Diaphragm pacing (and even earlier as electrophrenic respiration) is the rhythmic application of electrical impulses to the

diaphragm Diaphragm may refer to: Anatomy * Thoracic diaphragm, a thin sheet of muscle between the thorax and the abdomen * Pelvic diaphragm or pelvic floor, a pelvic structure * Urogenital diaphragm or triangular ligament, a pelvic structure Other * Diap ...

to provide

artificial Artificiality (the state of being artificial or manmade) is the state of being the product of intentional human manufacture, rather than occurring naturally through processes not involving or requiring human activity. Connotations Artificiality ...

ventilatory support for

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...

sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...

. Historically, this has been accomplished through the electrical stimulation of a

phrenic nerve The phrenic nerve is a mixed motor/sensory nerve which originates from the C3-C5 spinal nerves in the neck. The nerve is important for breathing because it provides exclusive motor control of the diaphragm, the primary muscle of respiration. In ...

by an implanted receiver/electrode, though today an alternative option of attaching

percutaneous {{More citations needed, date=January 2021 In surgery, a percutaneous procedurei.e. Granger et al., 2012 is any medical procedure or method where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using ...

wires to the diaphragm exists.

History

The idea of stimulating the diaphragm through the phrenic nerve was first firmly postulated by German physician

Christoph Wilhelm Hufeland Christoph Wilhelm Friedrich Hufeland (12 August 1762, Langensalza – 25 August 1836, Berlin) was a German physician, naturopath and writer. He is famous as the most eminent practical physician of his time in Germany and as the author of numero ...

, who in 1783 proposed that such a technique could be applied as a treatment for asphyxia. French neurologist

Duchenne de Boulogne Guillaume-Benjamin-Amand Duchenne (de Boulogne) (September 17, 1806 in Boulogne-sur-Mer – September 15, 1875 in Paris) was a French neurologist who revived Galvani's research and greatly advanced the science of electrophysiology. The era of mo ...

made a similar proposal in 1855, though neither of them tested it. It was not until a year later that

Hugo Wilhelm von Ziemssen Hugo (Wilhelm) von Ziemssen (13 December 1829 – 21 January 1902) was a German physician, born in Greifswald. He studied medicine at the universities of Greifswald, Berlin, and Würzburg. In 1863 he was called to the University of Erlangen as a ...

demonstrated diaphragm pacing on a 27-year-old woman asphyxiated on charcoal fumes by rhythmically faradizing her phrenic nerves, saving her life. Duchenne would later in 1872 declare the technique the "best means of imitating natural respiration". However, advances in

mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...

by the likes of

George Poe George Poe, Jr. (May 8, 1846 – February 3, 1914) was a pioneer of mechanical ventilation of asphyxiation victims. He was the first person to manufacture nitrous oxide for commercial use in his Trenton, New Jersey company. Birth He was t ...

in the early twentieth century ended up being initially favored over phrenic nerve stimulation. Harvard researchers Sarnoff et al. revisited diaphragm pacing via the phrenic nerve in 1948, publishing their experimental results on dogs. In a separate publication a few days before, the same group also revealed they had an opportunity to use the technique "on a five-year-old boy with complete respiratory paralysis following rupture of a cerebral aneurysm". Referring to the process as "electrophrenic respiration", Sarnoff was able to artificially respirate the young boy for 52 hours. The technology behind diaphragm pacing was advanced further in 1968 with the publication of doctors John P. Judson and William W. L. Glenn's research on the use of radio-frequency transmission to at whim "adjust the amplitude of stimulation, and to control the rate of stimulation externally". Teaming up with Avery Laboratories, Glenn brought his prototype device to commercial market in the early 1970s. The Avery Breathing Pacemaker received pre-market approval from the FDA in 1987 for "chronic ventilatory support because of upper motor neuron respiratory muscle paralysis" in patients of all ages. In the 1980s, "sequential multipole stimulation" was developed in Tampere, Finland. This technology was commercialized as the Atrostim PNS system and became commercially available in Europe in 1990. By the early 1990s, long-term evaluations of the technology were being published, with some researchers such as Bach and O'Connor stating that phrenic nerve pacing is a valid option "for the properly screened patient but that expense, failure rate, morbidity and mortality remain excessive and that alternative methods of ventilatory support should be explored". Others such as Brouillette and Marzocchi suggested that advances in encapsulation and electrode technologies could improve system longevity and reduce damage to diaphragm muscle. Additionally, new surgical techniques such as a thoracoscopic approach began to appear in the late 1990s. In the mid-2000s, U.S. company Synapse Biomedical began researching a new diaphragm pacing system that would not have to attach to the phrenic nerve but instead depended on "four electrodes implanted in the muscle of the diaphragm to electronically stimulate contraction". The marketed NeuRx device received several

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

approvals under a Humanitarian Device Exemption (HDE), one in 2008 and another in 2011.

