The present study shows 4 major findings. 1) Diaphragmatic ultrasonography is a reliable tool to assess whether the ICU patients require NIV therapy. 2) The patient’s oxygenation status and diaphragm function are related to the need of NIV. 3) We also observed a significantly higher velocity of diaphragm contraction in patients receiving NIV than those who received continuous low-flow oxygenation therapy, although no statistical difference was observed in E-T index between groups. 4) Assessing the patients’ need of NIV using the combination of parameters from arterial blood gas and diaphragmatic ultrasound provided better accuracy and specificity compared with using parameters from a single test.
Several studies have shown better association between inspiratory muscle strength and diaphragm function assessed by diaphragmatic ultrasound6,17. Physicians could perform real time assessment of patient’s inspiratory muscle strength through monitoring the diaphragm thickness and movement distance, achieving early diagnosis of diaphragmatic atrophy and prediction of extubation outcomes in mechanically ventilated patients14,15,20−22. The real time assessment can also be used to determine if NIV is needed for patients with dyspnea in the emergency department, further predicting the NIV outcome12,16. Despite the limited amount of studies regarding the velocity of diaphragm contraction, the great association between VD and inspiratory muscle strength has been demonstrated and used for extubation outcome prediction, which proved the reliability of VD6,18. In this study, we not only assessed the regular diaphragmatic ultrasound parameters, but also introduced a new index to better predict the need of NIV in ICU patients. Palkar et al. showed that E-T index represents the work performed by the diaphragm during spontaneous breathing trial and can well predict the outcome of extubation12. The higher the E-T index is, the more work is done to overcome the inspiratory load and thus the better the diaphragm functions and the subsequent success rate of extubation. Moreover, patient oxygenation status and inspiratory muscle strength are determinants of the need of NIV clinically, we therefore presented the novel VOX index to predict the opportune time of NIV therapy for ICU patients.
Surprisingly, we did not observe intergroup differences in DE and E-T index, which might be related to patients’ respiratory statuses. The data obtained indicating resting state diaphragm movement as the diaphragmatic ultrasound was measured when patients performed quiet breathing. We noticed that most of the patients receiving NIV were under hypoxia condition when taking the diaphragmatic ultrasound where subjects presented respiratory distress, contraction of accessory muscle of respiration, and significantly lower Ti compared with patients receiving continuous low-flow oxygen (0.99 vs. 0.66, P < 0.001). Most NIV patients thus hardly maintain quiet breathing and displayed forced inspiration. Although study had shown significant difference in DE between quiet breathing and deep breathing among healthy adults23, other study indicated that subjects with dyspnea exhibited significantly shorter DE when performing forced inspiration compared with healthy adults and ICU patients due to inherent diaphragm fatigue16. This can explain why we did not observe statistical difference in DE between the two groups. In addition, as E-T index represents the product of DE and Ti at resting state, it can also contribute to the lack of intergroup statistical difference in E-T index in our study.
There was no respiratory acidosis observed in both groups based on the arterial blood gas test as the medians of PaCO2 in control and NIV group were 37.10 mmHg and 42.00 mmHg respectively. The test performed upon admission to ICU showed medians of pH 7.41 in both groups and a lower Ti in the 23 NIV patients. We supposed that NIV patients mitigated dyspnea condition through increasing respiratory frequency and oxygen consumption, compensating the existing hypoxia and decreased diaphragm muscle strength.
In consistent with our presumption, P/F and VD were well associated with predicting the need of NIV where patients receiving NIV present greater VD and poor oxygenation status compared with those receiving continuous low-flow oxygen. VD closely represents the patients diaphragm movement condition. During quiet breathing, the more obvious manifestation of dyspnea presented with bigger movement of forced inspiration, the greater the diaphragm contraction and the subsequent VD. Previous study demonstrated that the increased inspiratory resistive loading induces significant changes in respiratory patterns in healthy adults. Ti and Ti/TOT (inspiratory time to total cycle time) decreases first in volunteers without changes in DE24. VD therefore better manifests early dyspnea symptoms in patients compared with DE as Ti, which is more sensitive to inspiratory resistive loading, is involved in the calculation of VD. P/F generally decreases in patients with hypoxia and is an indicator of the need of NIV. However, both P/F and VD assess patients’ condition through a single aspect which the former represents patient oxygenation status and the later measures the inspiratory muscle strength and diaphragm movement. In this study, we presented novel VOX index which integrated patient oxygenation status and inspiratory muscle condition. We have demonstrated that VOX index combines the parameters of oxygenation status and diaphragm strength, serving as a better determinant for predicting patients requiring NIV.
There were several shortfalls of our study. The major limitation of this study was that the diaphragmatic ultrasonography was performed under quiet breathing, whereas other studies performed the ultrasonography during deep breathing16,25. This is done for the following reasons. First, deep breathing imposes additional work consumption to ICU patients who might need NIV, and it affects measurement accuracy if patients had shown dyspnea symptoms as subjects had difficulty completing the task. Additionally, obscuration of the diaphragm by the descending lung can interfere the accuracy of the measurement23. Moreover, several researches have established great correlation between VD and twPdi under quiet breathing in both healthy adults and patients with respiratory muscle weakness. Resting state diaphragmatic ultrasound thus provides reliable measures to the inspiratory muscle strength17,26,27.
As a single center study, the other limitation was the small sample number included and further investigations and verifications conducted under similar clinical environment should be performed. The third shortfall was that only the right diaphragm was evaluated in patients as measuring the left diaphragm during emergency condition can be difficult. Forth, the fact that decisions of patients needing NIV were made solely by the physicians despite the VOX index proposed could impose certain impacts on the study results. Lastly, we compared only the clinical parameters upon admission to ICU without dynamic monitoring during patients’ stay in ICU. The therapy and time in ICU could also influence the outcome and thus require further investigation in our future study.