Scientific Articles
Since its introduction in the 1970's, there have been dozens of articles written on pacing the diaphragm to treat a wide variety of conditions. Much of that literature was written about earlier versions of the equipment which are now obsolete. The following is a synopsis of the most recent and most relevant articles:
"Intrathoracic Phrenic Pacing: A 10-Year Experience in France" The Journal of Thoracic and Cardiovascular Surgery. E-Pub May 2011.
"Phrenic pacing is an alternative to positive-pressure ventilation in selected patients, mostly in cases of upper spinal cord injury. We evaluated results of phrenic pacing performed by video-assisted thoracic surgery (VATS)....Phrenic pacing, performed as soon as neurologic and orthopedic stabilization is achieved, is the most important prognostic factor for successful weaning."
"Vagal Nerve Stimulator Placement for Medically Refractory Seizures in a Child Treated with Phrenic Nerve Pacing for Congenital Central Hypoventilation Syndrome" Journal of Neurosurgery: Pediatrics. April 2011, Vol. 7 pp. 413-415.
"In this report, the authors discuss the use of vagal nerve stimulation (VNS) to treat a medically refractory seizure disorder in a child who had previously undergone placement of bilateral phrenic nerve stimulators for treatment of CCHS. Concomitant use of phrenic and vagal nerve stimulators has not previously been reported in the literature. No adverse reactions were noted with both devices working. Diaphragmatic pacing (DP) was clinically unaffected by VNS."
"Re-Innervation of the Paralyzed Diaphragm: Application of Nerve Surgery Techniques Following Unilateral Phrenic Nerve Injury" CHEST. E-Pub February 2011.
"Diaphragmatic pacemakers, though proven successful in cases of bilateral phrenic nerve injury, are not commonplace for unilateral injury due to the inability of the pacemaker to synchronize with spontaneous respiratory drive. Phrenic nerve grafting for acutely injured nerves has been shown to be effective in rare case reports...Diaphragmatic pacemakers consist of phrenic nerve electrodes implanted in the cervical region or the thorax...They allow ventilator dependent tetraplegics to be maintained permanently or temporarily without the use of mechanical assist devices. Freedom from the ventilator has been demonstrated to allow greater mobility, improved speech, improved overall health and quality of life, and reduced health care costs."
"Survival after Short- or Long-Term Ventilation after Acute Spinal Cord Injury: a Single-Centre 25-Year Retrospective Study" Spinal Cord. E-Pub October 2010, Vol. 49, pp. 404-410.
"The underlying cause of respiratory failure, whether progressive or essentially static, in patients having long-term ventilatory support will in itself have a part in determining life expectancy...It has been of considerable interest whether diaphragmatic pacing offers survival advantages over mechanical ventilation and some indication that this is so..."
"A Rare Instance of "Cardio-Respiratory Pacing": Permanent Pacemaker Insertion for Symptomatic Bradycardia in a Quadriplegic Man Dependent on Diaphragmatic Pacing by Phrenic Nerve Stimulators" Cardiology. June 2010, Vol. 116, pp. 98-100.
"We report an instance of bipolar lead permanent pacemaker insertion for ventricular standstill in a man with quadriplegia following C2 fracture and the measures we adopted to minimise electromagnetic interference with phrenic nerve stimulators."
"Le Traitment Chirugical des Eventrations et Paralysies Diaphragmatiques (Surgical Treatment of Diaphragmatic Eventrations and Paralyses)" Revue des Maladies Respiratoires. May 2010, Vol. 27, No. 6, pp. 565-578.
"Some cases of diaphragmatic paralysis of central causation result in a life of ventilator dependence,even though the peripheral neuromuscular and respiratory systems are intact. In selected cases, following a complete functional investigation, phrenic nerve pacing may be attempted to achieve ventilator weaning." (Translated from the original French)
"Phrenic Nerve Stimulation: The Australian Experience" Journal of Clinical Neuroscience. February 2010, Vol. 17, No. 2, pp. 205-208.
"The most common indications for this procedure are central alveolar hypoventilation and high quadriplegia. This paper reviews the available data on the 19 patients treated with phrenic nerve stimulation in Australia to date."
"Implantation of a Breathing Pacemaker in a Tetraplegic Patient in Hong Kong" Hong Kong Journal of Medicine. June 2009, Vol. 15, No. 3, pp. 230-233.
"A 22-year-old healthy man sustained a traumatic fracture of the cervical spine at the level of C1/C2 when doing some exercises in the gymnasium in June 1991...Today, he can talk and be more interactive with his environment and the people around him."
"Long Term Recovery of Diaphragmatic Function in a Patient with Unilateral Diaphragmatic Pacemaker" Current Respiratory Medicine Reviews. February 2009, Vol. 5, No. 1, pp. 59-61.
