Efficacy of external diaphragm pacing combined with high-flow oxygen via tracheostomy for weaning in patients requiring prolonged mechanical ventilation: a study protocol for a randomized controlled trial

This randomized controlled trial protocol outlines a study in a Chinese rehabilitation hospital to evaluate whether combining external diaphragm pacing with high-flow oxygen via tracheostomy improves weaning outcomes and mitigates ventilator-induced diaphragmatic dysfunction in adult patients requiring prolonged mechanical ventilation.

The Gist

Imagine a patient in the Intensive Care Unit (ICU) who has been so sick that they've been on a breathing machine (a ventilator) for weeks. Think of the ventilator as a tough, overprotective bodyguard that does all the heavy lifting for the patient's lungs.

While this bodyguard is necessary to keep the patient alive, it has a side effect: because the bodyguard is doing all the work, the patient's breathing muscle (the diaphragm) starts to get lazy, weak, and shrinks, much like a muscle that hasn't been used in a gym for months. This is called "muscle atrophy." When the doctors try to take the bodyguard away (wean the patient off the machine), the patient's muscle is too weak to breathe on its own, leading to a dangerous cycle of failure.

This study is a new experiment to see if a two-part "rehabilitation team" can help these patients get their breathing muscles back in shape faster than standard care alone.

The Two-Part Team

The researchers are testing a combination of two tools:

1. The "Electric Coach" (External Diaphragm Pacing):
   Imagine the patient's diaphragm is a tired athlete. The "Electric Coach" is a non-invasive device that sticks to the skin (like a TENS unit for back pain) and sends gentle electrical pulses to the phrenic nerve. This acts like a personal trainer giving the muscle a gentle nudge to contract and exercise, even while the patient is resting. It wakes up the muscle and prevents it from shrinking.

2. The "Warm Breeze" (High-Flow Oxygen via Tracheostomy):
   Patients with a breathing tube in their neck (tracheostomy) often struggle to breathe comfortably. The "Warm Breeze" is a machine that blows a steady, warm, and humid stream of oxygen directly into that tube. Think of it as a gentle tailwind for a cyclist. It doesn't force the air in; it just makes the air easier to push through, reducing the effort the patient's lungs have to make. This gives the tired muscle a chance to rest and recover without struggling against the wind.

The Experiment

The researchers want to see if using both the Electric Coach and the Warm Breeze together works better than just the standard care (which is usually just a simple oxygen mask).

• The Players: They will recruit 60 adult patients who have been on the ventilator for a long time (more than 21 days) and have a tracheostomy.
• The Teams:
  • Team A (The Experimental Group): Gets the Electric Coach + The Warm Breeze + Standard Care.
  • Team B (The Control Group): Gets Standard Care only (just the oxygen mask).
• The Goal: The main goal is to see which team can get their "bodyguard" (the ventilator) to leave the room first. Specifically, they want to know who can breathe on their own for 24 hours without needing the machine again.

Why This Matters

Currently, many patients get stuck in the ICU for weeks or months because their breathing muscles are too weak to take over. This study is like testing a new rehabilitation strategy to see if it can speed up recovery.

• If it works: It could mean patients spend less time in the ICU, have fewer complications, and get home sooner. It offers a way to "wake up" the breathing muscle without needing risky surgery.
• If it doesn't work: At least we'll know that this specific combination isn't the magic bullet, and doctors can focus on other methods.

The Rules of the Game

• Safety First: The doctors will watch closely for any side effects, like skin irritation from the electric pads or discomfort from the airflow.
• Fair Play: The patients and doctors won't know who is getting the special treatment (well, actually, they will, because the machines are visible, but the people measuring the muscle strength and the statisticians analyzing the data will be kept in the dark to ensure fairness).
• The Timeline: The study is planned to run for about six months, recruiting patients starting late 2025.

In short, this paper is a blueprint for a clinical trial asking: "Can we use a gentle electrical nudge and a warm, steady breeze to wake up a sleeping breathing muscle and help a patient breathe on their own again?"

Technical Summary

Based on the provided study protocol, here is a detailed technical summary of the research:

1. Problem Statement

Prolonged Mechanical Ventilation (PMV) is a critical challenge in intensive care, defined as requiring invasive mechanical ventilation for >6 hours/day for more than 21 consecutive days. PMV is associated with high morbidity, mortality, and significant healthcare resource utilization.

