Dexmedetomidine and propofol differentially alter human immune cell metabolism

Abstract

IntroductionProlonged treatment with sedatives such as dexmedetomidine or propofol is common in the critically ill patient, yet their differential impact on immune cell metabolism, specifically, on mitochondrial function, remains to be elucidated. Here we hypothesize that propofol and dexmedetomidine differentially impact human immune cell mitochondrial function.Material and MethodsBlood was drawn from healthy male and female human donors and peripheral blood mononuclear cells (PBMCs) were isolated and treated with dexmedetomidine and propofol at concentrations achieved in human plasma. Intralipid was used as the control for propofol. Metabolic function (mitochondrial stress and glycolysis) was assessed using the Seahorse XF analyzer.ResultsCells treated with dexmedetomidine showed decreased maximal respiration, reserve capacity, increased non‐mitochondrial respiration, and overall decreased mitochondrial health as determined by an overall decreased respiratory control ratio (RCR) compared to buffer control in a dose dependent manner. Propofol decreased basal respiration, ATP‐linked respiration, reserve capacity, and non‐mitochondrial respiration dose dependently when compared to intralipid control. Glycolysis assay revealed that propofol treated cells had an increased glycolytic rate with glucose treatment compared to intralipid control and this rate could not be further increased upon addition of Oligomycin A, suggesting a potential glycolytic compensation.ConclusionHuman immune cell mitochondrial function is significantly and differentially altered by commonly used clinical sedatives. The phenomenon of “immune cell paralysis” has been shown to be associated with increased mortality in septic patients that are commonly treated with sedatives. Mitochondrial function has been tied to immune cell fate and our finding may therefore pose a relevant consideration when treating patients in the intensive care unit.Support or Funding InformationAngela Meier is supported by the Mentored Research Award of the International Anesthesia Research Society. Furthermore this research was supported by funds from the UCSD Department of Anesthesiology.