Short-Term Physiological Effects of Moderate PEEP Levels in Invasively Ventilated Patients Without Acute or Chronic Lung Disease

Background/Objectives: Positive end-expiratory pressure (PEEP) is a standardized component of the invasive mechanical ventilation (IMV) settings to improve oxygenation; however, its physiological effects in patients with no documented prior lung disease remain poorly defined. This study evaluated the impact of moderate PEEP variations on macrohemodynamic parameters, gas exchange, and driving pressure (ΔP). Methods: This single-arm, non-randomized, crossover study included adult intensive care unit (ICU) patients with no documented prior lung disease during the early phase of IMV. Sequential PEEP levels of 6, 8, and 10 cmH2O were applied for 30 min each within the first 24 h of ICU admission, while all other ventilatory parameters were kept constant. Arterial blood gases partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), and arterial oxygen saturation (SaO2), oxygenation index PaO2/fraction of inspired oxygen (FiO2), systolic, diastolic, and mean arterial pressures, ΔP, and static compliance (Cstat) were measured. Friedman and Mann–Whitney U tests were used, with adjustment for multiple comparisons. Results: A total of 150 patients were enrolled (64.7% male). The observed mortality rate was 53.3%; however, mortality was not defined as a primary or secondary outcome, and was used only as a grouping variable for comparative analyses. Intraindividual comparison across PEEP levels of 6, 8, and 10 cmH2O showed small but significant reductions in systolic and mean arterial pressure at higher PEEP (p-value < 0.05), with Bonferroni-adjusted significance for PEEP 6 vs. 10. No significant differences were observed in oxygenation (SaO2, PaO2, and PaO2/FiO2), PaCO2, ΔP, or Cstat. These results suggest that moderate PEEP changes produced limited macrohemodynamic effects without relevant impact on gas exchange or respiratory mechanics. Overall, no clinically relevant or statistically significant differences were observed in gas exchange, macrohemodynamic parameters, ΔP, or Cstat across PEEP levels when mortality was used as the grouping variable. Among survivors, higher PEEP was associated with modest reductions in systolic and mean arterial pressures and higher PaCO2 values; however, these findings did not translate into consistent physiological benefits. Conclusions: In mechanically ventilated patients with no documented prior lung disease, PEEP may exert divergent effects on macrohemodynamics, gas exchange, and ΔP, supporting a cautious and individualized approach to PEEP selection in this population.