Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine), 4th Ed.

CHAPTER 130. Recreational Substances

Navneet Cheema

Steven E. Aks

HIGH-YIELD FACTS

• Bi-directional nystagmus is a unique finding of phencyclidine and ketamine toxicity.

• Myocardial ischemia and cerebral vascular accidents are potential significant morbidities of cocaine toxicity.

• There is greater morbidity associated with synthetic marijuana toxicity than for conventional marijuana; potential adverse effects include seizures, renal injury, and myocardial infarction.

• Synthetic cathinone toxicity presents with the sympathomimetic toxidrome.

Recreational drugs are substances used for nonmedical purposes to enhance one’s personal experience or enjoyment. There is a wide range of substances available and this chapter will focus on well-known drugs including phencyclidine, ketamine, and cocaine as well as newer “designer drugs” including synthetic marijuana and cathinone products. Other recreational drugs that are often abused in the pediatric population but are beyond the scope of this chapter include solvents, hallucinogenic mushrooms, lysergic acid diethylamide (LSD), ecstasy, and dextromethorphan.

PHENCYCLIDINE AND KETAMINE

Phencyclidine (PCP) first came to the market as a surgical anesthetic and sedative in the 1950s as Sernyl by Parke Davis Pharmaceutical Company. However, it was removed from the market due to adverse side effects such as hallucinations. In the late 1960s, PCP made its return to commercial use as a veterinary tranquilizer. In the same year, PCP was first reported as an illicit drug used for recreational purposes in San Francisco, where it was called the “Peace Pill.” The Controlled Substance Analogue Enforcement Act of 1986 made PCP and its derivatives illegal. The drug has various street names such as “angel dust,” “hog,” “horse tranquilizer,” “crystal joint,” and “illy.”1

Ketamine is a legal analogue of PCP used in humans for sedation and anesthesia. Ketamine is also a drug of abuse. Adolescents use it regularly at raves and nightclubs for its hallucinatory, out of body experiences. It has various street names such as “Special K,” “K,” “KitKat,” and “Vitamin K.” It has a relatively short duration of action of 15–45 minutes and is one-tenth as potent as PCP. Because of its abuse potential, ketamine is in the Controlled Substance Act of 1999.2 Reports of a new designer drug and ketamine analogue, methoxetamine, recently surfaced. It is likely additional ketamine and PCP analogues will be developed as further “legal” highs are sought.3

image PHARMACOLOGY AND PATHOPHYSIOLOGY

Phencyclidine is classically categorized as a dissociative anesthetic because when anesthetized, the patient is conscious, yet experiences a feeling of dissociation from themselves, the “out of body” experience. After ingestion, PCP absorption occurs in the upper intestine. The drug has an enterogastric circulation; it is secreted by the stomach and then absorbed in the small intestine. Because the drug recirculates in this way, it produces a cyclical effects.4 It interacts at many receptor sites, including N-methyl-D-aspartic acid-type glutamate receptors, the neuronal dopamine/norepinephrine/serotonin (DA/NE/5HT) reuptake complex site, and the sigma opiate receptor complex.5

The therapeutic doses for endotracheal intubation and procedural sedation are 1–2 mg/kg IV over 1 minute and 1 mg/kg IV, respectively. The onset of action is rapid; the dissociative state is achieved within seconds.6

image CLINICAL FINDINGS

The clinical presentation in the ED after PCP use depends on the dose, route of administration, concomitant drug use, and the patient’s susceptibility to the drug. Typically, abnormal vital signs and psychomotor abnormalities are present. Mild hypertension, tachycardia, and hyperthermia can all be present. Respiratory drive is not compromised and hypoventilation is rare unless extremely high doses are used. Laryngeal and pharyngeal reflex hyperactivity in children has been documented.7 Horizontal, vertical, and rotary nystagmus can be present with PCP toxicity. Pupils may be miotic or mydriatic, but react to light. A fluctuating level of consciousness is typical of PCP intoxication. Patients may exhibit remarkable strength and completely disregard lacerations, fractures, or other traumatic injuries.4

