Prone positioning in awake non-ICU patients with ARDS caused by COVID-19

To the Editor,

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world in the past four months. Many of the patients admitted to the hospital with COVID-19 show fatigue and dyspnea, needing intensive care admission due to an acute respiratory distress syndrome (ARDS) [1]. Prolonged prone positioning (PP) during mechanical ventilatory support was recommended in patients with severe ARDS, increasing oxygenation, thereby reducing mortality [2]. However, there is limited information on the use of prone positioning in awake non-ICU patients with ARDS caused by COVID-19.

We prospectively evaluated non-ICU patients admitted to the University Clinical Hospital of Santiago, Spain, between March 31 and April 11, 2020, with laboratory-confirmed COVID-19 disease who had mild or moderate ARDS requiring oxygen therapy (face mask or nasal cannulas). The objective was to determine whether prone position would impact the oxygenation. Secondary outcomes were to describe outcomes as well as treatments used. Patients were enrolled if they met the following criteria: adults with mild or moderate ARDS needing oxygen therapy (PaO2/FiO2 < 300 mmHg) and being able to adopt PP. Exclusion criteria were unstable haemodynamic status and patients with ARDS needing high-flow nasal cannula or non-invasive ventilation. The study protocol was approved by the ethics committee of Galicia (code No. 2020-184) and all participating subjects provided informed consent.

Patients were instructed to remain first in supine position, posteriorly in PP for one hour, and then again in supine position. All patients were monitored with oxygen saturation (SpO2) during the study period. To evaluate the clinical effects of one-hour PP in PaO2, and PaO2/FiO2, we obtained blood arterial gases in these patients before and following the PP session. Then, we recommended PP sessions for at least thirty minutes three times a day until the patient becomes too tired and uncomfortable to keep that position. Demographic data, clinical course, treatments and outcomes were collected (Table 1 ).

Table 1.

Demographics data, coexisting conditions, radiological and laboratory findings of the study patients.

Clinical characteristics of the patients
Demographics	Patients (29)
Age, mean ± SD, yr	64 ± 12
Female sex, n (%)	8 (28%)
Weight, mean ± SD, kg	83 ± 10
BMI, mean ± SD, cm	29.2 ± 3.6
Coexisting conditions, n (%)
Hypertension	13 (45%)
Diabetes	8 (27%)
Chronic obstructive pulmonary disease	5 (17%)
Heart disease	3 (10%)
Others	5 (17%)
Radiological findings, n (%)	28 (96%)
Local patchy shadowing	6 (21%)
Bilateral patchy shadowing	19 (66%)
Interstitial abnormalities	6 (21%)
Laboratory parameters, median (IQR) and n (%)
Leukocytes	6350 (5330−7567)
Lymphocytes	990 (720−1380)
< 1000	16/29 (55%)
C-reactive protein, mg/L	6,1 (3.4−14.5)
> 10	11/29 (38%)
D-dimer, ng/mL	662 (501−1030)
> 500	19/29 (66%)
> 1000	8/29 (28%)
Lactate dehydrogenase, U/L	484 (304−584)
> 300	23/29 (79%)
Creatine kinase, ng/mL	71 (44−127)
> 100	10/29 (34%)
Serum Ferritin, μg/L	632 (243−1500)
> 600	14/29 (48%)
Interleukin-6, pg/mL	28.8 (5.7−58.5)
> 40	7/29 (24%)
PCT ≥ 0.05 ng/mL, No. (%)	3/29 (10%)
Triglycerides	165 (126−224)

Data presented as number (%), mean ± SD, or median (IQR).

PP = prone position, BMI = body mass index.

It was estimated that 27 patients were necessary to detect a significant improvement of SpO2 (≥ 2%) during PP compared with previous supine position in 50% of the patients, and a significant worsening of SpO2 (≥ 2%) in 5% of the patients, for a 5% alpha error and a power of 80% using a McNemar´s chi-square test. Numerical variables were compared using the paired Wilcoxon or Kruskal-Wallis test, and factor variables were compared with either the Pearson or the McNemar Chi-square tests. All analyses were performed in R v.3.6.

