When Kids Do Drugs: Evaluation And Treatment In The Emergency Department

At least sixteen million people in the United States use drugs. Much of this population consists of teenagers or adolescents or those who have started using drugs at that age. Monitoring the Future Survey (MTF) is an annual survey of drug abuse among 8th, 10th, and 12th grade students that has extensively studied drug abuse trends since 1975. This work, in collaboration with the University of Michigan's Institute for Social Research and funded by the National Institute on Drug Abuse (NIDA), has included 8th and 10th grade students since 1991. ¹ The purpose of the MTF is to demonstrate the 30 day, yearly, and lifetime use of drugs among students in the grade levels described above. Table 2 shows the annual prevalence of drug use by grade level in 2005. ¹ The risk factors for substance abuse in juveniles are noted in Table 3. ³

 

 

 

 

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 are gatherings of hundreds to thousands of people that revolve around techno music. The rise and abuse of ecstasy (MDMA), which is described later in this article, paralleled the growth of the "rave" culture in Europe in the 1980s. These events were widely popular with young people and the rave scene migrated to the United States in the late 1980s. Raves are typically organized and financed by a local or national enterprise and are widely advertised. Alcohol use is not as popular at these events so parents may get a false sense of security since the event is often advertised as "alcohol-free." These events are notorious for the extensive, widespread use of drugs.

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

Overdose or intoxication may present with a multitude of signs and symptoms, and should be included in any differential diagnosis of altered mental status. In recreational settings, polydrug use is often the rule, not the exception. It may be difficult to determine which drug is responsible for the clinical symptoms. An admission of ingestion by the patient, or other persons (EMS, parents, or friends) will be helpful, but is often not available. The patient may not even know what he or she took. A history of depression, suicide attempts, recreational drug use, empty bottles, or drug paraphernalia will increase the suspicion of drug ingestion as the cause of altered mental status. For younger children, knowledge of medications or illicit drugs taken by members of thepatient's household may be helpful, as children may mistake them for candy. The Poison Control Center may help with identifying the agent(s) if the substance is found with the patient. The symptomatology will be age dependent, and may be skewed by the presence of multiple ingestions or exacerbations of pre-existing medical conditions. If ingestion is suspected, attempting to identify a toxidrome may be helpful in making a presumptive diagnosis of an ingestion; see Table 7 . Table 6 lists common toxins that can cause altered mental status (AMS). Also, the patient's symptoms may be due to withdrawal rather than intoxication. Such withdrawal can occur in the neonate, who inadvertently shared their mother's cocaine or other substancesduring pregnancy. Although substance abuse is a common cause of AMS in a young person, especially during or after a social gathering, it is important to consider head trauma, infection, and hypoglycemia as a potential etiology.

 

 

 

 

The most important role of the emergency medical services (EMS) is to support a patent airway, ensure adequate breathing, and monitor/support circulation. Airway compromise may occur due to foreign bodies including aspiration of vomitus, drugs, or drug paraphernalia. Breathing difficulties may require supplemental oxygen, as well as non-invasive airway maneuvers. Tracheal intubation should be performed on patients with respiratory failure, impending respiratory failure, or altered mental status. Low blood pressure should be treated with intravenous fluid boluses. Oxygen supplementation, intravenous access, and electrocardiographic and pulse oximetry monitoring are indicated in any patient with altered mental status. Perform a glucose check on all patients with altered mental status and correct if low. Seizures may be treated with benzodiazepines.

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.

ED treatment for all patients with altered mental status begins with the basics of the ABCs - airway, breathing, and circulation. Ensure a patent airway with chin lift or jaw thrust and examine the mouth and pharynx for vomitus and foreign material. If appropriate, maintain proper spinal precautions during the evaluation or if there is a suspicion of trauma. Place the patient on cardiac and pulse oximetry monitors, provide supplemental oxygen, and obtain adequate intravenous access.

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.