• Core Pathophysiology: A primary driver of poor outcomes in PMV is Ventilator-Induced Diaphragmatic Dysfunction (VIDD), characterized by rapid atrophy and functional decline of the diaphragm due to disuse and mechanical ventilation.
• Current Limitations: While strategies like diaphragm pacing exist, traditional methods (surgically implantable devices) are invasive, costly, and technically demanding. Non-invasive alternatives and optimized weaning support for tracheostomized patients remain under-evaluated.
• The Gap: There is a lack of randomized controlled trial (RCT) evidence evaluating the synergistic effect of combining External Diaphragm Pacing (EDP) with High-Flow Oxygen via Tracheostomy (HFT) to facilitate weaning in this specific population.

2. Methodology

This is a single-center, randomized, controlled, open-label trial conducted at Ningbo Zhenhai Longsai Hospital, China.

• Study Design:

  • Type: RCT (1:1 allocation).
  • Population: 60 adult patients (≥18 years) with tracheostomies requiring PMV who have failed ≥2 weaning attempts.
  • Inclusion Criteria: Hemodynamically stable, >21 days of ventilation, capable of undergoing EDP.
  • Exclusion Criteria: Absent respiratory drive, rapidly progressive neuromuscular diseases, septic shock, implanted cardiac devices (pacemakers/ICDs), morbid obesity (BMI ≥35 kg/m²), or skin lesions at electrode sites.

• Interventions:

  • Experimental Group (EDP + HFT):
    • EDP: Non-invasive phrenic nerve stimulation using the EDP-2023 device. Electrodes placed on the sternocleidomastoid and mid-clavicular line. Parameters: 40 Hz, 9 breaths/min, 30 mins/session, 2 sessions/day, 5 days/week. Intensity titrated up to 20 mA.
    • HFT: High-flow oxygen via tracheostomy interface (e.g., Fisher & Paykel Optiflow™). Initiated during spontaneous breathing trials (SBTs). Initial settings: 60 L/min, 37°C, FiO₂ 40%, titrated to maintain SpO₂ ≥92%.
  • Control Group (Standard Care):
    • Receives standard ICU weaning protocols (daily screening, SBTs, nutritional support, sedation management) with conventional oxygen therapy via tracheostomy mask. No EDP or HFT.

• Outcomes:

  • Primary Endpoint: Time (days) from randomization to successful 24-hour separation from invasive mechanical ventilation (without reconnection within 48 hours) by Day 28.
  • Secondary Endpoints:
    • Diaphragm function: Changes in thickness and thickening fraction (via ultrasound).
    • Clinical metrics: ICU length of stay, 28-day survival.
    • Safety: Incidence of adverse events (AEs) such as skin burns, arrhythmias, or barotrauma.

• Statistical Analysis:

  • Sample Size: 60 participants (30 per group), based on clinical relevance and prior similar studies (e.g., RESCUE-2).
  • Analysis: Intention-to-treat (ITT) and Per-protocol (PP) populations.
  • Methods: Kaplan-Meier curves and log-rank tests for time-to-event; mixed-effects models for longitudinal ultrasound data; competing-risk analysis for death/withdrawal.

• Bias Control:

  • Open-label for clinicians/patients.
  • Blinded: Ultrasound assessors, statisticians, and outcome adjudicators (for primary endpoint derived from logs).

3. Key Contributions

• Novel Combination: This is the first RCT to investigate the combined efficacy of non-invasive EDP and HFT for weaning PMV patients.
• Mechanistic Synergy: The study hypothesizes a dual-mechanism approach: EDP directly counteracts VIDD by stimulating diaphragmatic contractility, while HFT reduces respiratory workload and optimizes oxygenation, potentially creating a synergistic effect for liberation from ventilation.
• Rigorous Protocol: Adherence to SPIRIT guidelines, use of blinded ultrasound assessment, and standardized weaning protocols ensure high internal validity despite the open-label design.
• Feasibility Focus: The protocol addresses practical barriers by using non-invasive, bedside-applicable technologies suitable for rehabilitation settings.

4. Results

• Status: No results are available yet.
• Reason: This document is a study protocol (preprint) outlining the methodology and design before data collection.
• Timeline: Recruitment is scheduled from November 1, 2025, to April 30, 2026, with results anticipated by December 31, 2026.

5. Significance

• Clinical Impact: If successful, this intervention could provide a non-invasive, accessible, and cost-effective strategy to mitigate VIDD, reduce the duration of mechanical ventilation, and lower ICU length of stay for a high-risk patient population.
• Resource Optimization: Reducing PMV duration directly addresses the high economic burden and resource strain associated with long-term ventilator dependence.
• Future Directions: Positive findings would justify larger, multi-center trials to validate the efficacy of the EDP+HFT combination and potentially establish it as a new standard of care for difficult-to-wean tracheostomized patients.
• Safety Profile: The study will establish a critical safety profile for the combined use of transcutaneous pacing and high-flow oxygen in critically ill patients.