Anesthetic choice impacts mortality and bacterial clearance in a murine experimental pneumonia model.

Abstract

Background: Animal models of infectious pneumonia often require the use of anesthetics, but their choice and impact on outcome is rarely discussed. This study investigates the impact of the most commonly used anesthetics on mortality and bacterial clearance in a murine model of Pseudomonas aeruginosa pneumonia.

Methods: Isoflurane or ketamine/xylazine were determined to be the most commonly utilized anesthetics for murine pneumonia models. Mice were anesthetized with either ketamine/xylazine or isoflurane during intratracheal infection with P. aeruginosa strains PA14 or PA01. Mortality, bacterial clearance, and lung tissue damage were compared. Additional in vitro assays assessed the effects of ketamine on human whole blood killing, serum killing, and neutrophil functions (reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) production, chemotaxis, and phagocytosis).

Results: Mice anesthetized with ketamine/xylazine and infected with PA14 had significantly increased mortality (p = 0.004), and significantly higher bacterial burdens in the blood (p = 0.01) and lungs (p < 0.001). In separate experiments with PA01, mice anesthetized with ketamine/xylazine had significantly increased mortality (p = 0.01), higher bacterial burdens in the blood (p = 0.01), and higher bacterial burdens in the lungs (p = 0.02), along with increased lung tissue pathology (p = 0.03) compared to mice anesthetized with isoflurane. Increased mortality and colony forming units were also observed in mice infected under propofol anesthesia, recovered, and subsequently exposed to ketamine versus control (p = 0.004 and p < 0.001, respectively). Ketamine marginally reduced the killing of PA14 in freshly drawn human whole blood (p = 0.0479), but had no significant effect on the serum's ability to kill PA14. In addition, ketamine reduced in vitro NETosis and chemotaxis (all p < 0.05), but had no significant effect on ROS production or phagocytosis of human neutrophils. These in vitro effects were observed only at supraclinical ketamine concentrations.

Conclusions: Our study emphasizes that the choice of anesthetic impacts key outcomes in murine models of pneumonia, and should therefore be an important consideration in experimental design and when comparing results across different studies.