Activation thresholds for electrical phrenic nerve stimulation at the neck: evaluation of stimulation pulse parameters in a simulation study.

Phrenic nerve stimulation reduces ventilator-induced-diaphragmatic-dysfunction, which is a potential complication of mechanical ventilation. Electromagnetic simulations provide valuable information about the effects of the stimulation and are used to determine appropriate stimulation parameters and evaluate possible co-activation.Using a multiscale approach, we built a novel detailed anatomical model of the neck and the phrenic nerve. The model consisted of a macroscale volume conduction model of the neck with 13 tissues, a mesoscale volume conduction model of the phrenic nerve with three tissues, and a microscale biophysiological model of axons with diameters ranging from 5 to 14 m based on the McIntyre-Richardson-Grill-model for myelinated axons. This multiscale model was used to quantify activation thresholds of phrenic nerve fibers using different stimulation pulse parameters (pulse width, interphase delay, asymmetry of biphasic pulses, pulse polarity, and rise time) during non-invasive electrical stimulation. Electric field strength was used to evaluate co-activation of the other nerves in the neck.For monophasic pulses with a pulse width of 150 s, the activation threshold depended on the fiber diameter and ranged from 20 to 156 mA, with highest activation threshold for the smallest fiber diameter. The relationship was approximated using a power fit function. Biphasic (symmetric) pulses increased the activation threshold by 25 to 30 %. The use of asymmetric biphasic pulses or an interphase delay lowered the threshold close to the monophasic threshold. Possible co-activated nerves were the more superficial nerves and included the transverse cervical nerve, the supraclavicular nerve, the great auricular nerve, the cervical plexus, the brachial plexus, and the long thoracic nerve.Our multiscale model and electromagnetic simulations provided insight into phrenic nerve activation and possible co-activation by non-invasive electrical stimulation and provided guidance on the use of stimulation pulse types with minimal activation threshold.