Pharmacologic Impact on Sedation Assessments

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.

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.