Potentially modifiable respiratory variables contributing to outcome in ICU patients without ARDS: a secondary analysis of PRoVENT

Fabienne D Simonis, Carmen S V Barbas, Antonio Artigas-Raventós, Jaume Canet, Rogier M Determann, James Anstey, Goran Hedenstierna, Sabrine N T Hemmes, Greet Hermans, Michael Hiesmayr, Markus W Hollmann, Samir Jaber, Ignacio Martin-Loeches, Gary H Mills, Rupert M Pearse, Christian Putensen, Werner Schmid, Paolo Severgnini, Roger Smith, Tanja A Treschan, Edda M Tschernko, Marcos F Vidal Melo, Hermann Wrigge, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz, Ary Serpa Neto, PRoVENT investigators, PROVE Network investigators, Ary Serpa Neto, Carmen S V Barbas, Antonio Artigas-Raventós, Jaume Canet, Rogier M Determann, Barry Dixon, Goran Hedenstierna, Sabrine N T Hemmes, Greet Hermans, Michael Hiesmayr, Markus W Hollmann, Samir Jaber, Ignacio Martin-Loeches, Gary H Mills, Rupert M Pearse, Christian Putensen, Werner Schmid, Paolo Severgnini, Roger Smith, Tanja A Treschan, Edda M Tschernko, Marcos F Vidal Melo, Hermann Wrigge, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz, Fabienne D Simonis, Fabienne D Simonis, Carmen S V Barbas, Antonio Artigas-Raventós, Jaume Canet, Rogier M Determann, James Anstey, Goran Hedenstierna, Sabrine N T Hemmes, Greet Hermans, Michael Hiesmayr, Markus W Hollmann, Samir Jaber, Ignacio Martin-Loeches, Gary H Mills, Rupert M Pearse, Christian Putensen, Werner Schmid, Paolo Severgnini, Roger Smith, Tanja A Treschan, Edda M Tschernko, Marcos F Vidal Melo, Hermann Wrigge, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz, Ary Serpa Neto, PRoVENT investigators, PROVE Network investigators, Ary Serpa Neto, Carmen S V Barbas, Antonio Artigas-Raventós, Jaume Canet, Rogier M Determann, Barry Dixon, Goran Hedenstierna, Sabrine N T Hemmes, Greet Hermans, Michael Hiesmayr, Markus W Hollmann, Samir Jaber, Ignacio Martin-Loeches, Gary H Mills, Rupert M Pearse, Christian Putensen, Werner Schmid, Paolo Severgnini, Roger Smith, Tanja A Treschan, Edda M Tschernko, Marcos F Vidal Melo, Hermann Wrigge, Marcelo Gama de Abreu, Paolo Pelosi, Marcus J Schultz, Fabienne D Simonis

Abstract

Background: The majority of critically ill patients do not suffer from acute respiratory distress syndrome (ARDS). To improve the treatment of these patients, we aimed to identify potentially modifiable factors associated with outcome of these patients.

Methods: The PRoVENT was an international, multicenter, prospective cohort study of consecutive patients under invasive mechanical ventilatory support. A predefined secondary analysis was to examine factors associated with mortality. The primary endpoint was all-cause in-hospital mortality.

Results: 935 Patients were included. In-hospital mortality was 21%. Compared to patients who died, patients who survived had a lower risk of ARDS according to the 'Lung Injury Prediction Score' and received lower maximum airway pressure (Pmax), driving pressure (ΔP), positive end-expiratory pressure, and FiO2 levels. Tidal volume size was similar between the groups. Higher Pmax was a potentially modifiable ventilatory variable associated with in-hospital mortality in multivariable analyses. ΔP was not independently associated with in-hospital mortality, but reliable values for ΔP were available for 343 patients only. Non-modifiable factors associated with in-hospital mortality were older age, presence of immunosuppression, higher non-pulmonary sequential organ failure assessment scores, lower pulse oximetry readings, higher heart rates, and functional dependence.

Conclusions: Higher Pmax was independently associated with higher in-hospital mortality in mechanically ventilated critically ill patients under mechanical ventilatory support for reasons other than ARDS. Trial Registration ClinicalTrials.gov (NCT01868321).

Keywords: Mechanical ventilation; Mortality; Outcome; Ventilator settings.

