title: Special comments - Neonatal Intensive Care Drug Manual
text: Special comments
  Flumazenil is a specific benzodiazepine antagonist and may be used (very limited experience in the neonate) to rapidly reverse respiratory depression − 10 microgram/kg/dose IV push.
  May repeat every minute for up to 4 more doses.
  Evidence
  Efficacy
  There are insufficient data to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. Although all studies included in the review reported better sedation, none of the scales used had been validated in preterm infants and thus the effectiveness could not be evaluated [1] (Level 1, Grade B).
  Midazolam was effective in neonates with refractory seizures that did not respond to phenobarbital (phenobarbitone), phenytoin or pentobarbital (pentobarbitone) [2] (Level IV, Grade D).
  Safety
  One study showed a statistically significant higher incidence of adverse neurological events (death, grade III or IV IVH, PVL) and meta-analysis of data from two studies showed a statistically significant longer duration of NICU stay in the midazolam group compared to the placebo group [1] (Level1, Grade B).
  Administration of midazolam in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful [3] (Level III, Grade C).
  Intravenous bolus doses of midazolam in association with fentanyl should be used with great caution in the newborn, especially if very premature or with unstable blood pressure [4] (Level IV, Grade D).
  Sedation with midazolam has a transient effect on the background aEEG activity [5] (Level III, Grade C).
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