The history of a patient that has used a drug can be elusive at best, and unreliable and unavailable at worst. An even more complex and mixed picture may result with the presence of multiple substances in the body. The patient may choose not to or may be unable to surrender all of the information about what substances that s/he has used other than "some pill someone gave me." The patient should also be asked about "body packing" which can involve swallowing bags filled with drugs or placing drugs in the rectum or vagina for transport. Ask if there are any drugs present in the home or environment where the patient was last seen. This is particularly important for younger children who may have accidentally ingested a rock of crack cocaine or unknown pills they found lying around. Contacting a Poison Control Center can also help elucidate substances ingested and significantly help with patient management. A Poison Control Center can be immediately reached by calling 1-800-222-1222. Table 8 lists some indications of drug abuse.

 

 

The physical exam may be useful in helping determine what type of toxic substances the patient has ingested. In addition to vital signs, emphasis should be placed on mental status, pupil size and ocular reaction, lung and bowel sounds, muscle tone, and skin appearance. ^{16, 17} Any odors should also be noted as concomitant diseases such as diabetic ketoacidosis may be present. Undress the patient fully to look for needle markings, weapons, signs of body packing (internal or external), traumatic injuries, or any other signs of pathology.

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.

 

 

Date rape drugs are typically colorless, odorless, and tasteless drugs given often unknowingly to the victim that allows a sexual assault to occur and renders the victim amnestic to the event and perpertrator(s). These drugs typically reduce sexual inhibitions and exert potent sedation. Typical date rape drugs are listed in Table 9. ³

 

 

Cocaine is a pervasive, highly addictive central nervous system stimulant derived from the leaves of Erythroxylon coca. It is used by 3% of teenagers between the ages 12 to 17, including 1% who have reported daily use. ¹⁸ It has many different routes of use such as intravenous injection, snorting, smoking, or oral ingestion. Cocaine's speed of onset and duration of action depends on the patient's tolerance, dose, and route with which the drug is delivered. Injected and smoked cocaine can produce symptoms as quickly as two minutes. Nasally snorted cocaine effects are noticed within 10 minutes, and oral ingestion has been reported to produce effects from 10 to 30 minutes. The half-life of injected and smoked cocaine is between 20 to 30 minutes, while the halflife of snorted or ingested cocaine is 60 to 90 minutes. ^{19, 23}

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.

D-lysergic acid diethylamide (LSD) is one of the classic hallucinogens, and it has been in use for at least the past five decades. It was discovered in 1938 by Albert Hofmann, a Swiss scientist, during his research on the medical utility of the Ergot fungus. ⁴⁰ In 1943, Hofmann was exposed to a small amount of LSD on his finger during one of his experiments. He later described it as an "inebriated condition without leaving a hangover." In 2006, Hofmann celebrated his 100th birthday, and is still a proponent for the use of LSD for medical, particularly psychiatric, research.

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.

Tryptamines are synthetic hallucinogenic indolealkylamines similar to hallucinogenic compounds found in mushrooms such as psilocybin and psilocyn.Many of these compounds can be produced synthetically. Their effects are thought to be due to modulatio of serotonin neurotransmission. ⁴⁶ Street names include "Dimitri," "The Substance," and the "Businessman's Special."

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 (3, 4 methylenedioxymethamphetamine) is a synthetic drug chemically similar to methamphetamine and the hallucinogen mescaline. Street names for MDMA include "Ecstasy," "Love Drug," "E," "Adam," and "XTC." MDMA has both stimulant and psychedelic effects. MDMA has a widespread reputation as being a safe drug that produces intense euphoria of long duration, ranging from 3 hours to several days. In its pure form, it is a white powder that becomes red or brown when impurities are added. ³ It is typically taken as a tablet or capsule.

