Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort.
COVID-19
Mortality
Ventilator-associated pneumonia
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
25 05 2021
25 05 2021
Historique:
received:
22
02
2021
accepted:
27
04
2021
entrez:
26
5
2021
pubmed:
27
5
2021
medline:
2
6
2021
Statut:
epublish
Résumé
Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. The study was registered at ClinicalTrials.gov, number NCT04359693.
Sections du résumé
BACKGROUND
Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients.
METHODS
Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox's regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event.
FINDINGS
Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 (adjusted HR 1.70 (95% CI 1.16-2.47), p = 0.006), and influenza groups (1.75 (1.03-3.02), p = 0.045), but not in the no viral infection group (1.07 (0.64-1.78), p = 0.79). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups.
INTERPRETATION
VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality.
CLINICAL TRIAL REGISTRATION
The study was registered at ClinicalTrials.gov, number NCT04359693.
Identifiants
pubmed: 34034777
doi: 10.1186/s13054-021-03588-4
pii: 10.1186/s13054-021-03588-4
pmc: PMC8146175
doi:
Banques de données
ClinicalTrials.gov
['NCT04359693']
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
177Investigateurs
Raphaël Favory
(R)
Sébastien Préau
(S)
Mercé Jourdain
(M)
Julien Poissy
(J)
Piehr Saint Leger
(PS)
Thierry Van der Linden
(T)
Anne Veinstein
(A)
Elie Azoulay
(E)
Frédéric Pene
(F)
Maelle Martin
(M)
Keyvan Razazi
(K)
Gaëtan Plantefeve
(G)
Muriel Fartoukh
(M)
Didier Thevenin
(D)
Bertrand Guidet
(B)
Nicolas Weiss
(N)
Achille Kouatchet
(A)
Charlotte Salmon
(C)
Guillaume Brunin
(G)
Safaa Nemlaghi
(S)
David Meguerditchian
(D)
Laurent Argaud
(L)
Sebastian Voicu
(S)
Charles-Edouard Luyt
(CE)
Benjamin Kowalski
(B)
Edgar Moglia
(E)
Luis Morales
(L)
Antonia Koutsoukou
(A)
Spyros D Mentzelopoulos
(SD)
David Nora
(D)
Sean Boyd
(S)
Julien Maizel
(J)
Pierre Cuchet
(P)
Quentin Delforge
(Q)
Jean-Pierre Quenot
(JP)
Déborah Boyer
(D)
Catia Cilloniz
(C)
Commentaires et corrections
Type : ErratumIn
Références
COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2021;47:60–73.
doi: 10.1007/s00134-020-06294-x
Rouzé A, Martin-Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M, Lambiotte F, Metzelard M, Cuchet P, Boulle Geronimi C, Labruyere M, Tamion F, Nyunga M, Luyt C-E, Labreuche J, Pouly O, Bardin J, Saade A, Asfar P, Baudel J-L, Beurton A, Garot D, Ioannidou I, Kreitmann L, Llitjos J-F, Magira E, Mégarbane B, Meguerditchian D, Moglia E, Mekontso-Dessap A, et al. Relationship between SARS-CoV-2 infection and the incidence of ventilator-associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med. 2021;47:188–98.
Maes M, Higginson E, Pereira-Dias J, Curran MD, Parmar S, Khokhar F, Cuchet-Lourenço D, Lux J, Sharma-Hajela S, Ravenhill B, Hamed I, Heales L, Mahroof R, Solderholm A, Forrest S, Sridhar S, Brown NM, Baker S, Navapurkar V, Dougan G, Bartholdson Scott J, Conway Morris A. Ventilator-associated pneumonia in critically ill patients with COVID-19. Crit Care. 2021;25:25.
doi: 10.1186/s13054-021-03460-5
Pickens CO, Gao CA, Cuttica M, Smith SB, Pesce L, Grant R, Kang M, Morales-Nebreda L, Bavishi AA, Arnold J, Pawlowski A, Qi C, Budinger GS, Singer BD, Wunderink RG, Investigators for the NC. Bacterial superinfection pneumonia in SARS-CoV-2 respiratory failure. medRxiv 2021:2021.01.12.20248588.
