The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation.

The aim of this study was to assess the association between regional tidal volume (Vt), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB/c mice (n = 8 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional Vt and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.e., specific [s]Vt and specific [s]FRC). RNA concentrations of 21 genes in 10 different lung regions were quantified using a quantitative PCR array. sFRC at baseline varied regionally, independent of ventilation strategy, whereas sVt varied regionally depending on ventilation strategy. The expression of IL-6 (P = 0.04), Ccl2 (P < 0.01), and Ang-2 (P < 0.05) was associated with sVt but not sFRC. The expression of seven other genes varied regionally (IL-1ß and RAGE [receptor for advanced glycation end products]) or depended on ventilation strategy (Nfe2l2 [nuclear factor erythroid-derived 2 factor 2], c-fos, and Wnt1) or both (TNF-α and Cxcl2), but it was not associated with regional sFRC or sVt. These observations suggest that regional inflammatory responses to mechanical ventilation are driven primarily by tidal stretch.

Effects of Dexmedetomidine Infusion on Inflammatory Responses and Injury of Lung Tidal Volume Changes during One-Lung Ventilation in Thoracoscopic Surgery: A Randomized Controlled Trial.

One-lung ventilation in thoracic surgery provokes profound systemic inflammatory responses and injury related to lung tidal volume changes. We hypothesized that the highly selective a2-adrenergic agonist dexmedetomidine attenuates these injurious responses. Sixty patients were randomly assigned to receive dexmedetomidine or saline during thoracoscopic surgery. There is a trend of less postoperative medical complication including that no patients in the dexmedetomidine group developed postoperative medical complications, whereas four patients in the saline group did (0% versus 13.3%, p = 0.1124). Plasma inflammatory and injurious biomarkers between the baseline and after resumption of two-lung ventilation were particularly notable. The plasma high-mobility group box 1 level decreased significantly from 51.7 (58.1) to 33.9 (45.0) ng.ml-1 (p < 0.05) in the dexmedetomidine group, which was not observed in the saline group. Plasma monocyte chemoattractant protein 1 [151.8 (115.1) to 235.2 (186.9) pg.ml-1, p < 0.05] and neutrophil elastase [350.8 (154.5) to 421.9 (106.1) ng.ml-1, p < 0.05] increased significantly only in the saline group. In addition, plasma interleukin-6 was higher in the saline group than in the dexmedetomidine group at postoperative day 1 [118.8 (68.8) versus 78.5 (58.8) pg.ml-1, p = 0.0271]. We conclude that dexmedetomidine attenuates one-lung ventilation-associated inflammatory and injurious responses by inhibiting alveolar neutrophil recruitment in thoracoscopic surgery.

Potent inflammatory cytokine response following lung volume recruitment maneuvers with HFOV in pediatric acute respiratory distress syndrome.

OBJECTIVE: Lung volume recruitment maneuver (LVRM) may improve gas exchange but inflating the lungs to nearly vital capacity may cause further lung injuries. Our aim was to determine the potent inflammatory cytokine response following lung volume recruitment (LVRM) with high frequency oscillator ventilation (HFOV) in pediatric acute respiratory distress syndrome (ARDS). METHODS: We prospectively recruited pediatric patients (age >1 month - <15 year old) with a diagnosis of ARDS within 72 hrs of PICU admission. They underwent the LVRM protocol combined with HFOV. Any enrolled subject who had a 20% improvement in PaO2/FiO2 (PF ratio) 1 hr after the LVRM we classified as a responder. Baseline clinical data were recorded. Blood was also drawn at baseline, 1 & 24 hrs after LVRM and kept for further sICAM-1, IL-6 & IL-8 analysis. RESULTS: Eighteen children with ARDS were enrolled. Their mean age was at 6.8 +/- 6.1 years (mean +/- SD). The initial oxygen index (iOI) was at 26.8 +/- 17.8 (11.5-84.9). There was no significant differences in sICAM-1, IL-6 and IL-8 levels at baseline; (34 +/- 17.5, 121.7 +/- 115.15, 601.5 +/- 675 pg/ml); 1 hr (39.6 +/- 28.7, 99.8 +/- 75.5, 617.4 +/- 692.5 pg/ml) and at 24 hrs (44.23 +/- 34.4, 109.4 +/- 63.9, 737.6 +/- 922.3 pg/ml) following LVRMs, respectively. However, there was significant difference in the elevation of sICAM-1 levels (%change) from baseline in responders (-1.8 +/- 12.2%) vs. non-responders (47.65 +/- 43.5%) at 1 hr. Additionally, sICAM-1 levels were also significantly higher at baseline, 1 hr and 24 hrs in non-survivors as compared with survivors. CONCLUSION: There was no significant elevation of potent inflammatory cytokines that may indicate further lung injuries in the majority of our patients. However, there was significant elevation of sICAM-1 levels in non-responders and in those who did not survive that may indicate more lung injuries in these individuals.

Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial.

OBJECTIVES: Respiratory support for patients recovering from cardiopulmonary bypass and cardiac surgery uses large tidal volumes and a minimal level of positive end-expiratory pressure. Recent data indicate that these ventilator settings might cause pulmonary and systemic inflammation in patients with acute lung injury. We examined the hypothesis that high tidal volumes and low levels of positive end-expiratory pressure might worsen the inflammatory response associated to cardiopulmonary bypass. METHODS: Forty patients undergoing elective coronary artery bypass were randomized to be ventilated after cardiopulmonary bypass disconnection with high tidal volume/low positive end-expiratory pressure (10-12 mL/kg and 2-3 cm H2O, respectively) or low tidal volume/high positive end-expiratory pressure (8 mL/kg and 10 cm H2O, respectively). Interleukin 6 and interleukin 8 levels were measured in the bronchoalveolar lavage fluid and plasma. Samples were taken before sternotomy (time 0), immediately after cardiopulmonary bypass separation (time 1), and after 6 hours of mechanical ventilation (time 2). RESULTS: Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and plasma significantly increased at time 1 in both groups but further increased at time 2 only in patients ventilated with high tidal volume/low positive end-expiratory pressure. Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and in the plasma at time 2 were higher with high tidal volume/low positive end-expiratory pressure than with low tidal volume/high positive end-expiratory pressure. CONCLUSION: Mechanical ventilation might be a cofactor able to influence the inflammatory response after cardiac surgery.