Transvenous Phrenic Nerve Stimulation in Patients Who Are Difficult to Wean

To the Editor:

This letter is in response to a Journal article by Dres and colleagues (1). The authors have done a commendable study to evaluate the role of phrenic nerve stimulation in patients with presumed diaphragmatic dysfunction. However, I have a few concerns and suggestions related to the methodology and interpretation of the finding of this study.

The exhaustive exclusion criteria did not rule out clinicopathologic factors other than diaphragmatic dysfunction, which could have hindered liberation from the mechanical ventilation (2). The differential distribution of lung collapse, atelectasis, lung fibrosis, diastolic dysfunction, and pulmonary hypertension in the control and treatment arm could have affected the outcomes. Lung ultrasound-based aeration score and diastolic dysfunction parameters can help predict failed weaning (3). Assessment of ventilation, perfusion, and regional variation in aeration by electrical impedance tomography could have led credential to this study. Of note, in this study population, there were several risk factors for diastolic dysfunction present, including old age, smoking, hypertension, diabetes, hypercholesteremia, and coronary artery disease. In the study design, patients with overt congestive heart failure were to be excluded; however, the authors reported congestive heart failure in 9% of patients and valvular heart disease in 19% of patients in the treatment arm. The extent and severity of valvular heart disease and congestive heart failure in the treatment and control arm could have affected the weaning from ventilation. The exclusion of congenital heart disease and inclusion of valvular heart disease in this study is indeed surprising. In fact, both these cardiac diseases may lead to congestive lung pathology because of congestive heart failure, volume overload, elevated pulmonary capillary wedge pressure, or excessive pulmonary blood flow (4).

The difference in maximum inspiratory pressure (MIP) despite similar diaphragmatic thickening fraction in both the arms suggests extradiaphragmatic pathologies. The change in MIP reflects the cumulative pathologies of the lung, pleura, diaphragm, chest wall, and abdomen. The MIP is effort-dependent, and it represents the combined power generated by the inspiratory muscles, including diaphragmatic contraction. Therefore, MIP measurement as a tool to assess and follow diaphragmatic contractility is limited (5). The diaphragmatic muscle weakness could be best assessed by the regional (subdiaphragmatic) change in inspiratory pleural pressure. Moreover, twitch transdiaphragmatic pressure (difference in gastric and esophageal pressures) in response to electrical or magnetic phrenic nerve stimulation can best assess the extent of diaphragmatic dysfunction.

Half of the patients were tracheostomized, and liberation from mechanical ventilation in these patients could be less challenging than in those who were intubated (6). And weaning from ventilation in patients who are endotracheally intubated involves both liberation from ventilation and successful extubation. Moreover, respiratory load and work of breathing have been reported to be lower in patients who are tracheostomized than endotracheally intubated. The clinical predictors and severity of pathologies are generally different between patients who are tracheostomized and endotracheally intubated. Therefore, these two clinical phenotypes require a separate analysis to assess the effect of phrenic nerve stimulation. In conclusion, considerable heterogeneity in the study population seemed to influence the finding and interpretation of this study.