"Prone ventilation treatment for COVID-19" questioned? BMJ Releases Disruptive Research...

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THE BMJ: Prone ventilation does not significantly improve COVID-19 patients with mild hypoxemia

Written by | Kreeche Li Feng

Source | "Medical Respiratory Channel" public number

In the face of severe patients with typical novel coronavirus pneumonia (COVID-19), since the outbreak of the epidemic in Wuhan, prone ventilation has been recommended by experts to improve survival rate! Indeed, hypoxemia due to low blood oxygen saturation (SpO2) is one of the leading causes of death in patients with COVID-19, and prone ventilation is thought to re-open the alveoli that are dorsal withering, increase the oxygenation index, and thus improve the hypoxia status of patients.

In the new version of the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia" in mainland China, it is also recommended that prone ventilation be used as one of the means of treatment for patients with rapid disease development and severe illness [1].

Figure 1 Source Of the new version of the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia"

Recently, the BMJ published a more "subversive" study, arguing that prone ventilation interventions are not very good at improving the prognosis of COVID-19 patients with moderate to mild hypoxemia.

Figure 2 Source BMJDOI: https://doi.org/10.1136/bmj-2021-068585

An average of 2.5 hours of prone ventilation is performed daily

But the ending doesn't seem to have improved much

As a treatment for COVID-19 patients, prone ventilation has always been recommended by major consensus guidelines, but the reality is always full of contradictions! In fact, some studies have shown that prone ventilation does not significantly improve hypoxia in patients with COVID-19 [2]. In this way, it is still unclear whether the prone position can improve the new crown pneumonia, and randomized trials are needed to evaluate its effect.

The study was a multicenter, practical, randomized clinical trial that included 570 patients from 15 hospitals in the United States and Canada who were diagnosed or suspected of COVID-19, of which 126 patients were randomly assigned to the prone ventilation group, 122 patients were assigned to the control group, and the remaining patients withdrew from the trial because they did not meet the conditions for participation.

The median age of the participants was 56 years (36% female), and nasal (90%) oxygen was the most commonly used oxygen delivery method in these patients. According to the investigators' assessment, the blood oxygen in the prone and control groups was low, but it had not yet progressed to the point of critical illness, and the median SpO2 and oxygen fraction (FiO2) in the two groups were 94% and 32%, respectively, and SpO2 and FiO2 could be used as indicators to assess the severity of the patient's disease. In terms of drug use, 95% of patients were treated with dexamethasone, 42% with remdesivir, and 1% with tocilizumab.

First, the data within 72 hours after randomization were counted, and a total of 6 hours (median time) of prone ventilation (approximately an average of 2.5 hours per day) was performed in the prone group, and 0 hours in the control group. However, because the confidence interval for the study was too large to find a pre-specified amount of effect, the trial was stopped prematurely.

Table 1 Findings (primary/secondary outcomes)

Although the trial was discontinued early, because the study was multicentric and pragmatic, certain conclusions could be drawn from the data obtained. Well, from the table above, the risk of primary outcomes (including death, mechanical ventilation, and worsening of respiratory failure) was similar in the prone group (18 patients) and the control group (17 patients) (OR 0.92, 95% CI 0.44-1.92). Moreover, the median ratio (S/F) of SpO2 to FiO2 in the prone and control groups over 72 hours was basically the same.

Fig. 3 Changes of S/F values over 72 hours after randomization (purple for prone group, yellow for control group)

Well, here comes the conclusion! To put it simply, the data results of prone obstruction and control groups were not very different; specifically, for patients with non-critically ill pulmonary COVID-19 with mild hypoxaemia (94% oxygen saturation), the use of prone ventilation did not improve the prognosis well.

Director Li Feng, Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, commented:

Prone Positioning (PP) significantly improves the prognosis of moderate to severe acute respiratory distress syndrome (ARDS) due to various infectious factors, including coronavirus pneumonia (COVID-19), which has been confirmed by several studies [3]. Prone ventilation, pulmonary protective ventilation (small tidal volume, moderate PEEP, confined platform/drive pressure), and muscle relaxants are important means of rescuing patients with severe ARDS [4], and significantly reduce mortality in critically ill patients with COVID-19 [5]. Multiple studies have found that prone ventilation reduces the chance of intubation in patients with moderate to severe COVID-19 and is associated with a good prognosis [3,6-8]. The APPNOX study, which included 827 patients in the awake prone position (SPO2/FiO2189.5 ±81.6), reached the same conclusion and found that SPO2/FiO2<199 was one of the influencing factors leading to intubation [9]. As a result, the awake prone position is being implemented in an increasing number of treatment centres.

