Effect of rate and inspiratory flow on ventilator-induced lung injury

Background: We examined the effects of decreasing respiratory rate (RR) at variable inspiratory times (I-t) and reducing inspiratory flow on the development of ventilator-induced lung injury. Methods: Forty sheep weighing 24.6 +/- 3.2 kg were ventilated for 6 hours with one of five strategies (F-IO2 = 1.0, positive end-expiratory pressure = 5 cm H2O): (1) pressure-controlled ventilation (PCV), RR = 15 breaths/min, peak inspiratory pressure (PLP) = 25 cm H2O, n = 8; (2) PCV, RR = 15 breaths/min, PIP = 50 cm H2O, n = 8; (3) PCV, RR = 5 breaths/min, PLP = 50 cm H2O, I-t = 6 seconds, n = 8; (4) PCV, RR = 5 breaths/min, PIP = 50 cm H2O, I-t = 2 seconds, n = 8; and (5) limited inspiratory flow volume-controlled ventilation, RR = 5 breaths/min, pressure-limit = 50 cm H2O, flow = 15 L/min, n = 8. Results: Decreasing RR at conventional flows did not reduce injury. However, limiting inspiratory flow rate (LIFR) maintained compliance and resulted in lower Qs/Qt (HiPIP = 38 +/- 18%, LIFR = 19 +/- 6%, p < 0.001), reduced histologic injury (HiPIP = 14 +/- 0.9, LIFR = 2.2 +/- 0.9, p < 0.05), decreased intra-alveolar neutrophils (HiPIP = 90 +/- 49, LIFR 7.6 +/- 3.8,p = 0.001), and reduced wet-dry lung weight (HiPIP = 87.3 +/- 8.5%, LIFR = 40.8 +/- 17.4%, p < 0.001). Conclusions: High-pressure ventilation for 6 hours using conventional flow patterns produces severe lung injury, irrespective of RR or I-t. Reduction of inspiratory flow at similar PIP provides pulmonary protection.