Interventional procedure overview of phrenic nerve pacing for ventilator-dependent high cervical spinal cord injury

Baer GA, Talonen PP, Shneerson JM et al. (1990) Phrenic nerve stimulation for central ventilatory failure with bipolar and four-pole electrode systems. Pacing and clinical electrophysiology: PACE 13(8): 1061-72

Case series

n=10 (C2-tetraplegia, n=7; central sleep apnoea, n=3)

Diaphragmatic pacing may enable people who are tetraplegic to become completely independent of mechanical ventilators, and thereby be able to enter rehabilitation centres for people with SCIs. In selected people it is a valuable method of treatment that is not often considered, sequential four-pole stimulation of the PN seems to give clinical results no worse than those with unipolar diaphragm pacing.

Small sample; more recent studies included

Bolikal P, Bach JR and Goncalves M (2012) Electrophrenic pacing and decannulation for high-level spinal cord injury: a case series. The journal of spinal cord medicine 35(3): 170-4

Case series

n=4

Lack of ventilator-free breathing ability in people with high-level SCI does not mandate tracheostomy, or electrophrenic or diaphragm pacing.

Small sample

Campbell DA, Homan SD, McCulloch GA et al. (1992) Phrenic nerve pacing in two young quadriplegic ventilator-dependent patients. Australian and New Zealand journal of medicine 22(5): 463-8

Case series

n=2

PNP to achieve full-time or partial ventilator independence should be considered in people of all ages with high SCI as a means of improving quality of life and as a part of rehabilitation to achieve independence in the community.

Small sample; more recent studies included

DiMarco AF, Takaoka Y and Kowalski KE (2005) Combined intercostal and diaphragm pacing to provide artificial ventilation in patients with tetraplegia. Archives of physical medicine and rehabilitation 86(6): 1200-7

Prospective single-arm trial (case series)

n=4

follow up: 1 year?

Combined intercostal and unilateral diaphragm pacing may be a useful therapeutic modality capable of maintaining long-term ventilatory support in people with only unilateral PN function.

Small sample and combined intercostal and diaphragm pacing

Elefteriades JA, Quin JA, Hogan JF et al. (2002) Long-term follow-up of pacing of the conditioned diaphragm in quadriplegia. Pacing and clinical electrophysiology: PACE 25(6): 897-906

Case series (retrospective)

n=12

follow up: 8.8 years

This follow up confirms that people who are quadriplegic are able to meet long-term, full-time ventilation requirements using PN stimulation of the conditioned diaphragm. Careful review of diaphragmatic pacing candidates with respect to associated medical conditions, social support, and motivation is essential for appropriate patient selection and successful long-term results.

Small sample; more recent studies included

Fodstad H (1989) Pacing of the diaphragm to control breathing in patients with paralysis of central nervous system origin. Stereotactic and functional neurosurgery 53(4): 209-22

Case series

n=35

follow up: mean 46 months

At a mean follow-up time of 46 months, 15 people are entirely independent of respirator and 8 people with quadriplegia ventilate with pacers at different daytime intervals and use MV during the night. Five people have stopped pacing and 7 additional people have died of causes unrelated to electrophrenic stimulation.

Mixed indications and outcomes for SCI not reported separately. More recent studies included

Garrido-Garcia H, Mazaira Alvarez J, Martin Escribano P et al. (1998) Treatment of chronic ventilatory failure using a diaphragmatic pacemaker. Spinal cord 36(5): 310-4

Case series

n=22

Evidence shows that complete stable ventilation can be achieved using diaphragmatic pacing and that it improves the prognosis and life quality of people with severe chronic respiratory failure.

Mixed indications and outcomes for SCI not reported separately. More recent studies included

Glenn WWL, Brouillete RT, Dentz B et al. (1988) Fundamental considerations in pacing of the diaphragm for chronic ventilatory insufficiency: a multi-centre study. PACE, 11: 2121-7

Case series (retrospective)

n=475 (SCI, n=169)

Key recommendations:

1. A programme to assure long-term follow-up of people by physicians and paramedical personnel knowledgeable in pacing;

2. Facilities for regular monitoring of pacemaker performance and people's response to pacing;

3. Improved techniques of pacing the diaphragm, particularly the development of state-of-the-art neural stimulators;

4. Autopsy examination of all deceased people who have had a diaphragm pacemaker implanted, with detailed study of the PN and diaphragm muscle to determine the effects of electrical stimulation on these vital structures: Pathological studies will provide definitive factual information required to determine the future role of diaphragm pacing in the treatment of chronic ventilatory insufficiency and which will be applicable to other neuromuscular stimulation.

Mixed indications and key outcomes for SCI not reported separately. More recent studies included

Khong P, Lazzaro A and Mobbs R (2010) Phrenic nerve stimulation: the Australian experience. Journal of clinical neuroscience 17: 205-8

Case series (retrospective)

n=19

follow up: 1 to 21 years

The data suggests that PN stimulation can be used instead of mechanical ventilators for long-term ongoing respiratory support.

