Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure

toryfailurewasassociatedwithimprovedoxygenation.Inad-dition, patients with an Sp O 2 of 95% or greater after 1 hour of thepronepositionwasassociatedwithalowerrateofintuba-tion.Limitationsofourstudyarethelackofcontrolgroupand a small sample size. Randomized clinical trials are needed to establishwhetherimprovedoxygenationafteruseoftheprone position in awake, nonintubated patients improves survival.


Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure
Critically ill patients with coronavirus disease 2019 (COVID-19) severely strained intensive care resources in New York City in April 2020. 1 The prone position improves oxygenation in intubated patients with acute respiratory distress syndrome. 2,3 We investigated whether the prone position is associated with improved oxygenation and decreased risk for intubation in spontaneously breathing patients with severe COVID-19 hypoxemic respiratory failure. [4][5][6] Methods | We screened consecutive patients admitted to the Columbia University step-down unit (intermediate care unit) between April 6 and April 14, 2020 (N = 88). Inclusion criteria were laboratory-confirmed COVID-19 with severe hypoxemic respi- ratory failure defined as respiratory rate of 30 breaths/min or greater and oxyhemoglobin saturation (SpO 2 ) of 93% or less while receiving supplemental oxygen 6 L/min via nasal cannula and 15 L/min via nonrebreather face mask. A confirmed case of COVID-19 was defined by a positive result on a reverse transcriptase-polymerase chain reaction assay of a specimen collected on a nasopharyngeal swab. Exclusion criteria were altered mental status with inability to turn in bed without assistance (n = 13), extreme respiratory distress requiring immediate intubation (n = 23), or oxygen requirements less than those specified in the inclusion criteria (n = 23). We asked eligible patients (n = 29) to lie on their stomach for as long as tolerated up to 24 hours daily. They could use a pillow placed under the hips/pelvis if desired and rest in the lateral decubitus or supine position followed by repeat prone positioning. Do-not-resuscitate status did not affect the decision to initiate or continue the use of the prone position. The Columbia University institutional review board ap-proved the study and waived the need for informed consent from the participants, as we analyzed deidentified data collected from electronic medical records. The primary outcome was change in SpO 2 before and 1 hour after initiation of the prone position. We report the median change in SpO 2 with 95% CIs. We used the Wilcoxon test for analysis of change in SpO 2 . We assessed the mean risk difference in intubation rates for patients with SpO 2 of 95% or greater vs SpO 2 less than 95% 1 hour after initiation of the prone position. We assessed intubation rates across demographic and other clinical factors with RStudio, version 1.2.5019 (RStudio).
Results | Among 29 eligible patients, 25 had at least 1 awake session of the prone position lasting longer than 1 hour; 4 refused the prone position and were intubated immediately. One hour after initiation of the prone position, SpO 2 increased compared with baseline ( Figure). The range of improvement in SpO 2 was 1% to 34% (median [SE], 7% [1.2%]; 95% CI, 4.6%-9.4%). In all patients, the levels of supplemental oxygen were unchanged during the first hour of the prone position. One hour after initiation of the prone position, 19 patients had SpO 2 of 95% or greater; subsequently, 7 (37%) required intubation. Among 6 patients whose SpO 2 remained less than 95% 1 hour after initiation of the prone position, 5 (83%) were intubated. The mean difference in the intubation rate among patients with SpO 2 of 95% or greater vs SpO 2 less than 95% 1 hour after initiation of the prone position was 46% (95% CI, 10%-88%). The Table shows other patient characteristics, none of which were associated with the need for intubation. Among 12 patients who required intubation, 3 died subsequently in the intensive care unit. Among 13 patients who did not require intubation, 9 recovered and were discharged from the hospital, 2 were transferred to the medical ward, and 2 remained in the step-down unit at the time data were censored on May 25, 2020.
Discussion | In this small single-center cohort study, we found that the use of the prone position for awake, spontaneously breathing patients with COVID-19 severe hypoxemic respira-  Letters tory failure was associated with improved oxygenation. In addition, patients with an SpO 2 of 95% or greater after 1 hour of the prone position was associated with a lower rate of intubation. Limitations of our study are the lack of control group and a small sample size. Randomized clinical trials are needed to establish whether improved oxygenation after use of the prone position in awake, nonintubated patients improves survival.