Methodology and devices

The basic principle behind a diaphragm pacing device (the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

identifies the device as a "diaphragmatic/phrenic nerve stimulator") involves passing an

electric current An electric current is a stream of charged particles, such as electrons or ions, moving through an electrical conductor or space. It is measured as the net rate of flow of electric charge through a surface or into a control volume. The moving pa ...

through electrodes that are attached internally. The diaphragm contracts, expanding the chest cavity, causing air to be sucked into the

lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

s (

inspiration Inspiration, inspire, or inspired often refers to: * Artistic inspiration, sudden creativity in artistic production * Biblical inspiration, the doctrine in Judeo-Christian theology concerned with the divine origin of the Bible * Creative inspirat ...

). When not stimulated, the diaphragm relaxes and air moves out of the lungs (

expiration Expiration or expiration date may refer to: Expiration Expiration may refer to: *Death *Exhalation of breath, breathing out *Expiration (options), the legal termination of an option to take an action *Shelf life, or the time after which a product ...

). According to the United States Medicare system, phrenic nerve stimulators are indicated for "selected patients with partial or complete respiratory insufficiency" and "can be effective only if the patient has an intact phrenic nerve and diaphragm". Common patient diagnoses for phrenic nerve pacing include patients with

spinal cord injury A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. Symptoms may include loss of muscle function, sensation, or autonomic function in the parts of the body served by the spinal cor ...

, central

, congenital central hypoventilation syndrome (i.e.,

Ondine's curse Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep (and during wakefulness in severe cases). CHS can either be congenital (CCHS) or acquired ( ...

), and diaphragm paralysis. There are currently three commercially distributed diaphragm pacing devices: Synapse Biomedical, Inc.'s NeuRx (US), Avery Biomedical Devices, Inc.'s Mark IV Breathing Pacemaker (US), and Atrotech OY's Atrostim PNS (Finland). The Synapse and Avery devices are distributed worldwide and approved for use in the United States. The Atrotech device is not available in the U.S. As of December 2019, FDA Premarket Approval was given to Avery's Spirit Transmitter Device, replacing the Mark IV transmitter. In May 2020, Canadian company Lungpacer Medical received approval for emergency use by the USFDA amid the

COVID-19 pandemic The COVID-19 pandemic, also known as the coronavirus pandemic, is an ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The novel virus was first identif ...

.SFU professor's invention to help recovery of ventilator patients approved for emergency use in U.S.
- Meera Bains, CBC, 8 May 2020

Surgical procedure

In the case of the Atrostim and Mark IV devices, several surgical techniques may be used. Surgery is typically performed by placing an electrode around the

, either in the

neck The neck is the part of the body on many vertebrates that connects the head with the torso. The neck supports the weight of the head and protects the nerves that carry sensory and motor information from the brain down to the rest of the body. In ...

(i.e., cervically; an older technique), or in the

chest The thorax or chest is a part of the anatomy of humans, mammals, and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main divisions of the crea ...

(i.e., thoracically; more modern). This electrode is connected to a radiofrequency receiver which is implanted just under the skin. An external transmitter sends radio signals to the device by an antenna which is worn over the receiver. For the cervical surgical technique, the phrenic nerve is approached via a small (~5 cm) incision slightly above, and midline to, the clavic. The phrenic nerve is then isolated under the scalenus anticus muscle. For the thoracic surgical technique, a small (~5 cm) incisions over the 2nd or 3rd intercostal space. The electrodes are placed around the phrenic nerves alongside the pericardium. Use of a thorascope allows for this technique to be performed in a

minimally-invasive Minimally invasive procedures (also known as minimally invasive surgeries) encompass surgical techniques that limit the size of incisions needed, thereby reducing wound healing time, associated pain, and risk of infection. Surgery by definition ...

manner. In the case of the NeuRx device, a series of four incisions are made in the abdominal skin. Several tools such as a

laparoscope Laparoscopy () is an operation performed in the abdomen or pelvis using small incisions (usually 0.5–1.5 cm) with the aid of a camera. The laparoscope aids diagnosis or therapeutic interventions with a few small cuts in the abdomen.Medl ...

and probe are used to find the best four locations on the diaphragm to attach four electrodes, which have connections outside the body. A fifth electrode is placed just under the skin in the same area. All these connect to the device.

History

Methodology and devices

Surgical procedure

References

Further reading