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Objective: To compare the effectiveness of three dosing regimens of caffeine for preterm infants in the periextubation period. Methods: A randomized double-blind clinical trial of three dosing regimens of caffeine citrate ( 3, 15 and 30 mg/kg) for periextubation management of ventilated preterm infants was undertaken. Infants born 48 h were eligible for the study. Caffeine citrate was given as a once daily dose for a period of 6 days commencing 24 h prior to a planned extubation, or within 6 h of an unplanned extubation. The primary outcome measure was extubation failure, defined as neonates who were unable to be extubated within 48 h of caffeine loading or who required reventilation or doxapram dose within 7 days of caffeine loading. Continuous recordings of oxygen saturation and heart rate were undertaken in a subgroup of enrolled infants. Results: A total of 127 babies were enrolled into the study ( 42, 40, 45, in the 3, 15, and 30 mg/kg groups, respectively). No statistically significant difference was demonstrated in the incidence of extubation failure between dosing groups ( 19, 10, and 11 infants in the 3, 15, and 30 mg/kg groups, respectively), however, infants in the two higher dose groups had statistically significantly less documented apnoea than the lowest dose group. Of the 37 neonates with continuous pulse oximetry recordings, those on higher doses of caffeine recorded a statistically significantly higher mean heart rate, oxygen saturations and less time with oxygen saturations < 85%. Conclusions: This trial indicated there were short-term benefits of decreased apnoea in the immediate periextubation period for ventilated infants born < 32 weeks gestation receiving higher doses of caffeine. Further studies with larger numbers of infants assessing longer-term outcomes are necessary to determine the optimal dosing regimen of caffeine in preterm infants.

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.Physiological variables were measured at predetermined times in 10 infants with birthweightor = 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.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.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.