"We present a case of patient with respiratory insufficiency due to unilateral phrenic nerve injury as a result of radiation therapy for breast cancer. The patient had a diaphragmatic pacer inserted, with significant recovery on her symptoms. Three years after this procedure, the patient recovered her phrenic nerve function, and this was confirmed by nerve conduction study."
"Mechanical Ventilation or Phrenic Nerve Stimulation for Treatment of Spinal Cord Injury-Induced Respiratory Insufficiency" Spinal Cord. May 2008, Vol. 46, No. 11, pp. 738-742.
"PNS instead of MV for treatment of SCI-RDD reduces RIs, running costs of respiratory treatment and obviously improves patients' quality of life."
"Diaphragmatic Pacing for the Treatment of Congenital Central Alveolar Hypoventilation Syndrome" Journal of Pediatric Surgery. May 2008, Vol. 43, No. 5, pp. 792-796.
"Diaphragmatic pacing is an effective treatment of Ondine disease...Patients can lead a much more normal existence by being ventilator free at least during the day, enabling them to participate in normal daily activities."
"Functional Electrical Stimulation After Spinal Cord Injury: Current Use, Therapeutic Effects and Future Directions" Spinal Cord. April 2008, Vol. 46, No. 4, pp. 255-274.
"Compared to mechanical ventilation, EPR offers an attractive alternative that may increase the physical and emotional comfort, mobility, communication, cosmesis and social integration of persons with tetraplegia and respiratory insufficiency."
"Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans" New England Journal of Medicine. March 27 2008, Vol. 358, No. 13, pp. 1327-1335.
"We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers."
"Unilateral Diaphragmatic Pacing: An Innovative Solution for Unilateral Diaphragmatic Paralysis" Critical Care and Shock. October 2007, Vol. 10, No. 3, pp. 108-110.
"There are only a few reported cases of unilateral diaphragmatic pacing...Our patient became fully functional after the pacemaker was inserted. Since her pacemaker was inserted, her dyspnea has resolved and she can now walk long distances without dyspnea."
"Electricity in the Treatment of Nervous System Disease" Acta Neurochirurgica - Supplement. January 2007, Vol. 97, No. 1, pp. 11-19.
"Electricity has been used in medicine for almost two millenniums beginning with electrical chocks from the torpedo fish and ending with the implantation of neuromodulators and neuroprostheses. These implantable stimulators aim to improve functional independence and quality of life in various groups of disabled people. New indications for neuromodulation are still evolving and the field is rapidly advancing."
"Congenital Central Hypoventilation Syndrome: PHOX2B Mutations and Phenotype" American Journal of Respiratory and Critical Care Medicine. November 2006, Vol. 174, No. 10, pp. 1139-1144.
"Congenital central hypoventilation syndrome (CCHS), a unique disorder of respiratory control associated with Hirschsprung disease (HSCR) and tumors of neural crest origin, results from polyalanine repeat expansion mutations in the paired-like homeobox (PHOX)2B gene in more than 90% of cases, and alternative PHOX2B mutations in remaining cases."
"Cardiac Pacing in a Patient with Diaphragm Pacing for Congenital Central Hypoventilation Syndrome (Ondine's Curse)" Journal of Cardiovascular Electrophysiology. July 2006, Vol. 17, No. 7, pp. 789-791.
"This report is about a patient who was supplied with a bilateral diaphragm pacing system at early childhood. At the age of 17 years, he experienced multiple syncopes due to sinus nodal arrest, which was successfully treated by the implantation of a dual chamber pacemaker."
"Absence of Device-Device Interaction (DDI) in a Patient with Cardiac and Diaphragmatic Pacemakers for Congenital Central Hypoventilation Syndrome." Journal of Pacing and Clinical Electrophysiology. November 2005, Vol.28, pp.1238-1239.
"In a patient with CCHS and long sinus pause requiring cardiac pacemaker insertion, a diaphragmatic pacemaker inserted in early childhood caused diaphragmatic pacer spikes observed during the interrogation of the cardiac pacemaker. Diaphragmatic pacing did not interfere with the cardiac pacemaker function."
"Diaphragm Pacers as a Treatment for Congenital Central Hypoventilation Syndrome." Expert Review of Medical Devices. August 2005, Vol. 2, No. 5, pp. 577-585.
"Diaphragm pacers offer a modality of ventilatory support that affords congenital central hypoventilation syndrome patients with maximal mobility for full-time ventilatory patients and the may allow for a more normal lifestyle in the appropriate patient."
"Endoscopic, Robotically Assisted Implantation of Phrenic Pacemakers." Journal of Thoracic and Cardiovascular Surgery. August 2003, Vol. 126, No.2, pp. 582-583.