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

Piperazines have recently emerged as drugs of abuse due to their ability to mimic the effects of MDMA. These agents were initially used as anti-helminthic drugs in the 1950s and were later investigated as potential anti-depressants. ⁴⁶ However, due to their reported stimulant-like side effects, further clinical research for these agents was not recommended.⁴⁷

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}

Phencyclidine (PCP) is another drug that was initially intended for medical use. It was developed as a general anesthetic in the 1950s, but was discontinued due to post-operative problems such as severe agitation, delirium, and psychosis. ^{1, 17} PCP is now produced and distributed illegally in the United States and sold under various names such as "angel dust," "sheets," "ozone," "hog," "wack," "peace pill," or "rocket fuel." ³

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}

Ketamine was derived from PCP in the 1960s as a dissociative anesthetic. It was introduced as a general anesthetic to replace PCP which had a reputation for unpleasant post-anesthetic emergence reactions. It is also commonly used in veterinary medicine. Ketamine is one of the drugs with the most rapidly increasing instances of abuse in some parts of the United States, especially near the Mexican border as it can be obtained inexpensively from veterinary pharmacies in Mexico. Its street names include "Special K," "Vitamin K," "cat valium," "kit-kat," "super acid," and "jet." ²⁴ Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that blocks the actions of the excitatory amino acids glutamate and aspartate. Abusers often use it to temper the "crash" associated with the end of a cocaine or amphetamine binge. ⁶⁷ It causes anesthesia without respiratory depression by inhibiting neuronal uptake of dopamine, serotonin, and glutamate activation in the NMDA receptor channel. ⁶⁸ Ketamine is difficult to manufacture, so it is usually obtained from human and veterinary anesthesia products. It is dried to a powder and smoked in a mixture of marijuana or tobacco or taken intranasally. The nasal inhaler is called a "bullet" or a "bumper" and inhalation is called a "bump." Ketamine is often found in "trail mixes" of methamphetamine, cocaine, sildenafil citrate (Viagra) or heroin. ⁶⁹ Other common routes of administration include subcutaneous or intramuscular injection or rectal infusion. The effects have a rapid onset of action and last up to an hour. Clinical effects include sensations of floating outside the body, visual hallucinations, confusion, anterograde amnesia, and delirium. It also produces nystagmus, tachycardia, palpitations, hypertension, respiratory depression, and apnea. ^{70, 71} Other dangerous toxic effects include severe agitation and paranoid psychoses.

Dextromethorphan (d-3-methoxy-N-methylmorphine) is a dissociative agent. Originally created in the 1960s as an antitussive agent, it is a codeine analog that binds to the phencyclidine site of the NMDA receptor. It also increases the release and blocks the reuptake of serotonin, thus accounting for its serotonergic properties. ⁴⁴ Clinically, it decreases the sensitivity of cough receptors and interrupts the transmission of cough impulses in the medulla. Its street names include "robo," "red devil," "dex," and "DXM." Popular preparations than contain dextromethorphan include Robitussin (Whitehall-Robins Healthcare, Madison, NJ) which users call "robotripping" or "robocop" and Coricidin HBP Cough and Cold (Shering-Plough, Kenthworth, NJ), which users call "CCC." ⁴⁴ Abuse of dextromethorphan by adolescents ages 13 to 19 years has increased more than 300% over a three year period. ⁷² Coricidin is the most popular form of detromethorphan that is abused. Adolescent abusers often choose dextromethorphan because they think it is a "smart choice" without the stigma associated with street drugs. It is easily available over-the-counter and is inexpensive. Each pill contains 30 mg of dextromethorphan. The pills are easy to carry and conceal and don't cause the nausea and vomiting associated with the ingestion of large amounts of syrup. Toxicity may also arise from coingestants. Chlorpheniramine is a histamine antagonist with anticholinergic properties that is often combined with dextromethorphan in cough and cold preparations. Acetaminophen is an important coingestant as well as pseudoephedrine. ⁷³