Figures

Fig. 1
Fig. 1
Flowchart of inclusion
Fig. 2
Fig. 2
Unadjusted relative risks of hospital mortality in the overall cohort and in patients at risk and not at risk of ARDS and according to the median of the: aPmax; b PEEP; cP; and d tidal volume. Abbreviations: Pmax: maximum airway pressure; PEEP: positive end-expiratory pressure; VT: tidal volume; ∆P: driving pressure; RR: relative risk; CI: confidence interval
Fig. 3
Fig. 3
Odds ratio of hospital mortality according to increases in one standard deviation of Pmax and in the patients at risk and not at risk of ARDS. All curves are adjusted by the same set of variables described in Table 3

References

    1. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med. 2013;369:2126–2136. doi: 10.1056/NEJMra1208707.
    1. Sutherasan Y, Vargas M, Pelosi P. Protective mechanical ventilation in the non-injured lung: review and meta-analysis. Crit Care. 2014;18:211. doi: 10.1186/cc13778.
    1. Putensen C, Theuerkauf N, Zinserling J, et al. Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med. 2009;151:566–576. doi: 10.7326/0003-4819-151-8-200910200-00011.
    1. Burns KEA, Adhikari NKJ, Slutsky AS, et al. Pressure and volume limited ventilation for the ventilatory management of patients with acute lung injury: a systematic review and meta-analysis. PLoS ONE. 2011;6:e14623. doi: 10.1371/journal.pone.0014623.
    1. Serpa Neto A, Simonis FD, Barbas CSV, et al. Association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis. Intensive Care Med. 2014;40:950–957. doi: 10.1007/s00134-014-3318-4.
    1. Serpa Neto A, Simonis FD, Barbas CSV, et al. Lung-protective ventilation with low tidal volumes and the occurrence of pulmonary complications in patients without acute respiratory distress syndrome. Crit Care Med. 2015;43:2155–2163. doi: 10.1097/CCM.0000000000001189.
    1. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA. 2010;303:865–873. doi: 10.1001/jama.2010.218.
    1. Serpa Neto A, Filho RR, Cherpanath T, et al. Associations between positive end-expiratory pressure and outcome of patients without ARDS at onset of ventilation: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care. 2016;6:109. doi: 10.1186/s13613-016-0208-7.
    1. Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med. 2015;372:747–755. doi: 10.1056/NEJMsa1410639.
    1. Bellani G, Laffey JG, Pham T, et al. 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. doi: 10.1001/jama.2016.0291.
    1. Serpa Neto A, Barbas CSV, Simonis FD, et al. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study. Lancet Respir Med. 2016;4:882–893. doi: 10.1016/S2213-2600(16)30305-8.
    1. Thompson BT, Hayden D, Matthay MA, et al. Clinicians’ approaches to mechanical ventilation in acute lung injury and ARDS. Chest. 2001;120:1622–1627. doi: 10.1378/chest.120.5.1622.
    1. Esteban A, Anzueto A, Frutos F, et al. Characteristics and outcomes in adult patients receiving mechanical ventilation. JAMA. 2002;287:345–355. doi: 10.1001/jama.287.3.345.
    1. Esteban A, Frutos-Vivar F, Muriel A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188:220–230. doi: 10.1164/rccm.201212-2169OC.
    1. Britos M, Smoot E, Liu KD, et al. The value of positive end-expiratory pressure and Fio2 criteria in the definition of the acute respiratory distress syndrome. Crit Care Med. 2011;39:2025–2030. doi: 10.1097/CCM.0b013e31821cb774.
    1. Laffey JG, Bellani G, Pham T, et al. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med. 2016
    1. Serpa Neto A, Barbas CS, Artigas-Raventós A, et al. Rationale and study design of Provent-An international multicenter observational study on practice of ventilation in critically Ill patients without ARDS. J Clin Trials. 2013;3:2–7.
    1. The ARDS Definition Task Force Acute respiratory distress syndrome: the Berlin definition. JAMA. 2012;307:2526–2533.
    1. Zimmerman JE, Kramer AA, McNair DS, et al. Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today’s critically ill patients. Crit Care Med. 2006;34:1297–1310. doi: 10.1097/01.CCM.0000215112.84523.F0.
    1. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957–2963. doi: 10.1001/jama.1993.03510240069035.
