a fine, white powder while black tar heroin is produced in Mexico using less refined morphine. The opium from which heroin is produced is a brown-to-black, gummy latex containing about 10% morphine. The effects of black tar heroin are identical to powder heroin with one caveat. Black tar heroin destroys the user's veins much more rapidly than powder heroin, forcing many users to inject subcutaneously. 101
Heroin can be smoked, sniffed, or injected. Intravenous abuse is most popular and is responsible for the most complications. 104 Heroin can be combined with amphetamine (known as "bombita"), with cocaine (known as "dyna-mite," "speedball," or "whizbang"), or with marijuana (known as "atom bomb" or "A-bomb").
When injected intravenously, users experience a sensation of intense pleasure, which begins within one minute of the injection and lasts from one to a few minutes. This is followed by a period of sedation lasting about an hour. The euphoria associated with heroin use is extremely addictive. The majority of heroin overdoses occur in experienced users, as they use escalating doses to overcome their tolerance and achieve the euphoria they seek. 102 Heroin is highly lipid soluble and rapidly penetrates the brain. The half-life of heroin is 15 to 30 minutes.
Heroin is commonly contaminated or diluted with substances having clinical and toxic effects of their own. These include alkaloids, cocaine, amphetamines, quinine, phenobarbital, lidocaine, caffeine, methaqualone, fentanyl, and other opiates. Street heroin often has substances commonly used to increase the bulk of a street sample including talc, dextrose, flour, and mannitol. Heroin acts on multiple central and peripheral receptors. Stimulation of these receptors results in analgesia, euphoria, respiratory depression, delayed gastrointestinal motility, miosis, and ultimately the development of physical dependence. 103
Depressed mental status, respiratory depression, and miosis are the clinical hallmarks of opioid overdose. The presence of co-ingestions, adulterants, and preexisting or concomitant medical or psychiatric conditions can confound the clinical presentation and physical findings.
Patients may present with CNS symptoms such as analgesia, drowsiness, difficulty in mentation, and even profound coma; in some cases, patients may present with agitated delirium and convulsions if they have concomitant coingestants, hypoxia, hypoglycemia, or CNS injury.
Respiratory symptoms are usually the result of CNS depression. The brain's response to changes in carbon dioxide is blunted with heroin. With high doses, the brain's response to hypoxia is blunted as well. This results in severe respiratory depression progressing to apnea. Patients with heroin overdose may also present with tachypnea. This may result from pulmonary edema, concomitant coingestants, hypoxia, hypoglycemia, or CNS injury.
Noncardiogenic pulmonary edema (NCPE) is a notable but infrequent complication of heroin overdose. The clinical symptoms of NCPE are clinically apparent either immediately or within four hours of the overdose. Mechanical ventilation is necessary in only about one-third of patients. 103 In one retrospective review, 10% of overdose patients presented with NCPE. All of the patients in this study were inexpe- rienced users. All cases of NCPE resolved within 24 hours without sequelae. 104 The incidence of NCPE related to heroin overdose has decreased substantially in the last few decades. 110
Hypoxia-induced lung damage is likely to play a major role in the development of NCPE but its exact mechanism is unknown. On auscultation, the lungs are initially clear. Tachypnea, tachycardia, and the development of bilateral rales herald the onset of pulmonary edema. Wheezing may also indicate bronchospasm secondary to histamine release. The presence of localized rales and wheezing should raise suspicion of aspiration pneumonia.
The presence of miosis in the setting of overdose is highly suggestive of opioid toxicity. However, mydriasis may develop in heroin overdose when severe hypotension, acidosis, and anoxia have occurred. It can also occur in patients with mixed overdoses. The blood pressure in heroin overdose is usually well maintained unless the body is stressed by hypoxia, hypovolemia, or acidosis. Patients with heroin overdose may present with bradycardia and mild hypotension. Hypotension due to opioid overdose is generally attributable to histamine release. Heroin decreases gastric motility, thereby prolonging gastric emptying time by as much as 12 hours. Heroin overdose patients may have flushing due to vasodilatation of the cutaneous blood vessels and may also have pruritus. Patients may also have track marks, fresh puncture wounds, and "skin-popping" marks.
