Table 4.
Clinical trials of awake prone position in acute hypoxemic respiratory failure of COVID-19 etiology
| Publication | PMID | Study design | Setting | Patient Population | Treatment | Intubation Rate | Mortality Rate | Main finding | Secondary findings |
| Avdeev et al.[101], 2021 | 33494771 | Prospective multicenter observational study | Non-ICU | COVID-19 AHRF Responders PaO2/FiO2 136 [118–172] Non-Responders PaO2/FiO2 138 [113–177] | Awake PP n = 22 CPAP n = 16 STO n = 6 | 14% [95% CI 5 to 33] | 9% [95% CI 3 to 28] | Response to awake PP depends on localization of aeration loss, and lung ultrasound can predict it. | Sixteen (73%) patients improved oxygenation with awake PP, 3 patients (14%) improved dyspnea in 15 min, 12 (54%) improved dyspnea at 3 h. Responders (patient with a decrease in lung ultrasound score with PP) had shorter disease duration. |
| Bastoni et al.[102], 2020 | 32748797 | Prospective observational study | Non-ICU | COVID-19 AHRF PaO2/FiO2 68 (5) | Attempted awake PP n = 10 Awake PP failed in 4 (40%) patients. Helmet NIV or helmet CPAP, PEEP ranging from 10 to 20 cmH2O | 100% [95% CI 72 to 100] | Not available | Awake PP was feasible in 4 out of 10 patients | Awake PP improved the PaO2/FiO2 to 97 (8) but there was no difference in lung ultrasound |
| Burton-Papp et al.[103], 2020 | 33110499 | Retrospective study | ICU | COVID-19 AHRF PaO2/FiO2 123 (28) | Attempted awake PP n = 20 CPAP n = 4 CPAP: PEEP 10 [8–10] cmH2O BIPAP and CPAP n = 16 EPAP 10 [10–10] cmH2O IPAP 15 [14–16] cmH2O Median duration of each cycle 3 (IQR 2) hours Number of cycles 5 (IQR 6.3) per patients Time spent prone 18% (IQR 31) | 35% [95% CI 18 to 57] | 0% [95% CI 0 to 16] ECMO 10% [3 to 30] | In patients with moderate AHRF treated with CPAP or NIV awake PP can improve oxygenation without relevant adverse events. | Patients that needed ETI did not had a significant improvement during prone position in PaO2/FiO2 [5, 95% CI -9 to 20] vs nonintubated [41, 95% CI 29 to 53]. |
| Caputo et al.[104], 2020 | 32320506 | Pilot study | Non-ICU | COVID-19 AHRF SpO2 with supplemental oxygen was 82% [72–85] | Awake PP n = 50 | 36% [95% CI 24 to 50] | Awake early prone position in the emergency department demonstrated improved oxygen saturation in COVID-19 patients. | ||
| Cherian et al.[95], 2021 | 33845325 | Retrospective study | Non-ICU | COVID-19 AHRF Patients that required IMV PaO2/FiO2 100 [95–155] Patients that did not required IMV PaO2/FiO2 206 [100–293] | Awake PP n = 59 PP for at least 3 h/day. HFNO n = 52 NIV n = 20 | IMV in the overall cohort 39% [95% CI 28 to 52] | 32% [95% CI 22 to 45] | Awake PP can be safely performed with improvement in oxygenation. However, its institution may be beneficial only in patients with mild to moderate AHRF. | To avoid the risk of delayed intubation ROX index, improvement in PaO2/FiO2, reduction of LDH and D-Dimer should be monitored. |
| Coppo et al.[96], 2020 | 32569585 | Prospective, feasibility study | Respiratory High Dependency Unit | COVID-19 AHRF PaO2/FiO2 standard care 180.5 (76.6) | Attempted awake PP n = 56 PP was maintained for 3 [3–4] hours in 47 patients (84%) Helmet CPAP n = 44 (79%) PEEP 8.3 (2.3) Reservoir mask 9 (16%) Venturi Mask 3 (5%) | 25% [95% CI 15 to 40] | 11% [95% CI 5 to 23] | PP was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. | PaO2/FiO2 improvement in PP 104.9 [95% CI 70.9 to 134], PaO2/FiO2 not improved after resupination 12.3 [95% CI -10.9 to 35.5]. Only 23 (50%) of patients (responders) mainted the improvement, but it was was not significant. LDH and C-reactive protein were higher in responders. |
