Feasibility of transesophageal phrenic nerve stimulation

Abstract

Background: Every year, more than 2.5 million critically ill patients in the ICU are dependent on mechanical ventilation. The positive pressure in the lungs generated by the ventilator keeps the diaphragm passive, which can lead to a loss of myofibers within a short time. To prevent ventilator-induced diaphragmatic dysfunction (VIDD), phrenic nerve stimulation may be used.

Objective: The goal of this study is to show the feasibility of transesophageal phrenic nerve stimulation (TEPNS). We hypothesize that selective phrenic nerve stimulation can efficiently activate the diaphragm with reduced co-stimulations.

Methods: An in vitro study in saline solution combined with anatomical findings was performed to investigate relevant stimulation parameters such as inter-electrode spacing, range to target site, or omnidirectional vs. sectioned electrodes. Subsequently, dedicated esophageal electrodes were inserted into a pig and single stimulation pulses were delivered simultaneously with mechanical ventilation. Various stimulation sites and response parameters such as transdiaphragmatic pressure or airway flow were analyzed to establish an appropriate stimulation setting.

Results: Phrenic nerve stimulation with esophageal electrodes has been demonstrated. With a current amplitude of 40 mA, similar response figures of the diaphragm activation as compared to conventional stimulation with needle electrodes at 10mA were observed. Directed electrodes best aligned with the phrenic nerve resulted in up to 16.9 % higher amplitude at the target site in vitro and up to 6 cmH20 higher transdiaphragmatic pressure in vivo as compared to omnidirectional electrodes. The activation efficiency was more sensitive to the stimulation level inside the esophagus than to the inter-electrode spacing. Most effective and selective stimulation was achieved at the level of rib 1 using sectioned electrodes 40 mm apart.

Conclusion: Directed transesophageal phrenic nerve stimulation with single stimuli enabled diaphragm activation. In the future, this method might keep the diaphragm active during, and even support, artificial ventilation. Meanwhile, dedicated sectioned electrodes could be integrated into gastric feeding tubes.

Keywords: Critical care; Diaphragm activation; Esophageal catheter; Hospital mortality; Intensive care unit; Lung and diaphragm protective; Phrenic nerve stimulation; Transesophageal stimulation; Ventilation induced diaphragmatic dysfunction.

Fig. 1

Multipolar esophageal catheter equipped with ten electrode sections. All sections contain omnidirectional electrodes, except sections 6 and 8, which include three directed electrodes in the circumference

Fig. 2

In vitro test setup A used for the analysis of stimulation intensities with directed as compared to omnidirectional electrodes and animal trial setup B with dedicated stimulation and measurement equipment

Fig. 3

Peak-to-peak amplitude of the measured stimulation pulses at 10mA as a function of the interelectrode spacing, emulated distance to nerve and electrode type. The markers indicate measurements with directed electrodes facing toward the nerve (*) and pointing 120${}^{\circ }$away (o). At the distance of 20–30 mm to the nerve, a smaller interelectrode spacing of 20 mm to 40 mm produces a higher potential as compared to higher spacing. An additional gain of up to 16.9% is measured through aligned electrode segments.

Fig. 4

Posterior–anterior X-ray of the pig chest and neck during the trial. The locations of the stimulation electrodes are marked in green. A) Parasternal insertion site of the needle electrode used to puncture the left phrenic nerve at level rib 1 / C7. B) Esophageal electrodes #5 and #6 with the shortest expected distance to the phrenic nerve aligned at the same level, i.e., rib 1 / C7

Fig. 5

Capture of the multimodal signals after the delivery of a single stimulus with the punctured needle electrode (left) and esophageal electrodes symmetrical to level rib 1 and 40 mm spacing (right). Due to directed TEPNS, similar Pdi values are achieved compared with needle electrode stimulation, but with significantly higher bilateral acceleration values

Fig. 6

Stimulation-induced Pdi as a function of the esophageal stimulation level around rib 1 (orange shades) and C6 (green), and the electrode spacing (10–40 mm) with a stimulation intensity of 40 mA. The horizontal dashed line indicates phrenic nerve capture with the punctured needle electrode placed at rib 1. The zero level, aligned accordingly to rib 1 or C6, is depicted by a vertical line. A significantly higher Pdi is generated at the stimulation position of rib 1 than at the level of C6. Furthermore, a gain in Pdi can be observed by the best aligned directed electrode as compared to the omnidirectional electrode

Fig. 7

Left (L, filled markers) and right (R, empty markers) acceleration amplitude as a function of the esophageal stimulation level around rip 1 (orange-shades) and C6 (green) as well as the electrode spacing (10–40 mm) with a stimulation intensity of 40 mA. The average left and right acceleration amplitude achieved during stimulation with the needle electrode is indicated as an upper and lower dashed line, respectively. Compared to impulses from the needle electrode, significantly higher acceleration values are measured through stimulation with esophageal electrodes at the level of rib 1, which are as attributed to a higher amount of co-stimulation