Mixed indications and outcomes for SCI not reported separately

Hunt CE, Brouillette RT, Weese-Mayer DE et al. (1988) Diaphragm pacing in infants and children. Pacing and clinical electrophysiology: PACE 11(11pt2): 2135-41

Case series

n=34

Regardless of outcome of the efforts to achieve continuous long-term pacing, pacing is already an effective treatment in infants and young children, eliminating the need for positive pressure ventilation when awake breaking is normal and substantially improving quality of life in children requiring awake ventilatory support.

Small sample; more recent studies included

Kaufman MR, Bauer T, Campbell S et al. (2022) Prospective analysis of a surgical algorithm to achieve ventilator weaning in cervical tetraplegia. The journal of spinal cord medicine 45(4): 531-5

Case series

n=10

Although more investigation is necessary, PN reconstruction or diaphragm muscle replacement performed (when indicated) with pacemaker implantation may allow virtually all ventilator= dependent cervical people with tetraplegia to partially or completely wean.

Small sample, with most people having combined PNP with other procedures

Kaufman MR, Elkwood AI, Aboharb F et al. (2015) Diaphragmatic reinnervation in ventilator-dependent patients with cervical spinal cord injury and concomitant phrenic nerve lesions using simultaneous nerve transfers and implantable neurostimulators. Journal of reconstructive microsurgery 31(5): 391-5

Case series (retrospective)

n=14

Simultaneous nerve transfers and pacemaker implantation can result in reinnervation of the diaphragm and lead to successful ventilator weaning. The favourable outcomes support consideration of this surgical method for appropriate people who would otherwise have no alternative therapy to achieve sustained periods of ventilator independence.

Small sample and combined nerve transfer and PNP

Krieger LM and Krieger AJ (2000) The intercostal to phrenic nerve transfer: an effective means of reanimating the diaphragm in patients with high cervical spine injury. Plastic and reconstructive surgery 105(4): 1255-61

Case series

n=6

Intercostal to PN transfer with diaphragmatic pacing is a viable means of liberating people with high SCI from long-term MV.

Small sample and combined technique of nerve transfer and PNP; more recent studies included

Krishnan U, Ramrakha PS and Money-Kyrle A (2010) 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 116(2): 98-100

Case report

n=1

This paper describes a person who required cardiac pacemaker insertion in the presence of PN stimulators for ventilator support. This is the first reported instance of the successful combination of cardiac and respiratory pacemakers without electromagnetic interference.

Single case report

Lam JCM, Ho CTK, Poon TL et al. (2009) Implantation of a breathing pacemaker in a tetraplegic patient in Hong Kong. Hong Kong medical journal = Xianggang yi xue za zhi 15(3): 230-3

Case report

n=1

Use of a diaphragm pacing stimulation system is a viable alternative to MV in people with tetraplegia with chronic respiratory insufficiency. Implantation of the diaphragm pacers in appropriate subjects can lead to independent living, enhanced mobility, better quality of life, and ease their integration into society. A multidisciplinary team approach is crucial for achieving a successful outcome.

Small sample

Layachi L, Georges M, Gonzalez-Bermejo J et al. (2015) Diaphragm pacing failure secondary to deteriorated chest wall mechanics: When a good diaphragm does not suffice to take a good breath in. Respiratory medicine case reports 15: 20-3

Case report

n=2

The inspiratory action of the diaphragm does not only depend on diaphragm contractile properties, but also of a diaphragm "contractile environment" that includes diaphragm geometry, abdominal compliance, and rib cage compliance. It is also a reminder that breathing is intimately dependent on, and interferes with, spinal cord and costovertebral joints mechanics. That a "good diaphragm" is not sufficient to produce a "good inspiration" must be kept in mind when managing people with diaphragm pacing.

Small sample

Le Pimpec-Barthes F, Gonzalez-Bermejo J, Hubsch JP et al. (2011) Intrathoracic phrenic pacing: a 10-year experience in France. The Journal of thoracic and cardiovascular surgery 142(2): 378-83

Case series

n=20

follow up: 36 months

VATS implantation of 4-pole electrodes around the intrathoracic PN is a safe procedure. Ventilatory weaning correlates with the degree of diaphragmatic amyotrophy. Phrenic pacing, performed as soon as neurologic and orthopaedic stabilisation is achieved, is the most important prognostic factor for successful weaning.

Small sample with mixed indications, short follow up

Miller JI, Farmer JA, Stuart W et al. (1990) Phrenic nerve pacing of the quadriplegic patient. The Journal of thoracic and cardiovascular surgery 99(1): 35-40

Case series

n=23 (SCI, n=21)

follow up: 6 years

PNP in people with quadriplegia is a useful modality when appropriate patient selection, meticulous surgical technique and appropriate PN testing and training are completed. Excellent results can be anticipated. Long-term success depends on adequate follow up, support of the medical and surgical team, and the dedicated care and support of the person's family.

Small sample, more recent studies included

Nakajima K, Sharkey PC (1990) Electrophrenic respiration in patients with craniocervical trauma. Stereotact Funct Neurosurg 54-55:233–6

Case series

n=15

Of the 15 people, 11achieved full-time respiration with electrophrenic respiration and another 2 achieved half-time respiration. Despite the loss of people due to unrelated problems, 7 now use electrophrenic respiration continuously, 1 for 18 years.

