Hyponatraemia and death after "ecstasy" ingestion
Michael J A Parr, Heather M Low and Paull Botterill
A 15-year-old girl collapsed with respiratory arrest after taking "ecstasy" at a "dance party". She presented to hospital with hyponatraemia and cerebral oedema and later died. We postulate that ingestion of large amounts of water contributed to the hyponatraemia. Advice to those using ecstasy at dance parties should be modified to suggest moderate fluid intake only and to emphasise the need to seek prompt medical attention for non-resolving symptoms.
MJA 1997; 166: 136
For comment see White et al.
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Introduction - Clinical record - Discussion - Acknowledgements - References - Authors' details
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©MJA1997
The evening before admission, she had been at a "dance party",
where she had taken MDMA at about midnight. She was also believed to
have drunk large quantities of water at the party, as then advised by
health authorities (e.g., United Kingdom Health Education
Authority, and National Poisons Unit), to counteract the
hyperthermic effects of MDMA.
About 0500, while still at the dance party, she began to vomit.
After leaving the party she rested at a friend's house, where she had
episodes of dry retching, impaired consciousness, confusion and
some abnormal twitching movements.
At 1000, about ten hours after ingestion of the MDMA, she was
still drowsy and confused, and then collapsed with respiratory
arrest while being walked downstairs. There was an estimated 12
minutes of hypoventilation and apnoea, with no cardiopulmonary
resuscitation until an ambulance crew arrived.
At 1023, on arrival of the ambulance crew, she was found to be in
sinus tachycardia with palpable pulses, and she was intubated and
ventilated by the crew. Spontaneous cardiac output was maintained
throughout. She received naloxone, Hartmann's solution (1000 mL)
and polygeline (Haemaccel, Hoechst) (500 mL) before arrival at
hospital.
At 1118, in the Emergency Department she was found to have:
Glasgow Coma Scale score, 3; heart rate, 110 bpm; blood pressure,
80/50 mmHg; temperature, 32.8oC. She had bilateral papilloedema,
fixed dilated pupils, no eye movements, no corneal, gag or cough
reflexes and no reactions to pain. The hypotension did not respond to a
further 1000 mL of 0.9% saline, and a noradrenaline infusion was
started. This corrected the hypotension but did not improve the
neurological status.
At 1145, results of biochemical tests of blood taken before
treatment in the Emergency Department showed reduced
concentrations of serum electrolytes, suggesting haemodilution
(see Box [below]). The haemodilution was corrected within six hours with
infusion of 0.9% saline, moderate fluid restriction (total fluids,
60 mL/hour) and diuresis with frusemide and mannitol.
At 1205, a chest x-ray revealed changes consistent with
pulmonary oedema, and at 1245 computed tomography of the brain showed
cerebral oedema with marked effacement of basal cisterns and
inferior displacement of the brainstem. An electrocardiogram at
1400 was normal. Blood-gas analysis at 1500 showed respiratory
alkalosis. Maximum serum creatine kinase level was raised, and there
was no sign of coagulopathy (see Box [above]).
On the second day of admission, the patient was making
spontaneous efforts to breathe (on the ventilator) but otherwise her
neurological status had not changed. She required noradrenaline to
maintain blood pressure but had no cardiac arrhythmias. A nuclear
magnetic resonance scan confirmed diffuse cerebral oedema, with
decreased blood flow within the major cerebral vessels. Overnight,
the patient deteriorated, developing diabetes insipidus and
ceasing to breathe spontaneously.
On the third day of admission, results of clinical
examination were consistent with a diagnosis of brain death, and a
cerebral angiogram confirmed this diagnosis.
Postmortem findings showed diffuse brain swelling, with cerebellar
tonsillar herniation and pituitary necrosis. Analysis of
antemortem urine and blood revealed MDMA at levels of 430 ng/mL and
0.05 mg/L, respectively. No other drugs were detected.
The cerebral oedema is unlikely to have resulted from hypoxia after
the respiratory arrest, as it would then usually be accompanied by
bradycardia or asystole, neither of which was present. In addition,
there was no evidence that the patient suffered cardiac arrhythmia,
toxicity or infarction, which have caused other
amphetamine-related deaths.3
The contribution of intravenous therapy to the hyponatraemia,
fluid overload and cerebral and pulmonary oedema is unclear. Given
the volumes (1500 mL) and osmotic concentrations (hypertonic or
isotonic) of the solutions administered, any contribution is likely
to have been small.
