In this study, the RDE had a good ability to predict the need for IMV within 48 h in critically ill patients in ED and was better than the ratio of oxygen saturation to fraction of inspired oxygen and the SOFA score. Furthermore, a low RDE value was associated with longer IMV and increased mortality risk.

Point-of-care ultrasound (POCUS) has been found to be useful in the ICU and ED for guiding resuscitation of critically ill patients, such as fluid responsiveness, and the bedside lung ultrasound in emergency (BLUE) protocol for immediate diagnosis of respiratory failure [24,25,26]. Critical illness has been associated with diaphragm dysfunction that causes respiratory failure and difficulty in weaning from mechanical ventilation and with mortality [8, 9, 27]. Transdiaphragmatic pressure (Pdi) is used to measure diaphragmatic force; however, the gold standard of Pdi measurement is magnetic stimulation of phrenic nerves, which was unsuitable in ED [9]. Therefore, there is a need for evaluation of the ability of examination of the diaphragm by ultrasound to detect diaphragm dysfunction and predict the need for IMV.

The diaphragm ultrasound can assess diaphragm function by diaphragmatic excursion and diaphragmatic thickness fraction. In this study, we used the RDE, which is simpler to measure and more rapidly obtained than the diaphragmatic thickness fraction when assessing the function of the diaphragm and has demonstrated good reliability [27,28,29]. The diaphragm action is qualified for shortening and force generation, which are measured by volume change and inspiratory pressure, respectively. The relation between diaphragmatic excursion and tidal volume and inspiratory capacity (IC) in spontaneous breathing at rest and exercise in healthy was a linear correlation [30, 31]. Moreover, in COPD, inspiratory capacity was reduced compared to volunteers who had no chronic disease, and decreasing of the diaphragmatic excursion was associated with a reduced inspiratory capacity [32]. In a previous study, diaphragmatic excursion has been a reliable tool as fluoroscopy for measuring diaphragm contractile activity [33]. In spontaneous breathing, diaphragmatic excursion correlated well with Pdi and esophageal pressure in intubated patients with zero pressure [34].

Previous studies have shown that diaphragmatic excursion has poor accuracy when used to predict the need for use of a mechanical ventilator. Clément et al. showed that diaphragmatic excursion could not predict the need for NIV or IMV in patients with acute dyspnea in the ED [15]. A similar study by Barbariol et al. found that diaphragmatic excursion had a poor ability to predict failure of NIV in patients with acute hypoxic respiratory failure in the ICU [35]. These findings are in contrast with those of our present study, in which the RDE showed a good ability to predict IMV. Possible reasons for this inconsistency are that our study population included patients with shock or a change in mental status and different criteria for intubation. Furthermore, we found that the RDE could predict IMV regardless of whether or not the patient had AECOPD, especially when associated with COVID-19 pneumonia.

The diaphragmatic dysfunction in critical conditions was related to worsening outcomes. Previous studies have identified mechanical ventilation use, malnutrition, use of corticosteroids, inflammation, releases of cytokines, and mitochondrial impairment as causes of diaphragm dysfunction in critical illness due to the catabolic process occurring in the diaphragm and other respiratory muscles [8, 36, 37]. Many studies show that sepsis is one of the risks of diaphragmatic dysfunction. Increasing metabolic demands and inflammation in sepsis increased respiratory drive and effort. However, in animal studies, group B streptococcal sepsis in young piglets was associated decline in diaphragmatic contractility and tidal volume within 2 h [38], and endotoxin administration produced a reduction in diaphragmatic force generation in hamsters [39]. Similarly, other experimental studies in animals exposed to endotoxin showed increased ventilation in an early, then fall and decreased diaphragmatic function [40,41,42]. Chen et al. found that diaphragmatic thickening fraction and diaphragmatic excursion were significantly lower in sepsis with SOFA > 5 than in controls [43]. In ICU, diaphragm volume and strength were lower in sepsis when compared with non-septic. Moreover, diaphragm strength was correlated with diaphragm volume [44]. Systemic inflammation in sepsis increased diaphragm weakness and susceptibility to injury. In addition, diaphragm dysfunction may develop within 4 h of sepsis. Therefore, diaphragmatic evaluation may consider monitoring to choose ventilatory support to prevent worsening outcomes in delayed intubation and diaphragmatic weakness in mechanical ventilation [8, 22]. A previous study evaluated the performance of diaphragmatic function was found low diaphragmatic excursion values associated need for IMV, prolonged IMV, and mortality in sepsis [45]. Similarly, this study found RDE was a good performance to predict IMV within 48 h and mortality. In our population, respiratory rate was high, and accessory muscle used that indicated high respiratory effort was included in the inclusion criteria. However, low RDE was associated with requiring IMV, which results similar results to previous study [40,41,42, 45]. Therefore, the evidence of diaphragmatic ultrasound needs evaluation and validation in requiring intubation in sepsis.