Razazi K, Arrestier R, Haudebourg AF, Benelli B, Carteaux G, Decousser J, Fourati S, Woerther PL, Schlemmer F, Charles-Nelson A, Botterel F, de Prost N, Mekontso Dessap A. Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease. Crit Care. 2020;24:699.
doi: 10.1186/s13054-020-03417-0
Luyt C-E, Sahnoun T, Gautier M, Vidal P, Burrel S, Pineton de Chambrun M, Chommeloux J, Desnos C, Arzoine J, Nieszkowska A, Bréchot N, Schmidt M, Hekimian G, Boutolleau D, Robert J, Combes A, Chastre J. Ventilator-associated pneumonia in patients with SARS-CoV-2-associated acute respiratory distress syndrome requiring ECMO: a retrospective cohort study. Ann Intensive Care. 2020;10:158.
doi: 10.1186/s13613-020-00775-4
Llitjos J-F, Bredin S, Lascarrou J-B, Soumagne T, Cojocaru M, Leclerc M, Lepetit A, Gouhier A, Charpentier J, Piton G, Faron M, Stoclin A, Pène F. Increased susceptibility to intensive care unit-acquired pneumonia in severe COVID-19 patients: a multicentre retrospective cohort study. Ann Intensive Care. 2021;11:20.
doi: 10.1186/s13613-021-00812-w
Melsen WG, Rovers MM, Groenwold RHH, Bergmans DCJJ, Camus C, Bauer TT, Hanisch EW, Klarin B, Koeman M, Krueger WA, Lacherade JC, Lorente L, Memish ZA, Morrow LE, Nardi G, van Nieuwenhoven CA, O’Keefe GE, Nakos G, Scannapieco FA, Seguin P, Staudinger T, Topeli A, Ferrer M, Bonten MJM. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis. 2013;13:665–71.
doi: 10.1016/S1473-3099(13)70081-1
Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005;33:2184–93.
doi: 10.1097/01.CCM.0000181731.53912.D9
Nseir S, Di Pompeo C, Soubrier S, Cavestri B, Jozefowicz E, Saulnier F, Durocher A. Impact of ventilator-associated pneumonia on outcome in patients with COPD. Chest. 2005;128:1650–6.
doi: 10.1378/chest.128.3.1650
Rouzé A, Boddaert P, Martin-Loeches I, Povoa P, Rodriguez A, Ramdane N, Salluh J, Houard M, Nseir S. Impact of chronic obstructive pulmonary disease on incidence, microbiology and outcome of ventilator-associated lower respiratory tract infections. Microorganisms. 2020;8:165.
doi: 10.3390/microorganisms8020165
Robba C, Rebora P, Banzato E, Wiegers EJA, Stocchetti N, Menon DK, Citerio G. Collaborative European NeuroTrauma effectiveness research in traumatic brain injury participants and investigators: incidence, risk factors, and effects on outcome of ventilator-associated pneumonia in patients with traumatic brain injury: analysis of a large, multicenter, prospective, observational longitudinal study. Chest. 2020;158:2292–303.
doi: 10.1016/j.chest.2020.06.064
Papazian L, Klompas M, Luyt C-E. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020;46:888–906.
doi: 10.1007/s00134-020-05980-0
Martin-Loeches I, Povoa P, Rodríguez A, Curcio D, Suarez D, Mira J-PJ-PJ-P, Cordero MLML, Lepecq R, Girault C, Candeias C, Seguin P, Paulino C, Messika J, Castro AGAGAG, Valles J, Coelho L, Rabello L, Lisboa T, Collins D, Torres A, Salluh J, Nseir S, Fernández RO, Arroyo J, Gabriela M, Alvarez R, Reyes AT, Dellera C, Molina F, Franco DM, et al. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015;3:859–68.
doi: 10.1016/S2213-2600(15)00326-4
Guidelines for the management of adults with hospital-acquired. ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388–416.
doi: 10.1164/rccm.200405-644ST
Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54:4851–63.
