Interventional procedure overview of phrenic nerve pacing for congenital central hypoventilation syndrome

Domanski MC and Preciado DA (2012) Vocal cord collapse during phrenic nerve-paced respiration in congenital central hypoventilation syndrome. F1000Research 1: 42

Case report

n=1

No abnormal vocal cord stimulation was witnessed during engaging of either phrenic nerve stimulator. However, the lack of normal inspiratory vocal cord abduction during phrenic nerve-paced respiration resulted in vocal cord collapse and partial obstruction due to passive adduction of the vocal cords through the Bernoulli effect. Bilateral phrenic nerve stimulation resulted in more vocal cord collapse than unilateral stimulation.

Small sample

Flageole H, Adolph VR, Davis GM et al. (1995) Diaphragmatic pacing in children with congenital central alveolar hypoventilation syndrome. Surgery 118(1): 25-8

Case series

n=3

follow up: 6 months to 10 years

Paediatric surgeons should be aware of CCAHS because it may be treated with surgically implanted electrodes that allow for pacing of the diaphragm. The technique has an acceptable complication rate, and it can greatly decrease the impact of the disease on the lifestyle and activity of the patient. CCAHS also may be associated with Hirschsprung's disease.

Small sample; more recent studies included.

Fitzgerald D, Davis GM, Gottesman R et al. (1996) Diaphragmatic pacemaker failure in congenital central hypoventilation syndrome: a tale of two twiddlers. Pediatric pulmonology 22(5): 319-21

Case reports

n=2

Authors recommend that the chest radiographs that are undertaken to investigate diaphragmatic pacemaker dysfunction include the internal implant. As these cases illustrate, the chest radiograph will not necessarily demonstrate a reason for dysfunction of the pacemaker, although pacing wire coiling on a radiograph should suggest wire discontinuity from twiddling as a likely cause of pacemaker failure.

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 patients are entirely independent of respirator and 8 quadriplegics ventilate with pacers at different daytime intervals and use mechanical ventilators during the night. Five patients have stopped pacing and 7 additional cases have died of causes unrelated to electrophrenic stimulation.

Mixed indications and outcomes for CCHS 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 patients with severe chronic respiratory failure.

Mixed indications and outcomes for CCHS 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 (CCHS, n=35)

Key recommendations:

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

2. Facilities for regular monitoring of pacemaker performance and patient 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 patients who have had a diaphragm pacemaker implanted, with detailed study of the phrenic nerve and diaphragm muscle to determine the effects of electrical stimulation on these vital structures: Pathological studies will provide definitive factual information needed 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 CCHS not reported separately. More recent studies included.

Hirschfeld S, Huhtala H, Thietje R et al. (2022) Phrenic nerve stimulation experiences. A single centre, controlled, prospective study. Journal of clinical neuroscience: official journal of the Neurosurgical Society of Australasia 101: 26-31

Non-randomised comparative study

n=92 (CHS, n=2)

With PNS, authors found a tendency towards better survival compared to MV. The frequency of decubital ulcers and urological complications appear significantly more with MV than with PNS, proving enhanced mobility and facilitation of nursing with PNS. Patients prefer PNS and refuse randomisation, which may be taken as their opinion of the improved quality of life with PNS. The frequency of respiratory infections differed highly significantly in favour of PNS. Large savings are subsequently obvious.

Small sample

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.

More recent studies included.

Ilbawi MN, Idriss FS, Hunt CE et al. (1985) Diaphragmatic pacing in infants: techniques and results. The Annals of thoracic surgery 40(4): 323-9

Case series

n=8

PNP can be done safely in infants. It provides an effective alternative method for ventilatory support without the drawbacks of positive pressure ventilation.

