Choosing the frequency of deep inflation in mice: balancing recruitment against ventilator-induced lung injury

Abstract

Low tidal volume (Vt) ventilation is protective against ventilator-induced lung injury but can promote development of atelectasis. Periodic deep inflation (DI) can open the lung, but if delivered too frequently may cause damage via repeated overdistention. We therefore examined the effects of varying DI frequency on lung mechanics, gas exchange, and biomarkers of injury in mice. C57BL/6 males were mechanically ventilated with positive end-expiratory pressure (PEEP) of 2 cmH2O for 2 h. One high Vt group received a DI with each breath (HV). Low Vt groups received 2 DIs after each hour of ventilation (LV) or 2 DIs every minute (LVDI). Control groups included a nonventilated surgical sham and a group receiving high Vt with zero PEEP (HVZP). Respiratory impedance was measured every 4 min, from which tissue elastance (H) and damping (G) were derived. G and H rose progressively during LV and HVZP, but returned to baseline after hourly DI during LV. During LVDI and HV, G and H remained low and gas exchange was superior to that of LV. Bronchoalveolar lavage fluid protein was elevated in HV and HVZP but was not different between LV and LVDI. Lung tissue IL-6 and IL-1beta levels were elevated in HVZP and lower in LVDI compared with LV. We conclude that frequent DI can safely improve gas exchange and lung mechanics and may confer protection from biotrauma. Differences between LVDI and HV suggest that an optimal frequency range of DI exists, within which the benefits of maintaining an open lung outweigh injury incurred from overdistention.

Conflicting Physiological and Genomic Cardiopulmonary Effects of Recruitment Maneuvers in Murine Acute Lung Injury

“…In particular, DI reduced the striking increase in tissue damping and tissue elastance observed with TI ventilation. These findings are in line with previous reports highlighting a progressive alteration of lung mechanics during low tidal volume ventilation in mice, which can be attributed to atelectasis and prevented by DI (8).…”

“…DI maneuvers were supplied by the flexiVent ventilator (see online supplement for details) as a volume of 0.75 ml delivered twice per minute, as this recruitment strategy was previously shown to safely improve lung mechanics during a 2-hour ventilation protocol in a murine model while conferring protection from biotrauma (8).…”

“…Deep inflation (DI) recruitment maneuvers have been proposed as a means of periodically reopening regions of atelectasis. Experimental and clinical studies have demonstrated improvement in oxygenation, ventilation, and lung mechanical function after DI, without evidence of lung injury (8,9). However, several adverse cardiovascular effects have been noted with lung recruitment maneuvers, with both high intrathoracic pressures (potentially leading to a decrease in systemic venous return) and high transpulmonary pressures (with the potential for increases in right ventricular afterload via compression and stretch of small alveolar vessels) (10)(11)(12).…”

Respiratory mechanics and lung structure in rodent models of emphysema

“…4), the DIs caused a statistically significant increase only at 21 days. The increased thickness, which is a characteristic feature of severe AECOPD (1), is apparent on all three types of staining (Figs. 4 and 5).…”

“…Chronic obstructive pulmonary disease (COPD) is the third major cause of death worldwide after ischemic heart disease and stroke 1 . COPD is a type of obstructive lung disease characterized by airway narrowing, dyspnea, cough and sputum production.…”