Prone Positioning in Awake, Nonintubated Patients With COVID-19: Necessity Is the Mother of Invention
In this issue of JAMA Internal Medicine, Thompson and colleagues report the association of prone positioning with pulse oximetry in 25 awake, nonintubated patients with hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19). 1 This study included patients who were hypoxemic (oxyhemoglobin saturation [SpO 2 ] ≤ 93%) despite receiving 15 L/min oxygen by face mask and 6 L/min oxygen by nasal cannula and excluded patients who were unable to turn in bed without assistance and those determined to be in respiratory distress and requiring immediate intubation. The median (SE) improvement in oxygen saturation was 7% (1.2%) (95% CI, 4.6%-9.4%) after 1 hour of prone positioning. This study adds to a growing body of literature suggesting that prone positioning may improve oxygenation in patients with early acute respiratory distress syndrome (ARDS) prior to intubation.
Prone positioning has several beneficial effects on pulmonary physiology in patients with ARDS. 2 In the supine position, pulmonary edema accumulates in basilar regions, and the heart and abdominal contents further compress these dependent lung regions. This leads to heterogenous ventilation, with increased volume delivered to apical and anterior lung units, which are also the regions that receive less of the pulmonary circulation. Together, these factors lead to perfusion of poorly ventilated lung units and hypoxemia. Prone positioning of the patient leads to a more homogeneous distribution of ventilation, thus decreasing the shunt fraction and improving matching of ventilation and perfusion. Moreover, homogeneous ventilation may decrease lung injury by more evenly distributing mechanical force from the ventilator across the lung during inhalation. 2 Despite compelling experimental evidence of these physiologic changes, most of the early randomized clinical trials of the prone position in mechanically ventilated patients with ARDS did not demonstrate a benefit compared with standard care. These trials, however, may have been limited by the late initiation and short duration of the use of the prone position. To address these limitations, the Proning Severe ARDS Patients (PROSEVA) trial, 3 published in 2013, randomized patients with a ratio of arterial oxygen tension (PaO 2 ) to fraction of inspired oxygen (FIO 2 ) less than 150 mm Hg within 36 hours of intubation to be placed in the prone position for long durations-on average, 17 hours a day. The comparison group was patients ventilated in the supine position. The trial found a hazard ratio for death of 0.39 (95% CI, 0.25-0.63) in the study arm with prone positioning compared with standard care (mortality at 28 days, 16.0% vs 32.8%). The findings have led to increased adoption of prone positioning for mechanically ventilated patients with moderate to severe ARDS.
Before COVID-19, there was limited published research on prone positioning in nonintubated patients. 4 The COVID-19 pandemic, however, has led to a sudden and dramatic increase in the number of patients requiring respiratory support for ARDS, straining critical care resources at many hos- pitals and forcing clinicians to use innovative approaches to limit the need for mechanical ventilation, including so-called awake proning. In a report on 50 nonintubated hypoxemic patients with suspected COVID-19 who presented to an emergency department in New York City, Caputo and colleagues 5 found a significant increase in SpO 2 5 minutes after proning (preproning: 84%; interquartile range [IQR], 75%-85%; postproning: 94%; IQR, 90%-95%; P = .001). Elharrar et al 6 conducted an observational study of prone positioning in patients with confirmed COVID-19 and posterior lung opacities on chest computed tomography who were admitted to a single center in France, most of whom were on 4 L or less of oxygen delivered via nasal cannula. Among 24 eligible patients, the majority (15 [63%]) were able to tolerate being prone for at least 3 hours, but oxygenation increased with the prone position in only 6 patients (25%). Finally, Sartini et al 7 tested prone positioning in 15 patients admitted to a single center in Milan, Italy, who were hypoxemic despite 10 cm H 2 O continuous positive airway pressure and 0.6 FIO 2 , and SpO 2 increased in all 15 patients. The report by Thompson et al adds to this body of observational evidence by demonstrating that many patients with severe acute hypoxemic respiratory failure yet not on positive pressure ventilation had improved oxygenation in the prone position. 1 Although promising, these case series should be interpreted with caution because of the lack of randomization. Even in this selected group of patients, not all patients tolerated the prone position, and nearly half the patients in the case series from Thompson et al eventually required intubation. Although improved oxygen saturation with the prone position is important, hypoxemia has not been a reliable surrogate biomarker for mortality in clinical trials of ARDS. Notably, in the National Heart, Lung, and Blood Institute ARDS Network trial of low tidal volumes, 8 the PaO 2 /FIO 2 ratio was higher in the high-tidal-volume arm than the low-tidal-volume arm on study days 1 and 3. Nonetheless, mortality was lower in the low-tidal-volume arm (31.0% vs 39.8%). 8 One potential concern with the use of the prone position in spontaneously breathing patients is that it could delay intubation and mechanical ventilation. The optimal timing of intubation and mechanical ventilation for patients with ARDS is not known, but delayed intubation has been associated with increased mortality in patients with ARDS. 9 Spontaneously breathing patients with ARDS generate relatively large tidal volumes; the result could be inadvertent selfinflicted lung injury. Controlled modes of mechanical ventilation minimize progression of lung injury owing to barotrauma. These benefits should be balanced with the risks of mechanical ventilation, including the need for prolonged sedation and the risk of ventilator-associated pneumonia. Ongoing clinical trials of prone positioning in nonmechanically ventilated patients (eg, NCT04383613, NCT04359797) should help clarify the role of this simple, low-cost approach for patients with acute hypoxemic respiratory failure.