| Damarla et al.[105], 2020 | 32551807 | Retrospective study | Mixed setting | COVID-19 AHRF Median oxygen requirement was 40% to achieve SpO2 94% (91 to 95) | Awake PP n = 10 HFNO n = 4 Nasal cannula n = 5 Room air n = 1 | 20% [95% CI 6 to 51] | 0% [95% CI 0 to 28] | PP is potentially a low-cost, easily implemented, and scalable intervention, particularly in low- and middle-income countries. | After 1h of PP SpO2 improved to 98% [97–99] and respiratory rate was reduced to 22 [18–25] from 31 [28–39]. |
| Despres et al.[106], 2020 | 32456663 | Case series | ICU | COVID-19 AHRF PaO2/FiO2 183 (144 to 212) | Awake PP n = 6 A total of 9 PP sessions were performed. HFNO in 4 sessions. SOT in 5 sessions. | 50% [95% CI 19 to 81] | Not reported | Considering these observations, PP combined with either HFNO or SOT could be proposed in spontaneously breathing, severe Covid-19 patients. | The proportion of patients with PaO2/FiO2 ratio improvement after PP appeared to be higher with HFNO compared to conventional oxygen therapy. |
| Ehrmann et al.[128▪▪], 2021 | 34425070 | Prospective collaborative randomized controlled meta trial, | Mixed setting | COVID-19 AHRF SpO2/FiO2 awake PP 147.9 (43.9) SpO2/FiO2 standard care148.6 (43.1) | Awake PP n = 564 Standard care n = 557 All patients treated with HFNO FiO2 0.6 [0.5 – 0.8] Awake PP HFNO flow 50 l/min [40–55] Standard care HFNO flow 40 l/min [40–50] | Treatment failure Awake PP 40% [95% CI 36 to 44] Treatment failure Standard care 46% [95% CI 42 to 50] IMV Awake PP 33% [95% CI 29 to 37] IMV Standard care 40% [95% CI 36 to 44] | Awake PP 21% [95% CI 18 to 24] Standard care 24% [95% CI 20 to 27] | Awake PP reduces the proportion of patients intubated or dying within 28 days of enrolment, 223 (40%) in the awake PP group vs 257 (46%) in the standard of care, P = 0.007, relative risk reduction 0.86 [95% CI 0.75 to 0.98]. Patients that received PP for longer sessions had lower treatment failure rate. | Awake PP significantly improves blood oxygenation, respiratory rate and ROX index during PP. The benefit was maintained after supination. |
| Elharrar et al.[97], 2020 | 32412581 | Prospective before after | ICU | COVID-19 AHRF O2 supplement < 4l/min in 16 (67%) patients O2 supplement ≥ 4l/min in 8 (33%) patients PaO2 78 (14) | Attempted awake PP n = 24 PP was maintained for: less than 1 h n = 4 (17%) for 1 to 3 h n = 15 (63%) for more than 3 h n = 5 (21%) | Follow up to 10 days 21% [95% CI 9 to 40] | Not reported | Responders (increased PaO2 > 20% from standard care) n = 6 [25%, 95% CI 12–45]; 3 patients were persistent responders. | 63% of patients were able to prone for more than 3 h, and 42% reported back pain. |
| Fazzini et al.[107], 2021 | https://doi.org/10.1177/1751143721996542 | Prospective observational | Non-ICU | COVID-19 AHRF PaO2/FiO2 115 (43) | Awake PP n = 46 12 (26%) patients could not tolerate PP for > 1 h. 34 (74%) awake PP for 5 h per session, 1 to 6 sessions daily. Interface: HFNO, CPAP, face mask oxygen; HFNO was the most used. | Overall cohort 43% [95% CI 30 to 58] Awake PP for > 1 h 29% [95% CI 17 to 46] Awake PP for < 1 h 83% [95% CI 55 to 95] | Overall cohort 30% [95% CI 19 to 45] Awake PP for > 1 h 26% [95% CI 15 to 43] Awake PP for < 1 h 42% [95% CI 19 to 68] | Patients that were pronated for more than 1 h had less need for endotracheal intubation than patients that were proned for less than 1 h. | PaO2/FiO2 standard care 115 (43) vs 148 (70); Respiratory rate standard care 34 (7) vs 25 (7); Prone position > 1 h less need for ICU than prone position < 1hour (41% vs 83%). |
