Is Measurement of Inspiratory Effort and Respiratory Mechanics before Ventilator Weaning a Step toward Personalized Medicine?

Management of patients receiving mechanical ventilation according to their work of breathing could be the holy grail of medical precision. During the ventilator weaning period, the patient’s effort intensity could predict his ability to be successfully extubated. However, measuring esophageal pressure is the only accurate way to assess patient effort. Neither clinical examination nor tidal volumes can predict inspiratory effort intensity (1). However, surrogates can be used to estimate the work of breathing (2).

In this issue of the Journal, Murgolo and colleagues (pp. 2340–2351) conducted a multicenter physiological study (five ICUs in Italy) to assess whether changes in the work of breathing and respiratory mechanics during spontaneous breathing were associated with reintubation (3). The authors included 238 high-risk patients who were ready for extubation after having passed a 30-minute spontaneous breathing trial (SBT) using pressure-support ventilation (PSV) at 7 cm H₂O and positive end-expiratory pressure (PEEP) of 5 cm H₂O. After that, they performed a new SBT with similar respiratory support, but this time using proportional assist ventilation (PAV+), which allows measurement of the work of breathing and respiratory system compliance through automatic occlusions. Because the PAV+ ventilatory mode is available only on the Puritan Bennett 840 (Medtronic) ventilator, it was necessary to switch the ventilator to perform measurements for all patients. The authors also measured 1) respiratory drive, estimated using P0.1 (airway pressure drop during the first 100 ms of an occluded breath), and 2) patient inspiratory effort, estimated using airway pressure drop during a full end-expiratory occlusion maneuver (ΔPocc). Both of these measurements are measurable with all ventilators. After that, all patients were extubated and received high-flow nasal cannula oxygen. Extubation failure was defined as the need for reintubation within the 72 hours after extubation.

The main finding of the study was that patient effort (ΔPocc) increased from 12 [10–15] cm H₂O at the beginning of the SBT to 18 [15–20] cm H₂O at the end (P < 0.001) in patients who required reintubation. Meanwhile, respiratory system compliance decreased significantly. In contrast, patient effort and respiratory system compliance remained unchanged in patients who were successfully extubated. An increase in ΔPocc greater than 2 cm H₂O was the most accurate predictor of reintubation, with 89% sensitivity and 93% specificity. Regarding respiratory drive, P0.1 increased in both groups and consequently played a limited role in predicting reintubation.

This is the first large-scale, multicenter study to demonstrate an association between increased patient inspiratory effort (ΔPocc) or decreased respiratory compliance and reintubation. All measurements were standardized using the same ventilatory mode and type of ventilator, which further reinforces the internal validity of the study. Consequently, monitoring of ΔPocc during SBT plays a major role from a respiratory physiology point of view and may be a practical tool first to decide on extubation and then to individualize the most adequate noninvasive respiratory support after extubation. Although work of breathing can be measured only using PAV+, ΔPocc is measurable noninvasively on all ICU ventilators using PSV. Interestingly, this study highlights the fact that decreased respiratory system compliance could be a result of alveolar derecruitment during the SBT and would encourage the application of noninvasive ventilation (4).

However, several limitations must be taken into account before these measurements can have an impact on clinical practice. First, the threshold values of ΔPocc should be validated in other patient cohorts to confirm that it is indeed a strong predictor of reintubation, especially when using other types of SBTs. In the present study, the SBT was performed with PSV at 7 cm H₂O and PEEP of 5 cm H₂O, which is particularly easy to pass and markedly underestimates the work of breathing needed after extubation (5, 6). Before SBT, patients were ventilated with a median PSV of 9 cm H₂O and PEEP of 7 cm H₂O, indicating that the SBT induced only minimal changes in the work of breathing. A large-scale clinical trial recently showed that such an easy SBT may hasten extubation without increasing the risk of reintubation (7). However, this study included a majority of patients at low risk of extubation failure, and its safety in high-risk patients has yet to be proved. Up until now, large-scale clinical trials have compared more challenging SBTs using a T-piece or PSV without PEEP (8, 9).

The second major limitation of the study stems from the use of high-flow nasal oxygen alone after extubation. Prophylactic noninvasive ventilation is currently recommended, with an ever-increasing level of proof over time, in patients at high risk of extubation failure (10), especially after two large-scale clinical trials showing decreased risk of reintubation as compared with high-flow nasal oxygen (11, 12). Even though the factors helping to identify high-risk patients may differ from one study to another, a recent study showed that patients older than 65 years of age, those with chronic cardiac or lung disease, and those intubated for more than 7 days were particularly easy for clinicians to identify and were the most at risk for reintubation (13). In the present study, the actual rate of reintubation was not 19% as indicated in the results, but rather 24% (59 out of 251 patients), given that 13 patients were excluded because of their need for emergency surgery. To date, a 24% reintubation rate seems particularly high, because recent trials have reported rates lower than 15% in exactly the same population but receiving noninvasive ventilation after extubation (9, 11). Whether patients who would increase ΔPocc during the SBT may benefit the most from noninvasive ventilation, as suggested by the authors, is really a signally intriguing physiological concept. However, beneficial effects of noninvasive ventilation on a decrease in the work of breathing have already been demonstrated after extubation (14). Therefore, demonstrating the benefits of an individualized strategy based on measurements of patient effort would require significant clinical research for a strategy that is already recommended, which is why the goal would be only to demonstrate noninferiority rather than superiority. Despite these limitations, this study is a major step forward in assessment of individualization of clinical decisions and management before and after extubation according to patient inspiratory effort and respiratory mechanics.