The effects of MDMA are numerous and complex, and severe reactions are
unpredictable.1 There have
been many reports of MDMA-associated deaths caused by fulminant
hyperthermia, coagulopathy and rhabdomyolysis,1 and clinical awareness of these
problems seems high. However, many other complications of MDMA
ingestion, such as hyponatraemia, may result in death or serious
morbidity and have received less publicity. Instances of
hyponatraemia after MDMA ingestion have been reported, with
postulated causes that include ingestion of large quantities of
water, the syndrome of inappropriate antidiuretic hormone
secretion (SIADH) and contamination of the MDMA with other
chemicals.4-9
Hyponatraemia raises a diagnostic dilemma, as its signs may be
indistinguishable from those of MDMA intoxication. 10 There is evidence that morbidity
associated with hyponatraemia is highest in children and
women and is not related to either the magnitude or duration of the
hyponatraemia.11
To our knowledge, this is the first Australian report of a fatality
associated with ecstasy in which hyponatraemia and cerebral oedema
appeared to be the main pathological processes. However, dissecting
out the various factors involved in the death is extremely difficult.
The roles of MDMA, the dance party environment, water ingestion,
hyponatraemia, cerebral oedema, hypoxia, hypotension and SIADH are
intertwined. The dance party environment encourages heavy exercise
in a hot environment, with the advice to drink plenty of water. In the
presence of high salt losses, this may produce hyponatraemia. Water
ingestion may become uncontrolled as the individual attempts to
treat symptoms or as the MDMA impairs rational judgement or possibly
stimulates compulsive repetitive behaviour.12 Cerebral oedema as a result of
hyponatraemia is well recognised and may result in tentorial
herniation, respiratory arrest and cerebral hypoxia.11 SIADH has also been implicated in
ecstasy-associated hyponatraemia.9 Although the mechanism is unclear,
animal research suggests that serotonin increases secretion of
antidiuretic hormone.13
Given the many people who take ecstasy without apparent ill-effect,
it has acquired a safe reputation. Among the many adverse reactions,
we must now include life-threatening hyponatraemia, which may have
the same symptoms and signs as MDMA intoxication. To avoid adverse
reactions, individuals using MDMA at dance parties are often advised
to rest, avoid overheating, wear loose clothing and drink plenty of
cool drinks.14 However,
there is no evidence that this prevents adverse reactions.
Furthermore, because of the possibility of hyponatraemia, this
advice should be modified to suggest ingesting only moderate amounts
of liquids. The importance of seeking medical attention promptly for
non-resolving symptoms should also be emphasised.
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©MJA 1997
Introduction
Recent deaths associated with ingestion of the illicit drug
"ecstasy" have attracted widespread publicity and debate about the
cause of death. Ecstasy (3,4-methylenedioxymethamphetamine;
MDMA) is an ampheta mine derivative which has short-term
hallucinogenic and stimulant effects, but in the long term may
deplete brain serotonin by reducing numbers of serotonergic nerve
terminals.1 Previous
ecstasy-related deaths have involved hyperthermia,
rhabdomyolysis, coagulopathy and cardiac toxicity.2 We report a death after ecstasy
ingestion associated with hyponatraemia, a less well known
complication.
Clinical record
A previously healthy 15-year-old girl was admitted to the Intensive
Care Department in coma after a respiratory arrest.
Discussion
We report the death of a previously well young girl after ingestion of
MDMA. The cause of death was thought to be hypoxic encephalopathy
after respiratory arrest following acute water intoxication
secondary to ingestion of MDMA. It would seem likely that
hyponatraemia and cerebral oedema before the respiratory arrest
were major factors in her death.
Acknowledgements
The authors would like to thank the NSW Senior Deputy State Coroner, Mr
John Abernethy, for releasing this information for publication, and
Dr John A Henry of the National Poisons Unit, Guy's Hospital, London
(UK), for assistance with this case.
References
(Received 26 July, accepted 21 Nov, 1996)
Authors' details
Intensive Therapy Unit, Royal North Shore Hospital, Sydney, NSW.
Michael J A Parr, MRCP, FRCA, Senior Registrar; currently,
Consultant in Anaesthesia and Intensive Care, Frenchay Hospital,
Bristol, UK; Heather M Low, FRACP, Senior Staff Specialist.
NSW Institute of Forensic Medicine, Sydney, NSW.
Paull Botterill, FRCPA, Pathologist.
No reprints will be available. Correspondence: Dr H M Low,
Intensive Therapy Unit, Royal North Shore Hospital, St Leonards, NSW
2065.
<URL: http://www.mja.com.au/>
© 1997 Medical Journal of Australia.
- Heather M Low
- Paull Botterill