Ketamine has a similar clinical presentation. Respiratory drive remains intact, and hypoventilation is uncommon.2 Depression of cough reflex is not uncommon, and this coupled with ketamine’s potential to increase secretions has been reported to obstruct the airway. Rare cases of respiratory depression and apnea have been associated with rapid infusion. Infusing ketamine over 1–2 minutes decreases this risk.

image DIAGNOSIS AND LABORATORY STUDIES

Phencyclidine toxicity is diagnosed clinically. Diagnostic testing is required only in cases where child abuse or foul play is suspected. Qualitative tests are available as a part of the urine toxicology screen. In an acute PCP exposure, urinary metabolites are present for 7 days; in cases of chronic exposure metabolites can be present for up to 4 weeks. Useful laboratory studies include blood urea nitrogen and creatinine to assess renal function and creatine phosphokinase and myoglobin to screen for rhabdomyolysis. The white blood cell count is frequently elevated. Blood glucose should be obtained to exclude hypoglycemia.4

Ketamine may cross-react with PCP on urine immunoassay.8 Other drugs that can cause a false-positive result are dextromethorphan, diphenhydramine, doxylamine, ibuprofen, imipramine, meperidine, mesoridazine, metamizol, methyphenidate, thioridazine, tramadol, and venlafaxine.810

image MANAGEMENT

Management of the patient’s airway, circulation, and thermoregulation are of utmost importance. Potential airway threats caused by PCP or ketamine toxicity include increased salivation, increased tracheobronchial tree secretions, and laryngospasm. Emergence reactions and agitation have been reported and can be treated with benzodiazepines.

The risks of activated charcoal are usually greater than the potential benefits because of the risk of aspiration in an agitated or somnolent patient.

Urinary acidification to enhance renal elimination is not recommended. The benefit of the minor increase in renal clearance of PCP from ion trapping of the weak base is far outweighed by the potential harm created by systemic acidemia. Adequate hydration, supportive care, and symptomatic treatment are the mainstays of therapy.11

image DISPOSITION

Monitoring in the ED or the ICU is appropriate for the patient experiencing adverse reactions to PCP or ketamine until the signs and symptoms resolve. Supportive care is the recommended therapy. Patients with recreational exposures should be discharged with follow-up that includes referral for drug counseling.

COCAINE

Cocaine abuse and toxicity continue to be pervasive problems.12 Adolescents and adults predominantly use cocaine as a recreational drug. Children suffer toxicity when exposed to cocaine being used by others.13 Seizures have been reported in children who accidentally ingest cocaine, and toxicity has occurred in toddlers who inhaled cocaine being “freebased” by nearby adults.14 Cocaine, multiple-drug ingestions, and tricyclic antidepressants are among the most prominent causes of cardiac arrest for patients younger than 40 years.15

According to data obtained by the Drug Abuse Warning Network (DAWN) in 2009, there were a total of 2.0 million emergency department visits related to drug abuse or misuse. There were 422,896 involving cocaine. In children aged 12–17, there were 5394 ED visits.12 In one study, 2.4% of children in a group of inner city preschoolers tested positive for the cocaine metabolite benzoylecgonine in their urine.14

image PHARMACOLOGY AND PATHOPHYSIOLOGY

Cocaine is benzoylmethylecgonine, a naturally occurring local anesthetic. It is derived from the plant Erythroxylum coca and is rapidly absorbed from mucous membranes, lung tissue, and the gastrointestinal tract. It is a sympathomimetic that blocks fast sodium channels. The primary target organs are the central nervous system, cardiovascular system, lungs, gastrointestinal tract, skin, and thermoregulatory center.

image CLINICAL FINDINGS

Clinically, cocaine causes CNS stimulation that can result in agitation, hallucinations, abnormal movements, and convulsions. Paradoxically, children may present with lethargy. Both ischemic and hemorrhagic strokes have been reported.16

Cardiovascular manifestations of cocaine toxicity include sinus tachycardia, supraventricular and ventricular dysrhythmias. Elevation in blood pressure can range from mild to fulminant hypertension associated with strokes. Myocardial ischemia and infarction has been described in otherwise healthy individuals as young as 17 years old with normal coronary arteries.17

Multiple pulmonary effects from inhalation of cocaine have been described, including exacerbation of asthma, pulmonary infarction, pneumomediastinum, pneumothorax, and respiratory failure.

