Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study
Martin Urner, Peter Jüni, Bettina Hansen, Marian S Wettstein, Niall D Ferguson, Eddy Fan, Martin Urner, Peter Jüni, Bettina Hansen, Marian S Wettstein, Niall D Ferguson, Eddy Fan
Abstract
Background Mortality in acute respiratory failure remains high despite the use of lung-protective ventilation. Recent studies have shown an association between baseline ventilation parameters (driving pressure or mechanical power) and outcomes for patients with acute respiratory distress syndrome. Strategies focused on limiting these parameters have been proposed to further improve outcomes. However, it remains unknown whether driving pressure and mechanical power should be limited over the entire duration of mechanical ventilation and in all patients with acute respiratory failure. We aimed to estimate the association between exposure to different intensities of mechanical ventilation over time and intensive care unit (ICU) mortality in patients with acute respiratory failure.
Methods: In this registry-based, prospective cohort study, we obtained data from the Toronto Intensive Care Observational Registry, which includes all patients receiving mechanical ventilation for 4 h or more in nine ICUs that are affiliated with the University of Toronto (Toronto, ON, Canada). We included all adult (≥18 years) patients who received invasive mechanical ventilation between April 11, 2014, and June 5, 2019. Patients were excluded if they received treatment with extracorporeal life support. The primary outcome was ICU mortality. Bayesian joint models were used to estimate the strength of associations, accounting for informative censoring due to death during follow-up.
Findings: Of 13 939 patients recorded in the registry, 13 408 (96·2%) were eligible for descriptive analysis. The primary analysis comprised 7876 (58·7%) patients with complete baseline characteristics, and a secondary analysis included all 13 408 patients after multiple imputation in the joint model analysis. 2409 (18·0%) of 13 408 patients died in the ICU. After adjustment for baseline characteristics, including age and severity of illness, a significant increase in the hazard of death was found to be associated with each daily increment in driving pressure (hazard ratio 1·064, 95% credible interval 1·057-1·071) or mechanical power (hazard ratio 1·060, 95% credible interval 1·053-1·066). These associations persisted over the duration of mechanical ventilation.
Interpretation: Cumulative exposure to higher intensities of mechanical ventilation was harmful, even for short durations. Limiting exposure to driving pressure or mechanical power should be evaluated in further studies as promising ventilation strategies to reduce mortality in patients with acute respiratory failure.
Funding: Canadian Institutes of Health Research.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Figures
References
- Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet. 2010;376:1339–1346.
- Fan E, Del Sorbo L, Goligher EC. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;195:1253–1263.
- Bellani G, Laffey JG, Pham T. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.
- Goligher EC, Ferguson ND, Brochard LJ. Clinical challenges in mechanical ventilation. Lancet. 2016;387:1856–1866.
- Amato MBP, Meade MO, Slutsky AS. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747–755.
- Serpa Neto A, Deliberato RO, Johnson AEW. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018;44:1914–1922.
- Bugedo G, Retamal J, Bruhn A. Driving pressure: a marker of severity, a safety limit, or a goal for mechanical ventilation? Crit Care. 2017;21:199.
- Gattinoni L, Tonetti T, Cressoni M. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016;42:1567–1575.
- Simonis FD, Serpa Neto A, Binnekade JM. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: a randomized clinical trial. JAMA. 2018;320:1872–1880.
- Fan E, Rubenfeld GD. Driving pressure—the emperor's new clothes. Crit Care Med. 2017;45:919–920.
- Therneau TM, Grambsch PM. Springer Science and Business Media; New York: 2013. Modeling survival data: extending the Cox model.
- Sinha P, Calfee CS, Beitler JR. Physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2019;199:333–341.
- Rizopoulos D. The R package JMbayes for fitting joint models for longitudinal and time-to-event data using MCMC. J Stat Softw. 2016;72:46.
- Rizopoulos D, Ghosh P. A Bayesian semiparametric multivariate joint model for multiple longitudinal outcomes and a time-to-event. Stat Med. 2011;30:1366–1380.
- Andrinopoulou ER, Eilers PHC, Takkenberg JJM, Rizopoulos D. Improved dynamic predictions from joint models of longitudinal and survival data with time-varying effects using P-splines. Biometrics. 2018;74:685–693.
- Aoyama H, Pettenuzzo T, Aoyama K, Pinto R, Englesakis M, Fan E. Association of driving pressure with mortality among ventilated patients with acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med. 2018;46:300–306.
- Buuren S, Groothuis-Oudshoorn K. MICE: multivariate imputation by chained equations in R. J Stat Softw. 2011;45:67.
- Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.
- Loken C, Gruner D, Groer L. SciNet: lessons learned from building a power-efficient top-20 system and data centre. J Phys Conf Ser. 2010;256
- von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–1457.
- Esteban A, Anzueto A, Frutos F. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002;287:345–355.
- Schmidt MFS, Amaral ACKB, Fan E, Rubenfeld GD. Driving pressure and hospital mortality in patients without ARDS: a cohort study. Chest. 2018;153:46–54.
- Sahetya SK, Mallow C, Sevransky JE. Association between hospital mortality and inspiratory airway pressures in mechanically ventilated patients without acute respiratory distress syndrome: a prospective cohort study. Crit Care. 2019;23:367.
- Lanspa MJ, Peltan ID, Jacobs JR. Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS. Crit Care. 2019;23:424.
- Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308.
- Chiumello D, Carlesso E, Brioni M, Cressoni M. Airway driving pressure and lung stress in ARDS patients. Crit Care. 2016;20:276.
- Grieco DL, Chen L, Brochard L. Transpulmonary pressure: importance and limits. Ann Transl Med. 2017;5:285.
- Rizopoulos D. Chapman and Hall and CRC Press; London: 2012. Joint models for longitudinal and time-to-event data: with applications in R.
Source: PubMed