Background Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome. We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients. Methods Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter, randomized trial. The trial compared traditional ventilation treatment, which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration (plateau pressure) of 50 cm of water or less, with ventilation with a lower tidal volume, which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less. The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28. Results The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes (31.0 percent vs. 39.8 percent, P=0.007), and the number of days without ventilator use during the first 28 days after randomization was greater in this group (mean [+/-SD], 12+/-11 vs. 10+/-11; P=0.007). The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight (P Conclusions In patients with acute lung injury and the acute respiratory distress syndrome, mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.

Background In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. Methods We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection poin...

https://www.nejm.org/doi/pdf/10.1056/NEJM199802053380602

Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome

Introduction: Ventilator-induced Lung Injury: Not Only Air Leaks Ventilation-induced Pulmonary Edema and Related Findings: A Historical Perspective Ventilation-induced Pulmonary Edema: Hydrostatic or Permeability Edema? Experimental Evidence for Increased Vascular Transmural Pressure Evidence for Alterations in Alveolar–Capillary Permeability Contributions of the Static and Dynamic Lung Volume Components to Ventilator-induced Edema High-volume Lung Edema Low Lung Volume Injury Effects of High-volume Ventilation on Abnormal Lungs Effects of High-volume Ventilation on Injured Lungs Interaction between Severe Alveolar Flooding and Mechanical Ventilation Effects of Resting the Lung on Ventilator-induced Lung Injury Possible Mechanisms of Ventilation-induced Lung Injury Mechanisms of Increased Vascular Transmural Pressure Mechanisms of Altered Permeability Clinical Relevance

Ventilator-induced lung injury: lessons from experimental studies.

The members of the Writing Committee background Most patients requiring mechanical ventilation for acute lung injury and the acute res- piratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ven- tilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients. methods We randomly assigned 549 patients with acute lung injury and ARDS to receive me- chanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen. results Mean (±SD) PEEP values on days 1 through 4 were 8.3±3.2 cm of water in the lower- PEEP group and 13.2±3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5±10.4 days in the lower-PEEP group and 13.8±10.6 days in the higher-PEEP group (P = 0.50). conclusions These results suggest that in patients with acute lung injury and ARDS who receive me- chanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical out- comes are similar whether lower or higher PEEP levels are used.

Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome

BACKGROUND Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (V T ), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (C RS ) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP = V T /C RS ), in which V T is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than V T or PEEP in patients who are not actively breathing. METHODS Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease. RESULTS Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving “protective” plateau pressures and V T (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in V T or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P = 0.004 and P = 0.001, respectively). CONCLUSIONS We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundacao de Amparo e Pesquisa do Estado de Sao Paulo and others.)

http://intensivo.sochipe.cl/subidos/catalogo3/Driving%20Presuure%20in%20SDRA%20NEJM%202015.pdf

Driving Pressure and Survival in the Acute Respiratory Distress Syndrome

Intermittent positive pressure ventilation with large tidal volumes and high peak airway pressures can result in pulmonary barotrauma. In the present study, we examined the hypothesis that ventilation at very low lung volumes can also worsen lung injury by repeated opening and closing of airway and alveolar duct units as ventilation occurs from below to above the infection point (Pinf) as determined from the inspiratory pressure-volume curve. We ventilated isolated, nonperfused, lavaged rat lungs with physiologic tidal volumes (5 to 6 ml/kg) at different end-expiratory pressures (above and below Pinf) and studied the effect on compliance and lung injury. In the groups ventilated with positive end-expiratory pressure (PEEP) below Pinf compliance fell dramatically after ventilation. It did not change in either the control group or the group ventilated with PEEP above Pinf. Lung injury assessed morphologically was significantly greater in the groups ventilated with a PEEP below Pinf, and in these groups the ...

J. B. M. Mullen

Papers

Tidal ventilation at low airway pressures can augment lung injury.