Safety and Efficacy of Fentanyl Citrate in Children

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Safety and Efficacy of Fentanyl Citrate in Combination With Midazolam in Critically Ill Children With Mechanical Ventilation

Conditions
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Children

Intervention / Treatment
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* Drug: midazolam and fentanyl citrate infusion
* Drug: midazolam and normal saline infusion


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl<br>midazolam and fentanyl citrate infusion | Drug: midazolam and fentanyl citrate infusion<br>* comparing the sedative effect of combination of midazolam and fentanyl citrate versus combination of midazolam and normal saline for 48 hours during ventilator care<br>* Other names: fentanyl citrate injection;|
| Placebo Comparator: Control<br>midazolam and normal saline infusion | Drug: midazolam and normal saline infusion<br>* comparing the sedative effect of combination of midazolam and fentanyl citrate versus combination of midazolam and normal saline for 48 hours during ventilator care<br>* Other names: midazolam injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| difference between measured Comfort behavior scale and target Comfort behavior scale |  | from the start of fentanyl/placebo infusion to 48 hours after start of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse effect | category of adverse effects hypotension coma ileus | from the start of fentanyl/placebo infusion to 48 hour after start of infusion | 
| renal dysfunction | estimate GFR (Schwartz equation) < 50 mL/minute/1.73m2 | from the start of fentanyl/placebo infusion to 48 hour after start of infusion | 
| sedation failure | the case that can't reach target level of sedation, even though use of maximal infusion rate of midazolam and blind reagent. | from the start of fentanyl/placebo infusion to 48 hour after start of infusion | 
| mortality | in-hospital death | from the start of fentanyl/placebo infusion to 48 hour after start of infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical Ventilation, Sedation, Fentanyl, Midazolam, Comfort behavior scale