Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS

Luis Morales-Quinteros; Ary Serpa Neto; Antonio Artigas; Lluis Blanch; Michela Botta; David A Kaufman; Marcus J Schultz; Anissa M Tsonas; Frederique Paulus; Lieuwe D Bos; PRoVENT-COVID Study Group; Dennis Bergmans

doi:10.1186/s13054-021-03570-0

Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS

Luis Morales-Quinteros^*, Ary Serpa Neto, Antonio Artigas, Lluis Blanch, Michela Botta, David A Kaufman, Marcus J Schultz, Anissa M Tsonas, Frederique Paulus, Lieuwe D Bos, PRoVENT-COVID Study Group, Dennis Bergmans

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Web of Science)

Abstract

BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS.

METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS.

RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality.

CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model.

TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.

Original language	English
Article number	171
Number of pages	13
Journal	Critical Care
Volume	25
Issue number	1
DOIs	https://doi.org/10.1186/s13054-021-03570-0
Publication status	Published - 17 May 2021

Keywords

Adult
Biomarkers
COVID-19/complications
Female
Humans
Intensive Care Units
Male
Patient Acuity
Prognosis
ROC Curve
Respiration, Artificial
Respiratory Dead Space
Respiratory Distress Syndrome/etiology
Respiratory Function Tests
Respiratory Mechanics
Retrospective Studies
Acute respiratory distress syndrome
Ventilatory ratio
ACUTE LUNG INJURY
Dead space
PROGNOSTIC VALUE
COVID-19
VOLUMETRIC CAPNOGRAPHY
FRACTION
Prognostication
ARDS
Mortality
VENTILATORY RATIO
Respiratory dead space

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Cite this

@article{4e43d3c4942b421297c935f5854b0d54,

title = "Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS",

abstract = "BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS.METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS.RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality.CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model.TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.",

keywords = "Adult, Biomarkers, COVID-19/complications, Female, Humans, Intensive Care Units, Male, Patient Acuity, Prognosis, ROC Curve, Respiration, Artificial, Respiratory Dead Space, Respiratory Distress Syndrome/etiology, Respiratory Function Tests, Respiratory Mechanics, Retrospective Studies, Acute respiratory distress syndrome, Ventilatory ratio, ACUTE LUNG INJURY, Dead space, PROGNOSTIC VALUE, COVID-19, VOLUMETRIC CAPNOGRAPHY, FRACTION, Prognostication, ARDS, Mortality, VENTILATORY RATIO, Respiratory dead space",

author = "Luis Morales-Quinteros and Neto, {Ary Serpa} and Antonio Artigas and Lluis Blanch and Michela Botta and Kaufman, {David A} and Schultz, {Marcus J} and Tsonas, {Anissa M} and Frederique Paulus and Bos, {Lieuwe D} and {PRoVENT-COVID Study Group} and Dennis Bergmans",

