Time-Controlled Adaptive Ventilation Versus Volume-Controlled Ventilation in Experimental Pneumonia.

OBJECTIVES: We hypothesized that a time-controlled adaptive ventilation strategy would open and stabilize alveoli by controlling inspiratory and expiratory duration. Time-controlled adaptive ventilation was compared with volume-controlled ventilation at the same levels of mean airway pressure and positive end-release pressure (time-controlled adaptive ventilation)/positive end-expiratory pressure (volume-controlled ventilation) in a Pseudomonas aeruginosa-induced pneumonia model. DESIGN: Animal study. SETTING: Laboratory investigation. SUBJECTS: Twenty-one Wistar rats. INTERVENTIONS: Twenty-four hours after pneumonia induction, Wistar rats (n = 7) were ventilated with time-controlled adaptive ventilation (tidal volume = 8 mL/kg, airway pressure release ventilation for a Thigh = 0.75-0.85 s, release pressure (Plow) set at 0 cm H2O, and generating a positive end-release pressure = 1.6 cm H2O applied for Tlow = 0.11-0.14 s). The expiratory flow was terminated at 75% of the expiratory flow peak. An additional 14 animals were ventilated using volume-controlled ventilation, maintaining similar time-controlled adaptive ventilation levels of positive end-release pressure (positive end-expiratory pressure=1.6 cm H2O) and mean airway pressure = 10 cm H2O. Additional nonventilated animals (n = 7) were used for analysis of molecular biology markers. MEASUREMENTS AND MAIN RESULTS: After 1 hour of mechanical ventilation, the heterogeneity score, the expression of pro-inflammatory biomarkers interleukin-6 and cytokine-induced neutrophil chemoattractant-1 in lung tissue were significantly lower in the time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure groups (p = 0.008, p = 0.011, and p = 0.011, respectively). Epithelial cell integrity, measured by E-cadherin tissue expression, was higher in time-controlled adaptive ventilation than volume-controlled ventilation with similar mean airway pressure (p = 0.004). Time-controlled adaptive ventilation animals had bacteremia counts lower than volume-controlled ventilation with similar mean airway pressure animals, while time-controlled adaptive ventilation and volume-controlled ventilation with similar positive end-release pressure animals had similar colony-forming unit counts. In addition, lung edema and cytokine-induced neutrophil chemoattractant-1 gene expression were more reduced in time-controlled adaptive ventilation than volume-controlled ventilation with similar positive end-release pressure groups. CONCLUSIONS: In the model of pneumonia used herein, at the same tidal volume and mean airway pressure, time-controlled adaptive ventilation, compared with volume-controlled ventilation, was associated with less lung damage and bacteremia and reduced gene expression of mediators associated with inflammation.

Effects of crystalloid, hyper-oncotic albumin, and iso-oncotic albumin on lung and kidney damage in experimental acute lung injury.

BACKGROUND: Conflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer's lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI). METHODS: Male Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n = 24) to induce ALI. After 24 h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n = 6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava < 25%, mean arterial pressure > 65 mmHg). Rats were then mechanically ventilated for 6 h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses. RESULTS: The total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2-33.2] vs. 4.8[3.6-7.7] and 4.3[3.9-6.6] mL, respectively; p = 0.02 and p = 0.003). B-line counts on lung ultrasound (p < 0.0001 and p = 0.0002) and serum lactate levels (p = 0.01 and p = 0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5-12]) and 20%ALB (10.5[8.5-14]) than RL (16.5[12.5-20.5]) (p < 0.05 and p = 0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5-10]) than 20%ALB (18[15-28.5], p = 0.0006) and RL (16 [15-19], p = 0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4-129.3]) than in 5%ALB (27.0[7.8-49.7], p = 0.04) or 20%ALB (3.7[7.8-49.7], p = 0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p = 0.026 and p = 0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p = 0.01 and p = 0.01), respectively. CONCLUSIONS: In a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer's lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.