21-Year-Old Woman With Palpitations and Vomiting

A 21-year-old woman presented to the emergency department with chest palpitations, nausea, and vomiting of 6 hours' duration. Her symptoms originated as a bandlike tightness across the sternum that progressed to include a racing heart with “skipped beats.” She then began to feel nauseous and experienced more than 10 episodes of vomiting. She described the emesis as watery without any signs of blood with eventual progression to retching without output. Before experiencing these symptoms, she had slept for 6 hours without difficulty and had no symptoms entering into sleep. Her medical history was notable for 2 uncomplicated vaginal deliveries. She reported no surgical or psychiatric history. She did not use prescription medications. Although she lived with her mother and 2 children, she spent several nights per week at friends' homes. During these nights, she drank up to 10 shots of liquor (estimated at 148 mL [5 oz] of alcohol) and occasionally used illicit drugs, including marijuana and cocaine.

Physical examination yielded the following vital sign information: heart rate, 120 beats/min; blood pressure, 118/82 mm Hg; respiration rate, 19 breaths/min; and temperature, 36.5°C. The patient appeared uncomfortable. Cardiac examination revealed a regular, rapid tachycardia without murmur or extra heart sounds. Findings on lung and abdominal examinations were unremarkable, as were the remainder of the examination results.

Laboratory tests yielded the following results (reference ranges provided parenthetically): hemoglobin, 12.9 g/dL (12.0-15.5 g/dL); white blood cell count, 12.3 × 10⁹/L (3.5-10.5 × 10⁹/L); lactate, 3.6 mmol/L (0.6-2.3 mmol/L); and unremarkable levels of electrolytes, creatinine, troponin I, and D-dimer.

1. Which one of the following tests would provide the most diagnostic information at this stage in the evaluation?

   1. Computed tomography (CT) of the chest with intravenous contrast medium

   2. Toxicology screen

   3. Blood cultures

   4. Serial troponin I testing

   5. Erythrocyte sedimentation rate

   Intravenous contrast-enhanced CT of the chest is the confirmatory test of choice for pulmonary embolism. Although tachycardia is a sign of pulmonary embolism, negative findings on the D-dimer assay and the paucity of risk factors, such as oral contraception, history of venous thromboembolic disease, or recent immobilization, make this diagnosis unlikely and CT unnecessary. A toxicology screen, however, would be very helpful in evaluating this patient. Tachycardia is a common finding in toxidromes, and drug intoxication would be high in the differential diagnosis with the patient's history of drug abuse. Furthermore, the results of a toxicology screen could lead to alterations in the management of her condition. The patient qualifies for the systemic inflammatory response syndrome because of the tachycardia and elevated leukocyte count and, in combination with the elevated level of lactate, sepsis is a concern. However, blood culture results would not be available for several days and would not help narrow the differential diagnosis or guide initial therapy. Troponin I is a marker of cardiac ischemia that is most associated with myocardial infarction; however, it may also be elevated in pulmonary embolism or myocarditis. Although serial testing is recommended to rule out acute coronary syndrome, the patient's constellation of findings is inconsistent with this diagnosis. The erythrocyte sedimentation rate is a nonspecific marker of inflammation and would not be helpful in the initial work-up.

   Additional studies were performed to further evaluate the patient. A urine toxicology screen was negative for illicit and prescription drugs; however, her caffeine level of 16.6 μg/mL was in the toxic range (15-45 μg/mL). Electrocardiography revealed sinus tachycardia with a heart rate of 132 beats/min. When the results of the initial laboratory tests were presented to the patient, she admitted ingesting 2 tablets of an unknown substance and consuming a large number of alcoholic drinks, primarily rum mixed with cola, in the 24 hours before presenting to the emergency department.

2. Which one of the following drugs of abuse is most likely to be associated with the current symptoms and laboratory results?

   1. 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”)

   2. Oxycodone-acetaminophen

   3. Methylphenidate

   4. Lorazepam

   5. Phencyclidine

   Ecstasy, the slang name for the synthetic amphetamine MDMA, is a common drug of abuse. Tablets sold as ecstasy often contain a wide variety of chemical substances beyond MDMA. Caffeine is the most common psychoactive agent compounded into tablets sold as ecstasy, and the frequency of its inclusion is increasing.¹ In addition, urine assays have a low sensitivity for detection of MDMA, and a high concentration is needed to elicit positive results.² Thus, the negative urine drug screen does not rule out ingestion of ecstasy. Oxycodone-acetaminophen is a prescription narcotic medication that is often abused, but the symptoms of intoxication are inconsistent with the current presentation. Methylphenidate is structurally similar to amphetamines and could produce the symptoms of the patient. However, there is no connection to caffeine, and the results of the toxicology screen would not be explained by the ingestion of this medication. Lorazepam is a benzodiazepine that causes sedation and can lead to respiratory depression in high doses. Phencyclidine is an anesthetic that produces a wide variety of symptoms, including psychoses and violent hostility. Both these drugs are detectable on urine toxicology screens for at least 48 hours² and have no connection with caffeine.

