Control of end-tidal carbon dioxide during phrenic nerve stimulation with mechanical ventilation

Mechanical ventilation maintains the gas exchange of patients in the intensive care unit which is life-saving, but prolonged ventilation results in diaphragm atrophy. Phrenic nerve stimulation can keep the diaphragm active so that atrophy might be avoided. To use phrenic nerve stimulation in a clinical setting, it is important to implement a closed-loop control system that automatically adjusts stimulation parameters to achieve the desired ventilation. This study presents the development of a robust cascaded control system for end-tidal carbon dioxide using phrenic nerve stimulation. The control system was validated in simulations with 100 virtual patients, in which the conditions of the phrenic nerve stimulation and the patient's condition changed, as well as in animal trials using pigs. The control system proved to be robust to end-tidal carbon dioxide perturbations, such as changing stimulation efficiency, varying patient conditions, and disconnection, in both simulations and animal trials. Regarding reference tracking, the control system achieved a settling time of 5.5 min-14 min in simulations and of 7.3 min-38.8 min in animal trials. The proposed control system can be used for further development of feedback-controlled phrenic nerve stimulation in the intensive care unit.