Systemic markers of inflammation in mechanically ventilated brain-injured patients in the absence of sepsis and acute lung injury: the effect of positive end-expiratory pressure

Introduction

In mechanically ventilated (MV) brain-injured patients, pulmonary complications appear to be the leading cause of non-neurological morbidity, suggesting that the local and systemic inflammatory responses associated with brain damage and/or the mechanical ventilation itself may contribute to the pulmonary injury (that is, one or two hit model). We recently provided evidence for lung inflammation in brain-injured, mechanically ventilated patients with neither acute lung injury nor sepsis [1]. We now investigate whether positive end-expiratory pressure (PEEP) application in the same cohort (27 MV brain-injured subjects) is associated with systemic inflammatory changes that could probably contribute to the lung inflammation observed in these patients.

Methods

Patients were ventilated with 8 ml/kg tidal volume and were put on either zero PEEP (ZEEP, n = 12) or 8 cmH₂O PEEP (PEEP, n = 15). The following markers of systemic inflammation were recorded or measured in blood, on the first, third, and fifth days of MV: temperature, leukocyte and neutrophil counts, albumin, soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein, procalcitonin, IL-10, IL-1β, IL-6, IL-8, IL-12p70, and TNFα.

Results

Upon entry, the two groups were well balanced clinically and demographically. Significant differences between the two patient groups were observed in leukocyte counts, IL-6 and sTREM-1; all three parameters were constantly higher on ZEEP (P < 0.05; two-way ANOVARM), while the former two markers decreased with time in both groups (P < 0.05).

Conclusion

In our population of MV brain-injured patients, ZEEP is associated with increases in systemic inflammatory markers that are present early on and throughout the first 5 days of MV. Our findings suggest that PEEP application influences the systemic inflammatory response observed in the absence of sepsis and acute lung injury, and probably points to significant IL-6 and sTREM-1 roles in the systemic and pulmonary inflammation observed in this patient setting.