P/FP ratio: incorporation of PEEP into the PaO2/FiO2 ratio for prognostication and classification of acute respiratory distress syndrome

Sunitha Palanidurai, Jason Phua, Yiong Huak Chan, Amartya Mukhopadhyay, Sunitha Palanidurai, Jason Phua, Yiong Huak Chan, Amartya Mukhopadhyay

Abstract

Background: The current Berlin definition of acute respiratory distress syndrome (ARDS) uses the PaO2/FiO2 (P/F) ratio to classify severity. However, for the same P/F ratio, a patient on a higher positive end-expiratory pressure (PEEP) may have more severe lung injury than one on a lower PEEP.

Objectives: We designed a new formula, the P/FP ratio, incorporating PEEP into the P/F ratio and multiplying with a correction factor of 10 [(PaO2*10)/(FiO2*PEEP)], to evaluate if it better predicts hospital mortality compared to the P/F ratio post-intubation and to assess the resultant changes in severity classification of ARDS.

Methods: We categorized patients from a dataset of seven ARDS network trials using the thresholds of ≤ 100 (severe), 101-200 (moderate), and 201-300 (mild) for both P/F (mmHg) and P/FP (mmHg/cmH2O) ratios and evaluated hospital mortality using areas under the receiver operating characteristic curves (AUC).

Results: Out of 3,442 patients, 1,057 (30.7%) died. The AUC for mortality was higher for the P/FP ratio than the P/F ratio for PEEP levels > 5 cmH2O: 0.710 (95% CI 0.691-0.730) versus 0.659 (95% CI 0.637-0.681), P < 0.001. Improved AUC was seen with increasing PEEP levels; for PEEP ≥ 18 cmH2O: 0.963 (95% CI 0.947-0.978) versus 0.828 (95% CI 0.765-0.891), P < 0.001. When the P/FP ratio was used instead of the P/F ratio, 12.5% and 15% of patients with moderate and mild ARDS, respectively, were moved to more severe categories, while 13.9% and 33.6% of patients with severe and moderate ARDS, respectively, were moved to milder categories. The median PEEP and FiO2 were 14 cmH2O and 0.70 for patients reclassified to severe ARDS, and 5 cmH2O and 0.40 for patients reclassified to mild ARDS.

Conclusions: The multifactorial P/FP ratio has a greater predictive validity for hospital mortality in ARDS than the P/F ratio. Changes in severity classification with the P/FP ratio reflect both true illness severity and the applied PEEP strategy.

Trial registration: ClinialTrials.gov-NCT03946150.

Keywords: Acute respiratory distress syndrome; Mortality; PaO2/FiO2 ratio; Positive end-expiratory pressure.

Conflict of interest statement

The authors declare that they have no competing interest.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Change of severity classifications when P/FP ratio is used instead of P/F ratio for severities. Severe refers to a ratio of ≤ 100, moderate refers to a ratio of 101–200, mild refers to a ratio of 201–300, non-ARDS refers to a ratio of > 300 mmHg or mmHg/cmH2O. Green ovals represent patients who were reclassified to a more severe category. Blue ovals represent patients who were reclassified to a milder category. Red ovals represent patients whose categories remained unchanged. Definition of abbreviations: ARDS  acute respiratory distress syndrome; P/F  ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2); P/FP = (PaO2 * 10)/(FiO2 * positive end-expiratory pressure)
Fig. 2
Fig. 2
Scatter plots of patients according to P/F ratio and P/FP ratio. Each circle represents individual patients on a certain applied PEEP; each colour represents a different PEEP setting. Green bars represent patients who were classified by the P/FP ratio in each severity. Blue bars represent patients who were classified by the P/F ratio in each severity. Red bars represent patients whose categories remained unchanged. Definition of abbreviations: FiO2 = fraction of inspired oxygen; PEEP = positive end-expiratory pressure; P/F = ratio of the partial pressure of arterial oxygen (PaO2) to FiO2; P/FP = (PaO2 * 10)/(FiO2 * PEEP)
Fig. 3
Fig. 3
Receiver operating characteristic curves for the P/F ratio and the P/FP ratio for hospital mortality at different PEEP thresholds. AUC area under the curve; NS not significant, PEEP positive end-expiratory pressure, P/F = ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2); P/FP = (PaO2 * 10)/(FiO2 * PEEP); CI confidence interval

