Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure
Original Article

Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure

Eftychia Polydora1,2, Michaella Alexandrou1,2, Stamatios Tsipilis1,3, Nikolaos Athanasiou1,3, Michail Katsoulis4, Artemis Rodopoulou1, Apostolos Pappas1,2, Ioannis Kalomenidis1,2

1COVID-19 Unit, “Evaggelismos” General Hospital, Athens, Greece; 21st Department of Critical Care and Pulmonary Medicine, National and Kapodistrian University of Athens, Evaggelismos Hospital, Athens, Greece; 3Pulmonary Department, Evaggelismos Hospital, Athens, Greece; 4Institute of Health Informatics, University College London, London, UK

Contributions: (I) Conception and design: I Kalomenidis; (II) Administrative support: M Katsoulis; (III) Provision of study materials or patients: E Polydora, M Alexandrou, S Tsipilis, N Athanasiou, A Rodopoulou; (IV) Collection and assembly of data: E Polydora, M Alexandrou, S Tsipilis, N Athanasiou, A Rodopoulou; (V) Data analysis and interpretation: I Kalomenidis, A Pappas, M Katsoulis, M Alexandrou; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Eftychia Polydora, MD. Evaggelismos Hospital, 45-47 Ipsilandou street, 10676 Athens, Greece. Email: felicitypol@gmail.com.

Background: During COVID-19 pandemic, people who developed pneumonia and needed supplemental oxygen, where treated with low-flow oxygen therapy systems and non-invasive methods, including oxygen therapy using high flow nasal cannula (HFNC) and the application of bi-level or continuous positive airway pressure (BiPAP or CPAP). We aimed to investigate the outcomes of critical COVID-19 patients treated with HFNC and unveil predictors of HFNC failure.

Methods: We retrospectively enrolled patients admitted to COVID-19 wards and treated with HFNC for COVID-19-related severe hypoxemic respiratory failure. The primary outcome of this study was treatment failure, such as the composite of intubation or death during hospital stay. The association between treatment failure and clinical features was evaluated using logistic regression models.

Results: One hundred thirty-two patients with a median (IQR) PaO2/FiO2 ratio 96 (63–173) mmHg at HFNC initiation were studied. Overall, 45.4% of the patients were intubated. Hospital mortality was 31.8%. Treatment failure (intubation or death) occurred in 50.75% and after adjustment for age, gender, Charlson Comorbidity index (CCI) score and National Early Warning Score 2 (NEWS2) score on admission and PaO2/FiO2 ratio and acute respiratory distress syndrome (ARDS) severity at the time of HFNO initiation, it was significantly associated with the presence of dyspnea [adjusted OR 2.48 (95% CI: 1.01–6.12)], and higher Urea serum levels [adjusted OR 1.25 (95% CI: 1.03–1.51) mg/dL].

Conclusions: HFNC treatment was successful in almost half of the patients with severe COVID-19-related acute hypoxemic respiratory failure (AHRF). The presence of dyspnea and high serum Urea levels on admission are closely related to HFNC failure.

Keywords: COVID-19; acute respiratory distress syndrome (ARDS); respiratory failure; high flow nasal cannula (HFNC); intubation

Submitted Aug 20, 2021. Accepted for publication Jan 21, 2022.

doi: 10.21037/jtd-21-1373

Introduction

Acute hypoxemic respiratory failure (AHRF), resulting from COVID-19 pneumonia, is the hallmark of “severe” and “critical” disease (1) and it is the main reason for SARS-CoV-2-related mortality (2,3). Low-flow oxygen therapy systems can achieve adequate blood oxygenation in early COVID-19 pneumonia, but in up to 20% of hospitalized patients, lung disease may progress to acute respiratory distress syndrome (ARDS) (2). In that case, patients often need intubation and invasive mechanical ventilation (IMV). However, a proportion of them may be treated with non-invasive methods, including oxygen therapy using high flow nasal cannula (HFNC) and the application of bi-level or continuous positive airway pressure (BiPAP or CPAP) (4).