Small sample; 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 (CCHS, n=1)

follow up: 1 to 21 years

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

Small sample

Kolb C, Eicken A, Zrenner B et al. (2006) Cardiac pacing in a patient with diaphragm pacing for congenital central hypoventilation syndrome (Ondine's curse). Journal of cardiovascular electrophysiology 17(7): 789-91

Case report

n=1

follow up: 3 months

Patients with idiopathic congenital central hypoventilation syndrome (Ondine's curse) may develop an indication for cardiac pacing due to bradyarrhythmias. Cardiac pacing in the presence of a unipolar diaphragm pacing system is feasible and safe if thorough testing for possible interdevice interactions is done. However, the experience gained from this patient is not transferable to the implantation of other cardiac pacing systems, such as implantable cardioverter defibrillators, because the sensing behaviour is significantly different in these devices.

Small sample

Kwon A, Lodge M, McComb JG et al. (2022) An unusual cause of diaphragm pacer failure in congenital central hypoventilation syndrome. Journal of clinical sleep medicine: JCSM : official publication of the American Academy of Sleep Medicine 18(3): 949-52

Case report

n=1

This case suggests that calcium can encase DP receivers and that calcium deposition can accumulate to a significant amount over time. This case also underscores how increasing distance from skin surface, such as that occurring with weight gain, can interfere with DP function. Calcification of internal DP components is an uncommon cause of DP failure but suggests that calcium deposition and accumulation should be considered when evaluating patients for DP malfunction and/or failure, especially in those who have used DP long-term. The case emphasises the importance of routine follow-up and periodic evaluation of DP function to confirm optimal performance.

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 (CCHS, n=1)

follow up: 36 months

Video-assisted thoracic surgery implantation of 4-pole electrodes around the intrathoracic phrenic nerve is a safe procedure. Ventilatory weaning correlates with the degree of diaphragmatic amyotrophy. Phrenic pacing, done as soon as neurologic and orthopaedic stabilisation is achieved, is the most important prognostic factor for successful weaning.

Small sample

Pino-Diaz L, Leu RM and Kasi AS (2020) Polysomnographic artifacts in a child with congenital central hypoventilation syndrome. J Clin Sleep Med. 16(12):2123–5

Case report

n=1

This paper reports a 14-year-old boy with CCHS who uses DP with an uncapped tracheostomy during sleep. Polysomnography to titrate DP settings identified artifacts occurring in regular intervals coinciding with the onset of inspiration during all sleep stages in several channels including legs, snore, and electrocardiogram. Clinicians interpreting polysomnograms done during DP should become familiar with the multichannel artifacts due to DP impulses. The patient was hyperventilated on home DP settings that led to adjustment of DP settings during the polysomnogram to achieve optimal oxygenation and ventilation. This case also highlights the utility of polysomnography to ensure optimal gas exchange during sleep in children with CCHS using DP.

Small sample

Shah AS, Leu RM, Keens TG et al. (2021) Annual respiratory evaluations in congenital central hypoventilation syndrome and changes in ventilatory management. Pediatric allergy, immunology, and pulmonology, 34 (3)

Case series (retrospective)

n=10 (tracheostomy, n=7; diaphragm pacing, n=3)

This paper reports a high prevalence of changes in assisted ventilation management following an annual in-hospital respiratory evaluation. The results show the importance of regular annual in-hospital respiratory evaluations in patients with CCHS to assess their ventilatory requirements and optimise assisted ventilation.

Small sample, aiming to determine if annual in-hospital respiratory evaluations (Polysomnography with capnography) in patients with CCHS led to changes in ventilatory management.

Shaul DB, McComb, JG and Keens TG (1998) Thoracoscopic placement of phrenic nerve electrodes for diaphragm pacing. Pediatric Endosurgery and Innovative Techniques 2(3): 101-5

Case report

n=1

follow up: 6 weeks

Phrenic nerve electrodes for diaphragm pacing were successfully implanted in a 14-year-old girl by thoracoscopy. This was associated with successful diaphragm pacing and an improvement in the patient's condition.

