- Email: [email protected]
Ecstasy in the Emergency Department: MDMA Ingestion
Department
www.jpedhc.org
Case Studies—Acute and Specialty Care
Section Editors Terea Giannetta, MSN, RN, CPNP California State University, Fresno Fresno, California Andrea Kline, MS, RN, CPNP-PC/AC, CCRN, FCCM Children’s Memorial Hospital Chicago, Illinois Karin Reuter-Rice, PhD, RN, CPNP Rady Children’s Hospital San Diego, California
Ecstasy in the Emergency Department: MDMA Ingestion Karin Reuter-Rice, PhD, RN, CPNP
CHIEF COMPLAINT Friends of T.J. report he is ‘‘shaking and acting strangely.’’
Karin Reuter-Rice, Acute Care Pediatric Nurse Practitioner, Division of Pediatric Critical Care, Rady Children’s Hospital, San Diego, CA. Correspondence: Karin Reuter-Rice, PhD, RN, CPNP, Rady Children’s Hospital, Division of Pediatric Critical Care, MC 5065, 3020 Children’s Way, San Diego, CA 92123; e-mail: [email protected]. J Pediatr Health Care. (2009). 23, 49-53. 0891-5245/$36.00 Copyright Q 2009 by the National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.pedhc.2008.09.002
Journal of Pediatric Health Care
HISTORY OF CHIEF COMPLAINT T.J. is a 16-year-old male adolescent who was brought to the emergency department (ED) by friends after he was found shaking and ‘‘acting weird’’ at a party. His friends deny drug use or alcohol consumption. No vomiting occurred, and T.J. has no chronic illness that they are aware of. They described the ‘‘shaking’’ event as a generalized tonic-clonic seizure lasting approximately 1 minute. A call was placed to T.J.’s family for notification and to obtain additional medical information. In the ED, T.J. was noted to have age-appropriate hemodynamically stable vital signs. He had confused speech and was unresponsive to verbal stimuli but responsive to pain. His total Glasgow Coma Scale (GCS) score was 9. His pupillary reactions were brisk and equal bilaterally. Laboratory findings from the ED were as follows (normal ranges in parentheses): sodium, 117 mmol/L (135-145); potassium, 3.3 mmol/L (3.5-5.0); chloride, 89 mmol/L (97-107);
bicarbonate, 20 mmol/L (21-28); blood urea nitrogen, 6 mg/dL (520); creatinine, 0.6 mg/dL (0.51.2); glucose, 116 mg/dL (70-200); creatinine kinase, 2289 units/L (40-150); hemoglobin, 13 g/dL (10-18); hematocrit, 39% (31%55%); platelets, 220 thou/L (150400); white blood cell count, 16 109 cells/L (4.5-11 109); neutrophils, 70% (45%-75%); bands, 20% (0-5%); and lymphocytes, 10% (16%-46%). Urinalysis findings were remarkable for a specific gravity less than 1.005 (1.0081.035); urine sodium, 46 mmol/ day (143-208); potassium, 4.7 mmol/day (\15); and a serum osmolality of 247 mOsm/kg H2O (275-295). Cardiac isoenzymes showed a troponin I level of less than 0.1 ng/mL (\0.6 ng/mL), creatine kinase isoenzymes-MB fraction of 2 ng/mL (0-5), and brain natriuretic peptide, 45 pg/mL (\100 pg/mL). Diagnostic studies included a clear and well-aerated chest radiograph, 15-lead electrocardiogram for a normal sinus rhythm, and a negative computerized axial tomography (CT) scan of the head. A lumbar puncture performed after the CT scan reported all studies within normal limits with no organisms on the January/February 2009
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gram stain. Blood and urine cultures were sent. Lastly, T.J.’s serum ethanol level was reported as 0 mg/dL (\5-10), and he had a positive urine toxicology screen for amphetamines, which later was identified by serum toxicology as 3,4-Methylenedioxymethamphetamine (MDMA). MEDICAL HISTORY T.J. and his family denied prior surgeries, chronic illnesses, prior drug use, psychiatric illness, or a history of suicide. Family history is negative for seizure disorders and nervous system diseases. He has no medication, food, or environmental allergies and no routine medication use. All his immunizations were up to date. PHYSICAL EXAMINATION T.J. weighed 70 kg, and his vital signs revealed the following: temperature, 98.6 F; heart rate, 96 beats per minute; non-invasive blood pressure, 102/70 mm Hg; and respiratory rate, 20 breaths per minute in 21% fraction of inspired oxygen with oxygen saturations of 99%. He was a well-developed, well-nourished adolescent speaking incoherently. Findings of a head-to-toe examination were unremarkable except for a diaphoresis, persistent bruxism, full range of motion with increase tonicity, and no active seizure activity.