The value of HFNC in AHRF management was highlighted in the pre-pandemic era, when the emblematic FLORALI trial demonstrated lower mortality in patients treated with HFNC compared to standard oxygen therapy and non-invasive ventilation (NIV) (5). Intubation risk was reduced with HFNC in the sub-group of patients with PaO2/FiO2 <200 mmHg. In the same line of evidence, meta-analyses indicate that in patients with AHRF, HFNC is more effective than standard oxygen therapy in avoiding intubation, while a survival benefit is unclear (6-8). Not surprisingly, with the advent of COVID-19 pandemic, clinicians increasingly relied on this method to deal with the unprecedented number of AHRF patients and the restricted Intensive Care Unit (ICU) resources during pandemic surges. HFNC is recommended for the treatment of COVID-19-related AHRF by international authorities (1,9,10). Early observations from common wards or ICUs (11-19) suggest that several HFNC-treated COVID-19 patients with AHRF may avoid intubation, while information on their final outcome and risk factors for treatment failure is relatively poor. We here aimed to study the clinical features, the intubation rates and the overall success (alive and discharged) of HFNC inpatients admitted at common hospital wards and required treatment with HFNC for critical COVID-19 (1) and to identify factors associated with failure of the method. We hypothesized that most of these patients would be successfully treated with HFNC and discharged from the hospital avoiding intubation and mechanical ventilation and that failure of the method could be predicted using patients’ features, available on their admission to the hospital or at HFNC initiation. We present the following article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1373/rc).

Methods

Patients and procedures

We retrospectively enrolled patients admitted to the COVID-19 Unit (common isolation wards) of our hospital between September 2020 and January 2021 and treated with HFNC for severe AHRF caused by SARS-CoV-2 pneumonia, anytime during their hospital stay. By protocol, patients failing to maintain an oxygen saturation (SpO2)>92% while treated with a Venturi mask with FiO2 50% and not requiring urgent endotracheal intubation were offered HFNC at 60 L/min and appropriate FiO2 to achieve a pulse SpO2 92–96%. All patients with COVID-19 pneumonia and respiratory failure treated with HFNC during the defined period were included in the study. Patients’ demographics, clinical, imaging, laboratory data and outcomes were extracted from the medical records. The primary outcome of this study was treatment failure, such as the composite of intubation or death during hospital stay. Success was considered discharged from the hospital without the need for intubation and mechanical ventilation. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Evaggelismos Hospital (Protocol No. 44-25/2/2021) and individual consent for this retrospective analysis was waived.

Statistical analysis

Continuous data are presented as mean ± standard deviation (SD) or median (interquartile range, IQR), if they are normally or non-normally distributed, accordingly. Categorical data are presented as percentage frequencies. Failure of the method was defined as intubation or in-hospital death. We applied logistic regression models to estimate the association between HFNC failure (intubation or in-hospital death) and patients’ demographic features, comorbidities [including Charlson Comorbidity Index (CCI)], duration of symptoms, clinical symptoms and signs, National Early Warning Score 2 (NEWS2) score, X-ray Lung Field Score (20), laboratory data, admission, PaO2/FiO2 ratio on admission and within two hours of HFNC initiation and ARDS severity at HFNC initiation as well. In these models, we applied both unadjusted and adjusted analyses. Data were treated as categorical (such as sex, racial origin, presence of a symptom or presence of a comorbidity, grade of ARDS severity) or continuous (rest of them). In the adjusted analysis, we mutually controlled for confounders including age, gender, CCI score and NEWS2 score on admission and PaO2/FiO2 ratio and ARDS severity at the time of HFNO initiation. We applied Student’s t-test to compare the duration of HFNC treatment, ICU stay and hospitalization between those intubated and those successfully treated with HFNC.

Results

One hundred thirty-two patients, with mean ± SD age 67±14 years old were included in the study. Co-morbidities were common (Table 1) and the median [IQR] CCI was 3 [2–4]. Five patients had deemed as “do-not-intubate” (DNI) due to serious comorbidities. On admission, 49% had respiratory failure (SaO2<90% while breathing ambient air). HFNC treatment was initiated 2 [0–7] days after hospital admission. The PaO2/FiO2 ratio within the first two hours of HFNC commencement was 96 [63–173] mmHg. At that time, all patients had bilateral alveolar infiltrates, and PaO2/FiO2 ratio <300 mmHg while receiving HFNC at 60 L/min which generates a positive airway pressure of 5–6 cm H2O (4), thus fulfilling typical ARDS criteria (21,22). ARDS was mild in 8%, moderate in 39% and severe in 53% of them (21). The median (IQR) duration of HFNC treatment was 5 [1–11] days.

Table 1

Patients’ demographics and co-morbidities

Characteristics N=132
Age (years) 67±14
Sex, male 91 (68.9%)
European origin 121 (91.7%)
Obesity (BMI ≥30 kg/m2) 34 (25.8%)
Smoking 43 (32.6%)
Hypertension 69 (52.3%)
Coronary artery disease 19 (14.4%)
Asthma/COPD 14 (10.6%)
Diabetes 39 (29.5%)
Cancer 9 (6.8%)
Immunosuppression 12 (9.1%)
Cerebrovascular disease 7 (5.3%)
Chronic hepatic disease 2 (1.5%)
Chronic renal failure 7 (5.3%)
Autoimmune disease 4 (3.0%)

BMI, body mass index; COPD, chronic obstructive pulmonary disease.

