key: cord-0795838-csfaahcl
authors: Vasques, Francesco; Sanderson, Barnaby; Formenti, Federico; Shankar-Hari, Manu; Camporota, Luigi
title: Physiological dead space ventilation, disease severity and outcome in ventilated patients with hypoxaemic respiratory failure due to coronavirus disease 2019
date: 2020-07-31
journal: Intensive Care Med
DOI: 10.1007/s00134-020-06197-x
sha: a61decd8206be7cf958c95121bb6f039f306b621
doc_id: 795838
cord_uid: csfaahcl

nan

The severity of acute hypoxemic respiratory failure (AHRF) in Coronavirus Disease 2019 (COVID-19) correlates correlates poorly with lung weight and lung mechanics, leading to the proposal of phenotypes that may be associated with similar degree of hypoxaemia but different lung volume, weight, and compliance [1] . The alteration of the pulmonary vascular tone and immune thrombosis of the alveolar capillaries [2] may account for these pathophysiological characteristics and for the high physiological dead space observed in these patients.

To describe estimated indices of physiological dead space-and their association with respiratory mechanics, severity of hypoxaemia, biomarkers, and outcomes-we performed a retrospective analysis of adult patients with COVID-19 respiratory failure requiring mechanical ventilation in four medical Intensive Care Units (ICU) within Guy's and St Thomas' NHS Trust-London, UK (Ethics reference: 10,796).

We used the recorded values at the time of worst PaO 2 / FiO 2 observed on the day of critical care admission. Continuous variables were compared using Mann-Whitney U test. This cohort included 213 patients (73% males), mean (95%CI) age 56 (54-57) years, and PaO 2 /FiO 2 128 (121-135) mmHg. When subdivided in four groups based on cut-off PaO 2 /FiO 2 of 150 mmHg and compliance of 40 mL/cmH 2 O; 72% (n = 154) had PaO 2 / FiO 2 < 150 mmHg, of these, 112 (73%, or 53% of the overall cohort) had compliance < 40 mL/cmH 2 O (eTable 1). The mean (95%CI) estimated physiological dead space fraction [3] was high in the entire cohort at 0.53 (0.51-0.56).

ICU outcome was available for 193 patients, where estimated physiological dead space fraction was higher in non-survivors [median (IQR), 0.57 (0.46-0.65) vs. 0.5 (0.4-0.64); p = 0.03]. All estimates of physiological dead space increased with the degree of hypoxaemia, but not with the reduction in lung compliance (Fig. 1) . Compared with patients with PaO 2 /FiO 2 > 150 mmHg, patients with PaO 2 /FiO 2 < 150 mmHg had higher estimated physiological dead space fraction [0.55 (0.52-0.57) vs. 0.5 (0.47-0.53); p = 0.036) (Fig. 1A) , mean (95%CI) corrected minute volume [4] [9.3(8.8-9.7) vs. 8.2 (7.6-8.8) L/min; p = 0.004] (Fig. 1B) , and ventilatory ratio [5] (Fig. 1C) . Although patients with compliance < 40 mL/cmH 2 O had a higher corrected minute volume [4] [9.4 (8.8-10) vs. 8.8 (8.4-9.3) L/min; p = 0.023] (Fig. 1C) , there was no difference in the two compliance groups in estimated physiological dead space fraction [0.55 (0.48-0.56) vs. 0.54 (0.52-0.56); p = 0.72] (Fig. 1A) and ventilatory ratio [5] 1.4 (1.3-1.5) vs. 1.4 (1.33-1.46); p = 0.76) (Fig. 1B) .

Physiological dead space correlated with hypoxaemia, but it was dissociated from alterations in lung mechanics in COVID-19 ventilated patients. Immunothrombosis is a mechanism that may explain both the increase in physiological dead space and hypoxaemia. Interestingly, we found that the highest median (IQR) levels of D-Dimers In conclusion, these data suggest that increased physiological dead space is a characteristic of patients with COVID-19 AHRF, with no relation with compliance of the respiratory system. Given that both PaO 2 /FiO 2 and physiological dead space are worse in non-survivors, it is unclear if dead space is independently associated with mortality or if its effect on outcome is mediated through hypoxaemia. 

COVID-19 pneumonia: different respiratory treatments for different phenotypes?

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

Estimating dead-space fraction for secondary analyses of acute respiratory distress syndrome clinical trials

A simple formula for adjusting arterial carbon dioxide tension

Ventilatory ratio: a simple bedside measure of ventilation

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