Initial Assessment of the Percutaneous Electrical Phrenic Nerve Stimulation System in Patients on Mechanical Ventilation

Abstract

Objectives: Maintaining diaphragm work using electrical stimulation during mechanical ventilation has been proposed to attenuate ventilator-induced diaphragm dysfunction. This study assessed the safety and feasibility of temporary percutaneous electrical phrenic nerve stimulation on user-specified inspiratory breaths while on mechanical ventilation. Design: Two-center, nonblinded, nonrandomized study. Setting: Hospital ICU. Patients: Twelve patients mechanically ventilated from 48 hours to an expected 7 days. Interventions: Leads were inserted to lie close to the phrenic nerve in the neck region using ultrasound guidance. Two initial patients had left-sided placement only with remaining patients undergoing bilateral lead placement. Percutaneous electrical phrenic nerve stimulation was used for six 2-hour sessions at 8-hour intervals over 48 hours. Measurements and Main Results: Data collected included lead deployment success, nerve conduction, ventilation variables, work of breathing, electrical stimulation variables, stimulation breath synchrony, and diaphragm thickness measured by ultrasound at baseline, 24, and 48 hours. Primary endpoints included ability to capture the left and/or right phrenic nerves and maintenance of work of breathing within defined limits for 80% of stimulated breaths. Lead insertion was successful in 21 of 22 attempts (95.5%). Analysis of 36,059 stimulated breaths from 10 patients with attempted bilateral lead placement demonstrated a mean inspiratory lag for phrenic nerve stimulation of 23.7 ms (p < 0.001 vs null hypothesis of <88ms). Work of breathing was maintained between 0.2 and 2.0 joules/L 96.8% of the time, exceeding the 80% target. Mean diaphragm thickness increased from baseline by 7.8% at 24 hours (p = 0.022) and 15.0% at 48 hours (p = 0.0001) for patients receiving bilateral stimulation after excluding one patient with pleural effusion. No serious device/procedure-related adverse events were reported. Conclusions: The present study demonstrated the ability to safely and successfully place percutaneous electrical phrenic nerve stimulation leads in patients on mechanical ventilation and the feasibility of using this approach to synchronize electrical stimulation with inspiration while maintaining work of breathing within defined limits.

Can Cardiopulmonary Rehabilitation Facilitate Weaning of Extracorporeal Membrane Oxygenation (CaRe-ECMO)? Study Protocol for a Prospective Multidisciplinary Randomized Controlled Trial

“…It was proven to be associated with a higher rate of mechanical ventilation weaning failure and prolonged length of mechanical ventilation (52). Upon this condition, we also included electrical stimulation of phrenic nerve to minimize the reduction of diaphragm atrophy and strength over time, possibly contributing to speed up respiratory functional recovery and subsequently leading to increased rate of ECMO weaning and shortened length of ECMO therapy (53)(54)(55). Taken together, it is reasonable to hypothesize that our protocolized cardiopulmonary rehabilitation may contribute to internal pathophysiological changes (e.g., cardiac output and maximal oxygen uptake) and spread it to external clinical outcomes (e.g., earlier weaning of ECMO and increased rated of ECMO weaning).…”

Evaluation of the Safety of Percutaneous Electrical Stimulation of the Phrenic and Femoral Nerves in a Chronic Porcine Model: A GLP Study

“…The above findings collectively indicated that the electrode placement procedure and the associated stimulation protocol would be transferable to humans in a clinical setting. The results of this GLP study served as the basis for developing the clinical protocol for the recently completed PEPNS first-in-human clinical study [6].…”

“…Intermittent electrical stimulation of the phrenic nerves to pace the diaphragm has been suggested as a strategy to minimize the reduction in diaphragm atrophy and to potentially reduce weaning failure [2]. Recently, O'Rourke et al demonstrated the ability to safely and successfully place percutaneous multipolar leads in the anatomical region of the neck close to phrenic nerves in patients on mechanical ventilation and to use these leads to deliver percutaneous electrical phrenic nerve stimulation (PEPNS) [6]. The authors reported that they were able to demonstrate the feasibility of using this approach to synchronize electrical stimulation with inspiration while maintaining Work of Breathing (WOB) within defined limits.…”

Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

“…Diaphragm protective ventilation can prevent diaphragm atrophy, compared with lung protective ventilation [ 58 ]. Furthermore, O’ Rourke et al reported that percutaneous electrical phrenic nerve stimulation increased diaphragm thickness by 15.1% within 48 h [ 59 ]. Extracorporeal support is also considered to prevent diaphragm injury [ 60 ], and in a case report, the early initiation of extracorporeal support prevented diaphragm atrophy, with a relatively suppressed level of urinary titin N-fragment of 24.1–38.4 pmol/mg Cr [ 61 ].…”