References

    1. Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, et al. 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(9):1253–1263. doi: 10.1164/rccm.201703-0548ST.
    1. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, 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(8):788–800. doi: 10.1001/jama.2016.0291.
    1. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–2533.
    1. Villar J, Perez-Mendez L, Lopez J, Belda J, Blanco J, Saralegui I, Suarez-Sipmann F, Lopez J, Lubillo S, Kacmarek RM, et al. An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2007;176(8):795–804. doi: 10.1164/rccm.200610-1534OC.
    1. Villar J, Perez-Mendez L, Blanco J, Anon JM, Blanch L, Belda J, Santos-Bouza A, Fernandez RL, Kacmarek RM, Spanish Initiative for Epidemiology et al. A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting–a prospective, multicenter validation study. Intensive Care Med. 2013;39(4):583–592. doi: 10.1007/s00134-012-2803-x.
    1. Villar J, Blanco J, del Campo R, Andaluz-Ojeda D, Diaz-Dominguez FJ, Muriel A, Corcoles V, Suarez-Sipmann F, Tarancon C, Gonzalez-Higueras E, et al. Assessment of PaO(2)/FiO(2) for stratification of patients with moderate and severe acute respiratory distress syndrome. BMJ Open. 2015;5(3):e006812. doi: 10.1136/bmjopen-2014-006812.
    1. Villar J, Perez-Mendez L, Kacmarek RM. The Berlin definition met our needs: no. Intensive Care Med. 2016;42(5):648–650. doi: 10.1007/s00134-016-4242-6.
    1. Del Sorbo L, Ranieri VM, Ferguson ND. The Berlin definition met our needs: yes. Intensive Care Med. 2016;42(5):643–647. doi: 10.1007/s00134-016-4286-7.
    1. Palanidurai S. The P/FP ratio: a pilot approach to calculate the severity of oxygenation/ARDS with PEEP [abstract] Am J Respir Crit Care Med. 2017;195:A3756.
    1. Acute Respiratory Distress Syndrome Network. 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(18):1301–1308. doi: 10.1056/NEJM200005043421801.
    1. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT, National Heart, Lung et al. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med. 2004;351(4):327–336. doi: 10.1056/NEJMoa032193.
    1. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, deBoisblanc B, Connors AF, Jr, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354(24):2564–2575. doi: 10.1056/NEJMoa062200.
    1. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, et al. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011;184(5):561–568. doi: 10.1164/rccm.201012-2090OC.
    1. Rice TW, Wheeler AP, Thompson BT, deBoisblanc BP, Steingrub J, Rock P, NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306(14):1574–1581. doi: 10.1001/jama.2011.1435.
    1. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307(8):795–803. doi: 10.1001/jama.2012.137.
    1. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014;370(23):2191–2200. doi: 10.1056/NEJMoa1401520.
    1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994. 149(31):818–824.
    1. Sahetya SK, Goligher EC, Slutsky AS. Searching for the optimal PEEP in patients without ARDS high, low, or in between? JAMA. 2020;324(24):2490–2492. doi: 10.1001/jama.2020.23067.
    1. Wiesen J. State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock. Heart. 2013;99(24):1812–1817. doi: 10.1136/heartjnl-2013-303642.
    1. Villar J, Fernandez RL, Ambros A, Parra L, Blanco J, Dominguez-Berrot AM, Gutierrez JM, Blanch L, Anon JM, Martin C, et al. A clinical classification of the acute respiratory distress syndrome for predicting outcome and guiding medical therapy. Crit Care Med. 2015;43(2):346–353. doi: 10.1097/CCM.0000000000000703.
    1. Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363(12):1107–1116. doi: 10.1056/NEJMoa1005372.
    1. Guerin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159–2168. doi: 10.1056/NEJMoa1214103.
    1. National Heart, Lung, and Blood Institute Petal Clinical Trials Network. Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, et al. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med. 2019;380(21):1997–2008. doi: 10.1056/NEJMoa1901686.
    1. Balzer F, Menk M, Ziegler J, Pille C, Wernecke KD, Spies C, Schmidt M, Weber-Carstens S, Deja M. Predictors of survival in critically ill patients with acute respiratory distress syndrome (ARDS): an observational study. BMC Anesthesiol. 2016;16(1):108. doi: 10.1186/s12871-016-0272-4.
    1. Hernu R, Wallet F, Thiolliere F, Martin O, Richard JC, Schmitt Z, Wallon G, Delannoy B, Rimmele T, Demaret C, et al. An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital. Intensive Care Med. 2013;39(12):2161–2170. doi: 10.1007/s00134-013-3122-6.
    1. Caser EB, Zandonade E, Pereira E, Gama AM, Barbas CS. Impact of distinct definitions of acute lung injury on its incidence and outcomes in Brazilian ICUs: prospective evaluation of 7,133 patients. Crit Care Med. 2014;42(3):574–582. doi: 10.1097/01.ccm.0000435676.68435.56.
    1. Jardin F, Prost JF, Bazin M, Desfond P, Ozier Y, Margairaz A. Outcome of the adult acute respiratory distress syndrome Predictive value of a severity index calculated from arterial oxygenation. Nouv Presse Med. 1982;11(1):29–33.
    1. Thille AW, Esteban A, Fernandez-Segoviano P, Rodriguez JM, Aramburu JA, Penuelas O, Cortes-Puch I, Cardinal-Fernandez P, Lorente JA, Frutos-Vivar F. Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med. 2013;187(7):761–767. doi: 10.1164/rccm.201211-1981OC.
    1. Villar J, Ambros A, Soler JA, Martinez D, Ferrando C, Solano R, Mosteiro F, Blanco J, Martin-Rodriguez C, Fernandez MM, et al. Age, PaO2/FIO2, and plateau pressure score: a proposal for a simple outcome score in patients with the acute respiratory distress syndrome. Crit Care Med. 2016;44(7):1361–1369. doi: 10.1097/CCM.0000000000001653.
    1. Gattinoni L, Marini JJ, Quintel M. Recruiting the acutely injured lung: how and why? Am J Respir Crit Care Med. 2020;201(2):130–132. doi: 10.1164/rccm.201910-2005ED.
    1. Chiumello D, Cressoni M, Carlesso E, Caspani ML, Marino A, Gallazzi E, Caironi P, Lazzerini M, Moerer O, Quintel M, et al. Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome. Crit Care Med. 2014;42(2):252–264. doi: 10.1097/CCM.0b013e3182a6384f.

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