Influence of frequency and pulse train duration on respiratory responses during transcutaneous phrenic nerve...

Objective.Mechanical ventilation frequently leads to ventilator-induced diaphragmatic dysfunction, complicating weaning. Phrenic nerve stimulation (PNS) has emerged as a potential strategy to preserve diaphragmatic function; however, the influence of stimulation parameters, particularly frequency and pulse train duration, on respiratory outcomes during non-invasive transcutaneous PNS remains poorly understood.Approach.We systematically investigated the effects of stimulation frequency and pulse train duration during bilateral transcutaneous PNS at the neck in twelve healthy volunteers. Stimulation was applied across frequencies from 10 Hz to 100 Hz using two paradigms: constant pulse number and constant pulse train duration. Respiratory responses were assessed using multimodal measurements, including spirometry, respiratory belts, and ultrasound.Main results.Bilateral stimulation elicited measurable respiratory responses in all participants. Stimulation with constant pulse train duration significantly increased inhalation volume (+27.4%), chest expansion (+51.4%), abdominal expansion (+26.1%), and peak inhalation flow (+14.0%). In contrast, short pulse trains increased peak flow but did not consistently generate inhalation volume, indicating insufficient temporal integration of diaphragmatic activation. Peak inhalation flow correlated strongly with stimulation frequency in both paradigms (R²⩾ 0.77), while inhalation volume showed frequency dependence only for prolonged pulse trains (R²= 0.79). Inter-individual differences were observed in the frequency associated with maximal responses.Significance.We successfully increased inhalation volume by cervical electrical stimulation and induced frequency-dependent respiratory responses in humans. These findings are consistent with bilateral transcutaneous PNS. Pulse train duration represents a critical determinant of effective volume generation, while the observed inter-individual variability indicates that stimulation responses may differ between individuals and should be investigated further in future studies.