Development of a closed-loop device for phrenic nerve stimulation to enable a new approach of intensive care ventilatory support – (DIA-STIM)

• Applicants: Dr. Thomas Breuer; Professor Dr.-Ing. Steffen Leonhardt
• Subject Area: Biomedical Systems Technology ; Anaesthesiology ; Medical Physics, Biomedical Technology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 420664178

• Final Report Year: 2025

Final Report Abstract

Mechanical ventilation is used in intensive care units for patients with acute respiratory insufficiency. During mechanical ventilation, the diaphragm remains inactive and is threatened by a pathophysiological syndrome called “ventilator-induced diaphragmatic dysfunction” (VIDD). Failed weaning from the ventilator is a significant factor in this context. Various studies show that maintaining the activity of the diaphragm during mechanical ventilation, for example by stimulating the phrenic nerve, could prevent atrophy of the diaphragm and consequently shorten the mechanical ventilation time. The project DIA-STIM hypothesised that controlled phrenic nerve stimulation could be a viable method of maintaining diaphragm function in deeply sedated patients. A suitable approach for the ICU allows immediate activation of the diaphragm after the start of mechanical ventila-tion without jeopardising the lung parenchyma and before the onset of VIDD. The hypothesis put forward was evaluated in tests on pigs. A minimally invasive way to stimulate the phrenic nerve was identified in the course of the preliminary tests with a duration of 24 hours on the first 7 pigs. In addition, the technical and experimental setup was established and data on the development of the control system was collected. It was determined which electrical stimulation settings were suitable and the measurement data was used to set up and validate mathematical models of the stimulation process. Based on this data, a control system was developed that automatically adjusts the phrenic nerve stimulation and mechanical respiration. The system was validated in silico and in vivo. A total of 17 pigs were examined in the main experiments. In the first group (n=6), the phrenic nerve was stimulated over a period of 96 hours using the regulated system. The second group (n=6) served as a control group in which the pigs were mechanically ventilated for 72 hours and spontaneous breathing was established in the last 24 hours to wean them off the ventila-tor. In the third group (n=5), the pigs were mechanically ventilated for 72 hours as in the con-trol group, but weaning with stimulation of the phrenic nerve was established in the last 24 hours. These data were analysed with regard to the hypothesis put forward. The technical system can be used as a prototype for the further development of automated phrenic nerve stimulation in the intensive care unit. The results have already been published in 4 journals and 5 conferences.

Publications

• “Flexible pattern generation for phrenic nerve stimulation”. 15. Interdisziplinäres Symposium - Automatisierungstechnische Verfahren für die Medizintechnik. Basel, Switzerland, Jun 08 – 09, 2021
  A. Lohse, M. Walter, M. M. Deininger, T. G. Seemann, D. Ziles, T. Breuer & S. Leonhardt
  
• Identification of the Tidal Volume Response to Pulse Amplitudes of Phrenic Nerve Stimulation Using Gaussian Process Regression. 2022 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), 135-138. IEEE.
  Lohse, Arnhold; von Platen, Philip; Benner, Carl-Friedrich; Leonhardt, Steffen; Walter, Marian; Deininger, Matthias Manfred; Ziles, Dmitrij; Seemann, Teresa & Breuer, Thomas
  
• Comparison of phrenic nerve stimulated breathing to mandatory ventilation using EIT in a pig model, Proceedings of the 23rd International Conference on Biomedical Applications of Electrical Impedance Tomography, vol. 23, p. 22
  D. Ziles et al.
  
• Development of a bellow-based test lung for spontaneous breathing. 16. Interdisziplinäres Symposium - Automatisierungstechnische Verfahren für die Medizintechnik. Gießen, Germany, Mar 30 – 31, 2023
  A. Lohse, H. Bommes, F. Röhren, S. Leonhardt & M. Walter
  
• Evaluation of electric phrenic nerve stimulation patterns for mechanical ventilation: a pilot study. Scientific Reports, 13(1).
  Lohse, Arnhold; von Platen, Philip; Benner, Carl-Friedrich; Deininger, Matthias Manfred; Seemann, Teresa Gertrud; Ziles, Dmitrij; Breuer, Thomas; Leonhardt, Steffen & Walter, Marian
  
• A physiological model of phrenic nerve excitation by electrical stimulation. Biomedical Physics & Engineering Express, 10(2), 025017.
  Lohse, Arnhold; Deininger, Matthias Manfred; Loeser, Johannes; Roehren, Felix; Ziles, Dmitrij; Breuer, Thomas; Leonhardt, Steffen & Walter, Marian
  
• Breath-by-breath comparison of a novel percutaneous phrenic nerve stimulation approach with mechanical ventilation in juvenile pigs: a pilot study. Scientific Reports, 14(1).
  Deininger, Matthias Manfred; Ziles, Dmitrij; Borleis, Annegret; Seemann, Teresa; Erlenkoetter, Fabian; Bleilevens, Christian; Lohse, Arnhold; Benner, Carl-Friedrich; Leonhardt, Steffen; Walter, Marian & Breuer, Thomas
  
• Robust flow control in a mechatronic test lung with spontaneous breathing. 2024 IEEE international conference on advanced intelligent mechatronics (AIM). Boston, United States of America, Jul 15 – 19, 2024
  A. Lohse, F. Hamidov, P. Borcher, P. von Platen, S. Leonhardt & M. Walter
  
• Control of end-tidal carbon dioxide during phrenic nerve stimulation with mechanical ventilation. Biomedical Signal Processing and Control, 105, 107649.
  Lohse, Arnhold; Röhren, Felix; von Platen, Philip; Benner, Carl-Friedrich; Ziles, Dmitrij; Hühn, Marius; Deininger, Matthias Manfred; Breuer, Thomas; Leonhardt, Steffen & Walter, Marian