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Summary

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. Acknowledgements
  6. References

A 17-month-old toddler became critically ill after an accidental overdose with ‘Ecstasy’. A single tablet was quickly retrieved intact from under her tongue, but within 5 min the child developed generalised tonic-clonic seizures requiring immediate transfer to hospital. She also had hyperthermia (38.5 °C), tachycardia (150 beats.min−1) and hypertension. Treatment to terminate the seizures necessitated intubation and ventilation, and cooling measures brought the temperature within normal limits. The child was admitted to the intensive care unit and made a rapid recovery. She was discharged to the ward 12 h later, and had no long-term sequelae.

Ecstasy is 3,4-methylenedioxymetamphetamine (MDMA), which is structurally related to the psychostimulant metamphetamine and the hallucinogen mescaline. It functions as an indirect sympathomimetic, acting at some adrenergic and dopaminergic receptors. MDMA also inhibits the re-uptake of serotonin from the synaptic cleft, which is thought to account for its mood-altering effects and possible psychomotor agitation [1].

Ecstasy is widely used by young adults in clubs and the ‘rave’ scene. Its consumption is second only to cannabis in a number of European countries [2], and it has been estimated that in the United Kingdom 500 000 people ingest the drug every weekend [1]. The lack of data about the lethal consequences of taking Ecstasy has led to the belief in many users that it is a safe drug [3]. Experience in dealing with Ecstasy toxicity is mainly obtained from case reports in adults, but this report suggests that there may be important differences in children.

Case report

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. Acknowledgements
  6. References

A 17-month-old girl was brought by ambulance to the Emergency Department with generalised tonic-clonic seizures. The mother reported that her daughter had been well previously. In the evening she had been playing in a room next door to her mother and had picked up a cigarette packet in which a single Ecstasy tablet was stored. An older child watched as the toddler placed the tablet in her mouth and immediately alerted the mother. On entering the room the mother picked up the child and was able to visualise the tablet sitting under her tongue. She then removed the tablet which appeared to be intact. Approximately 5 min after the Ecstasy tablet was removed, the toddler developed generalised seizures. An ambulance was called immediately and the child was transferred to hospital.

On admission the toddler had been convulsing continuously for 20 min. Her airway was clear and she was breathing spontaneously with good chest wall movement. Non-invasive pulse oximetry was unable to record a value because of movement, but she was not clinically cyanosed. She had a sinus tachycardia of 150 beats.min−1 and was hypertensive with a blood pressure of 130/70 mmHg. There was no evidence of a rash, her rectal temperature was 38.5 °C and she was normoglycaemic with a blood sugar pinprick test (Clinitest®) of 6.4 mmol.l−1.

Management followed advanced paediatric life support (APLS) principles [4]. High flow oxygen therapy via a reservoir mask was initiated, and she received diazepam 5 mg and paracetamol 180 mg via the rectal route whilst intravenous access was obtained. There was no response to rectal therapy, and subsequently lorazepam 1 mg was given intravenously. She appeared poorly perfused with a delayed capillary refill time, and therefore a fluid bolus of 10 ml.kg−1 of 0.9% saline and intravenous cefotaxime 500 mg were administered. The seizures continued and another 1 mg of lorazepam was given 10 min later without response. At this time there were increasing concerns that her airway was not being maintained. Copious clear secretions were making her breathing very noisy, and this was not relieved by simple airway manoeuvres, airway adjuncts or gentle suctioning. The saturation probe was now recording an Spo2 of 72%. Anaesthesia was induced with a rapid sequence induction using sodium thiopental 75 mg and suxamethonium 25 mg and the trachea was orally intubated with an uncuffed 4.5 mm tracheal tube. The child was then sedated with a midazolam infusion, and given a single bolus dose of atracurium 10 mg pending transfer for a computerised tomography scan of her brain, which was normal. An electrocardiogram (ECG) was performed, which showed a sinus tachycardia but was otherwise normal. A plain chest radiograph showed no abnormality, with the tracheal tube in good position.

The initial blood results are presented in Table 1. An immediate postintubation arterial blood gas analysis on 100% inspired oxygen can be seen in Table 2. A urinary catheter was passed and a specimen was sent for a urine toxicology screen. This was subsequently reported as positive for amphetamine derivatives. Serum was saved and later sent for more detailed toxicological analysis. The serum MDMA level was 0.30 mg.l−1; no other toxin was detected.

Table 1.  Initial blood tests.
TestResultNormal value
Na+139 mmol.l−1132–144 mmol.l−1
K+  5.1 mmol.l−13.5–5.5 mmol.l−1
Urea  5.2 mmol.l−12.5–6.6 mmol.l−1
Creatinine 34 µmol.l−121–36 µmol.l−1
Haemoglobin 12.1 g. dl−111–14 g.dl−1
White cell count 19.9 × 109.l−1 6–17 × 109.l−1
Neutrophils  8.4 × 109.l−11.5–8.5 × 109.l−1
Platelets633 × 109.l−1150–400 × 109.l−1
C-reactive protein< 3 mg.l−1  0–5 mg.l−1
Creatinine kinase288 U.l−1 24–170 U.l−1
Table 2.  Immediate postintubation arterial blood gas (FIo2 1.0).
ParameterValue
pH7.26
PaO259.4 kPa
PaCO24.47 kPa
Base deficit11.0 mmol.l−1
Standard bicarbonate15.8 mmol.l−1

She was transferred to the intensive care unit. There was no clinical evidence of further tonic-clonic seizures. Her temperature rapidly normalised with tepid sponging and a fan. She was cardiovascularly stable throughout and her tachycardia settled following cooling and termination of the seizures. Three hours after the emergency tracheal intubation she was neurologically appropriate and the midazolam sedation was turned off. She had the tracheal tube removed uneventfully shortly afterwards, and remained on the intensive care unit for a further 12 h. She was discharged home within 48 h, and was reviewed in an out-patient clinic 10 days later. She had made a full recovery and was clinically well with no apparent sequelae.