    1. Bos LD, Schouten LR, Cremer OL, et al. External validation of the APPS, a new and simple outcome prediction score in patients with the acute respiratory distress syndrome. Ann Intensive Care. 2016;6:89. doi: 10.1186/s13613-016-0190-0.
    1. Chatburn RL, Volsko TA. Documentation issues for mechanical ventilation in pressure-control modes. Respir Care. 2010;55:1705–1716.
    1. Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301–1308. doi: 10.1056/NEJM200005043421801.
    1. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685–1693. doi: 10.1056/NEJMoa050333.
    1. Brun-Buisson C, Minelli C, Bertolini G, et al. Epidemiology and outcome of acute lung injury in European intensive care units Results from the ALIVE study. Intensive Care Med. 2004;30:51–61. doi: 10.1007/s00134-003-2022-6.
    1. Dreyfuss D, Basset GUY, Soler P, et al. Intermittent Positive-Pressure Hyperventilation with High Inflation Pressures Produces Pulmonary Microvascular Injury in Rats. Am Rev Respir Dis. 1985;132:880–884.
    1. Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis. 1974;110:556–565.
    1. Amato MB, Barbas CS, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347–354. doi: 10.1056/NEJM199802053380602.
    1. Kregenow DA, Rubenfeld GD, Hudson LD, et al. Hypercapnic acidosis and mortality in acute lung injury. Crit Care Med. 2006;34:1–7. doi: 10.1097/01.CCM.0000194533.75481.03.
    1. Schmidt MFS, Amaral ACKB, Fan E, et al.: Driving pressure and hospital mortality in patients without ARDS: a cohort study. Chest 2017; 1–9.
    1. Serpa Neto A, Hemmes SNT, Barbas CSV, et al. Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data. Lancet Respir Med. 2016;4:272–280. doi: 10.1016/S2213-2600(16)00057-6.
    1. Goligher EC, Fan E, Herridge MS, et al. Evolution of diaphragm thickness during mechanical ventilation. Impact of inspiratory effort. Am J Respir Crit Care Med. 2015;192:1080–1088. doi: 10.1164/rccm.201503-0620OC.
    1. Estenssoro E, Dubin A, Laffaire E, et al. Incidence, clinical course, and outcome in 217 patients with acute respiratory distress syndrome. Crit Care Med. 2002;30:2450–2456. doi: 10.1097/00003246-200211000-00008.
    1. Serpa Neto A, Schmidt M, Azevedo LCP, et al. Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis. Intensive Care Med. 2016;42:1672–1684. doi: 10.1007/s00134-016-4507-0.
    1. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308:1651–1659. doi: 10.1001/jama.2012.13730.
    1. Serpa Neto A, Hemmes SNT, Barbas CSV, et al. Incidence of mortality and morbidity related to postoperative lung injury in patients who have undergone abdominal or thoracic surgery: a systematic review and meta-analysis. Lancet Respir Med. 2014;2:1007–1015. doi: 10.1016/S2213-2600(14)70228-0.
    1. Serpa Neto A, Hemmes SNT, Barbas CSV, et al. Protective versus conventional ventilation for surgery. Anesthesiology. 2015;123:66–78. doi: 10.1097/ALN.0000000000000706.
    1. Futier E, Constantin J-M, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369:428–437. doi: 10.1056/NEJMoa1301082.
    1. Simonis FD, Binnekade JM, Braber A, et al. PReVENT–protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial. Trials. 2015;16:226. doi: 10.1186/s13063-015-0759-1.
    1. Corporacion Parc Tauli: Corporacion Parc Tauli. Preventive Strategies in Acute Respiratory Distress Syndrome (ARDS) (EPALI). In: NLM Identifier: NCT02070666.
    1. PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology. Hemmes SNT, Gama de Abreu M, et al. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet (London, England) 2014;384:495–503. doi: 10.1016/S0140-6736(14)60416-5.
    1. Manzano F, Fernández-Mondéjar E, Colmenero M, et al. Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients. Crit Care Med. 2008;36:2225–2231. doi: 10.1097/CCM.0b013e31817b8a92.
    1. Protti A, Andreis DT, Milesi M, et al. Lung anatomy, energy load, and ventilator-induced lung injury. Intensive Care Med Exp. 2015;3:34. doi: 10.1186/s40635-015-0070-1.
    1. Nieman GF, Satalin J, Andrews P, et al. Lung stress, strain, and energy load: engineering concepts to understand the mechanism of ventilator-induced lung injury (VILI) Intensive Care Med Exp. 2016;4:16. doi: 10.1186/s40635-016-0090-5.

Source: PubMed

3
Suscribir