Diaphragm pacing may support daytime breathing off a ventilator

3 adults with late-onset, 3 children with early-onset Pompe disease in study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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An illustration of lungs laboring to breathe.

A diaphragm pacer may help people with Pompe disease who can’t breathe on their own rely less on a mechanical ventilator during the day, a small study suggests.

Many people with Pompe disease have respiratory problems and require full-time ventilation to support breathing, so being able to breathe without the help of a mechanical ventilator “would not be expected to occur in the natural course of the disease,” the study’s researchers wrote in “Diaphragm pacing and independent breathing in individuals with severe Pompe disease,” which was published in Frontiers in Rehabilitation Sciences.

Pompe disease occurs when an enzyme called acid alpha-glucosidase doesn’t work properly or isn’t made at all, impairing the ability to break down a complex sugar called glycogen. As a result, glycogen builds up to toxic levels in various tissues, particularly the muscles.

When this happens in the diaphragm, it can weaken it and compromise breathing. This can result in breathing problems, including respiratory failure, which occurs when the lungs can’t take enough oxygen to keep the body working.

The diaphragm lies just below the lungs, separating the chest cavity from the abdomen. Diaphragm pacing is a way to help the diaphragm contract (tighten) and flatten, so it moves down toward the abdomen, allowing the lungs to pull in air.

A diaphragm pacer is a device that stimulates this thin muscle. It involves a surgical procedure where four small electrode leads, or tiny wires, are attached to the phrenic nerves, which send the electrical signals that control the diaphragm and cause it to contract. A fifth electrode is placed just below the skin near the others. These electrodes run through the body to an exit site into a wire holder that plugs into a small battery-powered pulse generator (stimulator) worn on the skin. The stimulator is programmed to send out pulses of electrical signals to the electrodes. This stimulates the diaphragm, causing it to contract and help with breathing.

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Diaphragm pacing for Pompe disease patients

The study (NCT02354651) included three adults with late-onset Pompe disease, ages 25-53, and three children with early-onset Pompe disease, ages 3-5, who had chronic respiratory failure and were offered diaphragm pacing with NeuRx DPS technology as part of their clinical care plan.

Diaphragm pacing was started within five days after surgery and done for up to 30 minutes. The time was gradually increased every 2 to 5 days as tolerated with the goal being 24-hour diaphragm pacing by day 30 after surgery. The aim was to deliver a consistent stimulation that would maintain the amount of air a patient could breathe in while reducing the need for positive pressure mechanical ventilation.

Five patients (83%) used the diaphragm pacer for 24 hours within the first 30 days and started on diaphragm pacing-assisted breathing for short periods with less or no mechanical ventilation.

Five (83%) had at least one lead break, with four happening in a single patient. To prevent further damage, this patient, a 3-year-old girl, continued to breathe without support while awake and diaphragm pacing only happened when she was in a wheelchair at school.

All had complications related to Pompe disease and chronic breathing insufficiency, and two were hospitalized. The only side effect possibly related to diaphragm pacing was skin irritation or scabs where the electrodes touched the skin in three patients.

Diaphragm pacing helps with breathing

Before diaphragm pacing, all the patients required full-time ventilation support. After the diaphragm pacer was placed, they needed less help with breathing every day for up to seven years.

Responses ranged “from a small improvement to a substantial reduction in the amount of daytime during which [mechanical ventilation] was required,” the researchers wrote.

Three patients (one man, two girls) were weaned off daytime mechanical ventilation within six months of diaphragm pacing, meaning they no longer needed help during the day.

The average tidal volume, the amount of air that moves in and out of the lungs during a single breath, was significantly larger at two years than at 4-6 weeks after starting diaphragm pacing.

The three patients who were weaned off daytime mechanical ventilation had greater tidal volume early after diaphragm pacing compared to those who still required it during the day.

“It was noteworthy that following [two] years of [diaphragm pacing] use, an increase in unassisted tidal volume was detected in some subjects, accompanied by an increase in routine off-ventilator breathing time,” the researchers wrote.

All six patients were receiving treatment with Lumizyme (alglucosidase alfa), sold as Myozyme outside the U.S., an enzyme replacement therapy for Pompe disease.

“[Diaphragm pacing] may be an additional option beyond routine clinical care, particularly for those who are ineligible for other emerging treatments, such as next-generation enzyme replacement therapies or gene therapy,” the researchers wrote.