Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial

Abstract

Background Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. Methods In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). Results Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54–0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9–14] vs 13 [IQR, 10–17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. Conclusion In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. Trial registration: This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1

Awake prone positioning for patients with COVID-19-induced acute hypoxemic respiratory failure

“…They have found that patients with late APP (>24 h of HFNC initiation) had higher mortality than patients with early APP (45% vs. 26%, P =0.03). [47] Although these results should be considered exploratory, they are consistent with those obtained in the study by Ibarra-Estrada et al , [45] in which APP has been initiated at 11.1 h after HFNC initiation. Therefore, we suggest that APP should be initiated as soon as patients are indicated for HFNC treatment.…”

“…In the large randomized controlled study by Ibarra-Estrada et al , [45] several predictors for treatment success have been reported within the first 3 days after admission. First, at the initiation of HFNC, a ROX index of >6.0 (the ROX index is the ratio of SpO 2 /FiO 2 to respiratory rate; it is a clinical score combining a single number of the three main parameters used to monitor a patient with acute hypoxemic respiratory failure) and d -dimer concentrations of <1.4 mg/dL have been associated with APP treatment success.…”

“…Similar results have been observed in the single largest randomized controlled study from Mexico, in which the duration of APP has been linearly correlated with the probability of treatment success ( r =0.70, P <0.001), and a daily duration of APP ≥8 h/day has predicted success with a sensitivity of 90% and specificity of 87%. [45] However, given the observational nature of the data precluding causal inference, cautious interpretation is warranted. Interestingly, the presence of silent hypoxemia (i.e., hypoxemia without dyspnea) has been associated with a longer duration of APP (12.4 h/day vs. 7.6 h/day, P <0.001), which could partially explain the improved outcomes found in this subgroup.…”

Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study

“…Using a mean of pre-prone LUS score of 18.7 and standard deviation (SD) of 4.4 and post-supine LUS score at day 3 of 16.9 and SD of 4.6 [ 14 ], a confidence level (1-α) of 95% and power (1-ß) of 95%, the number of patients was 70. Considering an attrition rate of 5%, we calculated the total sample size as 74.…”

“…In our previous cohort study of prone-positioning in intubated patients with COVID-19, we found that although most patients had an improvement in oxygenation on the first session of prone positioning, only those who survived had a significant response over the second and third sessions of prone positioning, which suggests that serial measurements along the first three days of treatment rather than the first session only, might improve the accuracy of prediction regarding patient-centered outcomes [ 13 ]. Moreover, in a large randomized controlled trial investigating the effects of APP on non-intubated patients with COVID-19, we found that LUS scores after three days of APP treatment decreased only in patients who eventually avoided intubation/death [ 14 ]. Therefore, we performed this study with two aims: 1) to explore the aeration response to APP in patients with AHRF induced by COVID-19 by using LUS within the first three days, and 2) to explore whether the changes in LUS associated with APP can predict the need for intubation.…”