Lung and diaphragm ultrasound as predictors of success in weaning from mechanical ventilation

Although widespread use of MV in the intensive care unit (ICU) saves hundreds of lives daily, prolonged MV can lead to increased mortality and morbidity [1‐3]. On the one hand, therefore, weaning should be considered as early as possible. On the other hand, however, premature withdrawal can result in extubation failure, which is also associated with increased morbidity and mortality [1, 4, 5].

Several ventilatory indices have been developed for identifying the right time to extubate the patient who has required endotracheal intubation and MV, but none met the criteria required to provide suitably accurate success rates [6]. More recently, lung and diaphragm ultrasound methods have been introduced, assessing pulmonary airway patterns and diaphragm function. Bouhemad [7] was the first author to propose the LUS score for calculating lung aeration patterns in patients with ventilator-associated pneumonia. In later articles, this score was used to predict weaning outcome [8‐11], with promising results. Several parameters measured through diaphragm ultrasound have been proposed for the same purpose [11‐21]. These include diaphragm thickness, diaphragm movement or excursion during the respiratory cycle [22], and diaphragm thickening or thickening fraction (TI). Although some studies have shown diaphragm excursion and thickness to be of low predictive value in the assessment of diaphragm function [18, 19, 23], a recent meta-analysis corroborates this and the best use of TI to weaning outcome [24].

The data suggest that TI and LUS are good non-invasive indicators of weaning outcome. However, the reliability and accuracy of these studies is limited, mainly due to small sample sizes, inadequate spectra of patients and study heterogeneity [24]. The aim of this study is to assess the reliability and accuracy of lung and diaphragm ultrasound for predicting successful weaning in general critical care patients on mechanical ventilation.

In the interobserver agreement study, the quadratic-weighted kappa value for LUSm was 0.95 (95% CI 0.92, 0.98), which shows almost perfect interobserver agreement. For the TI variable, we calculated an ICC value of 0.78 (95% CI 0.65, 0.87), showing moderate to good interobserver agreement, and a difference in measurements according to the Bland–Altman method of ± 12.5% (Fig. 1).

Over the study period, 139 patients underwent MV, of whom 52 did not meet the inclusion criteria (48 deaths before attempted weaning, 2 self-extubations, 2 on MV for less than 24 h) and 17 were not included for reasons beyond the research team’s control (eight withdrawn more gradually from MV, two with no informed consent, two transferred to another hospital, four eligible patients of whom the investigator was not notified, one case of a non-functioning ultrasound scanner). The baseline characteristics of the 69 patients recruited are shown in Table 1. Pressure support was used in 49% of SBTs, a T-tube in 42% and both methods in 9%. Eight patients failed SBT and 61 were extubated, of whom 17 failed extubation. This means that a total of 25 patients failed weaning. Most patients who failed extubation recovered with non-invasive-ventilation (NIV) and high-flow nasal cannula (HFNC); only five patients (8.2%) were reintubated (Fig. 2).

If we compare the group that was successfully weaned (SW) with those who failed weaning (FW) (Table 1), we observe that the FW group was associated with more time on MV, more cases of chronic obstructive pulmonary disease (COPD), higher LUSm and mortality, and lower TI and SpO₂. The median difference in TI and LUSm between the SW and FW groups was 11% and 3 points, respectively.

The area under the ROC curve for predicting weaning success was 0.80 for LUSm (95% CI 0.69, 0.91), 0.71 for TI (95% CI 0.58, 0.84) (Fig. 3) and 0.83 for both (Fig. 4). Table 2 shows the sensitivity, specificity and likelihood ratios at the optimal cut-off points for successful weaning. The area under the ROC curve for predicting extubation success was 0.78 for LUSm (95% CI 0.64, 0.91) and 0.76 for TI (95% CI, 0.61–0.9) (Fig. 3). Table 3 shows the sensitivity, specificity and likelihood ratios at the same cut-off points as those shown in the previous two tables.

According to our data, the reproducibility of lung ultrasound is excellent for the variable LUSm and moderate to good for TI. Regarding the prognostic accuracy of ultrasound for weaning outcome, we found that if TI is below 24% or LUSm is greater than 7 points, the patient has a high risk of weaning failure, with an AUC of 0.8 for LUSm and 0.71 for TI. We found similar values for extubation outcome.

