Midazolam is a
benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t 1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults.
Midazolam is hydroxylated by
CYP3A4 and
CYP3A5; the activities of these
enzymes surge in the liver in the first weeks of life and thus the metabolic rate of
midazolam is lower in neonates than in adults.
Midazolam acts as a
sedative, as an
antiepileptic, for those infants who are refractory to standard
antiepileptic therapy, and as an anaesthetic. Information of
midazolam as an anaesthetic in infants are very little.
Midazolam is usually administered intravenously; when minimal sedation is required,
intranasal administration of
midazolam is employed. Disease affects the pharmacokinetics of
midazolam in neonates;
multiple organ failure reduces the Cl of
midazolam and
mechanical ventilation prolongs the t 1/2 of this
drug. ECMO
therapy increases t 1/2, Cl, and Vd of
midazolam several times. The adverse effects of
midazolam in neonates are scarce:
pain, tenderness, and
thrombophlebitis may occur.
Respiratory depression and
hypotension appear in a limited percentage of infants following
intravenous infusion of
midazolam. In conclusion,
midazolam is a safe and effective
drug which is employed as a
sedative, as
antiepileptic agent, for infants who are refractory to standard
antiepileptic therapy, and as an anaesthetic.