Electrical impedance tomography during spontaneous breathing trials and after extubation in critically ill patients at high risk for extubation failure: a multicenter observational study

Weaning is the whole process that leads patients to the discontinuation of mechanical ventilation and the removal of the endotracheal tube [1]. Weaning should be considered as early as possible to reduce the time spent on invasive mechanical ventilation (iMV), which is associated with morbidity and mortality [2, 3]. To assess whether patients are eligible for extubation, a spontaneous breathing trial (SBT) is often performed. The outcome of SBT is evaluated by clinical assessment and acquisition of objective parameters, such as the arterial blood gases (ABGs) and the respiratory rate (RR) to tidal volume (Vt) ratio (RR/Vt) [1]. In the case of SBT success, the patient can be extubated. However, post-extubation respiratory failure may occur, in particular in patients at increased risk [1], who may benefit from prophylactic non-invasive ventilation (NIV) application immediately after extubation [4‐9].

Electrical impedance tomography (EIT) is a non-invasive imaging technique that provides instantaneous monitoring of variations in overall lung volume and regional distribution of ventilation, as determined by variations over time in intrathoracic impedance, which is increased by air and reduced by fluids and cells. EIT allows for determining changes in end-expiratory lung impedance (EELI), a surrogate estimate of end-expiratory lung volume, assessing global and regional distribution of Vt, and obtaining indexes of the spatial distribution of ventilation, such as the global inhomogeneity index [10].

Because SBT failure and extubation failure are both major clinical problems, they have been repeatedly investigated, but the underlying mechanisms are not fully elucidated yet [1]. We reasoned that EIT could help comprehend the pathophysiology of SBT failure and extubation failure by providing additional insights. We, therefore, designed this observational study on patients at high risk of extubation failure, aimed at assessing variations in EELI (∆EELI) and Vt (∆Vt%), and the inhomogeneity index during SBT and after extubation.

The study was conducted from June 2015 to June 2016 in the intensive care units (ICUs) of three Italian hospitals (“Sant’Andrea” Hospital in Vercelli, “ARNAS Garibaldi” Hospital in Catania and “Infermi” Hospital in Rimini), in accordance with the principles outlined in the Declaration of Helsinki, after approval by the local Ethics Committees (Vercelli, protocol no AslVC.Rian.14.02, approved on 11/09/2014; Catania, protocol no 479/CE, approved on 30/06/2015; Rimini, protocol no 1313, approved on 18/03/2015). Written informed consent was obtained from all patients according to national regulations.

We enrolled 80 consecutive patients, as planned. Two patients, erroneously enrolled with no risk criteria for post-extubation respiratory failure, were excluded from the data analysis. The patients’ flow of study enrolment is shown in Additional file 1: Figure S1, while the protocol flow is depicted in Fig. 1. None of the patients interrupted the study protocol. Table 1 shows the patients’ characteristics at ICU admission and immediately before SBT, and the reasons for ICU admission and risk factors for post-extubation respiratory failure, for the overall population and separately for the SBT and extubation success and failure subgroups.

In this physiological study aimed at describing, in a general population of critically ill patients at the first SBT attempt, changes in lung aeration, ventilation distribution and inhomogeneity occurring during the weaning process, we found the following: (1) compared to SBT success, SBT failure is characterized by more lung de-recruitment, as suggested by the higher loss in ∆EELI and by the concomitant PaO₂/FiO₂ worsening, and greater lung inhomogeneity, as indicated by higher inhomogeneity index value; and (2) no EIT variables were significantly different between patients succeeding and failing extubation.

All patients considered ready-to-wean were considered eligible for inclusion in this study, and we did not focus only on patients with prolonged weaning, who represent only approximately 15% of the overall ICU population [1]. We found an SBT failure rate of 21% which was not different from those previously reported [22‐24], while in keeping with Ferrer et al. [6], the rate of extubation failure in our population at high risk of post-extubation respiratory failure amounted to 35%. Finally, consistent with recently published data in patients recovering from hypoxemic acute respiratory failure [25], 50% of all patients experiencing post-extubation respiratory failure required reintubation, 42% of whom after failing CPAP or NIV.