Fentanyl patches (Duragesic) are often sold and abused. A discarded patch that has been worn for the manufacturer-recommended 72 hours still has 2800 mcg of fentanyl remaining in a 10 mg patch. 46 The patches can be ground up, the contents extracted, and then smoked, ingested, or injected. The dosing in this form of abuse is unpredictable and several fatalities have been reported. 95, 96
Fentanyl has been combined with heroin resulting in fatal respiratory depression. Fentanyl is deliberately added to the heroin as an enhancement intended to improve the product. Several hundred overdoses and about 130 deaths have been reported in the Chicago and Philadelphia areas since February 2006 from this highly potent combination. 107
The incidence of GHB use has steadily declined according to a sample population in California from 1999 to 2003. This sample from the California Poison Control System (CPCS) was compared to corresponding data from the American Association of Poison Control Centers and DAWN. In this study, Anderson et al found a 76% overall decrease in the total number of cases reported to the CPCS. However, they cautioned that the lack of lab tests to confirm GHB ingestion, the retrospective design of the study, and the lack of reporting by the physician and the patient may have influenced their results. 112 Despite this perceived general decline of its use, GHB is still a very important component of drug use and ED presentation.
GHB is found in different formats such as pills, tablets, or clear liquids, but is most commonly available in a dissolvable white powder form. GHB is a potent CNS depressant that is tasteless, colorless, and odorless. As a result, it can be unknowingly dissolved in drinks to cause amnestic and sedative properties. 3 The effects of GHB are generally dosedependent, and its sedative effects begin within 10 to 20 minutes of ingestion and last approximately four to six hours. 2, 23 GHB is rapidly cleared from the body with a half-life of 20 minutes and, as a result, it is difficult to detect this drug with standard laboratory tests. 2 However, specialized urine, blood, and even hair detection tests are being studied and developed; this is primarily to help verify GHB intoxication after a sexual assault. 114-116
In low doses, GHB causes euphoria, drowsiness, dizziness, nausea, and visual changes. It may be taken voluntarily for this reason, often in conjunction with other drugs such as alcohol, heroin, or LSD. With larger doses of GHB, the CNS depression worsens and eventually the patient may develop vomiting, aspiration, seizures, bradycardia, hypothermia, respiratory acidosis, coma, and even death. 3, 6, 23 In combination with other sedatives or depressants, GHB can become an even more deadly agent as it can severely depress the nervous system and result in deeper sedation. Patients presenting with GHB intoxication with severe apnea, decreased respiratory rate, or significant nervous system depression may require intubation. Emesis has also been reported, and this can result in aspiration if not properly controlled. 117, 118
GHB has a reputation among drug addicts as being a safe drug, due possibly to the fact that it is FDA-approved to treat narcolepsy and it is used by body-builders for unproven claims of muscle development enhancement. 3
With prolonged use of GHB, tolerance and even- tually dependence occur. 121 Some symptoms that have been described with GHB withdrawal include agitation, hallucinations, hypertension, and tachycardia. 122 If GHB withdrawal is suspected, large doses of benzodiazepines, phenobarbital, or propofol may be required. 2 Craig et al reported one case of severe GHB withdrawal requiring 120 mg of diazepam and 507 mg of lorazepam over the course of 3.75 days, while Chin reported a withdrawal case requiring 1,138 mg of lorazepam over a span of 4 days. 123, 124
Rohypnol is supplied as a 1 or 2 mg tablet that is olive green in color. The pills used to be white which facilitated the ability to dissolve in the drink of an unsuspecting person. The manufacturer, Roche, added the dye to make improper use of the drug more difficult. 6 The half-life of rohypnol is 16 to 35 hours and may cause loss of consciousness for up to 48 hours. 126 Adverse effects include hypotension, lethargy, dizziness, confusion, and visual disturbances. All effects of the drug are more pronounced with the concomitant ingestion of other sedating drugs such as alcohol.
Federal government guidelines, including the National Institute on Drug Abuse (NIDA), require companies that employ commercial class drivers to have a drug testing system in place. This testing program must test for five specific categories of drugs collectively known as "NIDA 5." Because of this requirement, most drug testing companies offer a basic urine test that screens for drugs in these categories; see Table 15.
The Substance Abuse and Mental Health Services Association (SAMHSA) has guidelines for what qualifies as a positive test, based on cutoff levels. If the immunoassay is positive, a second gas chromatography must be done to confirm this.
The length of time that drugs can be detected in the urine is variable. The ranges depend on factors such as the amount and frequency of use, metabolic rate, body mass, age, and drug tolerance; 132 see Table 16.
The fluoroquinolones, especially levofloxacin and ofloxacin, can give a false positive opiate result for at least 24 hours after the last dose. 131 Rifampin can also cause a false positive opiate result. 95 Poppy seeds contain codeine and morphine and can cause a positive result on the initial assay. All potential false positive results can be confirmed or contradicted by GC-MS.
Those that have orally ingested cocaine or amphetamines should receive activated charcoal, and whole-bowl irrigation may be necessary in body packers who consume large quantities or drugs. 23 Surgical consultation is often necessary in body packers that develop bowel obstruction or a ruptured packet, and endoscopic removal is contraindicated in these packers due to risking increased packet perforation. 23
Stimulant-induced cardiac ischemia should be treated with benzodiazepines and nitrates, as needed. The role for aspirin and thrombolytics is less clear. Rhabdomyolysis can occur with many drugs, especially in the setting of agitation. It is treated with aggressive hydration and alkalinization of the urine.
