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Published in: Annals of Intensive Care 1/2020

Open Access 01-12-2020 | Acute Respiratory Distress-Syndrome | Research

Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study

Authors: Gustavo A. Ospina-Tascón, Diego F. Bautista, Humberto J. Madriñán, Juan D. Valencia, William F. Bermúdez, Edgardo Quiñones, Luis Eduardo Calderón-Tapia, Glenn Hernandez, Alejandro Bruhn, Daniel De Backer

Published in: Annals of Intensive Care | Issue 1/2020

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Abstract

Background

Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS.

Methods

Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production (\(V_{{{\text{CO}}_{2} }}\)) and CO2 exhaled fraction (\(F_{{{\text{ECO}}_{2} }}\)) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after.

Results

Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman’s rho = − 0.76 and − 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman’s rho = − 0.71, and − 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman’s rho = − 0.66, p < 0.001; R2 = 0.67, p < 0.001).

Conclusion

Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause–effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.
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Literature
1.
go back to reference Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.PubMed Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526–33.PubMed
2.
go back to reference Dantzker DR, Brook CJ, Dehart P, Lynch JP, Weg JG. Ventilation-perfusion distributions in the adult respiratory distress syndrome. Am Rev Respir Dis. 1979;120(5):1039–52.PubMed Dantzker DR, Brook CJ, Dehart P, Lynch JP, Weg JG. Ventilation-perfusion distributions in the adult respiratory distress syndrome. Am Rev Respir Dis. 1979;120(5):1039–52.PubMed
3.
go back to reference Ralph DD, Robertson HT, Weaver LJ, Hlastala MP, Carrico CJ, Hudson LD. Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome. Am Rev Respir Dis. 1985;131(1):54–60.PubMed Ralph DD, Robertson HT, Weaver LJ, Hlastala MP, Carrico CJ, Hudson LD. Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome. Am Rev Respir Dis. 1985;131(1):54–60.PubMed
4.
go back to reference Matamis D, Lemaire F, Harf A, Teisseire B, Brun-Buisson C. Redistribution of pulmonary blood flow induced by positive end-expiratory pressure and dopamine infusion in acute respiratory failure. Am Rev Respir Dis. 1984;129(1):39–44.PubMed Matamis D, Lemaire F, Harf A, Teisseire B, Brun-Buisson C. Redistribution of pulmonary blood flow induced by positive end-expiratory pressure and dopamine infusion in acute respiratory failure. Am Rev Respir Dis. 1984;129(1):39–44.PubMed
5.
go back to reference Radermacher P, Maggiore SM, Mercat A. Fifty years of research in ARDS. Gas exchange in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;196(8):964–84.CrossRefPubMed Radermacher P, Maggiore SM, Mercat A. Fifty years of research in ARDS. Gas exchange in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2017;196(8):964–84.CrossRefPubMed
6.
go back to reference Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988;138(3):720–3.CrossRefPubMed Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988;138(3):720–3.CrossRefPubMed
7.
go back to reference Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818–24.CrossRefPubMed Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 1994;149(3 Pt 1):818–24.CrossRefPubMed
8.
go back to reference Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, et al. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002;346(17):1281–6.CrossRefPubMed Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, et al. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002;346(17):1281–6.CrossRefPubMed
9.
go back to reference Cepkova M, Kapur V, Ren X, Quinn T, Zhuo H, Foster E, et al. Pulmonary dead space fraction and pulmonary artery systolic pressure as early predictors of clinical outcome in acute lung injury. Chest. 2007;132(3):836–42.CrossRefPubMed Cepkova M, Kapur V, Ren X, Quinn T, Zhuo H, Foster E, et al. Pulmonary dead space fraction and pulmonary artery systolic pressure as early predictors of clinical outcome in acute lung injury. Chest. 2007;132(3):836–42.CrossRefPubMed
10.
go back to reference Kallet RH, Zhuo H, Ho K, Lipnick MS, Gomez A, Matthay MA. Lung injury etiology and other factors influencing the relationship between dead-space fraction and mortality in ARDS. Respir Care. 2017;62(10):1241–8.CrossRefPubMed Kallet RH, Zhuo H, Ho K, Lipnick MS, Gomez A, Matthay MA. Lung injury etiology and other factors influencing the relationship between dead-space fraction and mortality in ARDS. Respir Care. 2017;62(10):1241–8.CrossRefPubMed
11.
go back to reference Dueck R, Wagner PD, West JB. Effects of positive end-expiratory pressure on gas exchange in dogs with normal and edematous lungs. Anesthesiology. 1977;47(4):359–66.CrossRefPubMed Dueck R, Wagner PD, West JB. Effects of positive end-expiratory pressure on gas exchange in dogs with normal and edematous lungs. Anesthesiology. 1977;47(4):359–66.CrossRefPubMed