Overall, 71.2% of the patients were transferred to the ICU, 45.4% were intubated and 31.8% finally died. NIV was not used as pre-intubation mean of respiratory support in any of the patients. HFNC failed (intubation or death) in 50.7% patients. Un-adjusted logistic regression analysis revealed a link between treatment failure and advanced age, high CCI score, as well as high respiratory rate, low PaO2/FiO2 ratio, presence of dyspnea, high NEWS2 score and high Urea and Creatinine levels on admission, and low PaO2/FiO2 ratio and ARDS severity soon after HFNC initiation (Table 2). However, when adjusted logistic regression analysis was used, only the presence of dyspnea and high Urea serum levels on admission, were found to be significantly associated to the failure of HFNC (Table 2). Only 1/10 of patients with mild ARDS were intubated and none died, 23% of those with moderate ARDS were intubated and 21% died and 67% of those with severe ARDS were intubated and 44% died.

Table 2

Clinical parameters associated with HFNC failure (intubation or in-hospital death)

Unadjusted odd ratios 95% CI P Adjusted odd ratios 95% CI P
Age (per year) 1.04 1.01–1.06 <0.05 1.03 0.99–1.07 NS
CCI score(per unit) 1.19 1.00–1.40 <0.05 1.02 0.80–1.30 NS
Respiratory rate (per breath/min) 1.05 1.00–1.11 <0.05 1.03 0.96–1.11 NS
PaO2/FiO2 on admission (per 10 mmHg) 0.96 0.92–0.99 <0.05 1.00 0.94–1.06 NS
Dyspnea 2.72 1.34–5.52 <0.05 2.48 1.01–6.12 <0.05
NEWS2 (per unit) 1.12 1.01–1.25 <0.05 1.04 0.91–1.19 NS
Urea (per 10 mg/dL) 1.30 1.09–1.55 <0.05 1.25 1.03–1.51 <0.05
Creatinine (per mg/dL) 6.37 1.88–21.61 <0.05 3.97 0.92–17.08 NS
PaO2/FiO2 at HFNC initiation (per 10 mmHg) 0.77 0.69–0.87 <0.05 0.84 0.68–1.04 NS
ARDS severity (per grade) 5.34 2.68–10.67 <0.05 1.82 0.43–7.72 NS

Grades for ARDS severity were defined as follows: mild, moderate, severe. All parameters except “PaO2/FiO2 at HFNC initiation” and “ARDS severity” refer to patients’ condition on admission. HFNC, High Flow Nasal Oxygen; CCI, Charlson Comorbidity Index; NEWS2, National Early Warning Score 2; ARDS, adult respiratory distress syndrome.

Less than half (47.3%) of full-treatment (including intubation) patients were intubated and 29.2% died. Mortality was 58,3% among those intubated. In the full treatment group, 9 of 10 patients with mild ARDS avoided intubation and all survived, 76% of those with moderate ARDS avoided intubation and 82% survived and 30% of those with severe ARDS avoided intubation and 58% survived. Compared to patients who avoided intubation, those intubated had a shorter HFNC treatment duration (4.56±4.7 vs. 6.5±3.5 days, P<0.05), longer ICU stay (26±21.4 vs. 4.2±5.5 days, P<0.05) and longer hospital stay (34.7±22.7 vs. 20.3±9.9 days, P<0.05).

Discussion

We here present the clinical features, the course and the outcome of patients who were admitted at common hospital wards, received treatment for COVID-19-related ARDS based on standard protocol and had definite outcomes (death or discharge). Our main findings are: (I) HFNC treatment succeeded (discharge without intubation) in 49.3 % of the patients and after adjustment for age, gender, CCI score and NEWS2 score on admission and PaO2/FiO2 ratio and ARDS severity at the time of HFNO initiation, this was significantly associated with the presence of dyspnea [adjusted OR 2.48 (95% CI: 1.01–6.12)] and higher Urea serum levels [adjusted OR 1.25 (95% CI: 1.03–1.51), by mg/dL on admission; (II) Intubation was avoided in 52.7% of the patients without a DNI-order (including almost 1/3 of those with severe ARDS); (III) Overall mortality was 31.8%.