   The patient was treated with prochlorperazine for her nausea and an intravenous bolus of 2 L of normal saline in the emergency department. When reassessed, she reported that her palpitations had resolved. No further episodes of vomiting occurred. However, she continued to manifest a regular tachycardia with a pulse rate greater than 120 beats/min.

3. At this point, which one of the following therapeutic strategies is the most appropriate to manage this patient's symptoms?

   1. Activated charcoal

   2. Metoprolol

   3. Normal saline

   4. Lorazepam

   5. Watchful waiting

   Ecstasy is rapidly absorbed through the gastrointestinal tract, and thus decontamination is rarely useful beyond 1 hour after ingestion.³ Metoprolol, a relatively specific β-blocker, should not be used in the setting of sympathomimetic intoxication. There is concern for increased α-adrenergic stimulation and thus arterial constriction, leading to hypertension and risk of hypoperfusion. Indiscriminate hydration is also inappropriate as the tachycardia is driven by increased sympathetic stimulation rather than dehydration. Fluid resuscitation should be dictated by the clinical impression of hydration status and physical examination findings in this setting. Lorazepam is an initial treatment option for hypertension and tachycardia in the setting of the use of sympathomimetic agents, specifically cocaine. However, directed treatment is not required in the absence of symptoms such as acute coronary syndrome or other end-organ damage.⁴ Therefore, watchful waiting is the most appropriate action for our patient. Although substantial morbidity is possible with the cardiovascular effects of ecstasy, there is no clinical evidence of complications requiring more aggressive interventions at this point.

   The patient was admitted to the internal medicine service for observation and further management. She reported a general restlessness and was unable to tolerate oral nutrition because of persistent nausea. She was monitored with frequent vital sign checks and mental status assessments.

4. Given this patient's ingestion of ecstasy, which one of the following is a common and serious complication for which the patient should be monitored?

   1. Hypothermia

   2. Hyponatremia

   3. Metabolic alkalosis

   4. Adrenal insufficiency

   5. Respiratory depression

   Hyperthermia, rather than hypothermia, is a known adverse effect of ecstasy. This adverse effect is thought to be worsened by the crowded environments in which the drug is often used. This symptom can also herald the onset of the serotonin syndrome if there is coingestion of other medications affecting serotonin levels. Severe hyponatremia is a serious consequence of ecstasy ingestion that is caused by the direct stimulation of antidiuretic hormone release³ and by the vigorous hydration regimens to which users often resort to avoid the better-known danger of hyperthermia. Fortunately, our patient did not experience this complication. No association has been reported between ecstasy use and adrenal insufficiency. Ecstasy has not been linked with metabolic alkalosis. It has been correlated with increased anion gap metabolic acidosis secondary to an elevated lactic acid level, which is hypothesized to be due to direct effects on muscle.⁵ Respiratory depression is associated with narcotic use rather than ecstasy ingestion.

   The patient's symptoms abated during the next 18 hours. She was seen in consultation by a chemical dependency counselor before dismissal and advised on the immediate dangers and possible long-term consequences of substance abuse. The counseling involved her illicit drug use and use of alcohol, which was consistent with alcohol dependence (eg, continued heavy drinking despite the time spent away from her children and the problems this caused within her family⁶). Unfortunately, despite demonstrating an understanding of the risks associated with her lifestyle and behaviors, she was ambivalent about changing. Information regarding local resources for outpatient substance use treatment was provided.

5. For which one of the following is a person using ecstasy at increased risk within a year of initiating use?

   1. Tooth decay

   2. Schizophrenia

   3. Reduction in intelligence quotient

   4. Memory impairment

   5. Hallucinogen persisting perception disorder

   Although there is a risk of increased dental wear due to bruxism with the use of ecstasy, accelerated tooth decay is primarily correlated with the use of methamphetamine and has been termed meth mouth. This is postulated to be secondary to poor oral hygiene and the increased use of sugared beverages to combat xerostomia when intoxicated.⁷ No link has been reported between the use of ecstasy and the development of schizophrenia. Although long-term effects on cognition are postulated, no evidence supports a reduction in intelligence quotient within a year of initiating ecstasy use. An association between ecstasy abuse and an impairment in memory, specifically in verbal recall, has been shown in a recent meta-analysis and is well supported in the literature.⁸ Hallucinogen persisting perception disorder, which is the recurrence of perceptual alterations similar to those experienced after hallucinogen use at a time distinct from the drug use, is associated primarily with lysergic acid diethylamide (more commonly known as LSD). There are no reports in the literature of this occurring with the use of ecstasy alone.

