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Published in: Critical Care 1/2019

Open Access 01-12-2019 | Hypoxemia | Research

Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure

Authors: Guillaume Dumas, Alexandre Demoule, Djamel Mokart, Virginie Lemiale, Saad Nseir, Laurent Argaud, Frédéric Pène, Loay Kontar, Fabrice Bruneel, Kada Klouche, François Barbier, Jean Reignier, Annabelle Stoclin, Guillaume Louis, Jean-Michel Constantin, Florent Wallet, Achille Kouatchet, Vincent Peigne, Pierre Perez, Christophe Girault, Samir Jaber, Yves Cohen, Martine Nyunga, Nicolas Terzi, Lila Bouadma, Christine Lebert, Alexandre Lautrette, Naike Bigé, Jean-Herlé Raphalen, Laurent Papazian, Dominique Benoit, Michael Darmon, Sylvie Chevret, Elie Azoulay

Published in: Critical Care | Issue 1/2019

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Abstract

Background

Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs.

Methods

Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers.

Results

The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30–1.72]; RCT: p value 0.004, median OR 1.51 [1.36–1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation.

Conclusion

Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.
Appendix
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Literature
1.
go back to reference Lemiale V, Mokart D, Resche-Rigon M, Pène F, Mayaux J, Faucher E, et al. Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial. JAMA. 2015;314:1711–9.CrossRef Lemiale V, Mokart D, Resche-Rigon M, Pène F, Mayaux J, Faucher E, et al. Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial. JAMA. 2015;314:1711–9.CrossRef
2.
go back to reference Asfar P, Meziani F, Hamel J-F, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583–93.CrossRef Asfar P, Meziani F, Hamel J-F, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583–93.CrossRef
3.
go back to reference Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, et al. Effect of high-flow nasal oxygen vs standard oxygen on 28-day mortality in immunocompromised patients with acute respiratory failure: the HIGH randomized clinical trial. JAMA. 2018;320:2099–107.CrossRef Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, et al. Effect of high-flow nasal oxygen vs standard oxygen on 28-day mortality in immunocompromised patients with acute respiratory failure: the HIGH randomized clinical trial. JAMA. 2018;320:2099–107.CrossRef
4.
go back to reference Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375:122–33.CrossRef Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375:122–33.CrossRef
6.
go back to reference Austin PC, Merlo J. Intermediate and advanced topics in multilevel logistic regression analysis. Stat Med. 2017;36:3257–77.CrossRef Austin PC, Merlo J. Intermediate and advanced topics in multilevel logistic regression analysis. Stat Med. 2017;36:3257–77.CrossRef
7.
go back to reference Merlo J, Chaix B, Ohlsson H, Beckman A, Johnell K, Hjerpe P, et al. A brief conceptual tutorial of multilevel analysis in social epidemiology: using measures of clustering in multilevel logistic regression to investigate contextual phenomena. J Epidemiol Community Health. 2006;60:290–7.CrossRef Merlo J, Chaix B, Ohlsson H, Beckman A, Johnell K, Hjerpe P, et al. A brief conceptual tutorial of multilevel analysis in social epidemiology: using measures of clustering in multilevel logistic regression to investigate contextual phenomena. J Epidemiol Community Health. 2006;60:290–7.CrossRef
8.
go back to reference Antonelli M, Conti G, Bufi M, Costa MG, Lappa A, Rocco M, et al. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA. 2000;283:235–41.CrossRef Antonelli M, Conti G, Bufi M, Costa MG, Lappa A, Rocco M, et al. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA. 2000;283:235–41.CrossRef
9.
go back to reference Hilbert G. Optimizing noninvasive ventilation in hematological patients with acute respiratory failure. In: Azoulay E, editor. Pulm Involv PATIENTS Hematol Malig; 2011. p. 607–16. Hilbert G. Optimizing noninvasive ventilation in hematological patients with acute respiratory failure. In: Azoulay E, editor. Pulm Involv PATIENTS Hematol Malig; 2011. p. 607–16.
10.
go back to reference Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-Benissan G, Dupon M, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481–7.CrossRef Hilbert G, Gruson D, Vargas F, Valentino R, Gbikpi-Benissan G, Dupon M, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481–7.CrossRef
11.
go back to reference Frat J-P, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185–96.CrossRef Frat J-P, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372:2185–96.CrossRef
12.