Orally ingested cocaine can cause ischemic complications in the gastrointestinal tract that include acute abdominal pain, hemorrhagic diarrhea, and shock.

Cocaine-induced hyperthermia, in association with agitation and hypertension can occur. Rhabdomyolysis may occur in the presence or absence of hyperthermia.18 The dermatologic manifestations of cocaine abuse are primarily related to intravenous injection and “skin popping.” These include localized areas of necrosis or infection.

image DIAGNOSIS AND LABORATORY STUDIES

Cocaine toxicity should be considered in a patient who exhibits signs and symptoms consistent with sympathomimetic stimulation. Occasionally, the sympathomimetic toxidrome is difficult to distinguish from that caused by anticholinergic toxicity. Both toxidromes are associated with CNS excitation, mydriasis, tachycardia, hypertension, and hyperthermia. Unlike sympathomimetic toxicity, however, anticholinergic toxicity will cause urinary retention and decreased bowel sounds. Also, sympathomimetic toxicity is often associated with diaphoresis while anticholinergic overdose is associated with dry skin.

Orally ingested cocaine by body stuffers or body packers may be difficult to diagnose without a direct history. Body stuffers ingest poorly wrapped packets hurriedly in order to avoid arrest.19 Body packers by contrast ingest well-wrapped packets with much higher content of drug in order to smuggle.

For patients in whom cocaine toxicity is suspected, a urine toxicology screen can confirm the ingestion. Benzoylecgonine, a cocaine metabolite, can be detected in the urine for up to 72 hours after ingestion. Blood levels of cocaine and cocaine metabolites correlate poorly with signs and symptoms. Cardiac monitoring is essential to assess for dysrhythmias. Patients who complain of chest pain require a 12-lead electrocardiogram, possibly cardiac enzymes, and a chest radiograph to evaluate for pneumothorax, pneumomediastinum, or infiltrate.

Laboratory studies help establish a baseline and are useful for patients with significant toxicity. They include a complete blood count, serum electrolytes, glucose, blood urea nitrogen, and creatinine. Serum creatine kinase and urine myoglobin can be considered to assess for rhabdomyolysis. For patients with severe headache or neurological deficit, a computed tomographic (CT) scan of the brain is indicated to rule out the possibility of a cocaine-induced cerebrovascular accident.

Plain radiographs are helpful in body packers, but are not useful for body stuffers. A CT scan with and without contrast may visualize packets in body stuffers if confirmation of the diagnosis is necessary.

image MANAGEMENT

Mildly toxic patients generally require observation. Moderate-to-severe agitation responds to benzodiazepines, which are also the drugs of choice for seizures. Persistent seizure activity may require treatment with high-dose benzodiazepines or phenobarbital. Patients with persistent seizures may suffer from a structural CNS lesion or toxicity from a coingestant. Benzodiazepines are also effective treatment for most patients with mild-to-moderate hypertension. In more severe cases, sodium nitroprusside or phentolamine may be used. In general β-blockers are contraindicated in the presence of cocaine-induced sympathetic overdrive since unopposed α-stimulation can exacerbate hypertension.

Patients with severe hyperthermia should be treated with aggressive cooling. Rhabdomyolysis is treated with intravenous fluid administration.

Activated charcoal adsorbs unpackaged orally ingested cocaine20 and can be considered in the management of body stuffers and body packers to adsorb cocaine that has escaped from these packages. Whole bowel irrigation has been used for body stuffers and packers, but its efficacy is unproven.21

image DISPOSITION

In asymptomatic or mild cases of cocaine toxicity, emergency department observation until the patient has been asymptomatic for 4–6 hours is adequate. Patients with moderate-to-severe symptoms should be admitted to a monitored bed.

