Pharmacologic Impact on Sedation Assessments

Children's Hospital of Philadelphia175 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

175

Conditions

Pediatric Acute Lung Injury

Interventions

Pharmacokinetic Sampling and pharmacogenetic analysisOTHER

Pharmacogenetic and pharmacokinetic samples will be obtained from a peripheral catheter, central catheter, or venipuncture coordinated with scheduled phlebotomies. Pharmacokinetic and pharmacogenetic analyses will be performed. Pharmacodynamic data will be collected.

Eligibility

Sex: ALLMin age: 1 YearMax age: 17 Years

Medical Language ↔ Plain English

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 * Family/medical team has decided not to provide full support (patient treatment considered futile) * Enrolled in any other sedation clinical trial concurrently or within the last 30 days * Known allergy to any of the study medications.

Locations (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

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.

This is a pharmacokinetic, pharmacogenetic and pharmacodynamic study examining heritable (specific polymorphisms) on drug exposure, metabolite formation and pharmacodynamic response.

Time frame: 36-48 months

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.

Polymorphisms in drug metabolizing systems.

Time frame: 36-48 months

Data from ClinicalTrials.gov

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