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), 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 ~8 mL/kg, PEEP 5 cmHO, FiO 0.4, RR 90 min, (b) "PEEP 1", (c) "PEEP 9" (d) "FiO 0.21", (e) "FiO 1.0", (f) "hypocapnia" with RR of 180 min, and (g) "hypercapnia" with RR of 60 min. 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-α (TNF-α) were driven by FiO 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 cmHO, P<0.05) and hypocapnia (P<0.05), and TNF-α 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, 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.