SYNTHETIC MARIJUANA

Cannabis is the most commonly used illicit substance. Its use is often initiated during adolescence.22 In the last several years, synthetic cannabinoid receptor agonists have been used as recreational drugs. They are often referred to as herbal marijuana, incense, or potpourri. They are sold in head shops, convenience stores, and widely on the Internet. Product names are diverse and include “K2,” “Spice,” and “Zombie.”22 Because of their low cost, ease of purchase and non-detectability in traditional urine drug screens, their popularity has grown. In 2010, the American Association of Poison Control Centers documented an increase from 13 to 2869 cases compared to the previous year.23

image CLINICAL FINDINGS

Synthetic cannabinoids act on the same receptors as marijuana and, thus, produce a similar clinical picture. Psychiatric manifestations, such as anxiety, agitation, psychosis, delusions, and paranoia, are usually most prominent. Other symptoms include hypertension, tachycardia, diaphoresis, conjunctival injection, and xerostomia.3 In contrast to marijuana, there have been several reports of seizures associated with synthetic cannabinoid use.24 There have also been case reports of myocardial infarction and renal injury.23,25

image DIAGNOSIS AND LABORATORY STUDIES

Synthetic cannabinoid exposure is diagnosed clinically through a combination of history and physical exam findings. Traditional urine drug screens do not detect these substances.3 Cardiac enzymes and a 12-lead electrocardiogram should be considered in those patients complaining of chest pain.23,25

image MANAGEMENT AND DISPOSITION

The mainstay is supportive care. Benzodiazepines should be used for agitation and seizures. Active cooling should be used to treat hyperthermia. Asymptomatic patients can be considered for discharge from the ED with appropriate referral for drug counseling. Symptomatic patients should be observed or admitted until resolution of vital sign abnormalities, symptoms, and psychiatric manifestations.3

SYNTHETIC CATHINONE

For centuries, the leaves of the Catha edulis plant (khat) have been chewed for their amphetamine-like effects. The active substance is cathinone, a monoamine alkaloid. It is chemically similar to amphetamines. In recent years, several synthetic cathinone derivatives, such as mephedrone, methylenedioxypyrovalerone (MDPV), and methcathinone have become popular recreational drugs of abuse. Manufacturers label their product as bath salts, plant food, and herbal incense with the disclaimer that they are not intended for human consumption in order to evade legal regulation.3 Numerous products have been identified and include names such as Ivory Wave, Cloud 9, Vanilla Sky, and White Dove. American poison centers first started receiving calls regarding adverse effects from synthetic cathinones in December 2010. The following year there were 6136 calls.26

image CLINICAL FINDINGS

Synthetic cathinones produce the sympathomimetic toxidrome. They prevent the reuptake of dopamine, serotonin, and norepinephrine. To a lesser extent, they also increase the presynaptic release of these same monoamines. They are usually in a powder form and most often nasally insufflated or ingested. Rectal, intravenous, and inhalation routes of administration have also been described. Desired effects that users describe include euphoria, openness, heightened alertness, increased energy, talkativeness, and increased libido. Adverse effects are most often cardiac, psychiatric, and neurologic. This includes tachycardia, hypertension, agitation, psychosis, violence, seizures, and myoclonus.3,27 There have been case reports of myocardial infarction, rhabdomyolysis, compartment syndrome, and hyponatremia.2729Deaths have been reported.

image DIAGNOSIS AND LABORATORY STUDIES

The diagnosis of synthetic cathinone intoxication is clinical. It can often be difficult though, as patients are not always willing or able to provide the necessary information. Laboratory tests to assess for the previously mentioned complications should be obtained as indicated. Currently none of the synthetic cathinones are detected on routine urine drug screens.3

image MANAGEMENT AND DISPOSITION

The mainstay of treatment is aggressive, symptom-based, supportive care. Benzodiazepines should be used to treat agitation, psychosis, tachycardia, and hypertension. Patients should be observed until their symptoms resolve.

REFERENCES

1. McCarron MM, Schulze BW, Thompson GA, Conder MC, Goetz WA. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med. 1981;10:237.

2. Moriarty AL. What’s “new” in street drugs: “illy”. J Pediatr Health Care. 1996;10:41.

3. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow... and back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, salvia divinorum, methoxetamine, and piperazines. J Med Toxicol. 2012;8:15.

