Mechanical Ventilation in Neonates, Sedation Complication
Conditions
Keywords
morphine, midazolam, pharmacokinetics, pharmacodynamics, analgesia, neonates
Brief summary
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.
Detailed description
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.).
Interventions
OTHERDose-effect relationship of morphine +/- midazolam administration
Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling
Sponsors
Centre Hospitalier Intercommunal Creteil
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
The main objective is to estimate a dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling.
Eligibility
Sex/Gender
ALL
Age
20 Weeks to 45 Weeks
Healthy volunteers
No
Inclusion criteria
* Neonates \< 45 weeks of corrected gestational age * Hospitalized in a Neonatal Intensive Care Unit * Undergoing mechanical ventilation * Patients that receive morphine alone or morphine and midazolam as continuous infusion * Affiliated to a social security system
Exclusion criteria
* Current weight \< 600g * Neonates under palliative care * Therapeutic hypothermia for perinatal anoxia * Neonates who underwent a surgical procedure during the past 72 hours * Neonates receiving concomitantly a paralytic or another drug for sedation or analgesia other than morphine or midazolam (except for paracetamol/acetaminophen) * Parents refusing that their child participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effective dose for 50% of patients (ED50 ) of morphine in continuous infusion in neonates ventilated in the neonatal intensive care unit | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution (L/kg) of morphine and midazolam | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling |
| Concentration of morphine | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | Morphine serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling |
| Clearance (ml/min/kg) of morphine and midazolam | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD |
| Doses of morphine and midazolam (µg/kg/h) | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | PKPD models will be used to simulate doses to determine optimal doses required according to gestational age, postnatal age, corrected age, weight and clinical context |
| To assess pain responses by the Newborn Infant Parasympathetic Evaluation (NIPE) index | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | 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 |
| Concentration of midazolam | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks | midazolam serum levels (mg/L) will be used to describe inter-individual variability by PKPD modeling |
Countries
France
Contacts
Primary ContactManon TAUZIN, MD
Outcome results
None listed