go back to reference Amado-Rodríguez L, Bernal T, López-Alonso I, Blázquez-Prieto J, García-Prieto E, Albaiceta GM. Impact of initial ventilatory strategy in hematological patients with acute respiratory failure: a systematic review and meta-analysis. Crit Care Med. 2016;44:1406–13.CrossRef Amado-Rodríguez L, Bernal T, López-Alonso I, Blázquez-Prieto J, García-Prieto E, Albaiceta GM. Impact of initial ventilatory strategy in hematological patients with acute respiratory failure: a systematic review and meta-analysis. Crit Care Med. 2016;44:1406–13.CrossRef
13.
go back to reference Squadrone V, Massaia M, Bruno B, Marmont F, Falda M, Bagna C, et al. Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy. Intensive Care Med. 2010;36:1666–74.CrossRef Squadrone V, Massaia M, Bruno B, Marmont F, Falda M, Bagna C, et al. Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy. Intensive Care Med. 2010;36:1666–74.CrossRef
14.
go back to reference Zhan Q, Sun B, Liang L, Yan X, Zhang L, Yang J, et al. Early use of noninvasive positive pressure ventilation for acute lung injury: a multicenter randomized controlled trial. Crit Care Med. 2012;40:455–60.CrossRef Zhan Q, Sun B, Liang L, Yan X, Zhang L, Yang J, et al. Early use of noninvasive positive pressure ventilation for acute lung injury: a multicenter randomized controlled trial. Crit Care Med. 2012;40:455–60.CrossRef
15.
go back to reference Biard L, Darmon M, Lemiale V, Mokart D, Chevret S, Azoulay E, et al. Center effects in hospital mortality of critically ill patients with hematologic malignancies. Crit Care Med. 2019;47(6):809–16.CrossRef Biard L, Darmon M, Lemiale V, Mokart D, Chevret S, Azoulay E, et al. Center effects in hospital mortality of critically ill patients with hematologic malignancies. Crit Care Med. 2019;47(6):809–16.CrossRef
16.
go back to reference Azoulay E, Mokart D, Pène F, Lambert J, Kouatchet A, Mayaux J, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium--a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:2810–8.CrossRef Azoulay E, Mokart D, Pène F, Lambert J, Kouatchet A, Mayaux J, et al. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium--a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:2810–8.CrossRef
17.
go back to reference Darmon M, Azoulay E. Critical care management of cancer patients: cause for optimism and need for objectivity. Curr Opin Oncol. 2009;21:318–26.CrossRef Darmon M, Azoulay E. Critical care management of cancer patients: cause for optimism and need for objectivity. Curr Opin Oncol. 2009;21:318–26.CrossRef
18.
go back to reference Larsen K, Merlo J. Appropriate assessment of neighborhood effects on individual health: integrating random and fixed effects in multilevel logistic regression. Am J Epidemiol. 2005;161:81–8.CrossRef Larsen K, Merlo J. Appropriate assessment of neighborhood effects on individual health: integrating random and fixed effects in multilevel logistic regression. Am J Epidemiol. 2005;161:81–8.CrossRef
19.
go back to reference Boumendil A, Angus DC, Guitonneau A-L, Menn A-M, Ginsburg C, Takun K, et al. Variability of intensive care admission decisions for the very elderly. PLoS One. 2012;7:e34387.CrossRef Boumendil A, Angus DC, Guitonneau A-L, Menn A-M, Ginsburg C, Takun K, et al. Variability of intensive care admission decisions for the very elderly. PLoS One. 2012;7:e34387.CrossRef
20.
go back to reference Biard L, Porcher R, Resche-Rigon M. Permutation tests for centre effect on survival endpoints with application in an acute myeloid leukaemia multicentre study. Stat Med. 2014;33:3047–57.CrossRef Biard L, Porcher R, Resche-Rigon M. Permutation tests for centre effect on survival endpoints with application in an acute myeloid leukaemia multicentre study. Stat Med. 2014;33:3047–57.CrossRef
21.
go back to reference Biard L, Labopin M, Chevret S, Resche-Rigon M, Acute Leukaemia Working Party of the EBMT. Investigating covariate-by-centre interaction in survival data Stat Methods Med Res 2018;27:920–932.CrossRef Biard L, Labopin M, Chevret S, Resche-Rigon M, Acute Leukaemia Working Party of the EBMT. Investigating covariate-by-centre interaction in survival data Stat Methods Med Res 2018;27:920–932.CrossRef
22.
go back to reference Fitzmaurice GM, Lipsitz SR, Ibrahim JG. A note on permutation tests for variance components in multilevel generalized linear mixed models. Biometrics. 2007;63:942–6.CrossRef Fitzmaurice GM, Lipsitz SR, Ibrahim JG. A note on permutation tests for variance components in multilevel generalized linear mixed models. Biometrics. 2007;63:942–6.CrossRef
23.
go back to reference Drikvandi R, Verbeke G, Khodadadi A, Partovi NV. Testing multiple variance components in linear mixed-effects models. Biostat Oxf Engl. 2013;14:144–59.CrossRef Drikvandi R, Verbeke G, Khodadadi A, Partovi NV. Testing multiple variance components in linear mixed-effects models. Biostat Oxf Engl. 2013;14:144–59.CrossRef
24.
go back to reference White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30:377–99.CrossRef White IR, Royston P, Wood AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med. 2011;30:377–99.CrossRef