"Phrenic nerve pacing can improve quality of life in quadriplegic patients and in patients with primary alveolar hypoventilation by eliminating the dependence on a ventilator...By avoiding multiple neck incisions, bilateral thoracotomies, or a sternotomy, an endoscopic approach is likely to yield a hastened postoperative recovery and improved quality of life."
"Breathing Pacemakers in Poliomyelitis - A Case Report." Indian Journal of Physical Medicine and Rehabilitation. April 2003, Vol. 14, pp. 1-4.
"Though the disease commonly affects the lower limbs, rapidly developing quadriplegia wiht progressive respiratory diffiultires are often encountered...Rehabilitation with a breathigng pacemaker system is an acceptable way of weaning the ventilator. Advantages of the breathing pacemaker system over the ventilator are numerous."
"Central Hypoventilation and Diaphragmatic Eventration: Diagnosis and Management." Seminars in Pediatric Surgery. February 2003, Vol. 12, No.1, pp. 38-45.
"In this article, the management of (congenital central alveolar hypoventilation) syndrome by diaphragmatic pacing is discussed...In children who also require ventilatory support while awake, pacing can substantially improve quality of life as it helps tremendously to increase their mobility and optimize the neurodevelopmental changes that normally occur in children that lead to independent living...The perioperative morbidity is minimal and the mortality approaches zero for establishing phrenic nerve pacing."
"Thorascopic Placement of Phrenic Nerve Electrodes for Diaphragm Pacing in Children." Journal of Pediatric Surgery. July 2002, Vol.37, No.7, pp.974-978.
"Phrenic nerve electrodes can be implanted thoracoscopically and allow the successful use of diaphragmatic pacing therapy. Avoidance of a thoracotomy with its associated perioperative morbidity and scarring may encourage wider utilization of diaphragmatic pacing in children."
"Long Term Follow-up of Pacing of the Conditioned Diaphragm in Quadriplegia." Journal of Pacing and Clinical Electrophysiology. June 2002, Vol.25, No.6, pp.897-906.
"The authors have previously shown that conditioning of the diaphragm for continuous bilateral pacing is a feasible and effective means of ventilation in patients with complete respiratory paralysis from high cervical (above C3) quadriplegia. The present study reports the long-term results of continuous diaphragmatic pacing."
"Prevention of Human Diaphragm Atrophy with Short Periods of Electrical Stimulation." American Journal of Respiratory and Critical Care Medicine. 1999, Vol.159, pp.2018-2020.
"We determined whether prolonged complete inactivation of the human diaphragm results in atrophy and whether this could be prevented by brief periods of electrical phrenic nerve stimulation. We studied a subject with high spinal cord injury who required removale of his left phrenic pacemaker (PNP) and the reinstitution of positive pressure ventilation for 8 months...We conclude that prolonged inactivation of the diaphragm causes atrophy which may be prevented by brief periods of daily phrenic nerve stimulation"
"The Intercostal to Phrenic Nerve Transfer: An Effective Means of Reanimating the Diaphragm in Patients with High Cervical Spine Injury." Plastic and Reconstructive Surgery. April 2000, Vol. 103, No.4, pp. 1255-1261.
"This series is the first to describe nerve transfers to reanimate the diaphragm in patients confined to long-term positive pressure ventilation because of high cervical spine injury."
"Speech Production and Speech With a Phrenic Nerve Pacer." American Journal of Speech-Language Pathology. May 1996, Vol.5, No.2, pp. 53-60.
"This report provides a description of the phrenic nerve pacer and contains a case study of a young man in whom speech production during phrenic nerve pacing was examined and contrasted to that during mechanical (positive-pressure) ventilation...Listener judgments indicated that speech produced with a phrenic nerve pacer was strongly preferred over that produced with a mechanical ventilator, primarily because it was more continuous and contained fewer and shorter pauses."
"Electrophrenic Respiration after Intercostal to Phrenic Anastomosis in a Patient with Anterior Spinal Artery Syndrome: Technical Case Report." Neurosurgery. October 1994, Vol.35, No.4, pp. 760-764.
"Diaphragm pacing requires an intact phrenic nerve to act as a conduit for the applied stimulus. Patients with damaged cell bodies at the C3-C5 level, or direct trauma to the phrenic nerve may not be able to pace by a traditional method. Through the use of an anastomosis of a viable intercostal nerve to a nonfunctional phrenic nerve, the distal phrenic nerve can be paced once successful axonal regeneration and diaphragmatic reinnervation have occurred."
"200 Cases With a New Breathing Pacemaker Dispel Myths about Diaphragm Pacing." Transactions of the American Society for Artificial Internal Organs. September 1994, Vol.40. No.3, pp. 244-252.
"Indeed most of the problems and questions (about diaphragm pacing) that were reported in earlier literature have, in fact, been solved though technologic developments, advances in surgical and anesthesia techniques, quantitative physiologic trials with patients, and clinical experience."
