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.


METHODS
Physiological variables were measured at predetermined times in 10 infants with birthweight < or = 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.
Harte
G J
GJ
Department of Neonatology, Mater Mothers' Hospital, South Brisbane, Australia.
Gray
P H
PH
Lee
T C
TC
Steer
P A
PA
Charles
B G
BG
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D019102:Infant, Very Low Birth Weight / Q000502:physiology*; D007262:Infusions, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D009207:Myoclonus / Q000139:chemically induced; D010146:Pain / Q000517:prevention & control; D012121:Respiration, Artificial / Q000379:methods; D016896:Treatment Outcome
D018686:Anesthetics, Intravenous; D008874:Midazolam