| Ferrando et al.[108], 2020 | 33023669 | Prospective, multicenter, adjusted observational study | ICU | COVID-19 AHRF PaO2/FiO2, HFNO 111 [83–144] PaO2/FiO2, HFNO + PP 125 [99–187] | Overall cohort n = 199 HFNO n = 144 HFNO + PP n = 55 Patients in group HFNO + PP underwent pronation for at least 16h/die | HFNO 42% [34 to 50%] HFNO + PP 40% [95% CI 28 to 53] | HFNO 10% [95% CI 6 to 16] HFNO + PP 11% [95% CI 5 to 22] | The combined approach of HFNO and PP did not decrease the risk of endotracheal intubation | Patients treated with HFNO + awake PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0–2.5) vs 2 IQR 1.0–3.0] days (P = 0.055), but Awake PP did not affect 28-day mortality (P = 0.92). |
| Golestani-Eraghi et al.[109], 2020 | 32473503 | Prospective, observational | ICU | COVID-19 AHRF PaO2/FiO2 < 150 | Awake PP n = 10 Helmet NIV (settings are not reported) Mean PP duration was 9 h | 20% [95% CI 6 to 51] | 20% [95% CI 6 to 51] | Authors report low intubation rate and high compliance to the intervention, suggesting that PP might be a useful tool to increase blood oxygenation in patients with moderate to severe AHRF related to COVID-19. | Improvement in oxygenation after PP: standard care PaO2 46.34 (5.2) vs PP PaO2 62.5 (4.6). |
| Hallifax et al.[110], 2020 | 32928787 | Retrospective study | Respiratory High Dependency Unit | COVID-19 AHRF FiO2 ≤ 60% n = 22 (46%) FiO2 > 60% n = 26 (54%) The proportion between patients with no limitations of treatment and patients with limitations of treatment is not specified. | Overall cohort n = 48 Attempt awake PP n = 30 Successfull proning defined as at least 2 h twice a day for 2 consecutive days. Full proning n = 11 Semiproning n = 17 Refused n = 2 CPAP only n = 22 HFNO + CPAP n = 26 CPAP PEEP ranging from 6–8 cmH2O | 23% [95% CI 13 to 37] | Patients with limitations of treatment 54% [95% CI 40 to 67] 6% [95% CI 2 to 19] died on IMV 4% [95% CI 1 to 14] still on IMV | Data from this cohort of patients managed on respiratory high dependency unit show that CPAP and awake proning are possible in a selected population of COVID-19. | Increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. |
| Jagan et al.[111], 2020 | 33063033 | Retrospective study | Non-ICU | COVID-19 AHRF PaO2/FiO2 not reported | Overall cohort n = 105 Standard care n = 65 Self-proning n = 40 Self-proning was defined as a time spent PP greater or equal to 1 h, for at least 5 times/day, and for at least 1 h overnight. Interface not specified | Standard care 27% [95% CI 18 to 40] Self-proning 10% [95% CI 4 to 23] | Standard care 25% [95% CI 16 to 36] Self-proning 0% [95% CI 0 to 9] | Awake self-proning was well tolerated, with good compliance in 38% of patients and was associated with lower intubation rates, that remained significant after adjustment for SOFA and APACHE II. | The difference in mortality was significant at the univariate analysis but become nonsignificant after adjustment for SOFA and APACHE II. |