Small sample

Sieg E P, 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 4 evidence)

The quality of the published literature for phrenic nerve stimulation is poor. The literature review suggests that PNS 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 (mainly SCIs), number of patients with CCHS unclear, and outcomes for CCHS not reported separately.

More recent studies included in the key evidence.

Shaul DB, Danielson PD, McComb JG et al. (2002) Thoracoscopic placement of phrenic nerve electrodes for diaphragmatic pacing in children. Journal of pediatric surgery 37(7): 974-8

Case series

n=9

follow up: 30 months

Phrenic nerve electrodes can be implanted thoracoscopically and allow the successful use of diaphragmatic pacing therapy. Avoidance of thoracotomy with its associated perioperative morbidity and scarring may encourage wider utilisation of diaphragmatic pacing in children.

Small sample; more recent studies included.

Takeda S, Fujii Y, Kawahara H et al. (1996) Central alveolar hypoventilation syndrome (Ondine's curse) with gastroesophageal reflux. Chest 110(3): 850-2

Case report

n=1

Trials for removal of the tracheostomy tube were unsuccessful due to upper airway obstruction during pacing. Except for a minor complication of wire breakage, the diaphragm pacing was uneventful and the patient was discharged from the hospital and continued electrophrenic respiration at home.

Small sample

Tibballs, James and Henning, Robert D (2003) Noninvasive ventilatory strategies in the management of a newborn infant and three children with congenital central hypoventilation syndrome. Pediatric pulmonology 36(6): 544-8

Case series

n=4 (PNP, n=1)

Authors suggest that management of a newborn diagnosed with CCHS could initially be with nasal mask BiPAP upon cessation of mechanical ventilation by endotracheal tube in the first few weeks of life. Tracheostomy can be avoided. However, preparations should be made to trial negative pressure chamber or cuirass ventilation as soon as practicable, to avoid the problems of midface hypoplasia and pseudoprognathism associated with prolonged nasal mask BiPAP. If upper airway obstruction occurs during negative pressure ventilation, limited mask CPAP may be beneficial. If hypoventilation is present during wakefulness, phrenic nerve pacing is the only practical alternative from the time the patient becomes ambulant, but airway obstruction during sleep with this technique may limit its usefulness.

Small sample; more recent studies included.

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 patients who are ventilator-dependent and tetraplegic from upper cervical trauma or in some cases of neurogenic apnoea; it may be life saving for patients with central alveolar hypoventilation.

Small sample with mixed indications and outcomes for CCHS not reported separately. More recent studies included.

Valika T, Chin AC, Thompson DM et al. (2019) Airway obstruction during sleep due to diaphragm pacing precludes decannulation in young children with CCHS. Respiration; international review of thoracic diseases 98(3): 263-267

Case series

n=3

Further research is needed to understand paediatric and adult airway physiology with unopposed pacer-induced diaphragm contractions as published literature has shown success of decannulation with phrenic nerve-diaphragm pacing in some older children and adults.

Small sample

Wang A, Kun S, Diep B et al. (2018) Obstructive sleep apnea in patients with congenital central hypoventilation syndrome ventilated by diaphragm pacing without tracheostomy. Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 14(2): 261-4

Case series

n=15

OSA occurs in patients with CCHS ventilated by DP. However, decreasing DP amplitude settings can lessen upper airway obstruction without compromising gas exchange.

Polysomnography – sleep study

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 phrenic nerve damage.

Mixed indications and outcomes for CCHS 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 paediatric as compared to adult patients, the incidence of complications was highest among the active paediatric patients with CCHS. Longitudinal study of these patients will provide invaluable information for modification and improvement of the quadripolar system.

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

Yasuma F, Nomura H, Sotobata I et al. (1987) Congenital central alveolar hypoventilation (Ondine's curse): a case report and review of the literature. European journal of pediatrics 146(1): 81-3

Case report

n=1

Follow up: 2 years

At a 2-year follow up, the patient respiratory status was satisfactory with overnight diaphragm pacing at home.

Small sample