Discussion

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. Acknowledgements
  6. References

Most paediatric poisonings occur in the home, either because toxic substances are within easy reach or are stored poorly [5]. The widespread use of Ecstasy within the community is likely to result in an increased risk of accidental poisonings in children. This may be exacerbated by the false perception that Ecstasy is a safe drug, and as a consequence may lead to a more relaxed attitude to supervision and security. Ecstasy tablets are also often very colourful and may therefore be particularly attractive to young children.

Public awareness was heightened when there were reports in the press of an actor's 2-year-old daughter who swallowed an Ecstasy tablet at a party [6]. However, severe Ecstasy toxicity is surprisingly rare in children and few cases have been reported in the literature [7–11]. In these reports the intoxication seems to present with symptoms sooner in children (20–30 min) than in adults, with convulsions being the initial manifestation. Other common features in children are hypertension, tachycardia, and moderate hyperthermia.

The toddler in this case was unusual in that she started having seizures only 5 min after what was believed to be the removal of the intact tablet from under her tongue. It would appear that this was due to the very rapid sublingual absorption of the drug. This is supported by the fact that her serum MDMA level at presentation was 0.30 mg.l−1– higher than the typical ‘recreational’ blood levels of 0.1–0.25 mg.l−1 found in adult users. However, it is known that Ecstasy toxicity is idiosyncratic, and does not appear necessarily to be related to either the amount ingested or the serum concentration of the drug [12, 13]. Fatalities have been reported in the literature with levels as low as 0.11 mg.l−1[14]. It is also known that there is a wide variation in how individuals tolerate MDMA. The principal pathway by which MDMA is metabolised is by CYP2D6 (a polymorphic isoenzyme of cytochrome P450) [15]. About 3–10% of the Caucasian population is deficient in this isoenzyme [16], and poor metabolisers may be at greater risk of toxic responses even at low doses of MDMA. In addition MDMA also shows non-linear pharmacokinetics, potentially leading to disproportionate rises in plasma MDMA concentrations [17].

Convulsions and agitation have been successfully treated with supportive measures and benzodiazepines [10, 11]. Chlormethiazole and haloperidol have also been used successfully [8], but are probably best avoided as they may cause hypotension and lower the seizure threshold [18]. Intractable seizures can be treated with phenytoin or barbiturates. Vigorous fluid therapy may be necessary to rehydrate patients, replace insensible losses and promote diuresis to clear myoglobin. However, care is necessary as water intoxication has been described in these patients. Fluid therapy should be guided by regular blood tests and invasive monitoring [18].

Severe hyperthermia has been recognised for some time as a complication of Ecstasy use [1]. This may be part of a central serotonergic overstimulation [7], and may be exacerbated by environmental factors when ‘recreational’ users excessively exert themselves in warm, crowded settings such as dance clubs or raves [12, 19]. The aetiology of the hyperthermia seen in the paediatric cases is unknown, but it should be noted that in this case report the recorded temperature was 38.5 °C; on review of the literature [7–11] the highest temperature recorded in children was only 39 °C [9]. It seems likely that the moderately elevated temperatures are mainly a result of the metabolic activity generated by the seizures. This case report suggests that termination of seizure activity combined with simple cooling measures may be sufficient to return the core temperature to within normal ranges. Dantrolene has been used successfully to treat the uncontrolled cycle of hyperthermia that can be associated with Ecstasy toxicity in adults [20, 21]. The role of dantrolene in the setting of Ecstasy-induced hyperthermia is controversial, particularly due to the potential risks of hepatotoxicity [22–24]. As hyperthermia may have a different aetiolgy in the paediatric population compared with the adult populations, the role of dantrolene is less certain.

A further consideration is that each 20 mg vial of dantrolene contains 3 g of mannitol and is reconstituted to a pH 9.5. Alkalinisation of the urine, which is usually recommended in rhabdomyolysis, will reduce renal clearance of MDMA. Conversely, acidification of the urine, which can increase urinary excretion of MDMA and other amphetamines, is not recommended if serum concentrations of creatinine kinase are raised, because it can promote renal myoglobin precipitation [25].

The problem with ingesting an illegally synthesised and marketed tablet is that the dose and purity are unknown. Ecstasy tablets are heterogeneous, and have been reported to contain between 80 and 150 mg MDMA [26]. There are reports of contamination with caffeine, ephedrine and ketamine [27]. Other tablets fail to contain any detectable trace of MDMA [28]. It is therefore important to perform a full toxicological screen even if there is a clear history.

The dangers of accidental Ecstasy ingestion have been reported previously. Children can become critically ill very quickly after accidental ingestion of Ecstasy. As highlighted in our case, toxic levels can occur even without ingestion of tablets, following rapid sublingual absorption. It should be considered as a rare, but possible differential, diagnosis in a child presenting with an atypical febrile seizure, and urine toxicology should be considered in addition to standard investigations.

Acknowledgements

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. Acknowledgements
  6. References

Informed consent was obtained from the mother of the child involved. There are no competing interests.

References

  1. Top of page
  2. Summary
  3. Case report
  4. Discussion
  5. Acknowledgements
  6. References
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