MANAGEMENT IN THE ED T.J.’s management included placement of two large-bore intravenous (IV) catheters followed by 1 L normal saline solution (NS) bolus; Narcan, 2 mg IV; and thiamine, 100 mg IV, ceftriaxone, 1 g IV, phenytoin, 1 g IV loading dose, and potassium chloride, 10 mEq IV over 2 hours. A re-evaluation of T.J.’s sodium level revealed an increase to 125 mmol/dL. An infusion of 5 mL/kg of 3% hypertonic saline solution was followed by second bolus of 1 L of NS. A repeat sodium level of 133 mmol/dL was concomitant to T.J.’s improving level of consciousness. Toxicology consultation suggested supportive care and monitoring serial GCS and chemistries in the ED observational unit. T.J. continued to demonstrate consistent improvement with no further seizures, normalized sodium, and osmolality. He returned to baseline mental status with a GCS score of 15 and relief of bruxism 8 hours after arriving at the ED. In a social work evaluation it was discovered that T.J. took ‘‘X’’ (MDMA) shortly after school. He claimed it had been the first time he had taken ‘‘X’’ and that he felt great until he began to experience some ataxia with some blurred vision. He had no recall of the events leading up to and immediately after the seizure. T.J. was transferred to the
step-down intensive care unit (ICU) for further observation. MANAGEMENT IN THE STEPDOWN ICU T.J. arrived at the step-down ICU with a GCS score of 15; he was afebrile and hemodynamically stable. IV fluids continued to be administered at a maintenance rate, maintaining stable sodium levels (140 mmol/L) and urine output. After 6 hours he began taking clear fluids, and his diet was advanced. His IV line was heparin locked. Neurologically he had a normally active electroencephalogram, was ambulating, and was appropriately interactive with staff. He tolerated oral phenytoin (Dilantin ER), 300 mg orally once a day, with a follow-up Dilantin level of 14 mg/mL (10-20 mg/mL). Follow-up blood and urine cultures were negative in the first 24 hours. Approximately 36 hours after ingestion of MDMA, the patient was discharged in stable condition with normalized chemistry values. He was instructed to take daily Dilantin ER and to follow up with his primary care provider (PCP) the next day and the neurologist the following week. Additionally, the social worker arranged weekly family counseling so that T.J. and his parents could explore T.J.’s motivation to try Ecstasy and promote safer and healthier lifestyle choices.
CASE STUDY QUESTIONS 1. 2. 3. 4. 5.
What is MDMA? What are presenting symptoms of MDMA ingestion? What laboratory and diagnostic considerations are important in evaluating a patient who has ingested MDMA? What are treatment recommendations for MDMA? What considerations must be included in a patient’s discharge instructions and follow-up plan?
CASE STUDY ANSWERS 1. What is MDMA? 3,4-Methylenedioxymethamphetamine is a semi-synthetic hallucinogen chemically resembling mescaline and amphetamine. It is
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known by various popular names such as Ecstasy, XTC, ‘‘X,’’ ‘‘E,’’ Adam, Eve, or Lover’s Speed (Britt & McCance-Katz, 2005; Klein & Kramer, 2004). First synthesized in
Germany and used as an appetite suppressant in the early 1900s, MDMA became an adjunct for psychotherapy in 1970s in the United States. MDMA was ultimately
Journal of Pediatric Health Care
placed on the schedule I substance list in 1985 by the Drug Enforcement Agency (Klein & Kramer; U.S. Department of Health and Human Services; 2006). MDMA found its way into dance clubs or ‘‘raves’’ in the mid 1990s and rapidly developed a reputation within the medical community for its lethal adverse effects as a disproportionate number of young people began to be treated in the ED. Recent studies indicate approximately 0.2% of persons 12 years of age or older had reported using MDMA in 2006, with the lifetime use increasing to 5% in these individuals (U.S. Health and Human Services, 2008). To date, MDMA remains the fifth leading drug reported with lasting serotonergic/ neurotoxic changes reported with a single and/or prolonged use (Office of National Drug Control Policy, 2008). 2. What are presenting symptoms of MDMA ingestion? MDMA primary metabolism is the CYP450–2D6 enzymatic pathway. MDMA is readily absorbed by the gastrointestinal tract, reaches a peak serum level in 1 to 2 hours (based on 80-150 mg doses), has a half-life of 8 hours, and is excreted (65%) unchanged in the urine. MDMA is an indirect serotonin agonist thought to inhibit tryptophan hydroxylase, which decreases the serotonin production. The lack of serotonin secretion induces serotonin release and blocks re-uptake, leading to the drug’s attraction. Serotonin surges create a sense of euphoria, self-confidence, impulsivity, and emotional closeness. However, the surge also can lead to potentially lethal serotonin toxicity and a number of other serious adverse effects. Although a wide variety of symptoms are manifested in patients who ingest MDMA, MDMAassociated serotonin toxicity is described as a classic triad of neuromuscular and autonomic hyperactivity and altered mental status (Boyer & Shannon, 2005; Gillman, Journal of Pediatric Health Care
2005). Characteristics of serotonin toxicity include tachycardia, hypertension, diaphoresis, hyperthermia, ataxia, muscle cramping
highly fetal toxic. Comprehensive laboratory evaluation for multisystem dysfunction should include all of the following: serum and