In COPD, expiratory flow is limited by airway narrowing resulting from chronic inflammation and mucus plugging, causing to required prolonged time to exhale volume in the lung. In critically ill, almost increased minute ventilation from increased tidal volume and respiratory rate that were increasing in end-expiratory lung volume and reduced IC. In COPD with limited IC, increasing the minute ventilation by increased respiratory rate cause of dynamic hyperinflation by insufficient expiratory time and causes hypercapnic respiratory failure, especially in AECOPD. In addition, the work of breathing increased during hyperinflation and resulting in diaphragmatic dysfunction [46]. Previous studies show diaphragmatic dysfunction was associated with required IMV [10, 12, 14]. Diaphragmatic thickening fraction was shown to correlate with Pdi during the sniff maneuver and accurately identified risks of NIV failure in AECOPD [12]. However, this study did not measure the diaphragmatic thickening fraction. Diaphragmatic excursion in COPD with acute hypercapnic respiratory failure could predict NIV failure more accurately than arterial pH and PaCO2 [14], similar to our study. This result was in line with previous findings that diaphragmatic excursion was correlated with inspiratory capacity and tidal volume [30,31,32]; in spontaneous breathing that result presumed the low value of diaphragmatic excursion was associated with decreased IC due to dynamic hyperinflation and caused requiring IMV in AECOPD.

In COVID-19, the theory of diaphragmatic dysfunction was related to critical illness myopathy, cytokine storm, ventilator-induced diaphragmatic dysfunction, and directly viral infiltration via expression of the angiotensin-converting enzyme 2 receptor [36, 37, 47]. Other studies have also found associations between diaphragm dysfunction with the requirement for IMV and adverse outcomes in patients with severe COVID-19 pneumonia [48, 49] that support the results of our study. However, the sample size in our study on COVID-19 pneumonia was small. Therefore, clinical application in diaphragmatic ultrasound should be assessed in further study.

The normal diaphragmatic excursion value in quiet breathing is about 2 cm in the general population and 1.0–1.4 cm in critically ill patients in a semi-recumbent position [27, 29, 50]. In our study, the median RDE value was 0.9 cm in critically ill patients requiring IMV and 1.8 cm in their counterparts who did not; both these values are lower than those in the general population. Moreover, our study showed different diaphragmatic excursion between gender, since the excursion in males was displace greater than in females, that result supports previous studies [29, 50]. Several other studies have shown an association between a low value of diaphragmatic excursion value and requirements for IMV [15, 35, 42]. Many studies have shown various cutoff values of diaphragmatic excursion to be associated with adverse events [27, 29]. Therefore, our study showed sensitivity, specificity, and probability in predicting requiring IMV in each range of RDE for physician decisions. This study identified an RDE of 1.2 cm as the cutoff value below which there was a high probability of requiring IMV and an RDE of ≥ 2.0 cm to be the value above which the probability was low.

Motion of the diaphragm, indicated by the diaphragmatic thickness fraction and excursion, has been assessed as a prognostic factor in weaning from mechanical ventilation in the ICU. Patients with a diaphragmatic excursion or diaphragmatic thickness fraction lower than the threshold were found to have a prolonged period of IMV, which was a predictor of failure to extubate [8, 9]. In our study, an RDE ≤ 1.2 cm was similarly associated with a significantly prolonged period of IMV.

In view of our results, we believe that the RDE could be useful to implement in POCUS for assessment of the risk of failure of non-invasive respiratory support and identifying patients at risk who require close monitoring. For example, patients who present in the ED with acute respiratory distress and an RDE ≤ 1.2 cm could be admitted to ICU or a respiratory care unit for close monitoring and early intubation for IMV to prevent adverse conditions, such as mortality. In contrast, patients with an RDE > 2 cm could safely receive non-invasive respiratory support and routine care outside the ICU. Furthermore, monitoring the RDE during the weaning process could help to predict the outcomes of weaning from IMV. Using diaphragmatic excursion with clinical parameters that indicated intubation criteria could benefit the decision for early intubation to prevent adverse outcomes. However, integrating diaphragmatic excursion into POCUS to guide the resuscitation setting requires further studies to confirm the cutoff value and the benefit of implementing care.

This study has several limitations. First, it was performed in the ED of a single tertiary care center, which limits the generalizability of its findings. However, the sample size was adequate for assessments of the primary outcome. Second, we used the average of the RDE values obtained on ultrasound by a single emergency physician for each patient; therefore, the intra-rater and inter-rater correlations were not analyzed. However, all the emergency physicians who measured the diaphragmatic excursion had already performed the procedure more than 50 times, and previous research has shown that measurement of diaphragmatic excursion is an easy skill to master with a steep learning curve and good reliability [27, 28]. Third, we measured only RDE and did not include the diaphragmatic thickness fraction, which has been shown to be associated with respiratory effort in patients receiving positive pressure ventilation [27, 51]. Nevertheless, RDE was measured during spontaneous breathing, which has been reported to produce reliable results [27, 29]. Fourth, ultrasound was performed only once and not repeated after resuscitation. Finally, confounding factors, such as pharmacologic treatment, setting, and parameters of non-invasive respiratory support, were not collected in this study. Finally, the RDE value was unblinded to physicians who decided on intubation; however, the emergency physician who performed the ultrasound was not involved in deciding on intubation. Further studies are needed to validate our cutoff value in multi-center studies and determine the diaphragmatic excursion and the thickness fraction or a variation of diaphragmatic parameters should be implemented in POCUS to predict worsening outcomes.