key: cord-0683081-36x2780j
authors: Giosa, Lorenzo; Payen, Didier; Busana, Mattia; Mattei, Alessio; Brazzi, Luca; Caironi, Pietro
title: Orthodeoxia and its implications on awake-proning in COVID-19 pneumonia
date: 2021-12-16
journal: Crit Care
DOI: 10.1186/s13054-021-03859-0
sha: 74c0426321baa5ba51f9352d7e8facf9a7c027f4
doc_id: 683081
cord_uid: 36x2780j

nan

When caring for patients with respiratory failure, decubitus is a daily challenge. In the acute-respiratorydistress-syndrome (ARDS), seated and prone position increase lung volume and, consequently, oxygenation [1] . In COVID-19, however, gas-exchange is often independent of lung volume [2] , and rather affected by perfusion dysregulation [3] . In similar settings, like the hepatopulmonary syndrome (HPS), recumbency may revert hypoxemia [4] : this phenomenon goes under the name of orthodeoxia, and here we hypothesize its presence in COVID-19. Clinical implications might be relevant: recumbency is the state of lying horizontally at 0°, supine or prone. Awake-proning has already proven beneficial on oxygenation in spontaneously breathing patients with early COVID-19 pneumonia [5] . However, as a heritage from ARDS, these patients are usually seated or semirecumbent, thereby the ventral decubitus is rarely compared to supination at 0°: the finding of orthodeoxia may lead to partially ascribe the oxygenation benefits of awake-proning [5] to recumbency rather than to the ventral decubitus itself.

At the University Hospital of Turin (Italy), following ethical approval (Città della Salute e della Scienza 00581/2020), we studied non-sedated COVID-19 patients requiring early (< 7 days) respiratory support with helmet continuous positive airway pressure (HCPAP) or high flow nasal cannula (HFNC). Concomitant pulmonary embolism and/or bacterial pneumonia represented exclusion criteria. After signing a written informed consent, participants were assigned to a random sequence of seated (trunk elevation > 60°, legs down at 45°), supine and prone position (both recumbent at 0°) during constant respiratory support as set by the attending physician. Blood gases, respiratory rate, dyspnea and discomfort, basic hemodynamics and, when available, cardiac output (CNAP ® , CNSystems Medizintechnik GmbH) were assessed twenty minutes from each decubitus. A threshold of ≥ 20% increase in PaO 2 defined supine responders (supine vs seated) and prone responders (prone vs supine). The primary outcome was the frequency of orthodeoxia (supine responders). R-3.5.2 was used for statistical computing: Wilcoxon test for median comparisons, Fisher exact test for contingency tables, two-sided p < 0.05 for significance.

After excluding 28 eligible patients (21 for pulmonary embolism, 7 for superimposed bacterial pneumonia), 30 were recruited in two months (February-March 2021); two declined to participate. Results and baseline characteristics of the 28 enrolled patients are summarized in Table 1 . Orthodeoxia was detected in 14 (50%) of them, with a far higher PaO 2 increase (31 [26-44] mmHg), than what normally required to define it (4 mmHg) [3] . Neither the starting decubitus (p = 0.33), nor the type of respiratory support (HCPAP or HFNC, p = 1.00) affected this result, and the stability of cardiac output from seated to supine minimizes the possibility that macro-hemodynamics played any significant role. A decrease in respiratory rate in the absence of dyspnea and discomfort was also associated with supination in our population. During proning, patients with and without orthodeoxia behaved similarly: respectively, 6 (46%) and 5 (36%) were prone responders (p = 0.70, median PaO 2 increase Open Access *Correspondence: pietro.caironi@unito.it 6 Department of Anesthesia and Critical Care, AOU S. Luigi Gonzaga, Turin, Italy Full list of author information is available at the end of the article . This suggests that orthodeoxia cannot anticipate the response to proning, likely because of the unpredictable balance between perfusion redistribution and parenchymal reaeration in the ventral position [6] . However, the finding of orthodeoxia avoided overestimating the benefits of awake-pronation in 6 patients (22%) whose oxygenation improvement was due to lying recumbent at 0°, irrespective of prone or supine specifically (Fig. 1, green dots) . Considering that the ventral decubitus was associated with discomfort, higher respiratory and heart rate, the decision to prone would be questionable in these patients.

In conclusion, orthodeoxia appears a common clinical feature of early COVID-19 pneumonia. This novel finding contributes to further distinguishing COVID-19 from other causes of ARDS [1, 2, 6] , while reinforcing its advocated similarity with HPS [3, 4] . Additionally, detecting orthodeoxia may help avoid awake-pronation when oxygenation simply benefits from recumbency: in a pandemic scenario, this possibly relevant clinical implication would deserve confirmation by larger studies. Fig. 1 Individual Partial Pressure of Arterial Oxygen (PaO 2 ) Variation in Supine responders (left) and Supine non-responders (right). In both groups solid lines represent prone responders, dashed lines prone non-responders (see Text for definitions). Red bars represent median PaO 2 values in each decubitus, and P values (* when significant) refer to their comparisons. As shown, 14 patients (50%) were supine responders (median PaO 2 increase from seated to supine: 31 [26-44] mmHg). Among these, one did not tolerate proning, six were prone responders (median PaO 2 increase from supine to prone: 67 [60-92] mmHg) and seven were prone non-responders (one worsened oxygenation during proning, while the 6 patients highlighted by green dots benefit from recumbency irrespective of supine or prone position specifically). The remaining 14 patients (50%) were supine non-responders. Among these, 5 were prone responders (median PaO 2 increase from supine to prone: 31 [30-68] mmHg), while in the 9 remaining subjects, PaO 2 did not significantly change between supination and proning

Effects of patient positioning on respiratory mechanics in mechanically ventilated ICU patients

Role of total lung stress on the progression of early COVID-19 pneumonia

Pulmonary vascular dilatation detected by automated transcranial Doppler in COVID-19 pneumonia

Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome

Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study

Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia

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None declared.

LG, DP, MB and PC conceptualised the study. LG and AM collected the data.LG, MB and PC analysed the data. LG drafted the manuscript and PC, MB, DP and LB revised it. All authors read and approved the final version of the manuscript.

None declared.

The dataset used and analysed for this study is available from the corresponding author upon reasonable request. 

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This study was approved by Città della Salute e della Scienza (00581/2020) University Hospitals' Research Ethics Board (Turin, Italy). Every patient approved to participate by signing a written informed consent.

Acquired (written and signed by each participant).

The authors declare that they have no competing interests.