Short case report

A male neonate (birth weight 2990 g, gestational age 37 weeks) with severe birth asphyxia (Apgar 0/4/7, lowest pH 6.7, maximum base excess −28 mmol/litre) after placental abruption was admitted on the 2nd hour of life to the neonatal intensive care unit for therapeutic hypothermia. In accordance with published study protocols for neonatal therapeutic hypothermia, morphine is routinely administered in our unit to neonates undergoing therapeutic hypothermia who show signs of distress.

After 36 h on therapeutic hypothermia, when the morphine infusion was increased to 15 µg/kg/h in response to increasing ‘neonatal pain, agitation and sedation scale’ (N-PASS) scores, the patient developed urinary retention without bowel constipation. Concomitant with increasing bladder volume, the patient's legs became progressively engorged and purple as a sign of impeded venous return through the iliac veins. The bladder volume reached a maximum of 63 ml (calculated from the formula L × D × W (in cm3) × 0.53) as measured by ultrasound (figure 1). After bladder catheterization was unsuccessful twice and followed by macrohaematuria, options (immediate suprapubic puncture or a single trial of methylnaltrexone as off-label use) were discussed with the parents. According to German law, responsibility for the use of a licensed drug in an orphan situation or an age group beyond the licence of the manufacturer (‘individuelle Heilversuche’ ie, compassionate use) rests with the physician in charge; local or state institutional review boards will not consider applications for individual off-label drug treatments. The published data about methylnaltrexone were discussed with the parents and they were informed that ‘if no clearly evident clinical improvement had occurred within 60 min after administration of methylnaltrexone, we would have considered further action’. After obtaining the written informed parental consent, the neonate received 0.15 mg/kg of methylnaltrexone intravenously (Relistor 12 mg/0.6 ml injection solution; Wyeth Pharma GmbH, Münster, Germany), while the morphine infusion remained at 15 µg/kg/h. The neonate passed urine spontaneously within 20 min after the first dose of methylnaltrexone. After voiding, the bladder volume was reduced to 6.4 ml as measured by ultrasound, and the clinical signs of impaired venous drainage from lower limbs resolved completely (figure 2).

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Figure 1

Clinical signs of opioid-induced urinary retention with massive bladder extension and corresponding ultrasound image of the bladder in the long section.

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Figure 2

Clinical findings and corresponding ultrasound image of the bladder in the long section after reversal of morphine-induced urinary retention 20 min after intravenous methylnaltrexone administration.

After 24 h, administration of intravenous methylnaltrexone (0.15 mg/kg) was repeated because there was again urinary retention. For a second time, voiding occurred within 20 min. No adverse events of methylnaltrexone were noted at any time. Methylnaltrexone did not appear to increase bowel movements.

There were no changes in pain scores as assessed by the N-PASS (maximum N-PASS score within 8 h before beginning of methylnaltrexone treatment 4/10, maximum N-PASS score during methylnaltrexone treatment until the end of therapeutic hypothermia 4/10) or evidence of central opioid withdrawal during the time of methylnaltrexone administration. Morphine was discontinued after elective cessation of hypothermia treatment after a total duration of 72 h and gradual rewarming. The patient had a full recovery, as judged by neurological examination, EEG and MRI brain scans on day 7 of life, and was discharged from the hospital on day 11 of life.