A total of 29 patients were included. All patients were treated with lopinavir/ritonavir, hydroxychloroquine, azithromycin, prophylactic anticoagulants, and oxygen therapy. Corticosteroids and tocilizumab were administered in 15 patients (51.7%) and 10 patients (34.5%) respectively. SpO2, PaO2, and PaO2/FiO2 showed an upward trend during and following PP session (Fig. 1 ). SpO2 was significantly higher during PP (95.8 ± 2.1; P = 0.0003) and after PP (95.4 ± 2.7; P = 0.0034) compared with previous supine position (93.6 ± 2.3). During and following PP, 23 patients (79%) and 18 patients (62%) had an increase of SpO2, respectively. PaO2/FiO2 was higher following PP (242 ± 107; P = 0.0072) as compared to before PP (196 ± 68). On April 23, 2020, 2 patients (7%) had died, 26 patients (89.6%) had been discharged from the hospital, and one patient was still hospitalised. Five patients needed ICU admission during their hospitalisation. The median duration of ICU stay and hospital stay were 11 [8–18] days and 15 [11–29] days, respectively.

Fig. 1.

pre: before prone position; prone: during prone position; post: after prone position. A: StO2 during the three study steps (pre, prone, post); P = 0.0003 SpO2 prone vs pre; P = 0.0034 SpO2 post vs pre. B: pO2 pre and post; P = 0.0086 pO2 post vs pre. C: pO2/FiO2 pre and post; P = 0.0072 pO2/FiO2 pre and post PP.

In the treatment of severe ARDS from COVID-19, different options have been described, including placing patients in prone position [2]. Potential explications for this improved oxygenation are that PP improves the mismatch of ventilation/perfusion, transpulmonary pressure along the ventral-to-dorsal axis becomes more homogeneously distributed in PP compared with supine position and PP promotes recruitment of non-aerated dorsal lung regions of the lung. This was demonstrated in intubated patients undergoing invasive mechanical ventilation with severe ARDS [2]. The use of PP in non-intubated patients was limited to ICU patients suffering from moderate or severe ARDS with the goal to avoid intubation [3], [4]. Ding et al. [3] studied the efficacy of PP combined with non-invasive ventilation (NIV) or high-flow nasal cannula (HFNC) in ICU patients with moderate to severe ARDS. They observed that early application of PP in non-intubated patients with HFNC or NIV may avoid the need for intubation, especially in patients with moderate ARDS and SpO2 > 95%. Similarly, Scaravilli et al. [4] observed, in a retrospective study of 15 non-intubated ICU patients with hypoxemic acute respiratory failure, that PP improved oxygenation. In the last month, several authors have described the use of PP for management of COVID-19 patients with severe hypoxemia [5].

In the present study, we observed that in non-ICU patients with COVID-19 who have mild or moderate ARDS, oxygenation was improved during and following 1 h of PP. This result may be very important because one of the biggest problems in the treatment of ARDS from COVID-19 is the lack of beds and ventilators in ICUs. This procedure performed several times a day can be beneficial and providing time for patients to respond to the COVID-19 treatments administered, trying to avoid ICU admissions. While the PP in intubated patients with mechanical ventilation is complicated, requiring several operators to perform it, the PP in awake patients outside of the ICU is easier. Patients can adopt PP by themselves, maintaining the appropriate posture for as long as possible. The patient can do it as many times as he/she sees fit. In the present study, our patients showed good tolerance for 1 h of PP. According to our experience, we recommended it for at least 30 min three times a day or until the patient becomes too tired and uncomfortable to keep that position. However, our study does not allow determining the best duration and frequency of PP. Randomised clinical trials to determine the benefits of PP and optimal regimens in awake patients with ARDS caused by COVID-19 are urgently needed.

Conflicts of interest

The authors declare the absence of conflict of interests.

Funding

No funding provided.

Authors’ contributions

Conception of the study: Manuel Taboada, Nuria Rodríguez; Study design: Manuel Taboada, Aurora Baluja; Data collection: Manuel Taboada, Nuria Rodríguez, Vanessa Riveiro; Data analysis: Aurora Baluja; Drafting the manuscript: All authors helped to revise the draft of the manuscript; Editing and approval of the manuscript: All authors.

Summary statement

In hospitalised non-ICU patients with mild or moderate ARDS by COVID-19 needing therapy with oxygen, prone positioning improves oxygenation.