Pharmacologic Impact on Sedation Assessment
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Pediatric Acute Lung Injury
- Sponsor
- Children's Hospital of Philadelphia
- Enrollment
- 175
- Locations
- 1
- Primary Endpoint
- In children who are mechanically ventilated, to quantitatively define the heritable factors that underlie the variability in 1) midazolam and 2) morphine exposure and response.
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
PISA is an ancillary study to the NIH funded clinical RESTORE Trial (U01 HL086622). This study will provide data that may allow for improved dosing recommendations in this critically ill population of children.
Detailed Description
PISA is an ancillary study to the NIH funded clinical RESTORE Trial (U01 HL086622). This project will use sophisticated modeling and simulation techniques to evaluate the impact of genetics and other variables such as degree of illness, age, weight and organ dysfunction on the pharmacokinetics and pharmacodynamics of morphine and midazolam in children who are mechanically ventilated for respiratory failure, and require sedation. This proposed work will allow the design of a pharmacologic model that can be used to individualize therapy in children requiring mechanical ventilation with the goal of optimizing sedation while minimizing the duration of mechanical ventilation. This study will provide data that may allow for improved dosing recommendations in this critically ill population of children.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Enrolled in RESTORE clinical trial
- •Be greater than or equal to 7 kg
- •Receiving morphine and/or midazolam continuous infusions
- •Give Informed Consent/Assent
Exclusion Criteria
- •Intubated and mechanically ventilated for immediate post-operative care and stabilization
- •Cyanotic heart disease with unrepaired or palliated right to left intracardiac shunt
- •History of single ventricle at any stage of repair
- •Congenital diaphragmatic hernia or paralysis
- •Primary pulmonary hypertension
- •Critical airway (e.g., post laryngotracheal construction) or anatomical obstruction of the lower airway (e.g., mediastinal mass)
- •Ventilator dependent (including noninvasive) on Pediatric Intensive Care Unit (PICU) admission (chronic assisted ventilation)
- •Neuromuscular respiratory failure
- •Spinal cord injury above the lumbar region
- •Pain managed by patient controlled analgesia (PCA) or epidural catheter
Outcomes
Primary Outcomes
In children who are mechanically ventilated, to quantitatively define the heritable factors that underlie the variability in 1) midazolam and 2) morphine exposure and response.
Time Frame: 36-48 months
This is a pharmacokinetic, pharmacogenetic and pharmacodynamic study examining heritable (specific polymorphisms) on drug exposure, metabolite formation and pharmacodynamic response.
Secondary Outcomes
- In children who are mechanically ventilated, to quantitatively define the non-heritable factors that underlie the variability in 1) midazolam and 2) morphine exposure and response.(36-48 months)