PhD Scientific Days 2024

Neurosciences

Impact of Sedation on Circadian Rhythms in Mechanically Ventilated Children

Text of the abstract

The relevance of sleep and circadian rhythms in adult ICUs is well-documented; however, this topic remains less studied in pediatric ICUs (PICUs). High doses of sedatives are commonly used in mechanically ventilated children to ensure comfort and compatibility with mechanical ventilation, but such practices may disrupt circadian rhythms, potentially hindering both physical and psychological healing.
This study aims to assess the influence of commonly used sedatives on circadian rhythms, specifically through the metrics of 6-sulfatoxymelatonin excretion and activity levels in PICUs.
In our ongoing cohort study concerning sleep and circadian rhythms within PICUs, we evaluated data from 25 mechanically ventilated children. Of these, 18 had at least two days of data on melatonin, and 24 had two days of actigraphy data after extubation. Urine samples were collected every six hours and analyzed for 6-sulfatoxymelatonin using ELISA. The data were modeled and analyzed using mixed-effect cosinor analysis, which considers individual variability. Actigraphy data were captured using the Empatica E4 device and processed using the mean activity difference method to calculate the Daytime Activity Ratio (DARE). Sedation levels, recorded in the medical files, were analyzed using beta regression, with patients divided into low and high dose groups based on median splits for opioids and midazolam.
Interim analysis indicates a significant delay in the acrophase (peak of the 24-hour cycle) of the melatonin curve in children receiving high doses of midazolam (>6.9 mg/kg, p = .044), especially those intubated for more than four days (p = .05). Opioid sedation did not significantly influence melatonin rhythmicity. A trend toward delayed acrophase was observed when comparing melatonin excretion in younger children (under 3 years) to older children (over 3 years), with a p-value of 0.058. No significant differences in DARE were noted when comparing high to low dose groups through beta regression.
The preliminary results of our study indicate that high doses of midazolam may significantly alter circadian rhythms, shifting peak melatonin concentrations from morning to afternoon hours.