About \~3/ 1000 live-born newborns may suffer from brain injury due to a transient drop in oxygen supply to the brain during the birth process. The degree of brain injury that ensues in the first 72 hours after the injury is directly proportional to the severity of long-term childhood disabilities (e.g., cerebral palsy and developmental delays). Whole-body cooling during the first 3 days of life is proven effective in reducing the severity of brain injury. However, cooling therapy leads to pain, shivering, stress, and discomfort. The best way to alleviate the pain and agitation of cooled newborns is unknown. Standard practice is to provide morphine infusion to reduce pain. Recently, a new drug called "dexmedetomidine" has been tested in small studies and has been found to be safe during cooling in newborns. Dexmedetomidine has added beneficial effects such as anti-inflammation, faster recovery, and shorter hospital stays. This study is going to test the feasibility of conducting a future clinical trial to compare the effects of using Dexmedetomidine versus morphine in the management of cooling-related pain/agitation on the severity of brain injury in the first week of life. The study will also examine the effect of dexmedetomidine compared to morphine on short-term clinical outcomes, parental experiences and developmental outcomes at 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
Dexmedetomidine infusion given for sedation during therapeutic hypothermia. Dexmedetomidine infusion at a starting dose of 0.2 μg/kg/h, with titration in 0.1 μg/kg/h increments with a maximum of 0.5 μg/kg/h based on objective assessment of sedation.
Morphine infusion given for sedation during therapeutic hypothermia. Morphine infusion at a starting dose of 4 μg/kg/h, with titration in 2 μg/kg/h increments with a maximum of 10 μg/kg/h based on objective assessment of sedation.
McMaster Children's Hospital
Hamilton, Ontario, Canada
Recruitment Rate
Proportion of eligible neonates enrolled. Calculation = (Number of neonates enrolled) X 100/(Total eligible neonates)
Time frame: Day 1
Follow Up Rate
Percentage of neonates completing the study. Calculation = (Neonates who completed the study) x 100/ (Total neonates consented)
Time frame: From enrollment to 1 year of age
Adverse Event Rate
Incidence of adverse events Measurement of Adverse Event Rate = (Number of neonates experiencing) x100/ (Total neonates exposed to the intervention)
Time frame: From enrollment to 7 days of life
Discontinuation Rate
Need for intervention discontinuation due to adverse effects. Measurement of Discontinuation Rate = (Number of neonates for whom the intervention discontinued) x 100/ (Total neonates consented)
Time frame: From enrollment to 7 days of life
Protocol Adherence Rate
Percentage of correct drug adjustment based on changes in COMFORTneo scale as per protocol. Calculation of Drug Administration Compliance = (Number of correctly administered medication per month) x 100/ (Total number of participant enrolled per month)
Time frame: through study completion, average 1 year
Severity of Brain Injury on Magnetic Resonance Imaging (MRI)
The T1 and T2 weighted images, diffusion-weighted images, and magnetic resonance spectroscopy (MRS) are additionally evaluated to determine the level of brain damage. MRI scoring system reported by Weeke et al. will be used to classify brain injury based on 4 subscores, including grey matter (basal ganglia, thalamus, PLIC, brainstem, perirolandic cortex, and hippocampus), white matter/cortex (including optic radiation and corpus callosum), and cerebellum.
Time frame: From enrollment to 10 days of life
Seizure Burden during Therapeutic Hypothermia
Total duration of seizures noted during the first 72 hours of life
Time frame: From enrollment to 72 hours of life
Stress levels measured by Salivary cortisol assay at 24 and 48 hours
Salivary cortisol levels will be used as an objective marker of neonatal stress measured in µg/dL.
Time frame: From enrollment to 48 hours of life
Neonatal Sedation and Discomfort Levels
COMFORT neo scores during the period of therapeutic hypothermia. It consists of 7 behavioural items (alertness, calmness/agitation, respiratory response, crying, body movement, facial tension and muscle tone), of which six items should be scored (respiratory response or crying depends on the presence of invasive ventilation). The neonate will be observed for 2 minutes to score. Total scores range from 7 to 35. A score \>14 is considered a sign of distress and undersedation. A score \< 9 suggests oversedation.
Time frame: From enrollment to 4 days of life
Time to Reach Full Oral Feeds
Days of life when participant is receiving all oral feeds either breast or bottle
Time frame: up to 4 weeks of life
Cumulative dose of PRN opioid boluses given during therapeutic hypothermia
Total dose of morphine and fentanyl given during therapeutic hypothermia measured in mg/kg of morphine equivalent
Time frame: up to 4 days of life
Length of Hospital Stay
Day of life when discharged home
Time frame: up to 4 weeks of life
Days on invasive and non-invasive respiratory support
Day of life when comes off all respiratory support to room air
Time frame: Up to 4 weeks of life
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