Mean time on MV [29, 30], mortality of the patients included in the study (16%) [4], and SBT failure rate (11.6%) [31] was consistent with previously published results. Extubation failure occurred in 24.6% of the patients, a slightly higher proportion than the 10% to 20% reported in a number of other studies [1, 5, 32‐35]. Of the 17 patients who failed extubation, only five (8.2%) required reintubation, a lower rate than reported in other studies [36, 37]. This shows that NIV plays a decisive role in reducing the need for reintubation without increasing morbidity or mortality [37, 38]. As such, through conceptually defined as a criteria of weaning failure [28], we consider that recovery with NIV in fact constitutes a success for the patient’s clinical situation. We observed that FW patients were more likely to have COPD. This is a logical finding, as COPD is a risk factor for extubation failure [39, 40]. Of the standard predictors of weaning assessed in our study (PI_Max, RSBI, P0.1), we found none to be useful. In a study with the largest number of patients performed for the study of weaning predictors [6], about 500 patients, to assess the predictability of many indices as possible weaning predictors (minute volume, respiratory rate, PaO₂, RSBI, PI_Max, Maximum expiratory pressure, dynamic respiratory compliance, CROP index), it is observed that none of them has value as a predictor of weaning.

The results obtained for LUSm are consistent with previously reported data [8‐11]. Our cut-off point is lower (7 LUSm points) because we assessed eight lung areas, whereas the other studies assessed 12. Our aim was to assess all the areas normally affected in critical patients [26], while simplifying the technique so that the patient did not have to be moved, and the associated complications could be avoided. We therefore consider LUSm to constitute a useful new proposal that is beneficial for both the patient and the operator. For TI, we found a cut-off point of 24% for predicting successful weaning, within the range of values reported in other studies (20–36%) [11‐20]. The LUS and TI variables tested in those studies showed a higher predictive value for weaning success (Table 2), but a number of factors may have influenced this result. In those studies, patient selection was in some cases very strict, resulting in a homogeneous sample with specific characteristics (patients with COPD [15], tracheotomised patients with prior weaning failure [13], patients with ICU-acquired weakness [17]). Since these samples already had a higher probability of weaning failure, their results cannot be generalised to the whole population of critical care patients. Other limitations in the reviewed studies included elimination of deceased patients [20], diaphragm ultrasound when the patient was on MV rather than during SBT [20], use of a non-validated probe for diaphragm measurement [18], periods of up to 36 h between the ultrasound scan and extubation [12], and using STB failure rather than extubation failure as an endpoint [13]. Only one of the reviewed studies included a reproducibility study comparing TI measurement by two observers, with results very similar to ours (ICC 0.81) [14].

In our study, we chose not to select specific populations of patients for our study, to obtain a heterogeneous sample and produce generalizable results. The ultrasound measurements were taken within the first minutes of pressure support ventilation, the physicians were blinded to the ultrasound data, no patients were lost to follow-up, and the median time between SBT and extubation was 120 min.

One limitation of our study is the small sample size, which led to imprecise results with broad confidence intervals, especially for TI. Further studies with larger samples of patients are required to establish the true predictive power of these ultrasound techniques.

It should be noted that the interobserver difference in TI measurement (± 12.5%) was greater than the median difference in TI between the SW/FW groups (11%). In our sample, therefore, a degree of uncertainty was associated with this parameter. This is probably because the formula for calculating TI is such that a difference of a tenth of a millimeter in the measurement of inspiratory or expiratory diaphragm thickness has a considerable effect on the result. None of the studies reviewed considers this possibility. We believe the problem can be overcome with better ultrasound equipment and a more effective TI measuring technique, so that the true value of this parameter can be reported.

In the future, in order that results can be compared across studies, we believe a number of items should be standardised: the ultrasound technique, the definitions of weaning failure and extubation failure, the time between ultrasound and extubation, blinding of ultrasound findings, and the protocol. If results are to be applied to the whole population of general critical care patients on MV, a heterogeneous sample should be used. Studies in this domain should also assess reproducibility by measuring interobserver agreement in ultrasound measurements. In addition, it may be useful to consider other parameters, such as time on MV, disease severity, comorbidities, etc., alongside lung and diaphragm ultrasound measurements, to better predict weaning success.

In our study, interobserver agreement was excellent in LUSm measurements and moderate to good in TI measurements. The TI variable showed a degree of uncertainty for predicting weaning outcome, but overall its predictive value was found to be acceptable. LUSm produced stronger results in this regard. Lung and diaphragm ultrasound are promising techniques for predicting weaning outcome, but more studies are required to verify their reproducibility. These studies should have a standardised design and should assess interobserver agreement of ultrasound techniques. Using a non-specific sample would ensure that results can be generalised to all patients on MV.