Letters to the Editor
Indian Pediatrics 2001; 38: 209-210
Use of Paraldehyde in Neonates – An Experience
We retrospectively analyzed our neonatal unit’s records for the last five years i.e., from 1 January 1995 to 31 December 1999 to collect the following information about the neonates in whom paraldehyde was used; gestational age, birth weight, postnatal age, diagnosis; and frequency of administration, side-effects, and total number of doses. Par-aldehyde was used in a total of 41 neonates (17 female and 24 male). The gestational age was 35.5 ± 8.39 weeks (range 28-43 week, preterm 23, fullterm 15, and post term 3) and birthweight 2104 ± 1692 g (range 870 g-4320 g; < 1500 g, 14; 1500 g-2500 g, 17; and > 2500 g, 10). Postnatal age at the time of Paraldehyde use ranged from 5 to 92 hours. Convulsions were caused by hypoxic ischemic encephalopathy in 17 neonates, intraventri-cular hemorrhage in 7 cases, cerebral mal-formation in 2 cases, inborn errors of metabolism in 5 cases and unidentified cause (10 cases).
In our unit, we use intramuscular par-aldehyde for the control of seizures resistant to first and second line anticonvulsants. As per the standard protocol of the unit, the first anticonvulsant used is intravenous pheno-barbitone (20 mg/kg), followed by another bolus of 10 mg/kg if seizures are not controlled. In case of non-response, intra-venous phenytoin (15 mg/kg) is used. The second bolus dose of phenobarbitone is omitted if therapeutic serum anticonvulsant levels can be demonstrated. Paraldehyde is used only when high doses of these drugs (or documented therapeutic levels) prove un-successful. Paraldehyde (Hindustan Pharma-ceuticals, Barauni) is used from a fresh ampoule each time using a disposable (Doctor®) 1 ml polypropylene syringe with 26-gauge needle, intramuscularly in the anterolateral thigh. The dose used is 0.1 ml/kg body weight and repeat doses are given at separate sites.
The clinical seizure activity was found to resolve within a few minutes in almost all cases, and no recurrence of seizures was noted up to 8 hours (range 3-8 hours, average 6.8 hours) after the dose. Total abolition of seizures and no change in seizure frequency were defined as response and non-response, respectively. Only four babies (9.75%) did not respond to the drug including one full term male baby with pyridoxine dependent seizures (diagnosed later). Two of the non-responders were pre term (gestational age 29 weeks and 30 weeks) with intraventricular hemorrhage and cerebral malformation (lissencephaly), respectively; and another was a full term with severe birth asphyxia (APGAR 0 at birth, died at 6 hour of age). A maximum of 12 doses were used in 2 full term and 1 post term neo-nate with hypoxic-ischemic encephalopathy. Only two neonates had complete seizure control with one dose of paraldehyde and both were full term with hypoxic-ischemic encephalopathy. Further, a sedative effect of paraldehyde was also noted lasting upto one hour, but the babies remained arousable.
None of the previously described toxic effect or adverse reaction was observed in our patients except for local cellulitis in 6 neonates (14.6%), five of these had received more than two doses. This cellulitis resolved within 15 days without any active manage-ment. Lung toxicity, as determined by deterioration in respiratory status or in oxygen saturation, was not noted in any neonate. Similarly, no clinical evidence of hepatitis was found and no increase in the hepatic enzymes was noted. A few neonates received up to 5 doses per day without any clinically detected adverse effects.
Paraldehyde is an effective anticonvulsant drug and is rapidly absorbed when administered by oral, rectal, or parenteral route, but is irritating to soft tissue. The exact mechanism of action of paraldehyde is unclear, though it may depress the reticular activating system. Severe toxicity has been reported after intra-arterial administration in neonates and intravenous and intramuscular administration(2). As it has been reported to produce pulmonary edema, pulmonary hemorrhage, and hypotension after intra-venous administration in older children(4), it should be used with caution in the neonate with respiratory distress(1). If possible, all glass syringes should be used with par-aldehyde, although, for immediate adminis-tration, the drug may be used with a plastic syringe(3). The reported half-life is 4-10 hours(3). An advantage of paraldehyde, in addition to its potent anticonvulsant action, is its significant rate of pulmonary elimination. This property is particularly important in patients, such as neonates, who have limited drug mobilizing capacity.
In view of its safety and efficacy, as demonstrated, the potential benefit of intra-muscular paraldehyde, therefore, warrants consideration as a third line agent in the management of refractory seizures in neonates.
The authors wish to thank Dr. Mahua Roy for assistance in data retrieval and statistical analysis.