Lung-borne systemic inflammation in mechanically ventilated infant rats due to high PEEP, oxygen, and hypocapnia

Background: Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO(2)), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response. Methods: Fourteen-day old Wistar rat pups were randomized to the following groups: (a) control with tidal volume similar to 8 mL/kg, PEEP 5 cmH(2)O, FiO(2) 0.4, RR 90 min(-1), (b) PEEP 1, (c) PEEP 9 (d) FiO(2) 0.21, (e) FiO(2) 1.0, (f) hypocapnia with RR of 180 min(-1), and (g) hypercapnia with RR of 60 min(-1). Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment. Results: Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were driven by FiO(2) 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH(2)O, P<0.05) and hypocapnia (P<0.05), and TNF-alpha was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected. Conclusion: Alterations of PEEP, FiO(2), and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants.

Automated summary

Changes in positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), and respiratory rate induce a significant systemic inflammatory response in infant rat plasma, emphasizing the importance of lung-protective ventilation strategies.