Characteristics of serotonin toxicity commonly seen include tachycardia, hypertension, diaphoresis, hyperthermia, ataxia, muscle cramping (bruxism), tremors, clonus, seizures, agitation, and confusion. (bruxism), tremors, clonus, seizures, agitation, and confusion. Hyponatremia associated with significant diaphoresis and water intoxication can lead to seizures and/or cerebral edema. Muscle degradation associated with intense dancing or exercise and dehydration can lead to rhabdomyolysis and acute renal failure. Sequelae to hyperthermia additionally include hepatotoxicity and disseminated intravascular coagulation (DIC). Arterial vasospasm has been associated with cerebral vascular accidents. Increased release of dopamine and norepinephrine has the potential to stimulate cardiac arrhythmias, and increased myocardial oxygen consumption can lead to myocardial ischemia and infarction (Britt & McCance-Katz, 2005; Gillman; Klein & Kramer, 2004; Oesterheld, Armstrong, & Cozza, 2004; U.S. Department of Health and Human Services, 2006, 2008; Weir, 2000). 3. What laboratory and diagnostic considerations are important in evaluating a patient who has ingested MDMA? Several studies have supported a high incidence of co-ingestion associated with MDMA use (Liechti, Kunz, & Kupferschmidt, 2005). Serum and urine toxicology panels provide both broad and narrowed drug class identity. In women of child-bearing age, a urine or serum pregnancy test should be obtained, as MDMA is
urine chemistries, osmolality, and urinalysis and renal function studies, especially if any signs of water intoxication or myoglobinuria exist. Obtaining liver function tests, a complete blood cell count, and coagulation studies can rule out the potential for DIC. Additionally, if the diagnosis is unclear, the complete blood cell count and differential will aid in determining possible infectious etiology. To assess for possible MDMA-induced autonomic dysregulation and/or myocyte dysfunction, a thorough cardiac evaluation should include cardiac enzymes (troponin I, creatine kinase isoenzymes-MB, brain natriuretic peptide), a 15-lead electrocardiogram, and an echocardiograph (Kalant, 2001; Klein & Kramer, 2004; Liechti et al.). Patients demonstrating only mild symptoms without any hemodynamic instability may not require imaging studies. Observation and supportive care often is recommended. Obtaining a chest radiograph ensures no overt pulmonary edema secondary to overzealous water ingestion and allows for baseline cardiac size/silhouette determination. A CT scan of the head should be performed prior to performing a lumbar puncture for cerebrospinal fluid studies. In patients with an altered level of consciousness, a head CT scan provides an evaluation for cerebral edema, cerebral hemorrhage, and infarction. Along with providing January/February 2009
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information of central nervous system injury, it also can aid in ruling out an infectious process or spaceoccupying lesion. Lastly, an electroencephalogram should be performed if the patient has persistent untreated seizures or evolving neurologic dysfunction (Kalant, 2001; Klein & Kramer, 2004; Liechti et al., 2005). 4. What are treatment recommendations for MDMA? Most patients with MDMA ingestion improve with supportive care, but some present with severe toxicity and life-threatening complications. Fatalities have been reported secondary to the adverse effects of severe hyperthermia accompanied by DIC, rhabdomyolysis, and acute renal failure. Reports of death by cerebral edema and seizures are commonly due to hyponatremia and syndrome of inappropriate antidiuretic hormone (Britt & McCanceKatz, 2005; Gillman, 2005; U.S. Department of Health and Human Services, 2006, 2008). Early consultation with medical toxicologists will assist with work-up and treatment regimen. Treatment therefore is best guided by history, physical examination, and laboratory/diagnostic imaging results. Crucial management requires establishing the stability of airway, breathing, and circulation with ongoing monitoring of vital signs and serial neurologic examination. Attributing diagnoses such as seizures, cardiovascular instability, or trauma may require oxygen and assisted ventilation in patients who cannot protect their airway or who have respiratory compromise. Establishing IV access via a peripheral IV line or central venous line is essential for blood draws, fluid, and medication infusions. Cardiac dysrhythmias may require chemical and/or electrical conversion. Management of hypertension, especially hypertensive crisis, will require aggressive antihypertensive medical management and should be guided by a cardiologist. 52
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Patients with stable or improving GCS scores respond better to assurance and avoidance of physical or pharmacologic restraints. Placing patients in calm, quiet rooms allows for their drug-associated agitation and anxiety to decrease and allows for more accurate mental status examinations. Use of sedation such as benzodiazepines and/or physical restraints should be used only in cases in which the patient is harmful to himself/herself or others. Patient presenting with altered mental status should receive frequent bedside glucose monitoring so hypoglycemia can be treated acutely with dextrose and thiamine and adequate serum glucose concentrations can be maintained. Any positive head CT scan findings should be treated appropriately and guided by neurosurgical consultation. Gastrointestinal decontamination by activated charcoal may be indicated in acute toxicity caused by known ingestion and in a neurologically stable patient. Orogastric lavage usually is not necessary unless the patient presents within 1 hour of ingestion or if a life-threatening co-ingestant is suspected. Full bowel decontamination is only advised in suspected body packing of drugs. Morbidity is directly related to the duration and severity of hyper-