DISCUSSION

The ring-substituted amphetamine MDMA, commonly referred to as ecstasy or E, causes the release of dopamine, serotonin, and norepinephrine through interaction with neuronal membrane transporters.⁹ Ecstasy administration has been noted to cause euphoria, empathy, and reduced social inhibition by users.¹⁰ These stimulatory effects have led to its widespread misuse as an intoxicant. Ecstasy is commonly associated with dance clubs or “raves,” and its use is increasing. In a recent survey of American youths aged 16 to 23 years, 13.6% admitted to use in their lifetime and 6% reported use within the past year.¹¹ As such, it is essential that medical personnel be familiar with the symptoms of its use and consider it in their differential diagnoses.

Ecstasy is primarily found in tablet form with widely variable contents. Surveillance analysis of seized ecstasy tablets has shown that the most common dose range of MDMA in tablets was between 50 and 75 mg, but 3.8% contained greater than 100 mg, and 4.5% contained less than 25 mg. Of the seized tablets, 7.5% were found to have substantial levels of caffeine, and 9.9% were found to be mixed with amphetamine, methamphetamine, or other synthetic amphetamine derivatives.¹

Initial signs of ecstasy use are consistent with the amphetamine structure and sympathomimetic cellular actions. These include mydriasis, hypertension, tachycardia, restlessness, and fine tremor. Severe intoxication can result in delirium, hyperthermia, and rhabdomyolysis with associated renal failure. Hyperthermia is postulated to occur as a result of the effects of serotonin and dopamine on central thermoregulation. This is also exacerbated by physical exertion, most often dancing, in the crowded conditions in which the drug is often consumed.⁵ In addition, caffeine ingestion has been shown to potentiate the lethality of ecstasy-induced hyperthermia in an animal model.¹² If hyperthermia is combined with altered mentation, hemodynamic instability, and diarrhea, then a diagnosis of the serotonin syndrome should be considered. This can be seen particularly with coingestion of selective serotonin reuptake inhibitors and monoamine oxidase inhibitors.

Hyponatremia is also a common complication and can result in cerebral edema. The hyponatremia is secondary to inappropriate antidiuretic hormone release caused by a breakdown product of ecstasy. It is exacerbated by the excessive amounts of water users often drink in misguided attempts to avoid hyperthermia, causing a concomitant dilutional worsening of the electrolyte abnormality.³

Like other amphetamines and derivatives, MDMA can be detected by urine and serum drug screens. However, the sensitivity for MDMA has been found to be 50% below the sensitivity for amphetamine or methamphetamine in the commonly used urine immunoassays. Specific monoclonal antibodies have been developed and can be used if MDMA use is specifically suspected.² A case series of ecstasy ingestion suggested that MDMA plasma levels correlate with toxicity and that levels greater than 0.6 mg/L are associated with fatality.¹³

Emergent treatment recommendations are primarily aimed at correcting the abnormalities noted on initial presentation. Activated charcoal and other gastric decontamination efforts have relatively little place in treatment because of the rapid absorption through the gastrointestinal tract. Mild symptoms, such as tachycardia or hypertension without morbidity, may be observed. Treatment should be used for symptomatic tachycardia, such as rate-induced myocardial ischemia or hypertensive emergency with end-organ damage. Benzodiazepines have been used successfully in patients with cocaine-induced hypertension and tachycardia and also may be used in patients with ecstasy intoxication. Of note, selective β-blockers should be avoided in this setting because they may lead to unopposed α-receptor stimulation and result in worsening of the hypertension.⁴ Hyperthermia should be treated with central cooling techniques. Dantrolene has been used; however, the success of this treatment is unclear.⁵ Hyponatremia induced by MDMA should initially be treated with fluid restriction. If the hyponatremia is associated with seizures or obtundation indicating cerebral edema, then rapid correction with hypertonic saline should be performed.

The most consistently described long-term effect of ecstasy use is memory impairment. Verbal recall, both immediate and delayed, was found to be the most compromised; however, multiple domains of executive function are likely to be hampered.⁸ Increased depression has been subjectively reported by ecstasy users, and this has been corroborated by some prospective studies. However, the evidence is conflicting and this is still an area of investigation.⁸

Ecstasy is a common drug of abuse in the United States. It has multiple intended and unintended effects that are concerning and carries the risk of severe, life-threatening complications such as hyperthermia, severe hyponatremia, and the serotonin syndrome. The long-term results of ecstasy use are still unclear and under investigation. As use continues to increase, the medical community needs to become more familiar with the possible complications and treatments.

Correct answers: 1. b, 2. a, 3. e, 4. b, 5. d