Table 1 Main findings from pre-clinical studies on mechanical ventilation and fluid management interactions

Rocha et al. [19]

Animal model:

Lung injured (intratracheal E. coli LPS) male Wistar rats randomized to receive restrictive (10 mL/kg/h) or liberal (30 mL/kg/h) fluids and mechanical ventilation under protective VT (6 ml/mg) and an abrupt or gradual PEEP decrease (directly from 9 to 3 cmH₂O or the same decrease in 30 min)

Main findings:

• Liberal fluids were associated with higher right and left ventricular end-diastolic areas in echocardiographic measurements despite PEEP decrease rate

• PAT/PET ratio was higher in abrupt than in gradual PEEP decrease despite fluid management

• Combined liberal fluids and abrupt PEEP decrease yielded more diffuse alveolar damage and higher interleukin-6 and endothelial growth factor expression,

• Restrictive fluids and gradual PEEP decrease yielded higher zona occludens-1 expression, suggesting epithelial cell preservation

• Abrupt PEEP decrease group showed higher club-16 protein expression regardless of fluid management, suggesting higher alveolar epithelial cell damage

• Kidney injury markers were higher in liberal fluid management despite PEEP decrease strategy

Carvalho et al. [7]

Animal model:

Lung injured (intratracheal E. coli LPS) male Wistar rats randomized to receive restrictive (minimum fluids to keep MAP ≥ 70 mmHg) or liberal (~ 4 times fluids received by restrictive groups) and protective PCV or PSV ventilation

Main findings:

• In PSV groups, restrictive fluids led to reduced diffuse alveolar damage and lung edema, preservation of occludin and claudin-4 and higher expression of zona occludens-1 in lungs (suggesting tight junctions’ integrity)

• Liberal fluids groups reduced interleukin-6 and neutrophil gelatinase-associated lipocalin expression, regardless of ventilatory strategy

Felix et al. [18]

Animal model:

Lung injured (intratracheal E. coli LPS) male Wistar rats randomized to receive restrictive (5 ml/kg/h) or liberal (40 ml/kg/h) fluids and volume-controlled ventilation under protective V_T (6 ml/kg)

Main findings:

• Liberal fluids led to a higher transpulmonary plateau pressure than restrictive fluids

• A combination of high PEEP (9 cmH₂O) and liberal fluids led to higher inflammatory gene expression than low PEEP-liberal fluids and high PEEP-restrictive fluids

• Fluid management did not affect lung mechanical power and heterogeneity index between high and low PEEP groups

• Liberal fluids led to higher perivascular edema despite PEEP strategy

• Under liberal fluids, high PEEP was associated with more intense epithelial and extracellular matrix damage

• Acute kidney injury biomarkers were higher in high PEEP regardless of fluid management