Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia.

BACKGROUND

Midazolam is used as an anticonvulsant in neonatology, including newborns with perinatal asphyxia treated with hypothermia. Hypothermia may affect the safety and effectiveness of midazolam in these patients.

OBJECTIVES

The objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety of midazolam in hypothermic newborns and to provide dosing guidance.

METHODS

Hypothermic newborns with perinatal asphyxia and treated with midazolam were included. Effectiveness was studied using continuous amplitude-integrated electroencephalography. Hemodynamic safety was assessed using pharmacokinetic-pharmacodynamic modeling with plasma samples and blood pressure recordings (mean arterial blood pressure) under hypothermia.

RESULTS

No effect of therapeutic hypothermia on pharmacokinetics could be identified. Add-on seizure control with midazolam was limited (23% seizure control). An inverse relationship between the midazolam plasma concentration and mean arterial blood pressure could be identified. At least one hypotensive episode was experienced in 64%. The concomitant use of inotropes decreased midazolam clearance by 33%.

CONCLUSIONS

Under therapeutic hypothermia, midazolam has limited add-on clinical anticonvulsant effectiveness after phenobarbital administration. Due to occurrence of hypotension requiring inotropic support, midazolam is less suitable as a second-line anticonvulsant drug under hypothermia.