The application of EIT during weaning has been recently reported only in small populations of patients characterized by prolonged weaning or prolonged mechanical ventilation [26‐28]. These studies report that, compared to patients undergoing a successful SBT, patients experiencing SBT failure are characterized by greater loss of EELI at the end of the SBT. While confirming this finding in a less selected patient population, we find that the loss of EELI occurs after only 5 min.

In the present study, the inhomogeneity index appears to be greater in SBT failure, as opposed to SBT success, which is also consistent with previously published data. In patients who had received prolonged iMV, Zhao et al. [27] also found that weaning was more likely to be successful when the ventilation distribution was more homogeneous at decreasing support levels. In 31 patients with prolonged weaning, Bickenbach et al. [26] found the inhomogeneity index to be greater in SBT failures, as opposed to successes. In our study, the inhomogeneity index was also significantly higher at baseline, while RR/Vt showed significant differences only in the course of SBT. In addition, after 5 min of SBT, we observed a remarkable increase in the inhomogeneity index, without important changes at SBT completion.

We also investigated potential variations in EIT parameters related to the outcome of extubation but found no differences in any of the EIT parameters considered between patients who succeeded and failed extubation. This finding may suggest, on the one hand, that the process leading to failure takes more than the 30-min period we observed in the present study, while on the other hand, that factors other than alterations of ventilation and homogeneity intervene in the pathophysiology of post-extubation respiratory failure. Indeed, in 7 patients (32%), the primary causes of extubation were either unmanageable secretions or haemodynamic instability or neurologic deterioration. In addition, we failed to observe differences in any EIT parameters between patients who succeeded and failed NIV as rescue treatment of overt post-extubation respiratory failure.

Our study has some points of strength. First, in contrast to previous investigations [26‐28], this is a multicentre study. Second, to reduce the risk of bias, the data analysis was performed in only one centre by a single investigator unaware of SBT and extubation outcomes. Third, we were extremely careful in maintaining the position of the EIT belt throughout the study period by marking the skin with a dermographic pencil, to prevent the risk of belt displacement, which is a well-known source of bias [10].

Our study also includes some limitations. We did not calculate the sample size because of the lack of published data at the time this study was designed and initiated. We did not register the trial prior to patient enrolment because the registration was not mandatory for observational studies when the study was initiated. We did not record the amount of fluids administered in the course of the study protocol. Fluid overload alters the measurement of EELI, mimicking a reduction in end-expiratory lung volume. One study in pigs showed that a rapid infusion (33 ml/kg/h) of fluids caused a significant reduction in overall relative impedance [29]. In another animal study, after a rapid (approximately 6 min) infusion of 500 ml of crystalloids the authors observed a decrease in EELI, corresponding to a mean virtual reduction in end-expiratory lung volume of 227 ml [30]. Conversely, a sudden increase in urine output up to 1200 ml consequent to a bolus of diuretics [31] or a loss of volume during haemodialysis [32] may determine EELI to increase. It should be noted, however, that a stable cardiovascular condition was a prerequisite for SBT eligibility in our study, which makes it highly unlikely that our patients received rapid liquid infusion or removal. In addition, none of the patients enrolled required haemodialysis or continuous veno-venous haemofiltration.

SBT failure is overall characterized early in the course of SBT by a greater reduction in EELI reflecting a fall in end-expiratory lung volume and more inhomogeneity of ventilation distribution, as opposed to patients succeeding SBT, but our data do not identify clear-cut thresholds. Whether EIT may be a useful adjunctive tool to monitor SBT remains to be determined by specifically designed clinical studies. No significant changes in lung aeration, ventilation distribution or homogeneity related to extubation outcome occurs up to 30 min after extubation.