Effects of high positive end-expiratory pressure versus inverse ratio ventilation on oxygenation and local cytokine response in patients with acute lung injury

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Abstract

Introduction

Positive end-expiratory pressure (PEEP) and inverse ratio ventilation (IRV) are techniques commonly used in the addition of low tidal volume ventilation in patients with acute lung injury (ALI) to improve oxygenation and reduce associated lung injury. In this study, we have attempted to compare their effects on the oxygenation status and local inflammation in the lung as determined by bronchoalveolar lavage (BAL) levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10.

Patients and methods

Forty-eight patients diagnosed with ALI with scores ranging from 0.1 to 2.5 were included. They were investigated for 10 days and were randomly divided into two groups: a PEEP group, which included 25 patients who were ventilated with the low tidal volume technique (6 ml/kg) with the addition of high PEEP [lower inflexion point (Pflex)+2 cmH2O], and an IRV group, which included 23 patients who received mechanical ventilation with low tidal volume (6 ml/kg) with adjustment of the ventilator setting to deliver IRV (I : E=2 : 1) with a low PEEP (5 cmH2O). Arterial blood gas parameters were reported every 12 h and the oxygenation index (PaO2/FiO2) was recorded every 6 h. Alveolar fluids were aspirated using a fiberoptic bronchoscope and the levels of TNF-α, IL-1β, and IL-10 were measured at the start (basal) and at the third, seventh, and 10th days after enrollment.

Results

The PaO2/FiO2 ratio showed no significant difference in its values during the first 4 days; subsequently, it increased in the IRV group compared with the PEEP group until the end of study, whereas all other arterial blood gas parameters showed no statistical difference between both groups. BAL levels of TNF-α were significantly increased in the IRV group at the third, seventh, and 10th days (43.39±5.52, 52.69±5.78, and 65.65±5.88 pg/dl, respectively) than the baseline level (30.44±2.56 pg/dl) (P<0.001). Similarly, its levels in the PEEP group increased significantly at the third, seventh, and 10th days (33.86±2.14, 35.34±2.02, and 39.15±3.18 pg/dl, respectively) than the baseline value (29.89±3.88 pg/dl) (P<0.001). BAL levels of TNF-α were significantly higher in the IRV group than the PEEP group at all time points of measurements (P<0.001) after the baseline reading. IL-1β levels in the IRV group increased significantly at the third, seventh, and 10th days (65.99±3.67, 85.93±2.47, and 95.13±6.36 pg/dl, respectively) compared with the baseline value (51.71±4.44 pg/dl) (P<0.001). Similarly, in the PEEP group, it increased significantly at the third, seventh, and 10th days (57.93±3.76, 63.80±3.98, and 72.12±5.27 pg/dl, respectively) compared with the baseline level (52.07±4.83 pg/dl). Moreover, IL-1β levels were significantly higher in the IRV group than the PEEP group. The levels of IL-10 increased significantly in the IRV group (P<0.001) at the third, seventh, and 10th days (37.19±5.10, 42.24±7.03, and 49.13±11.51 pg/dl) compared with the baseline level (11.71±2.14 pg/dl); also its levels in the PEEP group increased significantly (P<0.001) at the third, seventh, and 10th days (24.03±4.07, 26.32±8.01, and 27.09±10.62 pg/dl, respectively) compared with the baseline level (12.38±3.51 pg/dl). IL-10 was significantly higher in the IRV group than in the PEEP group at the third (P<0.01), seventh, and 10th days (P<0.001), respectively.

Conclusion

IRV showed better oxygenation than high PEEP when used with low tidal volume ventilation in patients with ALI, and it was associated with higher levels of lung proinflammatory cytokines (TNF-α and IL-1β) and of the anti-inflammatory cytokine IL-10, indicating the presence of balance between the proinflammatory and anti-inflammatory cytokines.

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