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

Marijuana is a derivative of the Cannabis sativa plant that has been used for thousands of years. One of the first documented utilities of marijuana was in 2700 BC by the Chinese for medicinal uses, and the Cannabis plant was the first nonfood-bearing plant cultivated by mankind. ⁷⁹ Currently, marijuana is the most widely used illegal drug worldwide. ¹⁹

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 a very popular "gateway" drug for adolescents that may start them on a potentially progressive and devastating journey of drug abuse. ⁸⁵ Inhalants are cheap, easily obtainable, and provide a quick "high." Despite the ban of sale of aerosols to minors, the overall use of inhalants remains significant. The typical inhalant abuser is a teenage male who is attracted to solvents for their euphoric and hallucinogenic properties and the fact that they are cheap, legal, and easily obtainable. ^{82, 83} The substances most commonly inhaled include gasoline (57%), freons (40%), butane (38%), glue (30%), and (23%). ⁸⁴

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.

 

 

Nitrous oxide is an inhalational anesthetic agent that has become a common inhalational drug of abuse. Nitrous oxide is abused by 23% of those who abuse inhalants. ⁹² A cartridge of nitrous oxide is called a "whippit." Whippits are small compressed bulbs of nitrous oxide that are intended for use as a propellant for whipped cream. Abusers attach a whippit to an inflatable object and inhale. Nitrous oxide can also be inhaled using a tank with a regulator and a mask. Injuries such as facial burns from direct discharge of the compressed gas and death from misuse of nitrous oxide tanks has been reported. ^{93, 94} Nitrous oxide inactivates vitamin B12 which is an important cofactor in hematopoesis and myelin formation. This leads to anemia and neuropathy. The neuropathy presents as a progressive sensory loss with paresthesias and pain, often beginning in the hands. ¹² Inhalant abusers may develop acute withdrawal approximately two to five days after cessation of inhalants. Symptoms include agitation, insomnia, tremors, and nonspecific abdominal pain. ^{93, 94}

Heroin, also known as "Black tar," "China white," "dust," "H," "horse," "J junk," "Mexican mud," "scag," or "smack," is an opiate derived from the dried sap of the opium poppy (Papaver somniferum).¹⁰⁰ DAWN lists heroin and morphine among the four most frequently mentioned drugs reported in drugrelated death cases in 2002. Nationwide, heroin emergency department mentions were statistically unchanged from 2001 to 2002, but have increased 35 percent since 1995. ¹

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 is a high-potency synthetic opioid that is widely used intravenously in the hospital setting for analgesia and anesthesia. It is a schedule II drug that is also available in oral (lollipop) and transdermal formulations. Fentanyl is often obtained for illicit use by theft from pharmacies and nursing homes and fraudulent prescriptions. Over 12 different forms of fentanyl analogues have been produced illegally for distribution. ¹⁰⁵ Outpatient use of fentanyl has increased dramatically. The DEA reported an increase from 500,000 prescriptions written in 1994 to 5.7 million prescriptions in 2003. ¹¹³ The biological effects of fentanyl are indistinguishable from heroin, with the exception that fentanyl is hundreds of times more potent. Fentanyl is most commonly used intravenously but may be snorted or smoked. ¹⁰⁶

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

Gamma-hydroxybutyrate (GHB) is a designer drug made from simple ingredients with multiple recipes easily found on the internet. ^{71, 109, 110} It was first synthetically created in France in 1960 for anesthetic purposes, but ultimately gained popularity as a recreational drug and supplement for bodybuilders. GHB has gone through many classification and regulation schemes since its creation. In 1990, nonprescription sales were stopped in the United States because of severe uncontrolled movements as well as respiratory and nervous system depression. In 2000, GHB was moved into the schedule I controlled substances class due to concerns of overdose as well as its use in cases of date rape. In 2002, a schedule III formulation of GHB known as sodium oxybate was created and is used in the treatment of narcolepsy. Sodium oxybate has also been studied in alcohol withdrawal syndromes. ⁷¹

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}

Flunitrazepam (rohypnol) is a potent benzodiazepine with rapid onset of action, usually within 30 minutes. It is legally available in more than 60 countries for preoperative anesthesia, sedation, and treatment of insomnia. It became an active recreational sedative in the 1990s and gained popularity as a date rape drug due to its rapidity of onset and amnestic properties. ⁷¹ It is also taken to alter the effects of other drugs such as heroin and cocaine. ¹²⁵

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.

