Efficacy of Dexmedetomidine Versus Midazolam Sedation on Extubation Time in Mechanically Ventilated Preterm Infants

Hypothesis : the use of dexmedetomidine (DEX), 0.05 to 0.2 μg/kg/h, for very preterm neonates (<32 weeks' gestation, WG), requiring prolonged sedation throughout the period of invasive mechanical ventilation (IMV) (usually after intubation and until extubation), may improve weaning, and thus reduce extubation time in neonatal intensive care units.

Population of study participants : Very preterm neonate (gestational age at birth < 32 WG) with corrected gestational age <45 WG).

In the experimental group, neonates will receive dexmedetomidine via continuous intravenous infusion, starting with a 0.05 μg/kg loading dose over 30 minutes, followed by a maintenance dose ranging from 0.05 to 0.2 μg/kg per hour.

In the control group, neonates will receive midazolam via continuous intravenous infusion, starting with a 10 μg/kg loading dose over 30 minutes, followed by a maintenance dose ranging from 10 to 40 μg/kg per hour.

To achieve the randomization of 292 patients, an estimated enrollment of about 380 participants is anticipated, resulting in an allocation of 146 patients per study arm.

During the inclusion visit, after verifying the inclusion and exclusion criteria, an investigator will inform the parents of eligible neonates. If the neonate requires invasive mechanical ventilation and meets the randomization criteria, the investigator will proceed with the randomization.

According to the allocation arm, the nurse in charge of the patient will be able to prepare the experimental treatment using the kit provided by the hospital pharmacy.

The experimental treatment will start with a 30-minute loading dose, followed by a maintenance dose. The infusion rate will be adjusted according to medical prescriptions to achieve the desired sedation level, ranging from 0.1 mL/hr to 0.4 mL/hr. This treatment can be administered via any venous line, either peripheral or central.

Vital signs will be regularly recorded at 5, 10, 30, and 60 minutes, then at 2, 3, 6, and 12 hours after the start of treatment. Following this, recordings will be taken every 12 hours until the treatment ends.

Pain scores will be recorded 30 and 60 minutes after the initiation of treatment, and then every 3 hours, following standard practice.

On the day of extubation, routine data recording will include the timing and duration of experimental treatment and opioid interruptions, the extubation time, vital signs before and after treatment discontinuation, and any adverse events.

The final study visit will occur when the child reaches 2 years of corrected age +/- 2 months. At this visit, weight, height, head circumference, cerebral palsy status, age of walking acquisition, and the Ages & Stages Questionnaire (ASQ) score will be recorded.

Inclusion criteria

• Patient admitted in NICU (intubated or not yet),
• Gestational age at birth < 32 weeks of gestation (WG),
• Corrected gestational age <45 weeks postmenstrual age Written or electronic informed consent signed by both parents.

Randomization Criteria :

• Indication for sedation in the context of invasive mechanical ventilation,
• Patient intubated or not yet,
• Elective sedation (acceptable delay between the decision to sedate and the administration of the sedative agent),
• Presence or plan of a venous access,
• No medical contraindication related to the administration of dexmedetomidine or midazolam,
• No previous use of dexmedetomidine or midazolam within 48 hours, except for the sedation procedure for intubation,
• No concomitant use of curare agent,
• No clonidine treatment,
• No previous extubation within 7 days,
• No hemodynamic instability
• No palliative care,

Exclusion criteria

• Patient admitted in NICU (intubated or not yet),
• Gestational age at birth < 32 weeks of gestation (WG),
• Corrected gestational age <45 weeks postmenstrual age Written or electronic informed consent signed by both parents.