Abstract
Intraoperative positive end-expiratory pressure (PEEP) has been proposed to restore lung volumes and improve respiratory function in obesity. However, the biological impact of different PEEP levels on the lungs in obesity remains unknown. We aimed to compare the effects of PEEP = 2 cmH2O versus PEEP = 6 cmH2O during ventilation with low tidal volumes on lung function, histology, and biological markers in obese and non-obese rats undergoing open abdominal surgery. Forty-two Wistar rats (21 obese, 21 non-obese) were anesthetized and tracheotomized, and laparotomy was performed with standardized bowel manipulation. Rats were randomly ventilated with protective tidal volume (7 ml/kg) at PEEP = 2 cmH2O or PEEP = 6 cmH2O for 4 h, after which they were euthanized. Lung mechanics and histology, alveolar epithelial cell integrity, and biological markers associated with pulmonary inflammation, alveolar stretch, extracellular matrix, and epithelial and endothelial cell damage were analyzed. In obese rats, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O was associated with less alveolar collapse (p = 0.02). E-cadherin expression was not different between the two PEEP groups. Gene expressions of interleukin (IL)-6 (p = 0.01) and type III procollagen (p = 0.004), as well as protein levels of tumor necrosis factor-alpha (p = 0.016), were lower at PEEP = 6 cmH2O than at PEEP = 2 cmH2O. In non-obese animals, PEEP = 6 cmH2O compared with PEEP = 2 cmH2O led to increased hyperinflation, reduced e-cadherin (p = 0.04), and increased gene expression of IL-6 (p = 0.004) and protein levels of tumor necrosis factor-alpha (p-0.029), but no changes in fibrogenesis. In conclusion, PEEP = 6 cmH2O reduced lung damage and inflammation in an experimental model of mechanical ventilation for open abdominal surgery, but only in obese animals.
Highlights
MATERIALS AND METHODSSeveral intraoperative ventilator strategies may prevent lung damage
The present study aimed to evaluate the impact of mechanical ventilation with high and low positive end-expiratory pressure (PEEP), both under low VT, on lung mechanics and histology, alveolar epithelial cell integrity, and biological markers associated with pulmonary inflammation, alveolar stretch, extracellular matrix, and epithelial and endothelial cell damage during open abdominal surgery in non-obese and obese rats
Est,L and mean arterial pressure were higher and PaO2/FiO2 were lower in Ob than in nonOb animals, regardless of PEEP levels
Summary
MATERIALS AND METHODSSeveral intraoperative ventilator strategies may prevent lung damage. Randomized clinical trials of intraoperative ventilation for abdominal surgery (Futier et al, 2013; Hemmes et al, 2014; Ferrando et al, 2018) have compared diverse ventilation strategies with respect to development of postoperative pulmonary complications (PPCs). In the PROVHILO trial (Hemmes et al, 2014), low-VT with high-PEEP levels and RMs, compared with low-VT and low-PEEP without RMs, did not protect against PPCs. In the iPROVE trial (Ferrando et al, 2018), higher PEEP or individualized PEEP setting compared with lower PEEP did not result in fewer PPCs. In an animal model of open abdominal surgery, both low-VT and moderate to high-PEEP and RMs resulted in lower driving pressure, mechanical power, and lung damage (Maia et al, 2017). The PROBESE trial (Bluth et al, 2019) compared high-PEEP and RM versus low-PEEP at low VT and found no significant differences in PPCs
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