HEMODYNAMIC-RESPONSES AND POPULATION PHARMACOKINETICS OF MIDAZOLAM FOLLOWING ADMINISTRATION TO VENTILATED, PRETERM NEONATES

Objective: To evaluate the effects of intravenous midazolam on haemody namic variables and cerebral blood flow velocity (CBFV) and to determi ne the pharmacokinetics using a population approach in very low birthw eight (VLBW) ventilated infants. Methodology: Physiological variables were measured at predetermined times in 10 infants with birthweight le ss than or equal to 1500 g following a bolus dose of intravenous midaz olam (0.1 mg/kg). Heart rate, mean arterial blood pressure (MAP) and t ranscutaneous CO2 (TcPCO2) were recorded and CBFV was assessed by Dopp ler ultrasound. Midazolam concentrations were also measured and pharma cokinetic parameters determined using a population modelling package. Results: No change in heart rate occurred during the non-significant f all in TcPCO2 was seen at 20 min. Mean CBFV decreased from the baselin e by 12% at 5 min, then returning to predose values. Midazolam concent rations were in the range shown to be effective in sedation of paediat ric intensive care infants with the elimination being delayed in compa rison to older children. Conclusions: As only minor cerebral and haemo dynamic effects were found with the use of midazolam in stable ventila ted preterm infants, it appears to be a safe, short-term sedative agen t.