Small sample with mixed indications; more recent studies included

Sharma V, Jafri H, Roy N et al. (2021) Thirty-six-month follow-up of diaphragm pacing with phrenic nerve stimulation for ventilator dependence in traumatic tetraplegia: the way forward for spinal cord injury rehabilitation in a developing country. Asian spine journal 15(6): 874-80

Case report

n=1

follow up: 36 months

At 36 months after implantation, the person is ventilator-free without any procedure-related complications or respiratory infections. Diaphragm pacing with PNP may be a way forward for ventilator-dependent people with tetraplegia in developing countries to pursue effective rehabilitation and improved quality of life.

Small sample

Sieg EP, Payne R A, Hazard S et al. (2016) Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation? Child's nervous system: ChNS: official journal of the International Society for Pediatric Neurosurgery 32(6): 1033-8

Systematic review

18 articles (class IV evidence)

The quality of the published literature for PN stimulation is poor. The literature review suggests that PNP is a safe and effective option for decreasing ventilator dependence in high SCI and central hypoventilation; however, there are critical questions that provide crucial directions for future studies.

No meta-analysis, mixed indications, number of people with SCI unclear, and outcomes for SCI not reported separately.

More recent studies (in the systematic review) included in the key evidence

Sharkey PC, Halter JA and Nakajima K (1989) Electrophrenic respiration in patients with high quadriplegia. Neurosurgery 24(4):529–35

Case series

n=15

Thirteen people (86%) achieved full-time respiration and 2 more achieved half-time respiration. Despite the loss of 8 people to unrelated problems, 7 now use electrophrenic respiration continuously, 1 having done so for 16 years. The cervical approach is preferred. Complications consisted primarily of equipment failures.

Small sample; more recent studies included

Son BC, Kim DR, Kim Il-S et al. (2013) Phrenic nerve stimulation for diaphragm pacing in a quadriplegic patient. Journal of Korean Neurosurgical Society 54(4): 359-62

Case report

n=1

follow up: 12 months

After diaphragmatic pacing, the person who was completely dependent on the mechanical ventilator could ambulate up to 3 hours every day without aid of MV during the 12 months of follow up. Diaphragm pacing through unilateral PNP with spinal cord stimulator was feasible in an apnoeic person with complete quadriplegia who was completely dependent on MV. Diaphragm pacing with the spinal cord stimulator is feasible and effective for the treatment of CHS.

Small sample

Tibballs J (1991) Diaphragmatic pacing: an alternative to long-term mechanical ventilation. Anaesthesia and intensive care 19(4): 597-601

Case report

n=1

During pacing, the fenestrated tracheostomy tube is capped, thus enabling inspiration of normally humidified air and normal phonation on exhalation. During sleep MV is administered via the tracheostomy.

Small sample

Vanderlinden RG, Epstein SW, Hyland RH et al. (1988) Management of chronic ventilatory insufficiency with electrical diaphragm pacing. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 15(1): 63-7

Case series

n=24

Diaphragm pacing is the treatment of choice for people who are ventilator= dependent and have tetraplegia from upper cervical trauma or in some cases of neurogenic apnoea; it may be life saving for people who suffer central alveolar hypoventilation.

Small sample with mixed indications. More recent studies included

Watt J, Wiredu E, Silva P et al. (2011) Survival after short- or long-term ventilation after acute spinal cord injury: a single-centre 25-year retrospective study. Spinal Cord 49:

404-10

Non-randomised comparative study (retrospective)

n=189 (19 people had diaphragm pacing)

The survival time for people with high tetraplegia on long-term ventilation compares with other datasets and older people have a proportionately greater loss in life expectancy. Self-ventilating people with tetraplegia remain at considerable risk from respiratory death and consideration needs to be given to more effective preventative measures.

Small number of people who had diaphragm pacing. Lack of information on the type of intervention (PNP)

Weese-Mayer DE, Morrow AS, Brouillette RT et al. (1989) Diaphragm pacing in infants and children. A life-table analysis of implanted components. The American review of respiratory disease 139(4): 974-9

Case series

n=33

The diaphragm pacing system is effective but not without risk of biomedical component failure. The system might be substantially improved by 1) a modified receiver design with a hermetic seal to prevent fluid penetration, 2) stronger, better insulated electrode wires, and 3) modifications of surgical technique and electrode type to present PN damage.

Mixed indications and outcomes for SCI not reported separately. More recent studies included

Weese-Mayer DE, Silvestri JM, Kenny AS et al. (1996) Diaphragm pacing with a quadripolar phrenic nerve electrode: an international study. Pacing and clinical electrophysiology: PACE 19(9): 1311-9

Analysis of questionnaire and registry data

n=64

Although pacer complications were not increased among children as compared to adults, the incidence of complications was highest among the active children with CCHS. Longitudinal study of these people will provide invaluable information for modification and improvement of the quadripolar system.

Mixed indications and outcomes for SCI not reported separately. More recent studies included