Table 1.
Studies that investigate the effect of prone position combined with HFNO compared to standard care in patients with COVID-19 pneumonia. HFNO=high flow nasal oxygen; APP=awake prone positioning; HR=hazard ratio; PaO2 =arterial partial pressure of oxygen; FiO2 =fraction of inspired oxygen; NA=not available; IMV=invasive mechanical ventilation; SpO2 =peripheral saturation of oxygen, OR=Odds Ratio, RR=Relative Risk.
| Reference | Country | Number of patients | HFNO Onset | Parameters of HFNO | APP Timing | APP/ HFNO discontinuation | Comments |
|---|---|---|---|---|---|---|---|
| (Ehrmann et al. (2021) | Canada France Ireland Mexico USA Spain |
1121 (HFNO/ APP 564, HFNO 557) | PaO2/FiO2 ≤ 300 or SpO2/FiO2 ≤ 315 | Maximum tolerated flow setting Titrated to SaO2 > 90–95 % |
As long as tollerated/ failure | Hospital discharge, intubation (respiratory rate >40 breaths min, fatigue, respiratory acidosis pH<7.25, copious tracheal secretions, SpO2 <90 % with FiO2 >0.8, hemodynamic instability, deteriorating mental status), death, improved oxygenation | Treatment failure (intubation or death) 40 % HFNO/ APP vs 46 % HFNO (RR 0.86), HR for intubation 0.75, for 28-day mortality 0.87. |
| (Xu et al., 2020) | China | 10 | PaO2/FiO2 < 300 | Flow NA SpO2 > 90 % |
> 16 h/day | NA | None of enrolled subject underwent IMV |
| (Tu et al., 2020) | China | 9 | HFNO > 2 days with PaO2/FiO2 < 150 | Initial flow rate 50–60 L/min targeted to SpO2 > 90 % | 2 h, 5 times/day | Scarce tolerance to APP. | Intubation rate 22.2 %, HFNO/ APP significantly increased SpO2 and PaO2 compared with HFNO |
| (Ferrando et al., 2020) | Spain | 1076 (55 HFNO/ APP) | Admission. SpO2 < 93% with oxygen 15 L/min. |
NA | > 16 h per day | NA | Intubation rate 40 %. HFNO/ APP did not reduce risk intubation (HR 0.87), but increased the time to intubation in comparison with HFNO alone. Similar length of ICU stay and 28-day mortality. |
| (Kaur et al., 2021) | USA | 125 | Admission PaO2/FiO2 < 240 |
Initial flow 50 L/min titrated to SaO2 > 90–95 % | As long as tollerated | FiO2 < 0.4 and HFNO flow 40 L/min. | Early APP lower mortality rate (26% vs 45%); no difference in intubation rate |
| (Ibarra-Estrada et al., 2022) | Mexico | 430 (216 HFNO/ APP, 214 HFNO) | Admission. SpO2 < 90 % with oxygen mask 15 L/min |
Max flow 40 L/min, FiO2 > 30 % Titrated to SpO2 90–95 % |
As long as tollerated. APP/HFNO success defined as respiratory rate< 25 breaths min, increased ROX> 1.25 after first session, APP> 8 h, lung ultrasound score reduced by 2 or more. | FiO2 ≤ 0.4 with flow ≤ 20 L/min to maintain SpO2 ≥ 90 % for 2 h, need for non-invasive mechanical ventilation, death. | HFNO/ APP group: lower intubation rate (30 %) than HFNO (43 %) RR= 0.7, shorter length of stay (11 % vs 13 %) |
| (Péju et al., 2022) | France, Belgium, Switzerland | 187 (8 HFNO/ APP) | According to the severity of respiratory failure and local protocol. | NA | NA | NA | Pregnant patients. Eight patients APP/ HFNO of whom 3 intubated. |
| (Kucukdemirci-Kaya et al., 2022) | Turkey | 35 (13 HFNO/ APP) | Admission. Respiratory rate > 30 breaths min with SpO2 < 92 % with oxygen 15 L/min, and/or PaO2/FiO2 < 150 | Flow 50–80 L/min, titrated to SpO2 > 88 % | 12 h for 1–2 times/day | Death, intubation. ROX index and PaO2/FiO2 at 2 h to predict intubation risk were higher in the treatment success group. |
No differences in treatment failure (intubation, death) between APP vs. non HFNO/ APP groups (OR 0.29), no difference in COVID-19 phenotype (OR 0.24). |
| (Qian et al. (2022) | USA | 501 (71 HFNO/ APP) | Admission, not specified. | Oxygen therapy targeted to SpO2 89 % | Admission 4 h/2 times day | NA | No clinical benefits on outcome of HFNO/ APP as compared to HFNO alone. |
| (Yang et al., 2020) | Canada | 51 (10 HFNO/ APP) | Admission, not specified. | At provider’s discretion | Daily If required FiO2 > 0.65 |
At provider’s discretion | 39 % not required intubation. |
| (Rosén et al., 2021) | Sweden | 75 (36 APP group of whom 31 HFNO/ APP, 39 control) | Admission. PaO2/FiO2 < 150 mmHg for more than 1 h |
Median flow 50 L/min | APP 16 h/day | Intubation, improvement (standard facemask with oxygen flow rate<5 L/min for 12 h), clincian discretion. | No differences. Intubation 13 patients control vs. 12 APP group (HR 1.01). |
| (Jouffroy et al., 2021) | France | 40 (37 HFNO/ APP) | Admission, not specified. | NA | 3–6 h, 2 times/ day | NA | No effects on intubation (HR 0.96) or 28-day mortality rates (HR 0.51) |
| (Vianello et al., 2021) | Italy | 93 | Admission, not specified. | FiO2 0.21–1.0 flow up to 60 L/min adjusted to maintain SpO2 > 93 % | > 2 h, 2 times/ day. | Non-invasive ventilation started when FiO2 > 0.6 needed to achieve SpO2 > 92%, intubation at provider’s discretion. APP failure was defined as inability to maintain APP> 2 h, refusal, inadequate cooperation, or lack of improvement/ deterioration in oxygenation. | Sixteen (17.2 %) patients were intubated, 27 (29 %) escalated to non-invasive ventilation, 9 died (9.7 %). In patients who passed the HFNO/ APP trial (around 50 %), survival benefits were observed without escalation of therapy. |