note = "Funding Information: Author{\textquoteright}s information : A complete list of members of the PRoVENT-COVID collaborative group is provided: STEERING COMMITTEE : (in alphabetic order) A.G. Algera, L.S. Boers; L.D.J. Bos; M. Botta; J. Pillay, D.A. Dongelmans, M.W. Hollmann; J. Horn; F. Paulus; A. Serpa Neto; M.J. Schultz; A.M. Tsonas, A.P. Vlaar. STUDY COORDINATORS : (in alphabetic order) M. Botta; A.M. Tsonas. Investigators : (in alphabetic order): J.P. van Akkeren; A.G. Algera; C.K. Algoe; R.B. van Amstel; Artigas A; O.L. Baur; P. van de Berg; A.E. van den Berg; D.C.J.J. Bergmans; D.I. van den Bersselaar; F.A. Bertens; A.J.G.H. Bindels; M.M. de Boer; S. den Boer; L.S. Boers; M. Bogerd; L.D.J. Bos; M. Botta; J.S. Breel; H. de Bruin; S. de Bruin; C.L. Bruna; L.A. Buiteman–Kruizinga; O. Cremer; R.M. Determann; W. Dieperink; D.A. Dongelmans; H.S. Franke; M.S. Galek–Aldridge; M.J. de Graaff; L.A. Hagens; J.J. Haringman; S.T. van der Heide; P.L.J. van der Heiden; N.F.L. Heijnen; S.J.P. Hiel; L.L. Hoeijmakers; L. Hol; M. W. Hollmann; M.E. Hoogendoorn; J. Horn; R. van der Horst; E.L.K. Ie; D. Ivanov; N.P. Juffermans; E. Kho; E.S. de Klerk; A.W.M.M Koopman-van Gemert; M. Koopmans; S. Kucukcelebi; M.A. Kuiper; D.W. de Lange; N. van Mourik; Morales-Quinteros L; S.G. Nijbroek; M. Onrust; E.A.N. Oostdijk; F. Paulus; C.J. Pennartz; J. Pillay; L. Pisani; I.M. Purmer; T.C.D. Rettig; J.P Roozeman; M.T.U. Schuijt; M.J. Schultz; A. Serpa Neto; M.E. Sleeswijk; M.R. Smit; P.E. Spronk; W. Stilma; A.C. Strang; A. M. Tsonas; P.R Tuinman; C.M.A. Valk; F.L. Veen-Schra; L.I. Veldhuis; P. van Velzen; W.H. van der Ven; A.P.J. Vlaar; P. van Vliet; P.H.J. van der Voort; L. van Welie; H.J.F.T. Wesselink; H.H. van der Wier-Lubbers; B. van Wijk; T. Winters; W.Y. Wong; A.R.H. van Zanten. Funding Information: Dr Bos receives funding from the Dutch lung foundation (longfonds), from the Innovative Medicine Initiative and from Amsterdam UMC via the AUMC fellowship. The remaining authors have disclosed that they do not have any potential conflicts of interest. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = may,

day = "17",

doi = "10.1186/s13054-021-03570-0",

language = "English",

volume = "25",

journal = "Critical Care",

issn = "1364-8535",

publisher = "BioMed Central Ltd",

number = "1",

}

TY - JOUR

T1 - Dead space estimates may not be independently associated with 28-day mortality in COVID-19 ARDS

AU - Morales-Quinteros, Luis

AU - Neto, Ary Serpa

AU - Artigas, Antonio

AU - Blanch, Lluis

AU - Botta, Michela

AU - Kaufman, David A

AU - Schultz, Marcus J

AU - Tsonas, Anissa M

AU - Paulus, Frederique

AU - Bos, Lieuwe D

AU - PRoVENT-COVID Study Group

AU - Bergmans, Dennis

N1 - Funding Information: Author’s information : A complete list of members of the PRoVENT-COVID collaborative group is provided: STEERING COMMITTEE : (in alphabetic order) A.G. Algera, L.S. Boers; L.D.J. Bos; M. Botta; J. Pillay, D.A. Dongelmans, M.W. Hollmann; J. Horn; F. Paulus; A. Serpa Neto; M.J. Schultz; A.M. Tsonas, A.P. Vlaar. STUDY COORDINATORS : (in alphabetic order) M. Botta; A.M. Tsonas. Investigators : (in alphabetic order): J.P. van Akkeren; A.G. Algera; C.K. Algoe; R.B. van Amstel; Artigas A; O.L. Baur; P. van de Berg; A.E. van den Berg; D.C.J.J. Bergmans; D.I. van den Bersselaar; F.A. Bertens; A.J.G.H. Bindels; M.M. de Boer; S. den Boer; L.S. Boers; M. Bogerd; L.D.J. Bos; M. Botta; J.S. Breel; H. de Bruin; S. de Bruin; C.L. Bruna; L.A. Buiteman–Kruizinga; O. Cremer; R.M. Determann; W. Dieperink; D.A. Dongelmans; H.S. Franke; M.S. Galek–Aldridge; M.J. de Graaff; L.A. Hagens; J.J. Haringman; S.T. van der Heide; P.L.J. van der Heiden; N.F.L. Heijnen; S.J.P. Hiel; L.L. Hoeijmakers; L. Hol; M. W. Hollmann; M.E. Hoogendoorn; J. Horn; R. van der Horst; E.L.K. Ie; D. Ivanov; N.P. Juffermans; E. Kho; E.S. de Klerk; A.W.M.M Koopman-van Gemert; M. Koopmans; S. Kucukcelebi; M.A. Kuiper; D.W. de Lange; N. van Mourik; Morales-Quinteros L; S.G. Nijbroek; M. Onrust; E.A.N. Oostdijk; F. Paulus; C.J. Pennartz; J. Pillay; L. Pisani; I.M. Purmer; T.C.D. Rettig; J.P Roozeman; M.T.U. Schuijt; M.J. Schultz; A. Serpa Neto; M.E. Sleeswijk; M.R. Smit; P.E. Spronk; W. Stilma; A.C. Strang; A. M. Tsonas; P.R Tuinman; C.M.A. Valk; F.L. Veen-Schra; L.I. Veldhuis; P. van Velzen; W.H. van der Ven; A.P.J. Vlaar; P. van Vliet; P.H.J. van der Voort; L. van Welie; H.J.F.T. Wesselink; H.H. van der Wier-Lubbers; B. van Wijk; T. Winters; W.Y. Wong; A.R.H. van Zanten. Funding Information: Dr Bos receives funding from the Dutch lung foundation (longfonds), from the Innovative Medicine Initiative and from Amsterdam UMC via the AUMC fellowship. The remaining authors have disclosed that they do not have any potential conflicts of interest. Publisher Copyright: © 2021, The Author(s).

