This study aims to describe a dose-effect relationship of morphine alone and morphine and midazolam administered as continuous infusion in neonates hospitalized in Neonatal intensive care unit and undergoing mechanical ventilation, through PKPD modelling.
This study will include all neonates receiving a sedo-analgesia with continuous infusion of morphine alone or morphine and midazolam during mechanical ventilation in 3 French NICUs. Comfort and pain will be assessed by COMFORTneo pain scores and Newborn Infant Parasympathetic Evaluation Index. Morphine, midazolam and their metabolites' concentrations will be determined on samples taken during a planned blood test. Through PKPD modelling, the dose-concentration-effect relationships will be found and interindividual variability of these drugs in neonates and simulate doses needed to achieve comfort in neonates according to their individual characteristics (gestational age, post-natal age, weight etc.).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
180
Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling
CHRU Morvan
Brest, France
RECRUITINGCH SUD Francilien
Corbeil-Essonnes, France
RECRUITINGCHI Créteil
Créteil, France
RECRUITINGEffective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit
To evaluate which dose is effective, cComfort will be assessed with COMFORTneo score (scale from 6 to 30 with decreasing score with increasing comfort). The dose-response relationship will be assessed with the correlation between a comfortable score (between 11 and 13) and the effective dose for 50% of patients (ED50), by PKPD modeling
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Clearance (ml/min/kg) of morphine and midazolam
Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Volume of distribution (L/kg) of morphine and midazolam
Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of morphine
Morphine serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Concentration of midazolam
midazolam serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
Doses of morphine and midazolam (µg/kg/h)
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CHU Lille
Lille, France
RECRUITINGCHU Tours
Tours, France
RECRUITINGPKPD models will be used to simulate doses to determine optimal doses required according to gestational age, postnatal age, corrected age, weight and clinical context
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks
To assess pain responses by the Newborn Infant Parasympathetic Evaluation (NIPE) index
NIPE Index which provides an observer-independent, quantitative assessment of comfort and analgesia based on analysis of heart rate variability. The NIPE Index ranges from 0 to 100 with increasing index with increasing comfort
Time frame: From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks