Midazolam - a potential first-line therapy for neonatal seizures

Midazolam should be investigated as first-line treatment of neonatal seizures, suggest authors of a small study showing rapid seizure control with midazolam after conventional treatment had failed.The investigators analysed outcome according to treatment in 45 neonates with EEG-confirmed seizures treated at their hospital between 1993 and 2003. From 1993 to 1998, 32 neonates received "conventional treatment" of phenobarbital with or without phenytoin for seizure control. After the change in protocol in 1998, midazolam was used in 13 neonates when conventional treatment (phenobarbital with or without phenytoin) had failed. The authors report that, "Despite aggressive treatment with phenobarbital/phenytoin, clinical and electrical control of neonatal seizures was unsatisfactory (46.8%)." Seizures were uncontrolled in 17 of 32 neonates who received phenobarbital plus phenytoin only. However, seizures were rapidly controlled in all neonates treated with midazolam after not responding to phenobarbital/phenytoin. Midazolam treatment was also found to result in fewer neonates with poor outcomes. Only two of the 17 non-responders receiving conventional treatment showed normal neurodevelopment at one year, thirteen had a poor outcome and four died. However, seven of the 13 non-responders to conventional treatment who were controlled with midazolam were reported to have normal neurodevelopment at one year, four had poor outcome and two died.Discussing the potential benefit of achieving rapid seizure control, the authors say, "In this study, midazolam was administered early (around 1 hour), on failure to control the seizures using the maximal doses of phenobarbital. Thus, at least in theory, major neurologic deterioration was avoided when control was achieved, as it was in all our neonates, and this should be reflected in their neurodevelopment."This small study was retrospective and nonrandomised, and may have also been biased towards midazolam by the improved neonatal care in the recent years, the authors say. However, they believe that these encouraging results support a prospective trial of midazolam as first-line treatment for neonatal seizures.Reference...