Ecstacy-associated hyponatremia: why are women at risk?

Hyponatremia, serum sodium <135 mEq/L, is the most common electrolyte abnormality affecting ∼30% of hospitalized patients [1]. An infrequent yet serious complication of hyponatremia is hyponatremic encephalopathy. Hyponatremia can result in an influx of water to the intracellular space. This results in cellular swelling that can lead to cerebral edema and encephalopathy. Patients at highest risk of developing hyponatremic encephalopathy in the hospital setting are postoperative patients and patients with SIADH receiving hypotonic fluids [2]. Hyponatremic encephalopathy in the outpatient setting is usually seen as a complication due to medications such as thiazide diuretics or SSRIs, or can result from exerciseassociated hyponatremia or psychogenic polydypsia [3]. A significant risk factor for developing hyponatremic encephalopathy is female gender, with the majority of cases of death or permanent neurological injury from hyponatremic encephalopathy reported in females [4]. An increasingly common cause of hyponatremic encephalopathy in the outpatient setting is use of the recreational drug ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) [5]. In this issue of NDT, van Dijken et al. [6] report on the high incidence of hyponatremia in females using ecstasy. Ecstasy is an illegal synthetic amphetamine that was initially developed as an appetite suppressant but never used for this purpose. It first emerged as a recreational drug in the 1980s popular with young adults at night club parties referred to as ‘rave parties’ [7]. A rave is typically a commercially arranged elaborate all-night dance party that combines electronic music played by disc jockeys with a laser light show. Rave parties are extremely popular in North America and Europe, with thousands of people in attendance at rave events. An annual New Year’s Eve rave party in Los Angeles is reported to have almost 50 000 attendants [8]. Ecstasy is frequently taken on such occasions for its mood-enhancement properties. Users experience feelings such as euphoria, increased empathy and sociability, happiness and a sense of well-being, and increased energy [9]. Ecstasy exerts its effect by the release of neuroactive compounds in the central nervous system, including serotonin, dopamine and norepinephrine [10]. With the rise in popularity of ecstasy, medical complications began to be reported including hyponatremia, non-traumatic rhabdomyolysis, seizures, acute kidney injury, hyperthermia, cardiac tachyarrhythmia and sudden death, to name a few [5, 11, 12]. Ecstasy is believed to be the third most commonly used illicit drug, following marijuana and amphetamines, and ahead of cocaine, with an estimated consumption of over 28 million tablets yearly [7]. Emergency medical services are frequently on site at large, commercially organized rave parties [8]. One of the most serious medical complications associated with ecstasy use is hyponatremic encephalopathy [11]. There are over 25 reports of ecstasy-associated hyponatremic encephalopathy in the literature, and over half of them are fatalities. Almost all cases are reported in young females between the ages of 15 and 30 with a serum sodium of ≤130 following the ingestion of just one dose of ecstasy [5]. Symptoms typically develop within 2–12 h of ecstasy ingestion. Presenting symptoms are headache, nausea and vomiting followed by altered mental status, coma, seizure, cardio respiratory arrest, brainstem herniation and death [5]. A common yet frequently unrecognized presenting feature in these patients is neurogenic pulmonary edema, also referred to as Ayus–Arieff syndrome (Figure 1). This complication was first reported in females with post-operative and exercise-associated hyponatremia [11, 13, 14]. This is a particularly dangerous complication as hypoxia impairs brain IN F O C U S