4. Weiner AL, Vieira L, McKay CA, Bayer MJ. Ketamine abusers presenting to the emergency department: a case series. J Emerg Med. 2000; 18:447.

5. Hahn I-H. Phencyclidine and ketamine. In: Erickson TB, Ahrens WR, Aks SE, et al., eds. Pediatric Toxicology: Diagnosis and Management of the Poisoned Child. New York: McGraw-Hill, Medical Pub. Division; 2005:xxiii.

6. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57(5):449–461.

7. Schwartz RH, Einhorn A. PCP intoxication in seven young children. Pediatr Emerg Care. 1986;2:238.

8. Shannon M. Recent ketamine administration can produce a urine toxic screen which is falsely positive for phencyclidine. Pediatr Emerg Care. 1998;14:180.

9. Marchei E, Pellegrini M, Pichini S, Martín I, García-Algar O, Vall O. Are false-positive phencyclidine immunoassay instant-view multi-test results caused by overdose concentrations of ibuprofen, metamizol, and dextromethorphan? Ther Drug Monit. 2007;29:671.

10. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83:66.

11. Patel R, Connor G: A review of thirty cases of rhabdomyolysis-associated acute renal failure among phencyclidine users. J Toxicol Clin Toxicol. 1985;23:547.

12. Substance Abuse and Mental Health Services Administration CfBHSaQ. The DAWN Report: Highlights of the 2009 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. Rockville, MD: Office of Applied Studies; 2010: p. v.

13. Lustbader AS, Mayes LC, McGee BA, Jatlow P, Roberts WL. Incidence of passive exposure to crack/cocaine and clinical findings in infants seen in an outpatient service. Pediatrics. 1998;102:e5.

14. Kharasch SJ, Glotzer D, Vinci R, Weitzman M, Sargent J: Unsuspected cocaine exposure in young children. Am J Dis Child. 1991;145:204.

15. Richman PB, Nashed AH. The etiology of cardiac arrest in children and young adults: special considerations for ED management. Am J Emerg Med. 1999;17:264.

16. Seaman ME. Acute cocaine abuse associated with cerebral infarction. Ann Emerg Med. 1990;19:34.

17. Minor RL Jr, Scott BD, Brown DD, Winniford MD. Cocaine-induced myocardial infarction in patients with normal coronary arteries. Ann Intern Med. 1991;115:797.

18. Roth D, Alarcon FJ, Fernandez JA, et al. Acute rhabdomyolysis associated with cocaine intoxication. N Engl J Med. 1988;319:673.

19. Aks SE, Vander Hoek TL, Hryhorczuk DO, Negrusz A, Tebbett I. Cocaine liberation from body packets in an in vitro model. Ann Emerg Med. 1992;21:1321.

20. Tomaszewski C, Voorhees S, Wathen J, Brent J, Kulig K. Cocaine adsorption to activated charcoal in vitro. J Emerg Med. 1992;10:59.

21. June R, Aks SE, Keys N, Wahl M. Medical outcome of cocaine bodystuffers. J Emerg Med. 2000;18:221.

22. Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL. “Spice” and “K2” herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict. 2012;21:320.

23. Mir A, Obafemi A, Young A, et al. Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics. 2011;128:e1622.

24. Schneir AB, Baumbacher T. Convulsions associated with the use of a synthetic cannabinoid product. J Med Toxicol. 2012;8:62.

25. Acute kidney injury associated with synthetic cannabinoid use – multiple States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62:93.

26. American Association of Poison Control Centers: Bath Salts Data. https://aapcc.s3.amazonaws.com/files/library/Bath_Salts_Data_for_Website_1.09.2013.pdf. Accessed February 7, 2013.

27. Prosser JM, Nelson LS: The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8:33.

28. Levine M, Levitan R, Skolnik A. Compartment syndrome after “bath salts” use: a case series. Ann Emerg Med. 2013;61(4)480–483.

29. Nicholson PJ, Quinn MJ, Dodd JD. Headshop heartache: acute mephedrone ‘meow’ myocarditis. Heart. 2010;96:2051.