Early Awake Prone Position Combined with High-Flow Nasal Oxygen Therapy in Severe COVID-19: A Case Series

Background Awake prone positioning has been used for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results are contradictory. We aimed to highlight the role of awake prone positioning combined with high-flow nasal oxygen therapy in severe COVID-19 patients infected with the Delta variant of SARS-CoV-2. Methods From June 12 to December 7, 2021, we successfully performed prone position(PP) combined with high-flow nasal oxygen(HFNO) therapy on two patients infected with the delta variant of SARS-CoV-2. HFNO was prescribed to reach SpO2 ≥ 92%. PP was proposed to patients with PaO2/FiO2(P/F) < 150 mmHg. Arterial blood gas (ABG) and hemodynamic were monitored before and after PP sessions. The target time of PP was more than 12 h per day and could be appropriately shortened according to the patient’s tolerance. Relevant clinical data, HFNO parameters, PICCO parameters, P/F ratio and PP duration were obtained from medical records. Results A total of 23 PP sessions and 6 PP sessions combined with HFNO were performed in case 1 and case 2, respectively. Compared with values before PP, GEDI, ELWI and Qs/Qt decreased significantly (GEDI: 869.50 ± 60.50 ml/m2 vs. 756.86 ± 88.25 ml/m2; ELWI: 13.64 ± 2.82 ml/kg vs. 12.43 ± 2.50 ml/kg; Qs/Qt: 15.32 ± 6.52% vs. 12.24 ± 5.39%; all p < 0.05), Meanwhile, the oxygenation improved significantly (P/F: 184.50 ± 51.92 mmHg vs. 234.21 ± 88.84 mmHg, p < 0.05), The chest CT revealed the lung infiltrates improved significantly after PP. Both cases were discharged to a dedicated COVID-19 ward without requiring intubation. Conclusions Combining PP with HFNO could be a useful treatment strategy for avoiding intubation in severe COVID-19 patients infected with the Delta variant of SARS-CoV-2 to improve pulmonary vascular involvement, improve oxygenation and avoid intubation, but further studies are needed to validate our approach.


Background
Since the first report of cases from India in late 2020, the delta variant of SARS-CoV-2(DVSC-2) has become the predominant strain in much of the world [1]. Awake prone positioning has been used for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure, but the results are contradictory. We aimed to highlight the role of awake prone positioning (PP) combined with high-flow nasal oxygen therapy (HFNO) in severe COVID-19 patients infected with the Delta variant of SARS-CoV-2.
Y. Chengfen and Z. Yongle and L. Jianguo contributed equally to this study. * X. Lei nokia007008@163.com 1 The  (Fig. 1). We successfully performed PP combined with HFNO therapy on them.
HFNO was prescribed to reach SpO 2 ≥ 92%. PP was proposed to patients with PaO 2 /FiO 2 (P/F) < 150 mmHg. The PICCO was proposed for hemodynamic monitoring and volume management on their admission to intensive care unit (ICU). Arterial blood gases (ABG) and hemodynamics were monitored before and after PP sessions. The target time of PP was more than 12 h per day and could be appropriately shortened according to the patient's tolerance. Relevant clinical data, HFNO parameters, PICCO parameters, P/F ratio and PP duration were obtained from medical records and are presented in Table 1.
A total of 23 PP sessions and 6 PP sessions combined with HFNO were performed in case 1 and case 2, respectively. ABG and hemodynamic were monitored before and after PP sessions during 10 PP sessions of case 1 and 4 PP sessions of case 2. The hemodynamic results showed their cardiac index (CI), systemic vascular resistance index (SVRI) and central venous pressure (CVP) were within normal range, however, global end-diastolic volume index (GEDI), intrapulmonary shunt fraction (Qs/Qt) and extravascular lung water index (ELWI)were higher than normal before PP. There was no volume responsiveness confirmed by passive leg rising test in both cases. Although their volume was limited, GEDI and ELWI were higher than normal. Compared   B CT scan taken on after PP in case 1. It revealed the lung infiltrates improved significantly compared with A. C CT scan taken before PP in case 2. D CT scan taken after PP in case 2. It revealed the lung infiltrates improved significantly compared with D heart rate (HR) and mean arterial pressure (MAP) between before and after PP (all p > 0.05). The chest CT revealed the lung infiltrates improved significantly after PP (Fig. 1). Both cases were discharged to a dedicated COVID-19 ward without requiring intubation. we used the paired t test for numerical variables to compare variables between before awake prone position and after awake prone position.
To our knowledge, this is the first description of severe COVID-19 patients infected with DVSC-2 managed effectively and improved pulmonary vascular involvement by PP combined with HFNO. Despres C et al. [2] showed similar findings in severe COVID-19 patients infected with the original version of SARS-CoV-2. People infected with DVSC-2 produce far more virus, acts on the angiotensin-converting enzyme 2 (ACE2), than do those infected with the original version of SARS-CoV-2 [1]. Alongside emerging understanding of the role of the ACE2 pathway in the pathogenic process, it has become clear that at least some COVID-19 patients, exhibit significant pulmonary vascular involvement [3,4]. Besides volume overload and inflammation response, pulmonary vascular involvement caused by DVSC-2 might be one reason for elevated GEDI. Previous studies have confirmed that PP recruited some collapsed pulmonary microvessels through increasing central blood volume and decrease PVR and RV afterload through increasing the lung volume [5]. HFNO create a positive end expiratory pressure effect, contributing to decreasing the work of breathing and enhance oxygenation [6].

Conclusion
Combining PP with HFNO could be a useful treatment strategy for avoiding intubation in severe COVID-19 patients infected with the Delta variant of SARS-CoV-2 to improve pulmonary vascular involvement, improve oxygenation and avoid intubation, but further studies are needed to validate our approach.
Author Contributions LX, the corresponding author, was responsible for the conceptualization of the study and the revision and approval of this manuscript. YZ and JL participated in the design and collected the data and were responsible for its accuracy. CY drafted the manuscript and revise the manuscript. All authors contributed to the data analysis and interpretation. All authors read and approved the final manuscript.
Funding This work was supported, in part, by the Tianjin Science and Technology Plan Project(18ZXDBSY00100) and Rui E (Rui Yi) Emergency Medicine Research Special Fund(R2019006).

Conflict of Interest
The authors have no competing interests.

Ethics Approval and Consent to Participate
The study was approved by ethics committee of Tianjin Third Central Hospital (approval number 2021-09-13). Oral consent was obtained from each patient.

Consent for Publication
All authors have approved the manuscript and its publication.
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