A newly published study by Michael Fralick et al. in BMJ (the COVID-PRONE study) found that prone ventilation did not improve the prognosis of COVID-19 patients with Moderate Hypoxaemia [10]. In the study, included patients were awake, able to independently perform prone movements, oxygen concentrations ≤ 50%, and median prone positions for 6 hours (first 72 hours). The results showed that compared with the control group, the prone position failed to improve the patient's hospital death, mechanical ventilation and respiratory deterioration, and there was no significant difference in oxygen saturation and inhaled oxygen ratio between the two groups.

Parameters of investigation: The COVID-PRONE study used noninvasive SPO2 and SPO2/FiO2 (S/F) as criteria for assessing oxygenation. The numerical determination of SPO2 is influenced by factors such as peripheral circulation, Hb level, finger skin color, temperature and thickness, the use of nail polish, and the fit of the measuring instrument to the fingertips [11]. There is currently no uniform standard for conversion between S/F and PaO2/FiO2 (P/F). Brown et al. found that there is a nonlinear quantification relationship between the two in mechanically ventilated patients [12]. In 2007, Rice et al. derived the formula S/F =64+0.84 x(P/F) (P<0.0001 based on ali and ARDS patient data; r=0.89; for P/F ratios of 200 and 300, S/F ratio thresholds of 235 and 315, sensitivity and specificity were 85% and 85%, 91%, and 56%, respectively [13]. Biland et al. obtained another formula S/F = 57 + 0.61× P/F (P<0.001) [14]. It should be noted that in the COVID-PRONE study, the S/F value was higher (prone ventilation group 303, control group 305), and P/F was estimated to be 284 and 287 according to rice et al.'s formula [13], corresponding to the severity of ARDS (Berlin definition) as mild [15].

Evaluation of benefits: The main pathophysiological changes in COVID-19 are impaired pulmonary vascular endothelium and microthrombosis, inflammatory infiltrates of the pulmonary interstitium and impaired alveolar epithelium, and ventilation-to-blood flow ratio imbalance leading to severe hypoxemia [16]. There is significant heterogeneity in lung involvement between patients with COVID-19, and patients themselves have non-uniform changes in their lungs and homogeneity of ventilation [17]. Prone ventilation improves pulmonary oxygenation by improving ventilation-to-blood ratio, promoting lower pulmonary reassonance, and improving drainage [18]. This means that not all patients can benefit from prone ventilation, and the likelihood of benefiting from prone ventilation should be assessed based on the patient's lung pathology and systemic condition. Possible methods of assessing lung lesions include bipulmonary CT, bedside ultrasound, and EIT. The LIKELIHOOD THAT PATIENTS BENEFIT FROM PRONE VENTILATION WAS NOT ASSESSED IN THE COVID-PRONE STUDY.

Prone ventilation time: The ventilation-to-blood flow ratio can change rapidly with postural changes, so dramatic changes in oxygenation within minutes can be seen in some patients with prone ventilation [19], which often suggests the presence of dorsal lobular dead-chamber ventilation or blood shunting. Pulmonary brancassia and postural drainage are slow processes that require prolonged prone positions to benefit, so long periods (12 to 16 hours) of sustained prone positions are used in patients with severe ARDS [20,21]. Measures to assess the effectiveness of patient prone position include improvement in oxygenation early (within 1 to 2 hours) of prone position implementation [19]. Prolonged prone ventilation in patients with aerobic improvements may improve prognosis, as evidenced by previously published prone studies in patients with severe COVID-19 [22]. In the COVID-PRONE study, the cumulative median time of prone ventilation in the experimental group was 6 hours (S/F improvement 14) in the first 72 hours, whether it had an impact on the final results is worth considering, and the confidence interval is too large and difficult to persist for a long time is also a problem that the authors' team has realized.

Therefore, the conclusion of the COVID-PRONE study should be understood to mean that for patients with mild (94% finger oxygen saturation) hypoxemia, the benefits of awake prone position therapy are unlikely. This is consistent with what we have clinically observed. At the moment of the popularity of Omicron strain, in the face of a large number of asymptomatic and mild patients, the implementation of reducing prone ventilation can not only reduce the consumption of medical resources, but also significantly reduce the tension and discomfort caused by prone ventilation to patients, which is undoubtedly beneficial to the recovery of patients.

Expert Profiles

Li Feng

Director of the Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center

Ph.D., Chief Physician, Master Supervisor of Fudan University School of Medicine

Vice Chairman of the Tuberculosis Committee of the Chinese Association of Research Hospitals

Vice Chairman of the Critical Care Committee of the Tuberculosis Branch of the Chinese Medical Association

Vice Chairman of the Tuberculosis Group of the Tropical Disease Branch of the Chinese Medical Association

Member of critical illness branch of Shanghai Medical Association

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