| Jayakumar et al.[125], 2021 | 33949237 | Multicenter, randomized, controlled feasibility trial with 3 parallel groups | Non-ICU | COVID-19 AHRF Standard care PaO2/FiO2 185.6 (126) Awake PP PaO2/FiO2 201 (119) Discharged against medical advice: 2 patients in each group. | Overall cohort n = 60 Standard care group n = 30 PP group n = 30 Encouraged to PP for at least 6 h/day. Median duration of PP per session was 2 h. 3 progressive interfaces: low flow oxygen (nonrebreather face mask) -> HFNO -> NIV (oronasal interface) | Standard care 13% [95% CI 5 to 30] Awake PP 13% [95% CI 5 to 30] | Standard care 7% [95% CI 2 to 21] Awake PP 10% [3 to 26] | In the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. 70% of the patients in the prone group were able to lie prone for 4 h a day. In the standard care group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 h. | PaO2/FiO2 after 2 h was not different in the two groups: Standard care 171.7 (100.6) vs awake PP 198 (87.6), P = 0.3. There were no adverse events in both groups. |
| Johonson et al.[126], 2021 | 33596394 | Pragmatic randomized controlled trial | Non-ICU | COVID-19 AHRF FiO2 at admission 21 [21–29], SpO2 at admission 94% [90–96]. Requiring supplemental O2 at admission: 11 (36.7%) patients. | Overall cohort n = 30 Standard care n = 15 Awake PP n = 15 Self-driven protocol. Only 6/15 (40%) patients were observed in PP in the first 72 h. Cumulative time spent in PP was 2.4% of total time (1.6 [95% CI 0.2 to 3.1] hours). | Standard care 7% [95% CI 12 to 30] Awake PP 13% [95% CI 4 to 38] | Standard care 0% [95% CI 0 to 20] Awake PP 13% [95% CI 4 to 38] | Patient-directed PP is not feasible in spontaneously breathing, nonintubated patients hospitalized with COVID-19. | No improvements in oxygenation were observed at 72 or 48 h. |
| Moghadam et al.[112], 2020 | 32427179 | Prospective observational study | Non-ICU | COVID-19 AHRF Mean SpO2 at arrival 85.6% | Awake PP n = 10 | 0% [95% CI 0 to 28] | 0% [95% CI 0 to 28] | SpO2 improved from 85.6% to 95.9% after awake PP. 40% of patients reported improved dyspnea. | |
| Ng et al.[113], 2020 | 32457195 | Case series | Non-ICU | COVID-19 AHRF Median room air SpO2 at arrival 91% (91 to 94) Oxygen supplementation at arrival 2l/min [2–3] | Awake PP n = 10 Cumulative median time in PP 21 h. Three (10%) patients were transferred to ICU: 1 (10%) HFNO 1 (10%) Venturi Mask 1 (10%) IMV | 10% [95% CI 2 to 40] | 10% [95% CI 2 to 40] | Awake PP can be a low-risk, low-cost maneuver which can help patients with COVID-19 pneumonia delay or reduce the need for intensive care. | Three out of 10 patients were transferred to ICU, and one died. |
| Padrao et al.[114], 2020 | 33107664 | Retroscpetive study | Non-ICU | COVID-19 AHRF Standard care SpO2 92.5% [90–94] O2 flow rate 6 l/min [5–10] SpO2/FiO2 < 235 in 56 (53%) patients Awake PP SpO2 92% [88–93] O2 flow rate 7 l/min [5–13.5] SpO2/FiO2 < 235 in 36 (63%) patients SpO2/FiO2 196 [128–254] | Overall cohort n = 166 Standard care n = 109 Awake PP n = 57 Nasal cannula 44% Venturi mask 10% Nonrebreather face mask 46% First session awake PP duration: < 1h (6%) 1–2h (14%) 2–3h (12%) 3–4h (10%) > 4h (58%) | Awake PP 58% [95% CI 45 to 70] Standard care 49% [95% CI 39 to 58] | Awake PP 11% [95% CI 5 to 21] Standard care 20% [95% CI 14 to 29] | Awake PP was not associated with a reduction of need of intubation, both at univariate or multivariate analysis. | Awake PP led to improvement in ROX index (from 5.7 [3.9–7.7] to 7.7 [5.4–11], SpO2/FiO2 (from 196 [128–254] to 224 [159–307]) and respiratory rate (from 34 [30–38] to 29 [26–32]) |