tient’s temperature is unresponsive to non-pharmacologic measures. Administration of a benzodiazepine to control shivering may also be required. Most seizures are self-limited and respond well to benzodiazepines, with refractory symptoms managed by phenytoin and phenobarbital. All electrolyte abnormalities, especially hyponatremia, should be treated with hypertonic saline solution (3-5 mL/ kg/dose), fluid restriction (as indicated by hemodynamics and hydration status), mannitol, and low-dose furosemide. Treatment of rhabdomyolysis and prevention of renal failure can best be achieved with fluids and urine alkalinization using sodium bicarbonate, furosemide, or mannitol. In cases of renal dysfunction, early consultation with a nephrologist for available renal adjuncts and possible hemodialysis may optimize renal integrity (Britt & McCance-Katz, 2005; Gillman, 2005; Henry, 2000; Weir, 2000). 5. What considerations must be included in a patient’s discharge instructions and follow-up plan? Considerations for discharge include the ability to follow up with toxicology (as indicated), neurology, a PCP and the availability of laboratory/emergency services. Although there are no specific treatments for MDMA (and coingestant) abuse and addiction,
Morbidity is directly related to the duration and severity of hyperthermia; therefore, patients presenting with severe hyperthermia require aggressive cooling. thermia; therefore, patients presenting with severe hyperthermia require aggressive cooling. A goal of 102 F or less should be obtained by undressing the patient, using ice packs, fans, cold IV fluids, and iced-gastric lavage. Dantrolene could be considered if the pa-
MDMA has been shown to have residual cognitive adverse effects. Different approaches have been tried in patients experiencing withdrawal. Short-acting benzodiazepines have been trialed to aid with insomnia and mood stabilization (Britt & McCance-Katz, 2005; Journal of Pediatric Health Care
Oesterheld et al., 2004; U.S. Department of Health and Human Services, 2008). Behavioral and psychiatric interventions may be required if abuse or cognitive defects exist. To avoid the theoretical risk of producing neuroleptic malignant syndrome, often resembling serotonin syndrome, the use of psychotropic medications has been cautioned against in the literature (Weir, 2000). Therefore, patients being discharged on any psychotropic therapy require close follow-up with the prescribing psychiatrist. Neurologic follow-up is recommended when a patient experiences any neurologic sequelae. Symptoms such as (a) long-term confusion, (b) depression, (c) attention deficits, and/or (d) memory deficits may manifest after initial and multiple uses. Follow-up imaging has demonstrated changes within the motor, cognition, and emotion regions of the brain. To date, there are no pharmacologic treatments that reverse the effects of MDMA, and ongoing research includes looking for antidotes as well as long-term drug effects on the human brain and body (Britt & McCance-Katz, 2005; Oesterheld et al., 2004; U.S. Department of Health and Human Services, 2008). Although T.J.’s seizure was likely in response to his hyponatre-
Journal of Pediatric Health Care
mic state, the decision to treat with an anticonvulsant was determined by the consulting neurologist. There is no specific literature that addresses the duration of anticonvulsant use in patients who have ingested MDMA who present with seizures; however, a meta-analysis performed by Zagnoni and Albano (2002) on psychostimulant-associated epilepsy found that MDMA has the highest seizure occurrence. Lastly, discussion with the PCP prior to the patient’s discharge should include the patient’s condition, prescribed medications and their possible adverse effects, therapy/counseling, and subspecialty follow-up. The family and patient should be provided with a detailed written discharge plan with clear instructions for medication use, follow-up, and when to seek medical attention. REFERENCES Boyer, E., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352, 1112-1120. Britt, G. C., & McCance-Katz, E. (2005). A brief overview of the clinical pharmacology of ‘‘Club Drugs.’’. Substance Use & Misuse, 40, 1189-1201. Gillman, P. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95, 434-441. Henry, J. (2000). Metabolic consequences of drug misuse. British Journal of Anaesthesia, 85, 136-142.
Kalant, H. (2001). The pharmacology and toxicology of ‘‘ecstasy’’ (MDMA) and related drugs. Canadian Medical Association Journal, 165, 917-928. Klein, M., & Kramer, F. (2004). Rave drugs: Pharmacological considerations. AANA Journal, 72, 61-67. Liechti, M., Kunz, I., & Kupferschmidt, H. (2005). Acute medical problems due to Ecstasy use. Swiss Medical Weekly, 135, 652-657, Retrieved August 29, 2008, from. www.smw.ch/dfe/set_ archiv.asp. Office of National Drug Control Policy. (2008). National drug control strategy; 2008 annual report. Retrieved August 29, 2008, from. www.whitehousedrugpolicy.gov/ publications/policy/ndcs08/2008ndcs. pdf. Oesterheld, J., Armstrong, S., & Cozza, K. (2004). Ecstasy: Pharmacodynamic and pharmacokinetic interactions. Psychosomatics, 45, 84-87. U.S. Department of Health and Human Services. (2008). MDMA (Ecstasy). National Institute on Drug Abuse. Retrieved August 29, 2008, from www.nida.nih. gov/PDF/Infofacts/MDMA08.pdf. U.S. Department of Health and Human Services. (2006). Research report series: MDMA (Ecstasy) abuse. National Institute on Drug Abuse. Retrieved August 29, 2008, from www.drugabuse.gov/ PDF/RRmdma.pdf. Weir, E. (2000). Raves: A review of the culture, the drugs and the prevention of harm. Canadian Medical Association Journal, 162, 1843-1848, Retrieved September 4, 2008, from. http://www. cmaj.ca/cgi/reprint/162/13/1843. Zagnoni, P., & Albano, C. (2002). Psychostimulants and epilepsy. Epilepsia, 43, 2831, Retrieved September 4, 2008, from. www.3.interscience.wiley.com/cgi-bin/ fulltext/118940645/PDFSTART.