12.
go back to reference Zuurbier CJ, van Iterson M, Ince C. Functional heterogeneity of oxygen supply-consumption ratio in the heart. Cardiovasc Res. 1999;44(3):488–97.CrossRefPubMed Zuurbier CJ, van Iterson M, Ince C. Functional heterogeneity of oxygen supply-consumption ratio in the heart. Cardiovasc Res. 1999;44(3):488–97.CrossRefPubMed
13.
go back to reference De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98–104.CrossRefPubMed De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002;166(1):98–104.CrossRefPubMed
14.
go back to reference De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med. 2010;36(11):1813–25.CrossRefPubMed De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the critically ill patient: current methods and future approaches. Intensive Care Med. 2010;36(11):1813–25.CrossRefPubMed
15.
go back to reference Ware LB, Matthay MA. Measuring microvascular blood flow in sepsis—a continuing challenge. Lancet. 2002;360(9341):1187–8.CrossRefPubMed Ware LB, Matthay MA. Measuring microvascular blood flow in sepsis—a continuing challenge. Lancet. 2002;360(9341):1187–8.CrossRefPubMed
16.
go back to reference Villar J, Pérez-Méndez L, López J, Belda J, Blanco J, Saralegui I, 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.CrossRefPubMed Villar J, Pérez-Méndez L, López J, Belda J, Blanco J, Saralegui I, 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.CrossRefPubMed
17.
go back to reference Ferguson ND, Kacmarek RM, Chiche JD, Singh JM, Hallett DC, Mehta S, et al. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med. 2004;30(6):1111–6.CrossRefPubMed Ferguson ND, Kacmarek RM, Chiche JD, Singh JM, Hallett DC, Mehta S, et al. Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial. Intensive Care Med. 2004;30(6):1111–6.CrossRefPubMed
18.
go back to reference de Matos GF, Stanzani F, Passos RH, Fontana MF, Albaladejo R, Caserta RE, et al. How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography. Crit Care. 2012;16(1):R4.CrossRefPubMedPubMedCentral de Matos GF, Stanzani F, Passos RH, Fontana MF, Albaladejo R, Caserta RE, et al. How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography. Crit Care. 2012;16(1):R4.CrossRefPubMedPubMedCentral
19.
go back to reference Borges JB, Okamoto VN, Matos GF, Caramez MP, Arantes PR, Barros F, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;174(3):268–78.CrossRefPubMed Borges JB, Okamoto VN, Matos GF, Caramez MP, Arantes PR, Barros F, et al. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006;174(3):268–78.CrossRefPubMed
20.
go back to reference Siobal MS, Ong H, Valdes J, Tang J. Calculation of physiologic dead space: comparison of ventilator volumetric capnography to measurements by metabolic analyzer and volumetric CO2 monitor. Respir Care. 2013;58(7):1143–51.CrossRefPubMed Siobal MS, Ong H, Valdes J, Tang J. Calculation of physiologic dead space: comparison of ventilator volumetric capnography to measurements by metabolic analyzer and volumetric CO2 monitor. Respir Care. 2013;58(7):1143–51.CrossRefPubMed
21.
go back to reference De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007;11(5):R101.CrossRefPubMedPubMedCentral De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, et al. How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007;11(5):R101.CrossRefPubMedPubMedCentral
22.
go back to reference Lamy M, Fallat RJ, Koeniger E, Dietrich HP, Ratliff JL, Eberhart RC, et al. Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis. 1976;114(2):267–84.PubMed Lamy M, Fallat RJ, Koeniger E, Dietrich HP, Ratliff JL, Eberhart RC, et al. Pathologic features and mechanisms of hypoxemia in adult respiratory distress syndrome. Am Rev Respir Dis. 1976;114(2):267–84.PubMed
23.
go back to reference Gattinoni L, Bombino M, Pelosi P, Lissoni A, Pesenti A, Fumagalli R, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA. 1994;271(22):1772–9.CrossRefPubMed Gattinoni L, Bombino M, Pelosi P, Lissoni A, Pesenti A, Fumagalli R, et al. Lung structure and function in different stages of severe adult respiratory distress syndrome. JAMA. 1994;271(22):1772–9.CrossRefPubMed
24.
go back to reference Hedenstierna G, White FC, Mazzone R, Wagner PD. Redistribution of pulmonary blood flow in the dog with PEEP ventilation. J Appl Physiol Respir Environ Exerc Physiol. 1979;46(2):278–87.PubMed Hedenstierna G, White FC, Mazzone R, Wagner PD. Redistribution of pulmonary blood flow in the dog with PEEP ventilation. J Appl Physiol Respir Environ Exerc Physiol. 1979;46(2):278–87.PubMed
25.
go back to reference Kallet RH, Zhuo H, Liu KD, Calfee CS, Matthay MA, Investigators NHLaBIAN. The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial. Respir Care. 2014;59(11):1611–8.CrossRefPubMed Kallet RH, Zhuo H, Liu KD, Calfee CS, Matthay MA, Investigators NHLaBIAN. The association between physiologic dead-space fraction and mortality in subjects with ARDS enrolled in a prospective multi-center clinical trial. Respir Care. 2014;59(11):1611–8.CrossRefPubMed