| Paternoster et al.[98], 2020 | 33067029 | Case series | High Dependency Unit | COVID-19 AHRF PaO2/FiO2 107.5 (21) | Awake PP n = 11 Awake PP cycles of 13 (1.2) hours Helmet CPAP PEEP 9.6 (1.74) cmH2O Seven (63.6%) patients needed dexmedetomidine during awake PP | 27% [95% CI 10 to 57] | 18 [95% CI 5 to 48] | In conclusion, helmet CPAP in prone position for COVID-19 severely hypoxemic acute respiratory failure resulted feasible and without complications; the infusion of dexmedetomidine to improve patients’ compliance to pronation was well tolerate. | PaO2/FiO2 at enrollment 107 (20) PaO2/FiO2 after 24 h 214.6 (73) PaO2/FiO2 after 48 h 224.6 (86.6) PaO2/FiO2 after 72 h 244.4 (106.2) P < 0.001 Respiratory rate at enrollment 27 (4) Respiratory rate after 24 h 24 (5) Respiratory rate after 48 h 22 (4) Respiratory rate after 72 h 20 (5) P < 0.001 |
| Perez-nieto et al.[124▪▪], 2021 | 34266942 | Retrospectivemulticenter study | Non-ICU | COVID-19 AHRF SpO2/FiO2 189.5 (81.6) | Awake PP n = 505 Standard care n = 322 Awake PP group was prones for at least 2 consecutive hours. Awake PP Nasal Cannula 50% HFNO 12.1% Nonrebreather face mask 37.6% Standard care Nasal Cannula 46.3% HFNO 6.8% Nonrebreather face mask 46.9% | Awake PP 24% [95% CI 20 to 27] Standard care 40% [95% CI 35 to 46] | Awake PP 20% [95% CI 17 to 24] Standard care 38% [33 to 43] | Awake PP reduces the risk for endotracheal intubation and for mortality. The reduction of risk remained significant at multivariate, and after propensity score match. | Main risk factors associated with endotracheal intubation were age, SpO2/FiO2 < 100, and the use of nonrebreather mask. |
| Prud’homme et al.[115], 2021 | 33516704 | Retrospective multicenter matched cohort study | Non-ICU | COVID-19 AHRF SpO2/FiO2 standard care 299 (45) SpO2/FiO2 awake PP 279 (84) | Awake PP n = 48 Standard care n = 48 Oxygen supplementation strategy: first line oxygen therapy, escalation to HFNO, escalation to NIV, escalation to IMV. 32 (67%) patients underwent PP from 3 to 8 h/day 16 (32%) patients underwent PP for > 8 h/day | Follow up to day 14 Awake PP 15% [95% CI 7 to 27] Standard care 17% [95% CI 9 to 30] | Follow up to day 14 Awake PP 8% [95% CI 3 to 20] Standard care 12% [6 to 25] | Awake PP reduced the need of upgrading oxygen delivery method at day 14 (15 (31.2%)) compared with conventional treatment (25 (52.1%)), P = 0.038 with a hazard ratio of 2.03 [95% CI, 1.07–3.86; P = 0.003]. | Awake PP did not decrease the need for endotracheal intubation or the mortality rate. |
| Retucci et al.[99], 2020 | 32679237 | Pilot prospective observational study | High Dependency Unit | COVID-19 AHRF PaO2/FiO2 143 [97–204] | Awake PP n = 26 Helmet CPAP Prone or lateral position lasted 1h Helmet CPAP PaO2/FiO2 180 [155–218] 39 sessions of attempted PP: 12 prone and 27 lateral positioning. | 27% [95% CI 14 to 46] | 8% [95% CI 2 to 24] | The target was an alveolar-arterial gradient decrease of more than 20% before and after PP. Of the 12 sessions of PP 33.3% of trials succeeded, 41.7% decrease in alveolar-arterial gradient of < 20% from supine position, and 25% failed. Of the 39 sessions of lateral positioning: 8% succeeded, 52% decrease in alveolar-arterial gradient < 20% from supine position, 40% failed. | Respiratory rate: standard care 23.7 (4.7), during PP 23.1 (4.5), after resupination 23.6 (4.7). PaO2/FiO2 182.9 (43), during awake PP 220 (64.5), after resupination 179.3 (43.9). |
| Ripoll-Gallardo et al.[116], 2020 | 32713387 | Retrospective case series | Non-ICU | COVID-19 AHRF PaO2/FiO2, 115 (13) | Awake PP n = 13 Interface: Helmet CPAP PEEP 10 cmH2O | 70% [95% CI 42 to 87] | 54% [95% CI 29 to 77] | Patients with moderate to severe AHRF have a high intubation rate, despite the treatment with CPAP and awake PP. | PaO2/FiO2, improved before and after PP (P = 0.003), but there was no difference in respiratory rate before and after. |