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www.jpedhc.org
Case Studies—Acute and Specialty Care
Section Editors Terea Giannetta, MSN, RN, CPNP California State University, Fresno Fresno, California Andrea Kline, MS, RN, CPNP-PC/AC, CCRN, FCCM Children’s Memorial Hospital Chicago, Illinois Karin Reuter-Rice, PhD, RN, CPNP Rady Children’s Hospital San Diego, California
Ecstasy in the Emergency Department: MDMA Ingestion Karin Reuter-Rice, PhD, RN, CPNP
CHIEF COMPLAINT Friends of T.J. report he is ‘‘shaking and acting strangely.’’
Karin Reuter-Rice, Acute Care Pediatric Nurse Practitioner, Division of Pediatric Critical Care, Rady Children’s Hospital, San Diego, CA. Correspondence: Karin Reuter-Rice, PhD, RN, CPNP, Rady Children’s Hospital, Division of Pediatric Critical Care, MC 5065, 3020 Children’s Way, San Diego, CA 92123; e-mail: [email protected]. J Pediatr Health Care. (2009). 23, 49-53. 0891-5245/$36.00 Copyright Q 2009 by the National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.pedhc.2008.09.002
Journal of Pediatric Health Care
HISTORY OF CHIEF COMPLAINT T.J. is a 16-year-old male adolescent who was brought to the emergency department (ED) by friends after he was found shaking and ‘‘acting weird’’ at a party. His friends deny drug use or alcohol consumption. No vomiting occurred, and T.J. has no chronic illness that they are aware of. They described the ‘‘shaking’’ event as a generalized tonic-clonic seizure lasting approximately 1 minute. A call was placed to T.J.’s family for notification and to obtain additional medical information. In the ED, T.J. was noted to have age-appropriate hemodynamically stable vital signs. He had confused speech and was unresponsive to verbal stimuli but responsive to pain. His total Glasgow Coma Scale (GCS) score was 9. His pupillary reactions were brisk and equal bilaterally. Laboratory findings from the ED were as follows (normal ranges in parentheses): sodium, 117 mmol/L (135-145); potassium, 3.3 mmol/L (3.5-5.0); chloride, 89 mmol/L (97-107);
bicarbonate, 20 mmol/L (21-28); blood urea nitrogen, 6 mg/dL (520); creatinine, 0.6 mg/dL (0.51.2); glucose, 116 mg/dL (70-200); creatinine kinase, 2289 units/L (40-150); hemoglobin, 13 g/dL (10-18); hematocrit, 39% (31%55%); platelets, 220 thou/L (150400); white blood cell count, 16 109 cells/L (4.5-11 109); neutrophils, 70% (45%-75%); bands, 20% (0-5%); and lymphocytes, 10% (16%-46%). Urinalysis findings were remarkable for a specific gravity less than 1.005 (1.0081.035); urine sodium, 46 mmol/ day (143-208); potassium, 4.7 mmol/day (\15); and a serum osmolality of 247 mOsm/kg H2O (275-295). Cardiac isoenzymes showed a troponin I level of less than 0.1 ng/mL (\0.6 ng/mL), creatine kinase isoenzymes-MB fraction of 2 ng/mL (0-5), and brain natriuretic peptide, 45 pg/mL (\100 pg/mL). Diagnostic studies included a clear and well-aerated chest radiograph, 15-lead electrocardiogram for a normal sinus rhythm, and a negative computerized axial tomography (CT) scan of the head. A lumbar puncture performed after the CT scan reported all studies within normal limits with no organisms on the January/February 2009
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gram stain. Blood and urine cultures were sent. Lastly, T.J.’s serum ethanol level was reported as 0 mg/dL (\5-10), and he had a positive urine toxicology screen for amphetamines, which later was identified by serum toxicology as 3,4-Methylenedioxymethamphetamine (MDMA). MEDICAL HISTORY T.J. and his family denied prior surgeries, chronic illnesses, prior drug use, psychiatric illness, or a history of suicide. Family history is negative for seizure disorders and nervous system diseases. He has no medication, food, or environmental allergies and no routine medication use. All his immunizations were up to date. PHYSICAL EXAMINATION T.J. weighed 70 kg, and his vital signs revealed the following: temperature, 98.6 F; heart rate, 96 beats per minute; non-invasive blood pressure, 102/70 mm Hg; and respiratory rate, 20 breaths per minute in 21% fraction of inspired oxygen with oxygen saturations of 99%. He was a well-developed, well-nourished adolescent speaking incoherently. Findings of a head-to-toe examination were unremarkable except for a diaphoresis, persistent bruxism, full range of motion with increase tonicity, and no active seizure activity.
