Mechanical ventilation strategies induce pulmonary cytokine response

Introduction: The choice of ventilation strategy influences the progression of lung injury. Strategies that avoid closure and overdistension of alveoli such as high frequency oscillatory ventilation (HFOV) are associated with improved oxygenation and attenuation of pulmonary leukostasis. We hypothesized that mechanical ventilation can promote pulmonary and systemic cytokine responses that can be attenuated by limiting alveolar closure and overdistension. Methods: 42 NZW rabbits were anesthetized and instrumented with a tracheostomy and vascular catheters. Lung injury was induced by saline lavage (PaO2<100torr). After 15min of HFOV (Paw:16cmH2O,Ti: 33%)to recruit lung and equalize volume history, animals were assigned to one of 4 strategies: (1)Low PEEP: Vt=10ml/kg,PEEP=2cmH2O;(2)High PEEP: Vt=10 ml/ kg,PEEP=10cmH2O; (3)Permissive hypercapnia(P-Hy): Vt=6ml/kg, PEEP>Pflex; (4)HFOV: Paw=16cmH2O,f=10Hz,Ti=33%. Uninjured rabbits ventilated with Vt= 10ml/kg,PEEP=5cmH2O served as controls. Animals were ventilated with FiO2=1.0 for 4h prior to sacrifice. Sera obtained at baseline and prior to sacrifice, and lung lavage fluid obtained at autopsy were assayed for tumor necrosis factor-alpha (TNF-α). Data were analyzed by one way ANOVA with post hoc comparisons by the SNK method. Values are means ± SD. Results: Serum and lung lavage TNF-α measurements are presented in the table. Measurements of TNF-α in lung fluid exhibited an inverse correlation with PaO2 at 4h by linear regression(R2=0.34,p=0.002). *p<0.05 vs control; †p<0.05 vs HFOV. Conclusions: In this model, mechanical ventilation is not associated with a systemic cytokine response. However, mechanical ventilation induces a pulmonary cytokine response that is attenuated by a lung protective strategy such as HFOV, and is inversely related to oxygenation. LowPEEP HighPEEP P-Hy HFOV Control Serum TNF-α(% from BL) 7.8±59 75.3±35 -3.5±32 24.3±74 4.9±25 LavageTNF-α(pg/ ml) 144±31*† 121±28 115±7 108±24 110±19.

Duke Scholars

Author Alexandre Tellechea Rotta Pediatrics, Critical Care Medicine