Physiological dead space ventilation, disease severity and outcome in ventilated patients with hypoxaemic respiratory failure due to coronavirus disease 2019

Nasal high flow (NHF) reduces minute ventilation and ventilatory loads during sleep but the mechanisms are not clear. We hypothesised NHF reduces ventilation in proportion to physiological but not anatomical dead space.11 subjects (five controls and six chronic obstructive pulmonary disease (COPD) patients) underwent polysomnography with transcutaneous carbon dioxide (CO2) monitoring under a metabolic hood. During stable non-rapid eye movement stage 2 sleep, subjects received NHF (20 L·min−1) intermittently for periods of 5–10 min. We measured CO2 production and calculated dead space ventilation.Controls and COPD patients responded similarly to NHF. NHF reduced minute ventilation (from 5.6±0.4 to 4.8±0.4 L·min−1; p<0.05) and tidal volume (from 0.34±0.03 to 0.3±0.03 L; p<0.05) without a change in energy expenditure, transcutaneous CO2 or alveolar ventilation. There was a significant decrease in dead space ventilation (from 2.5±0.4 to 1.6±0.4 L·min−1; p<0.05), but not in respiratory rate. The reduction in dead space ventilation correlated with baseline physiological dead space fraction (r2=0.36; p<0.05), but not with respiratory rate or anatomical dead space volume.During sleep, NHF decreases minute ventilation due to an overall reduction in dead space ventilation in proportion to the extent of baseline physiological dead space fraction.

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Measurement of dead space ventilation using a pHa servo-controlled ventilator

Journal of Applied Physiology ◽

10.1152/jappl.1981.51.1.154 ◽

1981 ◽

Vol 51 (1) ◽

pp. 154-159 ◽

Cited By ~ 7

Author(s):

R. L. Coon ◽

E. J. Zuperku ◽

J. P. Kampine

Keyword(s):

Dead Space ◽

Close Agreement ◽

Minute Volume ◽

Alveolar Ventilation ◽

Independent Method ◽

Servo Control ◽

Physiological Dead Space ◽

Arterial Ph ◽

Before And After ◽

Dead Space Ventilation

A control system for the systemic arterial pH (pHa) servo control of mechanical ventilation has recently been developed. If pHa is maintained constant by the change, separation of minute volume into alveolar ventilation and physiological dead space ventilation (VE = fVA VDp) can be manipulated to show that VDp = (VE1 - VE 2)/(f1 - fe) where f1 and f2 are different ventilator frequencies and VE1 and VE2 are expired minute volumes at these frequencies. Also, added dead space can be measured. VDadded = (VE2 - VE1)/f where VE1 and VE2 are the minute volumes before and after the dead space was added. The validity of these equations was tested in the anesthetized dog. The measured added dead space was in close agreement with the volume of dead space which was added and with that measured by another independent method. The measurement of VDp, probably as a result of tidal volume-related changes in VDp, did not agree as well with VDp measured by an independent method.

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Mechanisms of physiological dead space response to PEEP after acute oleic acid lung injury

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.5.1550 ◽

1983 ◽

Vol 55 (5) ◽

pp. 1550-1557 ◽

Cited By ~ 38

Author(s):

R. L. Coffey ◽

R. K. Albert ◽

H. T. Robertson

Keyword(s):

Oleic Acid ◽

Lung Injury ◽

Dead Space ◽

Random Sequence ◽

Inert Gas ◽

Positive End Expiratory Pressure ◽

Physiological Dead Space ◽

Anesthetized Dogs ◽

Dead Space Ventilation ◽

Haldane Effect

In acute increased-permeability edema, the Bohr physiological dead space (VD/VTCO2) can be influenced by changes in anatomic dead space, ventilation-perfusion (VA/Q) heterogeneity, shunt, and the Haldane effect. We used the multiple inert gas elimination technique to assess the effect of positive end-expiratory pressure (PEEP) on each of these components of VD/VTCO2 in 14 pentobarbital-anesthetized dogs with increased permeability edema induced by infused oleic acid. PEEP of 5, 10, 15, and 20 cmH2O was applied in random sequence. Following injury VD/VTCO2 increased. It decreased with 5 or 10 cmH2O PEEP but increased progressively at higher PEEP levels. The decrease in VD/VTCO2 at 5 or 10 cmH2O PEEP was due to reductions in shunt and midrange VA/Q heterogeneity. The increase in VD/VTCO2 that occurred with higher PEEP levels was due to increased ventilation to high VA/Q regions and a larger anatomic dead space. Haldane effect magnified the shunt component of VD/VTCO2 but reduced the influence of midrange VA/Q heterogeneity.

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Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study

Annals of Intensive Care ◽

10.1186/s13613-020-00716-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 8

Author(s):

J.-L. Diehl ◽

N. Peron ◽

R. Chocron ◽

B. Debuc ◽

E. Guerot ◽

...

Keyword(s):

Mechanical Ventilation ◽

Dead Space ◽

Respiratory Mechanics ◽

Invasive Mechanical Ventilation ◽

Endothelial Damage ◽

Circulating Endothelial Cells ◽

Pulmonary Mechanics ◽

High Peep ◽

Gas Exchanges ◽

Physiological Dead Space

Abstract Rationale COVID-19 ARDS could differ from typical forms of the syndrome. Objective Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. Methods Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1–4] day after intubation (median [IQR]). Measurements and main results Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1–44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721–2434] mL. Gas exchanges were characterized by hypercapnia 55 [44–62] mmHg, high physiological dead-space (VD/VT): 75 [69–85.5] % and ventilatory ratio (VR): 2.9 [2.2–3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12–46] cells per mL and 1483 [999–2217] ng/mL, respectively. Conclusions We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

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

Annals of Intensive Care ◽

10.1186/s13613-020-00651-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 6

Author(s):

Gustavo A. Ospina-Tascón ◽

Diego F. Bautista ◽

Humberto J. Madriñán ◽

Juan D. Valencia ◽

William F. Bermúdez ◽

...

Keyword(s):

Observational Study ◽

Dead Space ◽

Microcirculatory Dysfunction ◽

Dead Space Ventilation

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Serum uric acid, disease severity and outcomes in COVID-19

Critical Care ◽

10.1186/s13054-021-03616-3 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Inès Dufour ◽

Alexis Werion ◽

Leila Belkhir ◽

Anastazja Wisniewska ◽

Marie Perrot ◽

...

Keyword(s):

Mechanical Ventilation ◽

Uric Acid ◽

Respiratory Failure ◽

Confidence Interval ◽

Proximal Tubule ◽

Disease Severity ◽

Serum Levels ◽

Kidney Proximal Tubule ◽

Urate Transporter ◽

Low Serum

Abstract Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

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