We observed that HFNC commenced under a standard treatment protocol in patients with COVID-19-related ARDS admitted at common isolation hospital wards was successful in almost half of the patients who were discharged without the need for intubation and mechanical ventilation. Intubation was avoided in 47.3% of patients not deemed DNI and survival in this group was 68.2%. Patients who avoided intubation, had shorter ICU and hospital stay compared to those intubated. Among patients with severe ARDS (21), in which HFNC use is not suggested by the WHO guidelines (1) intubation was avoided in approximately 1/3 of the patients and survival was more than 50%. In our cohort of patients fulfilling ARDS criteria (21), with a median PaO2/FiO2 ratio <100 at the time of HFNC initiation, HFNC success rate was similar to those reported, by either retrospective (common wards or ICUs, 45–65% success) (11-16) and prospective (ICUs, 46–48% success) (17-19) observational studies or a clinical trial conducted at the ICU (23). From the data discussed above, it follows that an HFNC trial should be attempted in patients with COVID-19-related AHRF even in those with severe ARDS when urgent intubation is not otherwise required.

Predicting patients’ response to the HFNC is of major importance, especially during pandemic surges, when ICUs are overwhelmed, therapeutical means are scarce and optimal allocation of available non-invasive tools to treat severe COVID-19 AHRF and possibly avoid intubation becomes a task of paramount priority. After adjusting for age, gender, CCI score and NEWS2 score on admission and PaO2/FiO2 ratio and ARDS severity at the time of HFNO initiation, we found that the presence of dyspnea and, higher urea serum levels on admission are associated with increased risk of HFNC failure. In agreement with others (15,16) and similarly to an observation made with the use of NIV in COVID-19-related severe respiratory failure (24), increased age was linked to increased risk of HFNC failure (intubation or death) in unadjusted analysis. Previous work has shown that HFNC failure in COVID-19 patients can be predicted using physiological parameters including the ROX index (12,14,15,17,18), SAPS2 (14), SOFA score (16,18), which were not examined at the present study. We demonstrated that other physiological features, such as PaO2/FiO2 ratio (on admission and after HFNC initiation), grade of ARDS severity and the NEWS2 score (on admission), were not linked with treatment failure. Interestingly, abnormal renal function, expressed by increased serum urea levels was a robust predictor of HFNC failure. Taken together, the above demonstrates that the presence of dyspnea and abnormal renal function on admission can predict failure or the method.

The main limitations of our study are connected with its retrospective design. In connection to these, incomplete records on the respiratory rate did not permit us to calculate ROX index. It is very challenging to interpret the observed associations as causal because we may have unmeasured confounding, despite controlling for (I) all the significant variables from the univariate analysis and (II) the 6 most important confounders, i.e., age, gender, CCI score and NEWS2 score on admission and PaO2/FiO2 ratio and ARDS severity at the time of HFNO initiation, in the adjusted analysis. In addition, intubation was decided by the attending physicians on case-by-case basis and not according to pre-defined criteria. Nevertheless, it should be stressed that an “early intubation” strategy was unpopular in our institution and during that study period, the decision for intubation and mechanical ventilation was made using traditional criteria, i.e., resistive hypoxemia along with signs of respiratory distress and threatened respiratory arrest, altered mental status and cardiac arrest. On the other hand, advantages of the study include the fact that we used standard criteria for HFNC treatment throughout the study period and that all patients had definite outcomes (death or survival and discharge).

In conclusion, we showed that half of patients with COVID-19-related severe AHRF, treated with HFNC can be safely discharged without the need of intubation. The presence of dyspnea and high serum Urea levels on admission are closely related to HFNC failure. Randomized trials comparing HFNC to standard oxygen therapy are required to clarify its impact on COVID-19-related AHRF.

Acknowledgements

Funding: The publication of the present article was funded by the National & Kapodistrian University of Athens, Greece (Special Research Fund Account).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1373/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1373/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1373/prf

Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1373/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Evaggelismos Hospital (Protocol No. 44-25/2/2021) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. 1. World Health Organization. COVID-19 Clinical management. Living Guidance. [Accessed 5 May 2021]. Available online: https://apps.who.int/iris/bitstream/handle/10665/338882/WHO-2019-nCoV-clinical-2021.1-eng.pdf
  2. Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA 2020;324:782-93. [Crossref] [PubMed]
  3. Drake TM, Riad AM, Fairfield CJ, et al. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study. Lancet 2021;398:223-37. [Crossref] [PubMed]
  4. Raoof S, Nava S, Carpati C, et al. High-Flow, Noninvasive Ventilation and Awake (Nonintubation) Proning in Patients With Coronavirus Disease 2019 With Respiratory Failure. Chest 2020;158:1992-2002. [Crossref] [PubMed]
  5. Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372:2185-96. [Crossref] [PubMed]
  6. Lewis SR, Baker PE, Parker R, et al. High-flow nasal cannula for respiratory support in adult intensive care patients. Cochrane Database Syst Rev 2021;3:CD010172. [PubMed]
  7. Zhao H, Wang H, Sun F, et al. High-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy but not to noninvasive mechanical ventilation on intubation rate: a systematic review and meta-analysis. Crit Care 2017;21:184. [Crossref] [PubMed]
  8. Ni YN, Luo J, Yu H, et al. Can High-flow Nasal Cannula Reduce the Rate of Endotracheal Intubation in Adult Patients With Acute Respiratory Failure Compared With Conventional Oxygen Therapy and Noninvasive Positive Pressure Ventilation?: A Systematic Review and Meta-analysis. Chest 2017;151:764-75. [Crossref] [PubMed]
  9. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health 2021:74. [Accessed 5 May 2021]. Available online: https://www.covid19treatmentguidelines.nih.gov/
  10. Chalmers JD, Crichton ML, Goeminne PC, et al. Management of hospitalised adults with coronavirus disease 2019 (COVID-19): a European Respiratory Society living guideline. Eur Respir J 2021;57:2100048. [Crossref] [PubMed]
  11. Patel M, Gangemi A, Marron R, et al. Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure. BMJ Open Respir Res 2020;7:e000650. [Crossref] [PubMed]
  12. Chandel A, Patolia S, Brown AW, et al. High-Flow Nasal Cannula Therapy in COVID-19: Using the ROX Index to Predict Success. Respir Care 2021;66:909-19. [Crossref] [PubMed]
  13. Demoule A, Vieillard Baron A, Darmon M, et al. High-Flow Nasal Cannula in Critically Ill Patients with Severe COVID-19. Am J Respir Crit Care Med 2020;202:1039-42. [Crossref] [PubMed]
  14. Bonnet N, Martin O, Boubaya M, et al. High flow nasal oxygen therapy to avoid invasive mechanical ventilation in SARS-CoV-2 pneumonia: a retrospective study. Ann Intensive Care 2021;11:37. [Crossref] [PubMed]
  15. Xu J, Yang X, Huang C, et al. A Novel Risk-Stratification Models of the High-Flow Nasal Cannula Therapy in COVID-19 Patients With Hypoxemic Respiratory Failure. Front Med (Lausanne) 2020;7:607821. [Crossref] [PubMed]
  16. Hu M, Zhou Q, Zheng R, et al. Application of high-flow nasal cannula in hypoxemic patients with COVID-19: a retrospective cohort study. BMC Pulm Med 2020;20:324. [Crossref] [PubMed]
  17. Calligaro GL, Lalla U, Audley G, et al. The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study. EClinicalMedicine 2020;28:100570. [Crossref] [PubMed]
  18. Mellado-Artigas R, Mujica LE, Ruiz ML, et al. Predictors of failure with high-flow nasal oxygen therapy in COVID-19 patients with acute respiratory failure: a multicenter observational study. J Intensive Care 2021;9:23. [Crossref] [PubMed]
  19. Wendel Garcia PD, Aguirre-Bermeo H, Buehler PK, et al. Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort. Crit Care 2021;25:175. [Crossref] [PubMed]
  20. Eleni M, Evangelia M, Eleftheria K, et al. Clinical features and outcomes of hospitalized COVID-19 patients in a low burden region. Pathog Glob Health 2021;115:243-9. [Crossref] [PubMed]
  21. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307:2526-33. [PubMed]
  22. Matthay MA, Thompson BT, Ware LB. The Berlin definition of acute respiratory distress syndrome: should patients receiving high-flow nasal oxygen be included? Lancet Respir Med 2021;9:933-6. [Crossref] [PubMed]
  23. Grieco DL, Menga LS, Cesarano M, et al. Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial. JAMA 2021;325:1731-43. [Crossref] [PubMed]
  24. Avdeev SN, Yaroshetskiy AI, Tsareva NA, et al. Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19. Am J Emerg Med 2021;39:154-7. [Crossref] [PubMed]
Cite this article as: Polydora E, Alexandrou M, Tsipilis S, Athanasiou N, Katsoulis M, Rodopoulou A, Pappas A, Kalomenidis I. Predictors of high flow oxygen therapy failure in COVID-19-related severe hypoxemic respiratory failure. J Thorac Dis 2022;14(4):851-856. doi: 10.21037/jtd-21-1373

Article Options

Download Citation

Share