"Pacing of the Diaphragm to Control Breathing in Patients with Paralysis of Central Nervous System Origin." Stereotactic and Functional Neurosurgery. April 1989, 53(4), pp. 209-222.
"Thirty-five patients, 21 males and 14 females, aged 2-69 years (mean 25 years) with partial or total respiratory paralysis due to high cervical cord lesions, brain stem lesions, or central hypoventilation syndrome (sleep apnoea, 'Ondine's curse'), received phrenic nerve stimulators for pacing of the diaphragm. At a mean follow-up time of 46 months (range 2 months to 10 years) 15 patients are entirely independent of respirator and 8 quadriplegics ventilate with pacers at different daytime intervals and use mechanical ventilators during the night."
"Fundamental Considerations in Pacing of the Diaphragm for Chronic Ventilatory Insufficiency: A Multi-Center Study." Journal of Pacing and Clinical Electrophysiology. November 1988 Part II, Vol.11, pp.2121-2127.
"Records were reviewed of 477 patients who had diaphragm pacemakers implanted for treatment of chronic hypoventilation...A comprehensive analysis of pacing methods, complication and results from the Center group yielded information on the early experience with diaphragm pacing important to its future application."
"Transtelephonic Monitoring of Patients with Implanted Neurostimulators." The Lancet. January 24, 1987.
"In applying the transtelephonic technique to patients with diaphragm pacemakers, the threshold amplitudes at which the pacemakers first evoke a visible muscle twitch is a useful tool for tracking the diaphragm conditioning process after the pacemaker is first implanted...This technique has been used to diagnose remotely both neuromuscular fatigue and equipment failure, and to optimise diaphragm conditioning."
"Diaphragm Pacing by Electrical Stimulation of the Phrenic Nerve." Neurosurgery. December 1985, 17(6), pp. 974-984.
"Candidates for diaphragm pacing are those with ventilatory insufficiency due to malfunction of the respiratory control center or interruption of the upper motor neurons of the phrenic nerve...Long term stimulation of the phrenic nerves to pace the diaphragm is an effective method of ventilatory support in selected cases."
"Artificial Respiration by Phrenic Nerve Stimulation (Diaphragm Pacing) in Patients with Cervical Cord and Brain Stem Lesions.." Scandinavian Journal of Rehabilitation Medicine. April 1983, 15(4), pp. 173-181.
"In patients who are dependent upon respirators because of paralysis of respiratory muscles, pacemakers for electrical stimulation of the phrenic nerves, leading to contractions of the diaphragm, are available... Preoperatively, transcutaneous phrenic nerve stimulation in the neck was undertaken with simultaneous fluoroscopy of the diaphragm and quantitative studies of ventilation and blood gases... Postoperative studies showed sufficient ventilation with diaphragm pacing in both sitting and recumbent body position. Their quality of life has improved. "
"Electrophysiological Evaluation of Phrenic Nerve Function in Candidates for Diaphragm Pacing." Neurosurgery. September 1980, 53(3), pp. 345-354.
"The electrophyisological status of phrenic nerve function has been determined by an assessment of the conduction time and diaphragm muscle action potential in patients who were being evaluated as candidates for diaphragm pacing... In patients who were selected for implantation of a diaphragm pacemaker, a conduction time that was prolonged (10 to 14 msec) preoperatively did not preclude successful diaphragm pacing...The elucidation of phrenic nerve function by such electrophysiological studies serves as a valuable adjunct to the selection and management of patients undergoing diaphragm pacing."
"Long-Term Ventilatory Support by Diaphragm Pacing in Quadriplegia." Annals of Surgery. May 1976, 183(5), pp. 566-577.
"Total Ventilatory Support in a Quadriplegic Patient with Radiofrequency Electrophrenic Respiration." New England Journal of Medicine. March 1972, 286(10), pp. 513-516.
"Central Hypoventilation; Long-Term Ventilatory Assistance by Radiofrequency Electrophrenic Respiration." Annals of Surgery October 1970, 172(2), pp. 755-773.
"Radio-frequency electrophrenic respiration. Long-term application to a patient with primary hypoventilation." Journal of the American Medical Association. March 1968, 203(12), pp. 1033-1037.
"Electronic Pacemakers of the Heart, Gastrointestinal Tract, Phrenic Nerve, Bladder, and Carotid Sinus: Current Status." Surgery. August 1966, 60(2), pp. 480-94.
"Electrophrenic Respiration." Science. October 29, 1948, 60(2), Vol. 108, p. 482.
Reprints of several of these articles are provided in the information packets sent to physicians, medical professionals, prospective patients, and their caregivers. A packet may be obtained by filling out a request for additional information, located here.