MANAGEMENT IN THE ED T.J.’s management included placement of two large-bore intravenous (IV) catheters followed by 1 L normal saline solution (NS) bolus; Narcan, 2 mg IV; and thiamine, 100 mg IV, ceftriaxone, 1 g IV, phenytoin, 1 g IV loading dose, and potassium chloride, 10 mEq IV over 2 hours. A re-evaluation of T.J.’s sodium level revealed an increase to 125 mmol/dL. An infusion of 5 mL/kg of 3% hypertonic saline solution was followed by second bolus of 1 L of NS. A repeat sodium level of 133 mmol/dL was concomitant to T.J.’s improving level of consciousness. Toxicology consultation suggested supportive care and monitoring serial GCS and chemistries in the ED observational unit. T.J. continued to demonstrate consistent improvement with no further seizures, normalized sodium, and osmolality. He returned to baseline mental status with a GCS score of 15 and relief of bruxism 8 hours after arriving at the ED. In a social work evaluation it was discovered that T.J. took ‘‘X’’ (MDMA) shortly after school. He claimed it had been the first time he had taken ‘‘X’’ and that he felt great until he began to experience some ataxia with some blurred vision. He had no recall of the events leading up to and immediately after the seizure. T.J. was transferred to the
step-down intensive care unit (ICU) for further observation. MANAGEMENT IN THE STEPDOWN ICU T.J. arrived at the step-down ICU with a GCS score of 15; he was afebrile and hemodynamically stable. IV fluids continued to be administered at a maintenance rate, maintaining stable sodium levels (140 mmol/L) and urine output. After 6 hours he began taking clear fluids, and his diet was advanced. His IV line was heparin locked. Neurologically he had a normally active electroencephalogram, was ambulating, and was appropriately interactive with staff. He tolerated oral phenytoin (Dilantin ER), 300 mg orally once a day, with a follow-up Dilantin level of 14 mg/mL (10-20 mg/mL). Follow-up blood and urine cultures were negative in the first 24 hours. Approximately 36 hours after ingestion of MDMA, the patient was discharged in stable condition with normalized chemistry values. He was instructed to take daily Dilantin ER and to follow up with his primary care provider (PCP) the next day and the neurologist the following week. Additionally, the social worker arranged weekly family counseling so that T.J. and his parents could explore T.J.’s motivation to try Ecstasy and promote safer and healthier lifestyle choices.
CASE STUDY QUESTIONS 1. 2. 3. 4. 5.
What is MDMA? What are presenting symptoms of MDMA ingestion? What laboratory and diagnostic considerations are important in evaluating a patient who has ingested MDMA? What are treatment recommendations for MDMA? What considerations must be included in a patient’s discharge instructions and follow-up plan?
CASE STUDY ANSWERS 1. What is MDMA? 3,4-Methylenedioxymethamphetamine is a semi-synthetic hallucinogen chemically resembling mescaline and amphetamine. It is
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known by various popular names such as Ecstasy, XTC, ‘‘X,’’ ‘‘E,’’ Adam, Eve, or Lover’s Speed (Britt & McCance-Katz, 2005; Klein & Kramer, 2004). First synthesized in
Germany and used as an appetite suppressant in the early 1900s, MDMA became an adjunct for psychotherapy in 1970s in the United States. MDMA was ultimately
Journal of Pediatric Health Care
placed on the schedule I substance list in 1985 by the Drug Enforcement Agency (Klein & Kramer; U.S. Department of Health and Human Services; 2006). MDMA found its way into dance clubs or ‘‘raves’’ in the mid 1990s and rapidly developed a reputation within the medical community for its lethal adverse effects as a disproportionate number of young people began to be treated in the ED. Recent studies indicate approximately 0.2% of persons 12 years of age or older had reported using MDMA in 2006, with the lifetime use increasing to 5% in these individuals (U.S. Health and Human Services, 2008). To date, MDMA remains the fifth leading drug reported with lasting serotonergic/ neurotoxic changes reported with a single and/or prolonged use (Office of National Drug Control Policy, 2008). 2. What are presenting symptoms of MDMA ingestion? MDMA primary metabolism is the CYP450–2D6 enzymatic pathway. MDMA is readily absorbed by the gastrointestinal tract, reaches a peak serum level in 1 to 2 hours (based on 80-150 mg doses), has a half-life of 8 hours, and is excreted (65%) unchanged in the urine. MDMA is an indirect serotonin agonist thought to inhibit tryptophan hydroxylase, which decreases the serotonin production. The lack of serotonin secretion induces serotonin release and blocks re-uptake, leading to the drug’s attraction. Serotonin surges create a sense of euphoria, self-confidence, impulsivity, and emotional closeness. However, the surge also can lead to potentially lethal serotonin toxicity and a number of other serious adverse effects. Although a wide variety of symptoms are manifested in patients who ingest MDMA, MDMAassociated serotonin toxicity is described as a classic triad of neuromuscular and autonomic hyperactivity and altered mental status (Boyer & Shannon, 2005; Gillman, Journal of Pediatric Health Care
2005). Characteristics of serotonin toxicity include tachycardia, hypertension, diaphoresis, hyperthermia, ataxia, muscle cramping
highly fetal toxic. Comprehensive laboratory evaluation for multisystem dysfunction should include all of the following: serum and
