Objective: We examined the hypothesis that mechanical ventilation with a potentially injurious strategy would predispose animals to the detrimental effects of subsequent instillation of bacteria.
Design: Interventional animal study.
Setting: A university hospital research laboratory.
Subjects: Fifty Sprague-Dawley male rats.
Interventions: Rats were anesthetized and randomized to receive a protective (tidal volume 7 mL/kg, positive end-expiratory pressure 5 cm H(2)O, n = 25) or an injurious ventilatory strategy (tidal volume 21 mL/kg, zero positive end-expiratory pressure, n = 25). Hemodynamics were similar during the 1-hr ventilation period in the two groups. Animals were then disconnected from the ventilator and Pseudomonas aeruginosa was instilled intratracheally before extubation. Thereafter, animals breathed spontaneously; mortality rate was assessed up to 48 hrs, at which time the animals were killed.
Measurements and main results: The 48-hr mortality rate was 28% in the protective group and 40% in the injurious group (p = not significant). A positive bacterial culture from the lung was obtained in 56% of the surviving rats in the low tidal volume group and 67% in the high tidal volume group (p =.059). A positive blood bacterial culture was found in 11% of the low tidal volume group and 33% in the high tidal volume group (p <.05). The absolute bacterial count in the blood was lower in the low tidal volume group compared with the high tidal volume group (p <.05). Concentrations of blood tumor necrosis factor-alpha and macrophage inflammatory protein-2, and lung macrophage inflammatory protein-2 at 48 hrs were significantly higher in the low tidal volume group than in the high tidal volume group.
Conclusions: An injurious ventilatory strategy predisposes animals to subsequent bacteremia associated with an impaired host defense reflected by cytokine response.