Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates

Objective: To evaluate the effects of intravenous midazolam on haemodynamic variables and cerebral blood flow velocity (CBFV) and to determine the pharmacokinetics using a population approach in very low birthweight (VLBW) ventilated infants.
Methodology: Physiological variables were measured at predetermined times in 10 infants with birthweight ≤1500 g following a bolus dose of intravenous midazolam (0.1 mg/kg). Heart rate, mean arterial blood pressure (MAP) and transcutaneous CO₂ (TcPCO₂) were recorded and CBFV was assessed by Doppler ultrasound. Midazolam concentrations were also measured and pharmacokinetic parameters determined using a population modelling package.
Results: No change in heart rate occurred during the study period, while the MAP decreased by 3 mmHg 5 min after midazolam administration compared to baseline values. A non-significant fall in TcPCO₂ was seen at 20 min. Mean CBFV decreased from the baseline by 12% at 5 min, then returning to predose values. Midazolam concentrations were in the range shown to be effective in sedation of paediatric intensive care infants with the elimination being delayed in comparison to older children.
Conclusions: As only minor cerebral and haemodynamic effects were found with the use of midazolam in stable ventilated preterm infants, it appears to be a safe, short-term sedative agent.