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Introduction Propofol has long been used as an anesthetic agent during pediatric surgery. Its use in pediatric intensive care units has been largely controversial. A beneficial use of propofol is to facilitate weaning of other pain and sedation infusions such as opiates and benzodiazepines. However, some have advocated to not use propofol due to fear of possible adverse effects including propofol infusion syndrome and hemodynamic instability. The purpose of this study was to determine both the safety of propofol infusions in critically ill pediatric patients, as well as the change in the requirement of other pain and sedation infusions by use of a propofol infusion. Methods Single-center, retrospective data (January 2011 to January 2020) was obtained manually using a study-specific data extraction tool created for electronic medical records. The data obtained included variables of interest that measured physiological parameters and pain/sedation infusion (morphine, fentanyl, hydromorphone, midazolam, and dexmedetomidine) rates during three time periods: before propofol initiation, immediately after discontinuation, and four hours after discontinuation. The physiological parameters were then compared to the pain and sedation infusion rates using paired Wilcoxon signed-rank tests. Results There was a total of 33 patients with an average age of 11.1 years who were given a median initial propofol infusion of 50 mcg/kg/min with a peak dose of 75 mcg/kg/min over an average of eight hours. Age had a weak and insignificant correlation with initial rate and duration and a moderate and significant correlation with peak rate and duration. Physiological parameters did not vary at any time point measured. There was a significant reduction in other pain and sedation infusions after discontinuation of propofol. Conclusion Propofol infusions are hemodynamically tolerated and the majority of patients who are on other pain and sedation infusions tolerate complete discontinuation of these infusions following propofol discontinuation.
RESUMEN
Mitochondrial fission mediated by the GTPase dynamin-related protein 1 (Drp1) is an attractive drug target in numerous maladies that range from heart disease to neurodegenerative disorders. The compound mdivi-1 is widely reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate brain injury. Here, we show that mdivi-1 reversibly inhibits mitochondrial complex I-dependent O2 consumption and reverse electron transfer-mediated reactive oxygen species (ROS) production at concentrations (e.g., 50 µM) used to target mitochondrial fission. Respiratory inhibition is rescued by bypassing complex I using yeast NADH dehydrogenase Ndi1. Unexpectedly, respiratory impairment by mdivi-1 occurs without mitochondrial elongation, is not mimicked by Drp1 deletion, and is observed in Drp1-deficient fibroblasts. In addition, mdivi-1 poorly inhibits recombinant Drp1 GTPase activity (Ki > 1.2 mM). Overall, these results suggest that mdivi-1 is not a specific Drp1 inhibitor. The ability of mdivi-1 to reversibly inhibit complex I and modify mitochondrial ROS production may contribute to effects observed in disease models.