26.
go back to reference Cressoni M, Cadringher P, Chiurazzi C, Amini M, Gallazzi E, Marino A, et al. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014;189(2):149–58.PubMed Cressoni M, Cadringher P, Chiurazzi C, Amini M, Gallazzi E, Marino A, et al. Lung inhomogeneity in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2014;189(2):149–58.PubMed
27.
go back to reference van Genderen ME, Klijn E, Lima A, de Jonge J, Sleeswijk Visser S, Voorbeijtel J, et al. Microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock. Crit Care Med. 2014;42(2):e96–105.CrossRefPubMed van Genderen ME, Klijn E, Lima A, de Jonge J, Sleeswijk Visser S, Voorbeijtel J, et al. Microvascular perfusion as a target for fluid resuscitation in experimental circulatory shock. Crit Care Med. 2014;42(2):e96–105.CrossRefPubMed
28.
go back to reference Greene R, Zapol WM, Snider MT, Reid L, Snow R, O’Connell RS, et al. Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis. 1981;124(5):593–601.PubMed Greene R, Zapol WM, Snider MT, Reid L, Snow R, O’Connell RS, et al. Early bedside detection of pulmonary vascular occlusion during acute respiratory failure. Am Rev Respir Dis. 1981;124(5):593–601.PubMed
29.
go back to reference Zapol WM, Kobayashi K, Snider MT, Greene R, Laver MB. Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure. Chest. 1977;71(2 suppl):306–7.CrossRefPubMed Zapol WM, Kobayashi K, Snider MT, Greene R, Laver MB. Vascular obstruction causes pulmonary hypertension in severe acute respiratory failure. Chest. 1977;71(2 suppl):306–7.CrossRefPubMed
30.
go back to reference Bachofen M, Weibel ER. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis. 1977;116(4):589–615.CrossRefPubMed Bachofen M, Weibel ER. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis. 1977;116(4):589–615.CrossRefPubMed
31.
go back to reference Tomashefski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983;112(1):112–26.PubMedPubMedCentral Tomashefski JF, Davies P, Boggis C, Greene R, Zapol WM, Reid LM. The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol. 1983;112(1):112–26.PubMedPubMedCentral
32.
go back to reference Stein JC, Ellis CG, Ellsworth ML. Relationship between capillary and systemic venous PO2 during nonhypoxic and hypoxic ventilation. Am J Physiol. 1993;265(2 Pt 2):H537–42.PubMed Stein JC, Ellis CG, Ellsworth ML. Relationship between capillary and systemic venous PO2 during nonhypoxic and hypoxic ventilation. Am J Physiol. 1993;265(2 Pt 2):H537–42.PubMed
33.
go back to reference Coffey RL, Albert RK, Robertson HT. Mechanisms of physiological dead space response to PEEP after acute oleic acid lung injury. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(5):1550–7.PubMed Coffey RL, Albert RK, Robertson HT. Mechanisms of physiological dead space response to PEEP after acute oleic acid lung injury. J Appl Physiol Respir Environ Exerc Physiol. 1983;55(5):1550–7.PubMed
34.
go back to reference Doorduin J, Nollet JL, Vugts MP, Roesthuis LH, Akankan F, van der Hoeven JG, et al. Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study. Crit Care. 2016;20(1):121.CrossRefPubMedPubMedCentral Doorduin J, Nollet JL, Vugts MP, Roesthuis LH, Akankan F, van der Hoeven JG, et al. Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study. Crit Care. 2016;20(1):121.CrossRefPubMedPubMedCentral
35.
go back to reference Kuwabara S, Duncalf D. Effect of anatomic shunt on physiologic deadspace-to-tidal volume ratio—a new equation. Anesthesiology. 1969;31(6):575–7.CrossRefPubMed Kuwabara S, Duncalf D. Effect of anatomic shunt on physiologic deadspace-to-tidal volume ratio—a new equation. Anesthesiology. 1969;31(6):575–7.CrossRefPubMed
36.
go back to reference Tusman G, Sipmann FS, Bohm SH. Rationale of dead space measurement by volumetric capnography. Anesth Analg. 2012;114(4):866–74.CrossRefPubMed Tusman G, Sipmann FS, Bohm SH. Rationale of dead space measurement by volumetric capnography. Anesth Analg. 2012;114(4):866–74.CrossRefPubMed
37.
go back to reference Cavalcanti AB, Suzumura É, Laranjeira LN, Paisani DM, Damiani LP, Guimarães HP, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335–45.CrossRefPubMedPubMedCentral Cavalcanti AB, Suzumura É, Laranjeira LN, Paisani DM, Damiani LP, Guimarães HP, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335–45.CrossRefPubMedPubMedCentral
Metadata
Title
Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study
Authors
Gustavo A. Ospina-Tascón
Diego F. Bautista
Humberto J. Madriñán
Juan D. Valencia
William F. Bermúdez
Edgardo Quiñones
Luis Eduardo Calderón-Tapia
Glenn Hernandez
Alejandro Bruhn
Daniel De Backer
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Annals of Intensive Care / Issue 1/2020
Electronic ISSN: 2110-5820
DOI
https://doi.org/10.1186/s13613-020-00651-1

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