| Rosén et al.[127▪], 2021 | 34127046 | Multicenter randomized clinical trial | Non-ICU | COVID-19 AHRF Standard care n = 39 PaO2/FiO2 standard care 115 [94–130] Prone n = 36 PaO2/FiO2 prone 115 [86–130] | HFNO standard care n = 29 HFNO prone n = 31 NIV standard care n = 27 PEEP 8 [6–8] NIV prone n = 21 PEEP 7 [6–10] | Standard care group 33% [95% CI 20 to 49] Prone group 33% [95% CI 20 to 50] | Control group 8% [95% CI 3 to 20] Prone group 17% [95% CI 8 to 22] | The implemented protocol for awake PP increased duration of awake PP but did not reduce the rate of intubation in patients with AHRF due to COVID-19 compared to standard care. | Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group, P = 0.03, there were no difference in the use of NIV, vasopressors, continuous renal-replacement therapy, ECMO, VFD, hospital and ICU length of stay and mortality among the two groups. |
| Sartini et al.[117], 2020 | 32412606 | Cross sectional | Non-ICU | COVID-19 AHRF PaO2/FiO2 157 (43) | Awake PP n = 15 Interface: NIV, PEEP 10 cmH2O Number of PP cycles 2 [1–3], for a total duration of 3 [1–6] hours | Follow-up 14 days Awake PP failure 13% [95% CI 4 to 38] | Follow-up 14 days 7% [95% CI 1 to 30] | All patients had improvement in PaO2/FiO2 during PP, and 12 (80%) had maintained PaO2/FiO2 improvement after resupination. | All patients had a reduction in respiratory rate during PP, that was maintained after resupination. |
| Taboada et al.[118], 2021 | 33839432 | Prospective observational study | ICU | COVID-19 AHRF PaO2/FiO2 93 [72–108] | Awake PP n = 63 Treated with HFNO and dexmedetomidine For a median of 4 [2.5–8] sessions, each lasting 36 [24–72] hours. | HFNO and awake PP failure 32% [95% CI 22 to 44] | 11% [95% CI 5 to 21] | In patients with mild to moderate AHRF treatment with a combination of dexmedetomidine, HFNO and long periods of PP led to a mortality rate of 11%. | Application of HFNO, awake PP and dexmedetomidine was relatively safe, as bradycardia (<40 bpm) during DEX infusion was observed in 5 patients (7.9%). |
| Thompson et al.[119], 2020 | 32584946 | Prospective observational study | Intermediate Care Unit, | COVID-19 AHRF SpO2 ≤ 93% in nasal cannula 6 l/min or 15 l/min via nonrebreather face mask) | Awake PP n = 25 At least 1 session lasting at least 1hour | 48% [95% CI 30 to 66] | 12% [95% CI 4 to 30] | During awake PP the range of improvement in SpO2 was 1% to 34% (median [SE], 7% [1.2%]; 95% CI, 4.6%-9.4%). | An SpO2 of 95% or greater after 1 h of PP was associated with a lower rate of intubation. |
| Tonelli et al.[120], 2021 | 33824084 | Retrospectivemulticenter study | Respiratory ICU | COVID-19 AHRF PaO2/FiO2 overall cohort 149 [78–232] PaO2/FiO2 awake PP 141 [73–223] PaO2/FiO2 standard care 153 [84–232]; P = 0.03 | Awake PP n = 38 Standard care n = 76 Awake PP encouraged for at least 3 h; number of daily PP sessions: 1 to 4 Interface: HFNO 69 (61%) Helmet CPAP 25 (22%) CPAP 8 cmH2O and then adjusted Oro-nasal NIV 19% (17) PEEP 8 cmH2O and then adjusted Pressure support 10 cmH2O and then adjusted | Awake PP 18% [95% CI 9 to 33] Standard care 39% [95% CI 29 to 51] | Awake PP 13% [95% CI 6 to 27] Standard care 22% [95% CI 14 to 33] | Awake PP in awake and spontaneously breathing Covid-19 patients is feasible and can significantly reduce intubation rate (HR = 0.59 95% CI [0.3 to 0.94], P = 0.03 after adjustment) especially in those patients undergoing HFNO (HR = 0.34 95% CI [0.12 to 0.84], P = 0.04). | Awake PP increased the respiratory support free days (standard care 15 [2–22] vs 20 [2–24] P = 0.03) and decreased the respiratory ICU (standard care 15 [3–26] vs 10 [3–21] P = 0.02) and the hospital length of stay (standard care 24 [3–45] vs 20 [3–41], P = 0.03). |