doi: 10.1128/AAC.00627-10
Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data in the presence of competing risks. Circulation. 2016;133:601–9.
doi: 10.1161/CIRCULATIONAHA.115.017719
Therneau T-M, Grambsch P-M. Modeling survival data: extending the Cox model. New-York: Springer; 2000.
doi: 10.1007/978-1-4757-3294-8
Willke RJ, Zheng Z, Subedi P, Althin R, Mullins CD. From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer. BMC Med Res Methodol. 2012;12:185.
doi: 10.1186/1471-2288-12-185
van Burren S, Groothuis-Oudshoorn K. Multivariate imputation by chained equations in R. 2011. J Stat Softw 2011;45:1–24.
Gladitz J, Rubin DB. Multiple imputation for nonresponse in surveys. Biom J. 1989;31:131–2.
doi: 10.1002/bimj.4710310118
Makris D, Desrousseaux B, Zakynthinos E, Durocher A, Nseir S. The impact of COPD on ICU mortality in patients with ventilator-associated pneumonia. Respir Med. 2011;105:1022–9.
doi: 10.1016/j.rmed.2011.03.001
Bercault N, Boulain T. Mortality rate attributable to ventilator-associated nosocomial pneumonia in an adult intensive care unit: a prospective case-control study. Crit Care Med. 2001;29:2303–9.
doi: 10.1097/00003246-200112000-00012
Martin-Loeches I, Povoa P, Rodríguez A, Curcio D, Suarez D, Mira J-P, Cordero ML, Lepecq R, Girault C, Candeias C, Seguin P, Paulino C, Messika J, Castro AG, Valles J, Coelho L, Rabello L, Lisboa T, Collins D, Torres A, Salluh J, Nseir S. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015;3:859–68.
doi: 10.1016/S2213-2600(15)00326-4
Melsen WG, Rovers MM, Bonten MJM. Ventilator-associated pneumonia and mortality: a systematic review of observational studies. Crit Care Med. 2009;37:2709–18.
pubmed: 19885994
Bekaert M, Timsit JF, Vansteelandt S, Depuydt P, Vésin A, Garrouste-Orgeas M, Decruyenaere J, Clec’h C, Azoulay E, Benoit D. Attributable mortality of ventilator-associated pneumonia: a reappraisal using causal analysis. Am J Respir Crit Care Med. 2011;184:1133–9.
doi: 10.1164/rccm.201105-0867OC
Steen J, Vansteelandt S, De Bus L, Depuydt P, Gadeyne B, Benoit DD, Decruyenaere J. Attributable mortality of ventilator-associated pneumonia: replicating findings, revisiting methods. Ann Am Thorac Soc. 2021;18(5):830–7.
Barbier F, Lisboa T, Nseir S. Understanding why resistant bacteria are associated with higher mortality in ICU patients. Intensive Care Med. 2016;42(12):2066–9.
Martin-Loeches I, Torres A, Povoa P, Zampieri FG, Salluh J, Nseir S, Ferrer M, Rodriguez A. TAVeM study Group: the association of cardiovascular failure with treatment for ventilator-associated lower respiratory tract infection. Intensive Care Med. 2019;45:1753–62.
doi: 10.1007/s00134-019-05797-6
Nair GB, Niederman MS. Ventilator-associated pneumonia: present understanding and ongoing debates. Intensive Care Med. 2014;41:34–48.
doi: 10.1007/s00134-014-3564-5
Papazian L, Forel J-M, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal J-M, Perez D, Seghboyan J-M, Constantin J-M, Courant P, Lefrant J-Y, Guérin C, Prat G, Morange S, Roch A. ACURASYS Study Investigators: neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010;363:1107–16.
doi: 10.1056/NEJMoa1005372
Shintani AK, Girard TD, Eden SK, Arbogast PG, Moons KGM, Ely EW. Immortal time bias in critical care research: application of time-varying Cox regression for observational cohort studies. Crit Care Med. 2009;37:2939–45.
doi: 10.1097/CCM.0b013e3181b7fbbb