Characteristics of serotonin toxicity commonly seen include tachycardia, hypertension, diaphoresis, hyperthermia, ataxia, muscle cramping (bruxism), tremors, clonus, seizures, agitation, and confusion. (bruxism), tremors, clonus, seizures, agitation, and confusion. Hyponatremia associated with significant diaphoresis and water intoxication can lead to seizures and/or cerebral edema. Muscle degradation associated with intense dancing or exercise and dehydration can lead to rhabdomyolysis and acute renal failure. Sequelae to hyperthermia additionally include hepatotoxicity and disseminated intravascular coagulation (DIC). Arterial vasospasm has been associated with cerebral vascular accidents. Increased release of dopamine and norepinephrine has the potential to stimulate cardiac arrhythmias, and increased myocardial oxygen consumption can lead to myocardial ischemia and infarction (Britt & McCance-Katz, 2005; Gillman; Klein & Kramer, 2004; Oesterheld, Armstrong, & Cozza, 2004; U.S. Department of Health and Human Services, 2006, 2008; Weir, 2000). 3. What laboratory and diagnostic considerations are important in evaluating a patient who has ingested MDMA? Several studies have supported a high incidence of co-ingestion associated with MDMA use (Liechti, Kunz, & Kupferschmidt, 2005). Serum and urine toxicology panels provide both broad and narrowed drug class identity. In women of child-bearing age, a urine or serum pregnancy test should be obtained, as MDMA is
urine chemistries, osmolality, and urinalysis and renal function studies, especially if any signs of water intoxication or myoglobinuria exist. Obtaining liver function tests, a complete blood cell count, and coagulation studies can rule out the potential for DIC. Additionally, if the diagnosis is unclear, the complete blood cell count and differential will aid in determining possible infectious etiology. To assess for possible MDMA-induced autonomic dysregulation and/or myocyte dysfunction, a thorough cardiac evaluation should include cardiac enzymes (troponin I, creatine kinase isoenzymes-MB, brain natriuretic peptide), a 15-lead electrocardiogram, and an echocardiograph (Kalant, 2001; Klein & Kramer, 2004; Liechti et al.). Patients demonstrating only mild symptoms without any hemodynamic instability may not require imaging studies. Observation and supportive care often is recommended. Obtaining a chest radiograph ensures no overt pulmonary edema secondary to overzealous water ingestion and allows for baseline cardiac size/silhouette determination. A CT scan of the head should be performed prior to performing a lumbar puncture for cerebrospinal fluid studies. In patients with an altered level of consciousness, a head CT scan provides an evaluation for cerebral edema, cerebral hemorrhage, and infarction. Along with providing January/February 2009
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information of central nervous system injury, it also can aid in ruling out an infectious process or spaceoccupying lesion. Lastly, an electroencephalogram should be performed if the patient has persistent untreated seizures or evolving neurologic dysfunction (Kalant, 2001; Klein & Kramer, 2004; Liechti et al., 2005). 4. What are treatment recommendations for MDMA? Most patients with MDMA ingestion improve with supportive care, but some present with severe toxicity and life-threatening complications. Fatalities have been reported secondary to the adverse effects of severe hyperthermia accompanied by DIC, rhabdomyolysis, and acute renal failure. Reports of death by cerebral edema and seizures are commonly due to hyponatremia and syndrome of inappropriate antidiuretic hormone (Britt & McCanceKatz, 2005; Gillman, 2005; U.S. Department of Health and Human Services, 2006, 2008). Early consultation with medical toxicologists will assist with work-up and treatment regimen. Treatment therefore is best guided by history, physical examination, and laboratory/diagnostic imaging results. Crucial management requires establishing the stability of airway, breathing, and circulation with ongoing monitoring of vital signs and serial neurologic examination. Attributing diagnoses such as seizures, cardiovascular instability, or trauma may require oxygen and assisted ventilation in patients who cannot protect their airway or who have respiratory compromise. Establishing IV access via a peripheral IV line or central venous line is essential for blood draws, fluid, and medication infusions. Cardiac dysrhythmias may require chemical and/or electrical conversion. Management of hypertension, especially hypertensive crisis, will require aggressive antihypertensive medical management and should be guided by a cardiologist. 52
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Patients with stable or improving GCS scores respond better to assurance and avoidance of physical or pharmacologic restraints. Placing patients in calm, quiet rooms allows for their drug-associated agitation and anxiety to decrease and allows for more accurate mental status examinations. Use of sedation such as benzodiazepines and/or physical restraints should be used only in cases in which the patient is harmful to himself/herself or others. Patient presenting with altered mental status should receive frequent bedside glucose monitoring so hypoglycemia can be treated acutely with dextrose and thiamine and adequate serum glucose concentrations can be maintained. Any positive head CT scan findings should be treated appropriately and guided by neurosurgical consultation. Gastrointestinal decontamination by activated charcoal may be indicated in acute toxicity caused by known ingestion and in a neurologically stable patient. Orogastric lavage usually is not necessary unless the patient presents within 1 hour of ingestion or if a life-threatening co-ingestant is suspected. Full bowel decontamination is only advised in suspected body packing of drugs. Morbidity is directly related to the duration and severity of hyper-
