Dexmedetomidine Versus Fentanyl for Sedation of Postoperative Mechanically Ventilated Neonates

Study Overview
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Brief Summary
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Newborn infants experience pain after surgical procedures,prevention and management of pain in neonates is important due to its deleterious consequences. Fentanyl is a widely used analgesic which promotes rapid analgesia,however, is not free of adverse effects including chest wall rigidity, hypothermia, hypotension, respiratory depression and tolerance.Dexmedetomidine is a selective α 2-adrenergic agonist can cause sedation, anxiolysis, analgesia and minimal respiratory depression.Therefore, the objective of the study is to evaluate the safety and efficacy of dexmedetomidine compared to fentanyl in postoperative mechanically ventilated neonates.

Detailed Description
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A prospective, randomized trial, which was conducted upon neonates who needed postoperative mechanical ventilation in Neonatal Intensive Care Unit, Mansoura University Children's Hospital.The patients were randomized to two groups according to the drug they received for postoperative sedation. The first group received dexmedetomidine infusion and the second group received fentanyl infusion.Our primary outcome was the efficacy of postoperative sedation score, and the secondary outcomes were plasma cortisol level, time to extubation, time to reach 100ml/kg enteral feed, need for adjuvant sedative and skeletal muscle relaxant, length of the hospital stay, side effects of sedative drugs and mortality.

Official Title
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Dexmedetomidine Versus Fentanyl for Sedation of Postoperative Mechanically Ventilated Neonates

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates need postoperative ventilation. Exclusion Criteria: Major congenital cardiovascular anomalies. Chromosomal anomalies. Grade IV intraventricular hemorrhage. Tracheoesophageal fistula with wide gap (distance between proximal and distal end more than two centimeters).

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 4 Weeks

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fentanyl<br>Neonates received fentanyl infusion during postoperative phase. | Drug: Fentanyl<br>* Infants received Fentanyl IV continuous infusion: 1µg/ kg /hour. Weaning was done when the patient was about to be extubated or with maximum 5 days after the randomization.<br>|
| Active Comparator: Dexmedetomidine<br>Neonates received dexmedetomidine infusion during postoperative phase. | Drug: Dexmedetomidine<br>* Infants received dexmedetomidine IV loading dose: 0.5 mcg/kg given over 20 minutes followed by maintenance dose 0.3 µg/kg/hour by infusion over 24 hours.Weaning was done when the patient was about to be extubated or with maximum 5 days after the randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The efficacy of postoperative sedation according to pain score. | Assessment of Neonatal Pain, Agitation and Sedation Scale immediately after the operations then every 12 hours till 5 days | upto five days after surgical intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma cortisol level | Plasma as a base line after the operation and another two measures one after 24 hours from the operation and the other after 48 hours | Within 48 hours after surgical intervention | 
| Need of adjuvant analgesics or sedatives | Infants in both groups received open-label intravenous fentanyl boluses at a dose of 1µg/kg, as adjuvant analgesic when the pain score was more than 3 points. The dose was repeated, based on pain score assessment, at a minimum interval of 2-4 hours. Also, both groups received midazolam bolus at a dose of 0.1 mg/ kg/dose IV as adjuvant sedative in both groups when the patient was agitated. | upto five days after surgical intervention | 
| Need of skeletal muscle relaxant | Neonates in both groups received Pancuronium at a dose of 0.1 mg/ kg /dose IV as a skeletal muscle relaxant when two boluses of midazolam failed to control agitation | upto five days after surgical intervention | 
| Time to extubation. | Days upon mechanical ventilation | upto 21 days postoperative | 
| Time to reach 100ml/kg/day enteral feed. | Days to reach 100ml/kg/day enteral feed. | upto 21 days postoperative | 
| Length of hospital stay. | Days of hospital admission | upto 30 days postoperative | 
| Mortality | Death | upto 21 days postoperative | 
| Adverse effects of the sedative drugs | Hypotension, bradycardia, chest wall rigidity, feeding intolerance withdrawal signs,re-intubation within 48 hours | upto seven days after surgical intervention | 
| Culture-proven sepsis |  | upto 30 days after surgical intervention |