PY - 2021/5/17

Y1 - 2021/5/17

N2 - BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS.METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS.RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality.CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model.TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.

AB - BACKGROUND: Estimates for dead space ventilation have been shown to be independently associated with an increased risk of mortality in the acute respiratory distress syndrome and small case series of COVID-19-related ARDS.METHODS: Secondary analysis from the PRoVENT-COVID study. The PRoVENT-COVID is a national, multicenter, retrospective observational study done at 22 intensive care units in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The aim was to quantify the dynamics and determine the prognostic value of surrogate markers of wasted ventilation in patients with COVID-19-related ARDS.RESULTS: A total of 927 consecutive patients admitted with COVID-19-related ARDS were included in this study. Estimations of wasted ventilation such as the estimated dead space fraction (by Harris-Benedict and direct method) and ventilatory ratio were significantly higher in non-survivors than survivors at baseline and during the following days of mechanical ventilation (p < 0.001). The end-tidal-to-arterial PCO2 ratio was lower in non-survivors than in survivors (p < 0.001). As ARDS severity increased, mortality increased with successive tertiles of dead space fraction by Harris-Benedict and by direct estimation, and with an increase in the VR. The same trend was observed with decreased levels in the tertiles for the end-tidal-to-arterial PCO2 ratio. After adjustment for a base risk model that included chronic comorbidities and ventilation- and oxygenation-parameters, none of the dead space estimates measured at the start of ventilation or the following days were significantly associated with 28-day mortality.CONCLUSIONS: There is significant impairment of ventilation in the early course of COVID-19-related ARDS but quantification of this impairment does not add prognostic information when added to a baseline risk model.TRIAL REGISTRATION: ISRCTN04346342. Registered 15 April 2020. Retrospectively registered.

KW - Adult

KW - Biomarkers

KW - COVID-19/complications

KW - Female

KW - Humans

KW - Intensive Care Units

KW - Male

KW - Patient Acuity

KW - Prognosis

KW - ROC Curve

KW - Respiration, Artificial

KW - Respiratory Dead Space

KW - Respiratory Distress Syndrome/etiology

KW - Respiratory Function Tests

KW - Respiratory Mechanics

KW - Retrospective Studies

KW - Acute respiratory distress syndrome

KW - Ventilatory ratio

KW - ACUTE LUNG INJURY

KW - Dead space

KW - PROGNOSTIC VALUE

KW - COVID-19

KW - VOLUMETRIC CAPNOGRAPHY

KW - FRACTION

KW - Prognostication

KW - ARDS

KW - Mortality

KW - VENTILATORY RATIO

KW - Respiratory dead space

U2 - 10.1186/s13054-021-03570-0

DO - 10.1186/s13054-021-03570-0

M3 - Article

C2 - 34001222

SN - 1364-8535

VL - 25

JO - Critical Care

JF - Critical Care

IS - 1

M1 - 171

ER -