Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury

Objective: To investigate the kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury (ALI). Design: Prospective observational cross-over study. Setting: Intensive care unit of a university hospital. Patients: Twelve mechanically ventilated patients with ALI. Interventions: Mechanical ventilation was transiently changed from a lung protective setting with PEEP of 15 cmH(2)O and a V-T of 5 ml/kg predicted body weight to a more conventional ventilatory setting with PEEP of 5 cmH(2)O and VT Of 12 ml/kg predicted body weight for a period of 6 It. Measurements and results: We examined the profile of interleukin (IL)-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor in the plasma of all patients, and in the bronchoalveolar lavage (mini-BAL) fluid of six of these patients. Measurements were performed at baseline, 1 h, and 6 It after each change of the ventilatory setting. Switching to conventional mechanical ventilation was associated with a higher PaO2 (P < 0.05) and a marked increase (P < 0.05) of measured plasma cytokines in patients with and without mini-BAL with a maximum after I h. Similarly, intraalveolar cytokine concentrations increased with conventional mechanical ventilation. While plasma cytokine levels returned to baseline values, intraalveolar cytokine concentrations further increased when lung protective mechanical ventilation was reestablished. Conclusions: In patients with ALI, initiation of low PEEP and high V-T mechanical ventilation is associated with cytokine release into circulation which occurred within I h. It is independent from BAL procedures and can be reversed by reinstitution of lung protective mechanical ventilation.