tient’s temperature is unresponsive to non-pharmacologic measures. Administration of a benzodiazepine to control shivering may also be required. Most seizures are self-limited and respond well to benzodiazepines, with refractory symptoms managed by phenytoin and phenobarbital. All electrolyte abnormalities, especially hyponatremia, should be treated with hypertonic saline solution (3-5 mL/ kg/dose), fluid restriction (as indicated by hemodynamics and hydration status), mannitol, and low-dose furosemide. Treatment of rhabdomyolysis and prevention of renal failure can best be achieved with fluids and urine alkalinization using sodium bicarbonate, furosemide, or mannitol. In cases of renal dysfunction, early consultation with a nephrologist for available renal adjuncts and possible hemodialysis may optimize renal integrity (Britt & McCance-Katz, 2005; Gillman, 2005; Henry, 2000; Weir, 2000). 5. What considerations must be included in a patient’s discharge instructions and follow-up plan? Considerations for discharge include the ability to follow up with toxicology (as indicated), neurology, a PCP and the availability of laboratory/emergency services. Although there are no specific treatments for MDMA (and coingestant) abuse and addiction,
Morbidity is directly related to the duration and severity of hyperthermia; therefore, patients presenting with severe hyperthermia require aggressive cooling. thermia; therefore, patients presenting with severe hyperthermia require aggressive cooling. A goal of 102 F or less should be obtained by undressing the patient, using ice packs, fans, cold IV fluids, and iced-gastric lavage. Dantrolene could be considered if the pa-
MDMA has been shown to have residual cognitive adverse effects. Different approaches have been tried in patients experiencing withdrawal. Short-acting benzodiazepines have been trialed to aid with insomnia and mood stabilization (Britt & McCance-Katz, 2005; Journal of Pediatric Health Care
Oesterheld et al., 2004; U.S. Department of Health and Human Services, 2008). Behavioral and psychiatric interventions may be required if abuse or cognitive defects exist. To avoid the theoretical risk of producing neuroleptic malignant syndrome, often resembling serotonin syndrome, the use of psychotropic medications has been cautioned against in the literature (Weir, 2000). Therefore, patients being discharged on any psychotropic therapy require close follow-up with the prescribing psychiatrist. Neurologic follow-up is recommended when a patient experiences any neurologic sequelae. Symptoms such as (a) long-term confusion, (b) depression, (c) attention deficits, and/or (d) memory deficits may manifest after initial and multiple uses. Follow-up imaging has demonstrated changes within the motor, cognition, and emotion regions of the brain. To date, there are no pharmacologic treatments that reverse the effects of MDMA, and ongoing research includes looking for antidotes as well as long-term drug effects on the human brain and body (Britt & McCance-Katz, 2005; Oesterheld et al., 2004; U.S. Department of Health and Human Services, 2008). Although T.J.’s seizure was likely in response to his hyponatre-
Journal of Pediatric Health Care
mic state, the decision to treat with an anticonvulsant was determined by the consulting neurologist. There is no specific literature that addresses the duration of anticonvulsant use in patients who have ingested MDMA who present with seizures; however, a meta-analysis performed by Zagnoni and Albano (2002) on psychostimulant-associated epilepsy found that MDMA has the highest seizure occurrence. Lastly, discussion with the PCP prior to the patient’s discharge should include the patient’s condition, prescribed medications and their possible adverse effects, therapy/counseling, and subspecialty follow-up. The family and patient should be provided with a detailed written discharge plan with clear instructions for medication use, follow-up, and when to seek medical attention. REFERENCES Boyer, E., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352, 1112-1120. Britt, G. C., & McCance-Katz, E. (2005). A brief overview of the clinical pharmacology of ‘‘Club Drugs.’’. Substance Use & Misuse, 40, 1189-1201. Gillman, P. (2005). Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95, 434-441. Henry, J. (2000). Metabolic consequences of drug misuse. British Journal of Anaesthesia, 85, 136-142.
Kalant, H. (2001). The pharmacology and toxicology of ‘‘ecstasy’’ (MDMA) and related drugs. Canadian Medical Association Journal, 165, 917-928. Klein, M., & Kramer, F. (2004). Rave drugs: Pharmacological considerations. AANA Journal, 72, 61-67. Liechti, M., Kunz, I., & Kupferschmidt, H. (2005). Acute medical problems due to Ecstasy use. Swiss Medical Weekly, 135, 652-657, Retrieved August 29, 2008, from. www.smw.ch/dfe/set_ archiv.asp. Office of National Drug Control Policy. (2008). National drug control strategy; 2008 annual report. Retrieved August 29, 2008, from. www.whitehousedrugpolicy.gov/ publications/policy/ndcs08/2008ndcs. pdf. Oesterheld, J., Armstrong, S., & Cozza, K. (2004). Ecstasy: Pharmacodynamic and pharmacokinetic interactions. Psychosomatics, 45, 84-87. U.S. Department of Health and Human Services. (2008). MDMA (Ecstasy). National Institute on Drug Abuse. Retrieved August 29, 2008, from www.nida.nih. gov/PDF/Infofacts/MDMA08.pdf. U.S. Department of Health and Human Services. (2006). Research report series: MDMA (Ecstasy) abuse. National Institute on Drug Abuse. Retrieved August 29, 2008, from www.drugabuse.gov/ PDF/RRmdma.pdf. Weir, E. (2000). Raves: A review of the culture, the drugs and the prevention of harm. Canadian Medical Association Journal, 162, 1843-1848, Retrieved September 4, 2008, from. http://www. cmaj.ca/cgi/reprint/162/13/1843. Zagnoni, P., & Albano, C. (2002). Psychostimulants and epilepsy. Epilepsia, 43, 2831, Retrieved September 4, 2008, from. www.3.interscience.wiley.com/cgi-bin/ fulltext/118940645/PDFSTART.
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