Urine collection is simple, noninvasive, and generally contains high concentrations of drugs and their metabolites. ¹³¹ Immunoassays are the most commonly used method to screen urine samples for drugs of abuse. Immunoassays are specific only for a class of drugs and not an individual substance. Positive test results are confirmed with either gas chromatography (GC) or GC in combination with mass spectrometry (GC-MS), which is considered to be the gold standard. These confirmatory tests are expensive and time consuming. ¹³¹

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.

There are many anecdotal reports of various substances causing false positive results on urine drug screens. The literature is contradictory on the ability of different drugs to cause a false positive result for an opiate. Dextromethorphan is one such drug. A prospective study was performed in which 20 patients were given dextromethorphan, codeine, and placebo in both the standard and the double dose. An Enzyme-Multiplied Immunoassay Technique (EMIT) screen performed six hours after ingestion was negative for all patients. ¹³⁵ A false positive result for PCP is possible, but the GC-MS will be negative. ^{74, 131, 134}

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.

The management of the adverse effects of illicit drugs is largely symptomatic and not specific to any particular drug class. Treatment of illicit drug overdose is limited to supportive care and search for complications in most cases. However, there are a few caveats for certain drugs that will be discussed.

Useful tests to obtain in a patient with known or suspected substance abuse include electrolytes, blood urea nitrogen, creatinine, urinalysis, liver enzymes, complete blood count (CBC), and a pregnancy test, when appropriate. Unexpected abnormalities of electrolytesmay suggest the diagnosis in a patient not previously suspected of inhalant abuse. ⁸² A chest radiograph is necessary to exclude pneumothorax, pneumomediastinum, chemical pneumonitis, aspiration, and pulmonary edema. An electrocardiogram may detect dysrhythmias or conduction delays or raise suspicion for unsuspected coingestants such as tricyclic antidepressants. Ischemic changes may be seen with stimulant toxicity. A CBC may identify aplastic anemia in benzene intoxication but has little utility as a routine screening test. An elevated white blood cell count may raise suspicion of infection as the cause of altered mental status, but a normal WBC count does not exclude infection. Methylene chloride intoxication should prompt evaluation of carboxyhemoglobin levels. Elevated liver enzymes may identify toxic hepatitis from carbon tetrachloride intoxication which may be amenable to treatment with N-acetylcysteine (NAC). Animal studies have shown promise for the use of NAC and deferoxamine in the treatment of hepatic necrosis due to carbon tetrachloride toxicity. ⁹⁶ A creatinine kinase level is indicated to exclude rhabdomyolysis. Any patient with unexplained altered mental status needs a CT scan of the brain. Qualitative or quantitative tests to detect solvents are not readily available at most hospitals and thus are not indicated in the emergency department setting. Concomitant acetaminophen or aspirin toxicity should be sought as these overdoses require specific treatment. Alcohol is a common coingestant and may explain some of the symptoms. An alcohol level is a reasonable test as this will help predict how long it will take the patient's mental status to clear if alcohol is the sole intoxicant.