26.
go back to reference Azoulay E, Pickkers P, Soares M, Perner A, Rello J, Bauer PR, et al. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med. 2017;43:1808–19.CrossRef Azoulay E, Pickkers P, Soares M, Perner A, Rello J, Bauer PR, et al. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med. 2017;43:1808–19.CrossRef
27.
go back to reference Azoulay E, Thiéry G, Chevret S, Moreau D, Darmon M, Bergeron A, et al. The prognosis of acute respiratory failure in critically ill cancer patients. Medicine (Baltimore). 2004;83:360–70.CrossRef Azoulay E, Thiéry G, Chevret S, Moreau D, Darmon M, Bergeron A, et al. The prognosis of acute respiratory failure in critically ill cancer patients. Medicine (Baltimore). 2004;83:360–70.CrossRef
28.
go back to reference Allareddy V, Roy A, Rampa S, Lee MK, Nalliah RP, Allareddy V, et al. Outcomes of stem cell transplant patients with acute respiratory failure requiring mechanical ventilation in the United States. Bone Marrow Transplant. 2014;49:1278–86.CrossRef Allareddy V, Roy A, Rampa S, Lee MK, Nalliah RP, Allareddy V, et al. Outcomes of stem cell transplant patients with acute respiratory failure requiring mechanical ventilation in the United States. Bone Marrow Transplant. 2014;49:1278–86.CrossRef
29.
go back to reference Demoule A, Hill N, Navalesi P. Can we prevent intubation in patients with ARDS? Intensive Care Med. 2016;42:768–71.CrossRef Demoule A, Hill N, Navalesi P. Can we prevent intubation in patients with ARDS? Intensive Care Med. 2016;42:768–71.CrossRef
30.
go back to reference Bellani G, Laffey JG, Pham T, Madotto F, Fan E, Brochard L, et al. Noninvasive ventilation of patients with acute respiratory distress syndrome. Insights from the LUNG SAFE study. Am J Respir Crit Care Med. 2017;195:67–77.CrossRef Bellani G, Laffey JG, Pham T, Madotto F, Fan E, Brochard L, et al. Noninvasive ventilation of patients with acute respiratory distress syndrome. Insights from the LUNG SAFE study. Am J Respir Crit Care Med. 2017;195:67–77.CrossRef
32.
go back to reference Harhay MO, Wagner J, Ratcliffe SJ, Bronheim RS, Gopal A, Green S, et al. Outcomes and statistical power in adult critical care randomized trials. Am J Respir Crit Care Med. 2014;189:1469–78.CrossRef Harhay MO, Wagner J, Ratcliffe SJ, Bronheim RS, Gopal A, Green S, et al. Outcomes and statistical power in adult critical care randomized trials. Am J Respir Crit Care Med. 2014;189:1469–78.CrossRef
33.
go back to reference Bauer PR, Kumbamu A, Wilson ME, Pannu JK, Egginton JS, Kashyap R, et al. Timing of intubation in acute respiratory failure associated with sepsis: a mixed methods study. Mayo Clin Proc. 2017;92:1502–10.CrossRef Bauer PR, Kumbamu A, Wilson ME, Pannu JK, Egginton JS, Kashyap R, et al. Timing of intubation in acute respiratory failure associated with sepsis: a mixed methods study. Mayo Clin Proc. 2017;92:1502–10.CrossRef
34.
go back to reference de Montmollin E, Aboab J, Ferrer R, Azoulay E, Annane D. Criteria for initiation of invasive ventilation in septic shock: an international survey. J Crit Care. 2016;31:54–7.CrossRef de Montmollin E, Aboab J, Ferrer R, Azoulay E, Annane D. Criteria for initiation of invasive ventilation in septic shock: an international survey. J Crit Care. 2016;31:54–7.CrossRef
35.
go back to reference Kahan BC. Accounting for centre-effects in multicentre trials with a binary outcome - when, why, and how? BMC Med Res Methodol. 2014;14:20.CrossRef Kahan BC. Accounting for centre-effects in multicentre trials with a binary outcome - when, why, and how? BMC Med Res Methodol. 2014;14:20.CrossRef
36.
go back to reference Kahan BC, Harhay MO. Many multicentre trials had few events per centre, requiring analysis via random-effects models or GEEs. J Clin Epidemiol. 2015;68:1504–11.CrossRef Kahan BC, Harhay MO. Many multicentre trials had few events per centre, requiring analysis via random-effects models or GEEs. J Clin Epidemiol. 2015;68:1504–11.CrossRef
Metadata
Title
Center effect in intubation risk in critically ill immunocompromised patients with acute hypoxemic respiratory failure
Authors
Guillaume Dumas
Alexandre Demoule
Djamel Mokart
Virginie Lemiale
Saad Nseir
Laurent Argaud
Frédéric Pène
Loay Kontar
Fabrice Bruneel
Kada Klouche
François Barbier
Jean Reignier
Annabelle Stoclin
Guillaume Louis
Jean-Michel Constantin
Florent Wallet
Achille Kouatchet
Vincent Peigne
Pierre Perez
Christophe Girault
Samir Jaber
Yves Cohen
Martine Nyunga
Nicolas Terzi
Lila Bouadma
Christine Lebert
Alexandre Lautrette
Naike Bigé
Jean-Herlé Raphalen
Laurent Papazian
Dominique Benoit
Michael Darmon
Sylvie Chevret
Elie Azoulay
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Hypoxemia
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2590-7

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