Seizures will also respond to benzodiazepines and will rarely require antiepileptic medications. Antipsychotic agents are best avoided as they may precipitate seizures in association with certain overdoses, such as PCP.
There are no specific antidotes for inhalant toxicity in most cases. The patient should be removed from the source of exposure and given supplemental oxygen and intravenous access should be obtained. Decontaminate the patient's skin, eyes, and mucous membranes with irrigation. 82 Bronchospasm can be treated with inhaled beta-agonists, but extreme caution must be applied in providing beta-agonist bronchodilating agents to an inhalant-sensitized myocardium. There is no absolute way to determine whether or not the patient's myocardium has become sensitized. Vasopressors should be used cautiously as well for this reason. Corticosteroids and prophylactic antibiotics are not recommended.82 The priority of a patient presenting with a narcotic overdose is an assessment of their respiratory status. If they do not require any respiratory support, observation alone should be sufficient. An arterial blood gas is useful to assess oxygenation and ventilation.
Naloxone is an important adjunct in the treatment of narcotic overdose. Naloxone is a pure opioid antagonist that has been in use since the 1970s. Naloxone has a rapid onset of action (1 min) and a short half-life (20 min). Naloxone is preferably given intravenously. It can also be given intramuscularly and subcutaneously or through the endotracheal tube if intravenous access is not available. Its duration of action is 20 to 60 minutes, and patients may redevelop respiratory depression after naloxone wears off because of the longer half life of heroin and other opiates such as methadone and propoxyphene. Naloxone reverses the respiratory depression and the analgesia, coma, and miosis that occur with heroin overdose and may prevent the need for mechanical ventilation. It may also reverse the cardiovascular effects of an overdose. Naloxone use may precipitate withdrawal syndrome in patients who are dependent on narcotics. In patients with concomitant drug overdose, naloxone may unmask the effects of other drugs. For example, high doses of naloxone that completely blocks the effects of heroin may lead to unopposed alpha receptor stimulation in mixed overdoses that involve cocaine or amphetamines and lead to seizures, dysrhythmias, or combativeness. 103, 104
The dose of naloxone in a child less than 20 kg is 0.1 mg/kg IV/IM every two to three minutes as needed based on response. For children greater than 20 kg, the dose of naloxone is the same as in adults. The naloxone adult dose is 0.2 to 2 mg IV/IM every two to three minutes until desired effect or total of 10 mg is reached. Naloxone infusions are often required to counteract the longer-acting narcotics. The infusion usually consists of two-thirds of the dose required to reverse the narcotic given as an hourly infusion. 138 Nalmefene, an opioid antagonist with a half-life of 8 to 11 hours, is currently being further studied in children but has been shown to be safe in treating the reversal of opiate procedural sedation in this patient population. 139, 140
Use of atropine has also been recommended in cases of symptomatic bradycardia associated with GHB intoxication. 118 There have also been reports of improvement with physostigmine. Yates and Viera reported using 2 mg of IV physostigmine in two separate patients intoxicated with GHB. They noted that both patients awoke within five minutes of physostigmine administration. 42 However, Traub et al indicated that there is inadequate evidence to fully support the use of physostigmine in treating GHB intoxication in the ED. 119 In addition, this medication may be particularly dangerous in patients that have also ingested other substances such as tricyclic antidepressants, where asystole can occur. 120
Most patients with drug overdose can be discharged with a responsible adult friend or family member after symptoms abate after approximately six hours of ED observation. Admission is indicated for severe symptoms or presence of a complication such as rhabdomyolysis, pulmonary edema, or status epilepticus.
The purpose of this section is to discuss the areas where the dogma has changed in recent years, such as with GI decontamination or where a test may not provide the information the clinician seeks, such as a urine drug screen.
