Dataset Information

Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure.

ABSTRACT:

Rationale

Low-tidal volume ventilation (LTVV; 6 ml/kg) benefits patients with acute respiratory distress syndrome and may aid those with other causes of respiratory failure. Current early ventilation practices are poorly defined.

Objectives

We observed patients with acute respiratory failure to assess the feasibility of a pragmatic trial of LTVV and to guide experimental design.

Methods

We prospectively enrolled consecutive patients with acute respiratory failure admitted to intensive care units expected to participate in the proposed trial. We collected clinical data as well as information on initial and daily ventilator settings and inpatient mortality. We estimated the benefit of LTVV using predictive linear and nonlinear models. We simulated models to estimate power and feasibility of a cluster-randomized trial of LTVV versus usual care in acute respiratory failure.

Results

We included 2,484 newly mechanically ventilated patients (31% with acute respiratory distress syndrome) from 49 hospitals. Hospital mortality was 28%. Mean initial tidal volume was 7.1 ml/kg predicted body weight (95% confidence interval, 7.1-7.2), with 78% of patients receiving tidal volumes less than or equal to 8 ml/kg. Our models estimated a mortality benefit of 0-2% from LTVV compared with usual care. Simulation of a stepped-wedged cluster-randomized trial suggested that enrollment of 106,361 patients would be necessary to achieve greater than 90% power.

Conclusions

Use of initial tidal volumes less than 8 ml/kg predicted body weight was common at hospitals participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV versus usual care in acute respiratory failure, the PETAL Network deemed the proposed trial infeasible. A rapid observational study and simulations to model anticipated power may help better design trials.

SUBMITTER: Lanspa MJ

PROVIDER: S-EPMC6394119 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:OBJECTIVES:Despite decades of research, the acute respiratory distress syndrome remains associated with significant morbidity and mortality. This Concise Definitive Review provides a practical and evidence-based summary of treatments in addition to low tidal volume ventilation and their role in the management of severe respiratory failure in acute respiratory distress syndrome. DATA SOURCES:We searched the PubMed database for clinical trials, observational studies, and review articles describing treatment adjuncts in acute respiratory distress syndrome patients, including high positive end-expiratory pressure strategies, recruitment maneuvers, high-frequency oscillatory ventilation, neuromuscular blockade, prone positioning, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, glucocorticoids, and renal replacement therapy. STUDY SELECTION AND DATA EXTRACTION:Results were reviewed by the primary author in depth. Disputed findings and conclusions were then reviewed with the other authors until consensus was achieved. DATA SYNTHESIS:Severe respiratory failure in acute respiratory distress syndrome may present with refractory hypoxemia, severe respiratory acidosis, or elevated plateau airway pressures despite lung-protective ventilation according to acute respiratory distress syndrome Network protocol. For severe hypoxemia, first-line treatment adjuncts include high positive end-expiratory pressure strategies, recruitment maneuvers, neuromuscular blockade, and prone positioning. For refractory acidosis, we recommend initial modest liberalization of tidal volumes, followed by neuromuscular blockade and prone positioning. For elevated plateau airway pressures, we suggest first decreasing tidal volumes, followed by neuromuscular blockade, modification of positive end-expiratory pressure, and prone positioning. Therapies such as inhaled pulmonary vasodilators, glucocorticoids, and renal replacement therapy have significantly less evidence in favor of their use and should be considered second line. Extracorporeal membrane oxygenation may be life-saving in selected patients with severe acute respiratory distress syndrome but should be used only when other alternatives have been applied. CONCLUSIONS:Severe respiratory failure in acute respiratory distress syndrome often necessitates the use of treatment adjuncts. Evidence-based application of these therapies in acute respiratory distress syndrome remains a significant challenge. However, a rational stepwise approach with frequent monitoring for improvement or harm can be achieved.

Project description:OBJECTIVE:Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use. DESIGN:Retrospective cross-sectional study. SETTING:One academic and three community hospitals in the Chicago region. PATIENTS:A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013. MEASUREMENTS AND MAIN RESULTS:Seventy patients (19.3%) were treated with low tidal volume ventilation (tidal volume < 6.5?mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30?cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal volume ventilation, the mean (SD) percentage of acute respiratory distress syndrome time it was used was 59.1% (38.2%), and 34% waited more than 72 hours prior to low tidal volume ventilation initiation. Women were less likely to receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40% were associated with increased odds of low tidal volume ventilation use. Four attending physicians (6.2%) initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset for greater than or equal to 50% of their patients, whereas 34 physicians (52.3%) never initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset. In total, 54.4% of patients received a tidal volume less than 8?mL/kg predicted body weight, and the mean tidal volume during the first 72 hours after acute respiratory distress syndrome onset was never less than 8?mL/kg predicted body weight. CONCLUSIONS:More than 12 years after publication of the landmark low tidal volume ventilation study, use remains poor. Interventions that improve adoption of low tidal volume ventilation are needed.

Project description:OBJECTIVES:Low tidal volume (= tidal volume ? 6?mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints. DESIGN:We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5?mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. SETTING:Four Intermountain Healthcare tertiary ICUs. PATIENTS:Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. INTERVENTIONS:Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. MEASUREMENTS AND MAIN RESULTS:We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6?mL/kg; 95% CI, 7.8-9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3-8.9) than volume control (6.8; 95% CI, 6.2-7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. CONCLUSIONS:Airway pressure release ventilation resulted in release volumes often exceeding 12?mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.