Prehospital Care
Prehospital care is primarily supportive.
Address the ABCs, administer oxygen, obtain intravenous access, assess blood glucose level, monitor the patient, and perform frequent vital sign checks and serial assessment of consciousness (eg, AVPU [alert, responds to voice, responds to pain, unresponsive], Glasgow Coma Scale).
Anxiety, extreme agitation, panic reactions, and seizures may require short-acting benzodiazepines (eg, lorazepam) administered intravenously or intramuscularly. Restraints may be necessary if patients exhibit complete loss of control and are dangerous to themselves or others.
Emergency Department Care
While most patients with MDMA overdose improve with supportive care, life-threatening complications may result from severe toxicity. Fatalities have been reported because of severe hyperthermia (ie, heat stroke) accompanied by disseminated intravascular coagulation, rhabdomyolysis, and acute renal failure. Death from cerebral edema and seizures secondary to hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) has also been reported. As in any amphetamine toxicity, the danger of cardiac arrhythmias and cardiovascular instability always must be entertained.
Careful attention to the airway, breathing, and circulation (ABCs) and vital signs is standard in overdoses, and serial neurologic checks are required. Provide oxygen, obtain intravenous access, and perform cardiac monitoring.
A bedside glucose determination is indicated in any patient presenting with altered mental status. If a patient is hypoglycemic, administer thiamine and enough glucose to maintain adequate serum glucose concentrations with frequent monitoring.
If verbal communication is possible, providing reassurance is important. Avoid physical or pharmacologic restraints if possible. Place the patient in a calm, quiet room. If severe agitation or disruptive behavior persists, sedation using benzodiazepines and/or physical restraints may be necessary.
If acute toxicity caused by ingestion is known, perform gastrointestinal decontamination by administering activated charcoal. Orogastric lavage usually is not necessary unless a life-threatening co-ingestant is involved and the patient presents within 1 hour of ingestion. Whole-bowel irrigation may be indicated if body packing of drugs is suspected.
Although respiratory distress is uncommon, endotracheal intubation and mechanical ventilation may be required in patients who cannot protect their airway or have respiratory compromise because of conditions such as seizures, cardiovascular instability, or trauma.
Hyperthermia and the risk of serotonin syndrome can result in increased mortality with complications of disseminated intravascular coagulation, rhabdomyolysis, and acute kidney injury. Institute general cooling measures and treat rhabdomyolysis with generous intravenous hydration and alkalinization of the urine. Patients presenting with severe hyperthermia require aggressive cooling measures and adequate fluid resuscitation. Obtain a rectal temperature. Aggressively cool hyperthermic patients, attempting to reduce the core temperature to 101°F within 30-45 minutes.
Morbidity is directly related to the severity and duration of hyperthermia. Management considerations are as follows:
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Undress the patient
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Apply evaporative cooling; spray water onto the body and use an electric fan to circulate the air
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Apply ice packs to the groin and axilla
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Iced gastric lavage may be considered
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In extreme cases, ice-bath immersion may be required for the correction of hyperthermia
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Control shivering with a benzodiazepine
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Antipyretics are not useful
Dantrolene (1 mg/kg or 80 mg intravenously [IV]) has been used for the treatment of hyperpyrexia after conventional therapy. Dantrolene is typically used to treat malignant hyperthermia, a genetic disorder of the skeletal muscle due to a defect in the ryanodine receptor that allows for massive release of calcium from the sarcoplasmic reticulum during exposures to general anesthetics.
MDMA-induced hyperthermia is thought to be centrally mediated via serotonin toxicity. Although the mechanism of dantrolene does not seem to correlate with what is known about MDMA-induced hyperthermia, dantrolene was first used to treat hyperthermia in the setting of MDMA-related hyperpyrexia in 1992 due to the similarity of presentation.
A systematic compilation of MDMA case reports suggests possible evidence of benefit in using dantrolene to treat hyperthermia. [30] The study showed decreased morbidity and mortality with rare side effects from the dantrolene itself, especially in patients who present with temperatures above 40°C, and particularly above 42°C. The biggest caveat with using case series and case reports is recognizing the limitations of reporting and publication biases.
Monitor hyponatremia as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and excessive water intake for resultant cerebral edema and seizures. In severe cases, administration of 3% saline and furosemide may be indicated to correct the hyponatremia, but at a rate no greater than 0.5-1 mEq/L/h.
A study in an animal model found that clozapine resulted in a marked and immediate reversal of MDMA-induced hyperthermia, via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia, and labetalol was ineffective. [31]
Treat seizures with benzodiazepines. Most seizures are self-limited and respond well to benzodiazepines. Protect the airway and consider phenobarbital or propofol in patients with refractory symptoms. Treat the underlying cause and check electrolytes, especially hyponatremia. Start with fluid restriction, but consider adding hypertonic saline in refractory or severe cases; in these cases, adding 3% saline and furosemide may be indicated but at a rate no greater than 0.5-1 mEq/L/h.
Foley catheter placement is indicated to monitor urine output in patients with rhabdomyolysis. Check urinalysis for myoglobin and creatine kinase for rhabdomyolysis. Recognition and treatment of rhabdomyolysis with fluids, alkalinization of the urine, and furosemide may be indicated to prevent acute renal failure. Alkalinization of the urine with sodium bicarbonate is helpful. Administration of furosemide and mannitol may also be considered.
Obtain cardiac monitoring and an electrocardiogram in patients complaining of chest pain or palpitations. Order appropriate cardiac enzyme measurements if cardiac injury is suggested. Significant cardiac dysrhythmias may require pharmacotherapy or cardioversion and/or defibrillation.
Initially, manage hypertension with benzodiazepine sedation. In patients with refractory symptoms or signs of end-organ damage, nitroprusside or nitroglycerin can be used to lower the blood pressure.
Always perform pregnancy testing in female patients with overdose. MDMA, like all amphetamines, can be toxic to the fetus and may induce miscarriage or premature labor.
Admission to an intensive care unit may be needed in patients with any of the following:
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Significant hyperthermia
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Altered mental status
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Seizures
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Severe hyponatremia
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Respiratory depression
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Acute renal failure secondary to rhabdomyolysis
Patients may require transfer to a psychiatric facility for evaluation and treatment if they exhibit dangerous behavior or psychosis refractory to general supportive measures. However, patients must be stable, without hemodynamic instability and with no evidence of cardiac, cerebral, renal, hepatic, or pulmonary complications.
Consultations
A regional poison control center and medical toxicologist can provide valuable information and instructions for handling complex ingestions. Bedside consultation or admission (if necessary) by a medical toxicologist may be beneficial in these situations.
Obtain psychiatric consultation for patients who demonstrate suicidal thoughts or behavior. Refer the patient for drug abuse counseling and treatment.