| Tu et al.[121], 2020 | 32566624 | Pilot retrospective study | ICU | COVID-19 AHRF PaO2/FiO2 lower 150 | Awake PP n = 9 Treated with HFNO Awake PP sessions applied for 5 [3–8] times, with a duration 2 [1–4] hours. | 22% [95% CI 6 to 55] | Not reported | Awake PP could improve blood oxygenation and potentially avoid endotracheal intubation. | Mean PaO2 increased from 69 (10) to 108 (14) with awake PP (P < 0.00) and PaCO2 decreased from 47 (7) to 39 (5) (P = 0.007). |
| Winearls et al.[100], 2020 | 32895247 | Retrospective Study | Non-ICU | COVID-19 AHRF PaO2/FiO2 112 [106–194] Patients with no limitations of treatment n = 14 Patients with limitations of treatment n = 10 | Attempted awake PP n = 24 Treated with CPAP, maximum PEEP 12 [12–15] cmH2O Interface not specified 2 patients did not tolerate Awake PP 12 patients received full awake PP, 10 patients semiprone lateral position The mean (SD) time of awake PP was 8 (5) hours in first day. | Patients with no limitations of treatment 7% [95% CI 1 to 31] | Patients with limitations of treatment 40% [95% CI 17 to 69] | Awake PP alongside CPAP significantly increased both the ROX index and the PaO2/FiO2 from baseline values (ROX index: 7.0 (2.5) baseline vs 11.4 (3.7) CPAP + PP, P < 0.0001; PaO2/FiO2 143 (73) mm Hg baseline vs 252 (87) mm Hg CPAP + PP, P < 0.01). | No difference in respiratory rate at any timepoint was found. |
| Xu et al.[122], 2020 | 32448330 | Retrospective multicenter study | ICU | COVID-19 AHRF PaO2/FiO2 157 (46) | Awake PP n = 10 Target time was > 16 h/day | 0% [95% CI 0 to 28] | 0% [95% CI 0 to 28] | Early awake PP combined with HFNO therapy could be used safely and effectively in young, fit, severe COVID-19 patients, and it may reduce the conversion to critical illness and the need for tracheal intubation. | After awake PP PaO2/FiO2 and increased significantly, and respiratory alkalosis decreased significantly. |
| Zang et al.[123], 2020 | 32699915 | Prospective observational study | ICU | COVID-19 AHRF Patients with severe hypoxia | Awake PP n = 23 Standard care n = 37 | Not reported | Awake PP 43% [95% CI 26 to 63] Standard care 76% [60 to 87], P < 0.001 | Early awake PP might reduce hypoxia and improve mortality. | In the awake PP group SpO2 increased from 91% (1.5) to 95.5 (1.7), P < 0.01, respiratory rate decreased from 28.2 (3) to 24.9 (1.8), P < 0.01, and ROX index increased from 3.3 (0.5) to 4 (0.5), P < 0.01. |
Values are displayed as means (SD) or medians [Interquartile range].
Failure was defined as either intubation, death while still on noninvasive respiratory support, or escalation to other noninvasive respiratory support to avoid endotracheal intubation. AHRF, acute hypoxemic respiratory failure; ARDS, acute respiratory distress syndrome; awake PP, awake prone position; CPAP, continuous positive end-expiratory pressure; FiO2, fraction of inspired oxygen; HFNO, high-flow nasal oxygen; ICU, intensive care unit; IQR, interquartile range; NIV, noninvasive ventilation; PaO2, partial pressure of arterial oxygen; PEEP, positive end-expiratory pressure; SAPS, Simplified Acute Physiology Score; SOFA, Sequential Organ Failure Assessment; SpO2, peripheral capillary oxygen saturation; VFD, Ventilatory Free Days.