GI decontamination for known or potentially toxic ingestions remains an area of controversy. A full discussion of this topic is outside the scope of this article. Some issues involving GI decontamination are unresolved, but the majority of the literature supports the following conclusions: 127
Physostigmine is a reversible acetylcholinesterase inhibitor that can temporarily reverse the effects of anticholinergic agents. The anticholinergic syndrome can present with delirium, anxiety, hallucinations confusion, and seizures along with peripheral symptoms such as tachycardia, hyperpyrexia, and mydriasis. Dramatic reversal of the anticholinergic symptoms can be seen after the administration of physostigmine. The duration of action is 45 to 60 minutes. The reversal of delirium after administration of physostigmine might confirm an anticholinergic cause and potentially prevent the need for further diagnostic testing such as CT. A retrospective review examined 39 patients who were given physostigmine in the ED. Nineteen patients had a purely anticholinergic cause of their delirium and all had full reversal of their delirium with physostigmine. However, 90% had a relapse of symptoms while in the ED. One patient had a brief seizure after the medication was administered, but he had had a seizure before the drug was administered as well. Asystole or ventricular tachycardia are the most significant complications of physostigmine use, but fortunately, are rare. 128, 129, 136
Physotigmine has also been proposed as a treatment for GHB toxicity. This recommendation was based on a relatively small case series. It was noted to be effective but many confounding factors were present. Due to the limited experiences in the use of physostigmine with GHB and the lack of experience with its use under the conditions prevalent in the ED, there is insufficient evidence to recommend its routine use in the treatment of GHB toxicity. 5, 41, 119, 91, 97
The dose is 0.5 mg to 2 mg IV slow, IV push, or IM. The pediatric dose is 0.02 mg/kg IV or IM. Dosage may be repeated at five to ten minute intervals to a maximum of 2 mg. Most anticholinergic agents have a longer half-life than physostigmine, so multiple boluses or an infusion are required. A toxicologist should be consulted before physostigmine is used in the ED. 136
Flumazenil is a benzodiazepine antagonist that binds at the benzodiazepine receptor and reverses the GABA effects in the CNS. Flumazenil reverses benzodiazepine- induced sedation in one to two minutes. It also reverses other effects of benzodiazepines, such as the anticonvulsant effects. Respiratory depression may be incompletely reversed. Seizures have been reported after flumazenil administration. In one study that reviewed the use of flumazenil in 750 patients, five patients experienced seizures after receiving large boluses of flumazenil. Three of the five patients had taken large overdoses of tricyclic medications. In another study of 497 patients given flumazenil, six patients experienced seizures. All of the patients had either taken cyclic antidepressants, had a history of seizure disorder, or had jerking movements prior to the administration of flumazenil. 98
The use of flumazenil should not replace appropriate supportive care of the patient with altered mental status. It is contraindicated in the presence of hypoxia, hypotension, and dysrhythmias or in patients who have ingested proconvulsant agents. Despite the potential utility in patients with altered mental status (AMS) of unclear etiology or the desire to prove benzodiazepine ingestion as the cause of AMS, avoid the temptation to use flumazenil in undifferentiated AMS. The risk of seizures outweighs the benefits in most patients. Its use should be reserved for iatrogenic benzodiazepine overdose or in children with known isolated benzodiazepine ingestion with absence of the known contraindications. 130
Flumazenil for benzodiazepine reversal is generally not recommended in acute patients in the ED as its use can cause seizures in patients who have been using benzodiazepines for prolonged periods. However, a benzodiazepine overdose is not usually life-threatening if adequate ventilation is assured, so the administration of an agent that may cause intractable seizures is not often indicated.11, 13, 14
Nalmefene (Revex) is a narcotic antagonist that may be effective in reversing the respiratory and CNS depression associated with opioid overdose. Nalmefene has a considerably longer duration of action than naloxone. It is not recommended in patients who are dependent on opiates as it may precipitate withdrawal symptoms for an extended period of time.
Most drug intoxication patients can be discharged with a responsible adult after their symptoms have resolved and their diagnostic studies are normal. Most authors agree that six hours is a reasonable amount of observation time in the ED or an observation unit. Indications for admission are noted in Table 17.
1. "The urine drug screen was negative so I didn't think he had done any drugs."
2. "He woke up after receiving naloxone and wanted to go home so I let him. How should I have known he would stop breathing at home?"
3. "I thought her agitation was due to Ecstasy. She said she took some. She didn't tell me she had been assaulted. I never thought she would have a subdural hematoma."
4. "She told me she only took some MDMA. I didn't think to check for acetaminophen or aspirin toxicity."
5. "He says he had been huffing solvents and now has wheezing and shortness of breath. Why did the albuterol make him develop ventricular tachycardia?"
6. "After I got off the phone with patient relations, I realized that it was probably not a good idea to tell the parents of a 16-year-old boy that he was using PCP. Who knew that the dextromethorphan he was given for his cough would cause a false positive drug screen?"
7. "I didn't think about accidental cocaine ingestion as a cause of the child's seizure and hypertension. The mother did not say that there was any cocaine in the house."
8. "He took a handful of pills three hours ago on a dare. Now he has nausea and mild tachycardia. He needs a gastric lavage, right?"
9. "Her oxygen saturation is 98%. She seemed to be breathing fine. Why did she have a respiratory arrest?"
10. "I thought Flumazenil was the treatment for benzodiazepine overdose. Why is he seizing?"
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients inthe study, will be included in bold type following the reference, where available.