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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.).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-effect relationship of morphine +/- midazolam administration | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dose-effect relationship of morphine +/- midazolam administration | Other | Dose-effect relationship of morphine +/- midazolam administration as continuous infusion in neonates undergoing mechanical ventilation through PKPD modelling |
| Measure | Description | Time Frame |
|---|---|---|
| Effective 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 | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Clearance (ml/min/kg) of morphine and midazolam | Morphine and midazolam serum levels (mg/L) will be used to describe clearance by PKPD | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Manon TAUZIN, MD | Contact | 01 45 17 50 00 | 9479 | manon.tauzin@chicreteil.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU Morvan | Recruiting | Brest | 29609 | France |
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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.
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Morphine and midazolam serum levels (mg/L) will be used to describe volume of distribution by PKPD modeling |
| 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 | 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 | 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) | 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 | 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 | From date of inclusion until the date of end of morphine +/- midazolam treatment, up to 20 weeks |
| CH SUD Francilien | Recruiting | Corbeil-Essonnes | 91100 | France |
|
| CHI Créteil | Recruiting | Créteil | 94000 | France |
|
| CHU Lille | Recruiting | Lille | France |
|
| CHU Tours | Recruiting | Tours | France |
|
| ID | Term |
|---|---|
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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