Phrenic nerve stimulation to prevent diaphragmatic dysfunction and ventilator-induced lung injury - PubMed
- ️Sun Jan 01 2023
Review
Phrenic nerve stimulation to prevent diaphragmatic dysfunction and ventilator-induced lung injury
Alessandro Panelli et al. Intensive Care Med Exp. 2023.
Abstract
Side effects of mechanical ventilation, such as ventilator-induced diaphragmatic dysfunction (VIDD) and ventilator-induced lung injury (VILI), occur frequently in critically ill patients. Phrenic nerve stimulation (PNS) has been a valuable tool for diagnosing VIDD by assessing respiratory muscle strength in response to magnetic PNS. The detection of pathophysiologically reduced respiratory muscle strength is correlated with weaning failure, longer mechanical ventilation time, and mortality. Non-invasive electromagnetic PNS designed for diagnostic use is a reference technique that allows clinicians to measure transdiaphragm pressure as a surrogate parameter for diaphragm strength and functionality. This helps to identify diaphragm-related issues that may impact weaning readiness and respiratory support requirements, although lack of lung volume measurement poses a challenge to interpretation. In recent years, therapeutic PNS has been demonstrated as feasible and safe in lung-healthy and critically ill patients. Effects on critically ill patients' VIDD or diaphragm atrophy outcomes are the subject of ongoing research. The currently investigated application forms are diverse and vary from invasive to non-invasive and from electrical to (electro)magnetic PNS, with most data available for electrical stimulation. Increased inspiratory muscle strength and improved diaphragm activity (e.g., excursion, thickening fraction, and thickness) indicate the potential of the technique for beneficial effects on clinical outcomes as it has been successfully used in spinal cord injured patients. Concerning the potential for electrophrenic respiration, the data obtained with non-invasive electromagnetic PNS suggest that the induced diaphragmatic contractions result in airway pressure swings and tidal volumes remaining within the thresholds of lung-protective mechanical ventilation. PNS holds significant promise as a therapeutic intervention in the critical care setting, with potential applications for ameliorating VIDD and the ability for diaphragm training in a safe lung-protective spectrum, thereby possibly reducing the risk of VILI indirectly. Outcomes of such diaphragm training have not been sufficiently explored to date but offer the perspective for enhanced patient care and reducing weaning failure. Future research might focus on using PNS in combination with invasive and non-invasive assisted ventilation with automatic synchronisation and the modulation of PNS with spontaneous breathing efforts. Explorative approaches may investigate the feasibility of long-term electrophrenic ventilation as an alternative to positive pressure-based ventilation.
© 2023. The Author(s).
Conflict of interest statement
SJS received grants and non-financial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees and non-financial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), non-financial support from national and international societies (and their congress organisers) in the field of anesthesiology and intensive care medicine, outside the submitted work. Dr Schaller holds stocks in small amounts from Alphabeth Inc., Bayer AG and Siemens AG; these holdings have not affected any decisions regarding his research or this study.
AP holds stocks in small amounts from BioNTech SE, Taiwan Semiconductor, Sony, Pfizer, Arcutis Biotherapeutics Inc, Sangamo Therapeutics, NIO, and Ke Holdings; these holdings have not affected any decisions regarding his research or this study.
LB has received research grants from STIMIT, Medtronic, and Draeger and equipment from Sentec, Philips and Fisher Paykel.
All other authors do not report any conflicting interests.
Figures
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Possible causal factors (on the left) of the four types of ventilation-induced myotrauma of diaphragmatic weakness

Overview of different phrenic nerve stimulation techniques that have been applied in critically ill patients. The nomenclature of the stimulation techniques was adopted from the studies in which they were first used for this particular study population. Nevertheless, the terms "EDP" [57] and "DPS" [48] have been marginally revised to improve categorisation, differentiation and comprehensibility with respect to the other existing techniques [, –56]

Non-invasive electromagnetic phrenic nerve stimulation in pulmonary healthy patients with absent respiratory drive induces tidal volume with low airway pressures (from the STIMIT I study [11])
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