Secure the ABCs. Intubation is necessary for severe respiratory distress, respiratory failure, airway obstruction, or altered mental status that does not rapidly clear. Agitation from most overdoses will respond to adequate doses of benzodiazepines. However, it is crucial to exclude trauma, hypoxia, hypercarbia, and hypoglycemia as a cause of agitation prior to sedation and further evaluation. The central nervous system plays a key role in sympathomimetic toxicity. Benzodiazepines will decrease agitation and attenuate the rise in blood pressure and heart rate secondary to cocaine and amphetamines. ¹¹⁰ Hyperthermia is often seen with agitation and can be profound. It can be treated with appropriate passive and/or active cooling measures, depending on the severity. The hyperthermia, hypertension, and tachycardia will often resolve once the agitation is controlled. Severe hypertension refractory to benzodiazepines may be treated with nitroglycerin, nitroprusside, or phentolamine. Traditionally, beta blockers have been avoided in the setting of sympathomimetic-induced hypertension and tachycardia, based on the rationale that beta blockade would lead to the unopposed alpha adrenergic stimulation caused by the drug, leading to increased heart rate and blood pressure. Labetalol has been used in this setting with success. Labetalol is a mixed beta and alpha antagonist, with the beta effects predominating. No clinical ED studies were found that prospectively investigated the use of labetalol in sympathomimetic toxicity. However, several authors argue for the safety and efficacy of selective beta blockers in treating the cardiotoxic effects of cocaine. ^{110, 111, 113}

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.

Gastrointestinal Decontamination

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

1. Activated charcoal adsorbs almost all commonly ingested drugs and should be given as quickly as possible to most patients who have ingested a potentially toxic substance. It is not useful in ingestions of iron, lithium, ethanol, potassium, caustics, petroleum distillates, methanol, or ethylene glycol.
2. Gastric lavage is of unproven benefit for routine use. It is best reserved for patients who have recently ingested a toxic amount of a poison with life-threatening potential.
3. Cathartics are of unproven benefit.
4. There is theoretical but unproven benefit of whole bowel irrigation in ingestions such as sustained- release preparations or illicit drug packet ingestions.
5. Activated charcoal is typically given as a waterbased slurry via mouth or NG tube. The dose is 50 g for adults and 1 g/kg for children.

Physostigmine

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

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

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.

A basic urine drug screen is designed to detect the major drug classes. There are many substances of abuse that are not detected on basic screens. A negative screen does not rule out an intoxicant as the source of symptoms.

The duration of action of naloxone is shorter than the duration of action of many narcotics. Therefore the naloxone may wear off before the effects of the narcotic(s) do. There is a risk of recurrence of respiratory depression and the patient may not be safe for discharge.

Even with a history of drug ingestion, use caution in attributing symptoms solely to the drug without excluding other causes of altered mental status.

Aspirin and acetaminophen are common coingestants in intentional overdoses, but may also be present in a patient who has taken unknown pills that were given to them by someone else. Toxicity with these agents can be fatal but is treatable if detected in time. Consider checking these levels on any patient that has taken pills.

Volatile substance abuse can sensitize the myocardium to catecholamines. The use of a beta-agonist in this setting can be helpful, but its use is also dangerously unpredictable as cardiac dysrhythmias may develop.

Use caution when interpreting the results of a basic urine drug screen, as many things can cause a false positive result.

The presence of illegal drugs in a home is not something people will readily disclose. An unsupervised child will often put anything in their mouth that they find, including drugs. Inquiry about the presence of drugs is indicated in any clinical situation that raises suspicion. A urine drug screen may be helpful in situations where the possibility of accidental drug ingestion exists.

Gastric lavage is no longer recommended in most overdose patients. It is usually reserved for potentially lethal ingestions that present early, often within an hour of ingestion.

Patients with altered mental status and hypoventilation may have a normal or near normal oxygen saturation. However, inadequate ventilation will lead to respiratory acidosis and an increasing pCO2. The acidosis may progress to such severity that respiratory arrest occurs. An arterial blood gas (ABG) is useful in this setting to exclude hypercarbia, although the ABG should not be the sole determining factor in a patient clinically requiring intubation.

Flumazenil is useful in an acute overdose of a benzodiazepine in a patient who does not use

these drugs chronically. It can precipitate intractable seizures in someone who uses benzodiazepines chronically and should be used with caution.