Title: Safety and efficacy of fentanyl citrate in combination with midazolam in critically ill children with mechanical ventilation

Objective: To evaluate the safety and efficacy of fentanyl citrate in combination with midazolam in children with mechanical ventilation.

Design: Double-blind randomized controlled study

Patients: Patients age 2 months through 18 years who are admitted in Seoul National University Hospital pediatric intensive care unit, and applied with mechanical ventilation.

Interventions: After enrollment of patient, blind reagent (fentanyl citrate or normal saline) is prepared by assigned pharmacist. Investigators, caregivers, patient, and parents of the patient don't know whether the blind reagent is fentanyl citrate or not, but only preparing pharmacist knows that.

Protocol: All enrolled patients receive continuous infusion of midazolam and blind reagent. The start time of study is when the continuous infusion of midazolam and blind reagent are begun. Assigned research nurse check Comfort behavior scale of the patient every hour regularly, and whenever the patient seem to be overactive. Endpoint of the study is 48 hours after begining. If there is any adverse effect or unexpected event, however, the study can be early terminated.

Comfort behavior scale consists of 7 components of alertness, calmness, respiratory response, crying, physical movement, muscle tone, and facial tension. Because intubated patients cannot be evaluated 'crying', however, we use 6 components among total of all 7 components, except 'crying'.

Adverse effect of fentanyl include hypotension, coma, and ileus. Unexpected event means the situation which study cannot last in, such as withdrawal of consent, necessity of drugs which can affect the level of consciousness of the patient, emergent interventional procedure, etc.

Inclusion Criteria:

• children mechanically ventilated
• age : from 2 months to 18 years

Exclusion Criteria:

• children with neurologic disease
• children with drugs which can affect the level of consciousness
• children with renal disease
• children with hypotension (systolic blood pressure < 70 + (2 x age in year) mmHg)