Frontiers review
Phrenic nerve stimulation in patients with spinal cord injury

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Abstract

Phrenic nerve pacing (PNP) is a clinically useful technique to restore inspiratory muscle function in patients with respiratory failure secondary to cervical spinal cord injury. In this review, patient evaluation, equipment, methods of implementation, clinical outcomes, and the complications and side effects of PNP are discussed. Despite considerable technical development, and clinical success, however, current PNP systems have significant limitations. Even in patients with intact phrenic nerve function, PNP is successful in achieving full-time support in ∼50% of patients. Inadequate inspired volume generation may arise secondary to incomplete diaphragm activation, reversed recruitment order of motor units, fiber type conversion resulting in reduced force generating capacity and lack of coincident intercostal muscle activation. A novel method of pacing is under development which involves stimulating spinal cord tracts which synapse with the inspiratory motoneuron pools. This technique results in combined activation of the intercostal muscles and diaphragm in concert and holds promise to provide a more physiologic and effective method of PNP.

Introduction

Cervical spinal cord injury often results in disruption of the motor pathways from the respiratory center in the medulla to the inspiratory muscles causing respiratory failure and dependence upon artificial ventilatory support. Respiratory failure results in significant inconvenience, greater health care costs, and significant morbidity and mortality (Whiteneck et al., 1992, DeVivo and Stover, 1995, Hartkopp et al., 1997, Frankel et al., 1998, Shavelle et al., 2006, NSCISC, 2008). While ∼20% of patients may require mechanical ventilation following their acute injury, respiratory function generally improves in most patients over the subsequent weeks and months (National Spinal Cord Injury Statistical Center, 2008). Nonetheless, a substantial number of patients (200–400 per year in the USA) are dependent upon lifelong artificial ventilatory support due to irreversible spinal cord injury (Carter et al., 1987).

With the development of respiratory failure consequent to acute spinal cord injury, all patients are initially supported with mechanical ventilation since this is the most expeditious mode of restoring adequate ventilation and sustaining life. While effective in maintaining life support, mechanical ventilation is associated with significant discomfort, limitation of mobility and complications such as pneumonia, atelectasis, barotrauma, potential for diaphragm injury and higher rate of hospitalization (Fishburn et al., 1990, Claxton et al., 1998, Frankel et al., 1998, Pugin and Oudin, 2006, Levine et al., 2008). In selected patients, however, phrenic nerve pacing (PNP) may provide a clinically beneficial alternative to mechanical ventilation. In fact, PNP has been a clinically accepted modality in the management of patients with ventilator-dependent tetraplegia for more than 25 years (Glenn and Sairenji, 1985, Glenn et al., 1986).

In this report, a brief review of the clinical aspects of PNP is presented with an emphasis on more recent developments and the potential for future refinements in this field.

Section snippets

Characteristics of normal spontaneous breathing

Eupneic breathing is characterized by the coordinated contraction of several skeletal muscles, including the diaphragm, inspiratory intercostal and accessory muscles, and muscles of the upper airway. This action results in the development of a negative intra-thoracic pressure, dilation of the upper airway and movement of air into the lungs. Subsequent expiration is largely passive. Respiratory rhythm (inspired volume and respiratory rate) is generated by the respiratory control center in the

Comparison of spontaneous breathing with phrenic nerve pacing

With PNP, as with all peripheral nerve stimulation, the effects of the applied electric field are greatest on the larger diameter axons, resulting in preferential activation of fast motor units and reversal of the normal physiologic recruitment order. Moreover, all motor units are activated synchronously, eliminating the potential for any order effect.

The differences between PNP, as it is currently applied, and normal activation of the diaphragm is evident from the EMG patterns of activation.

Anatomical considerations

Each hemidiaphragm is innervated by a single phrenic nerve, which is formed by the cervical rootlets from the C3 to C5 spinal cord segments. The inspiratory intercostal muscles are innervated by the upper six intercostal nerves while the accessory muscles are innervated by the spinal accessory nerves and cervical nerves. Since the diaphragm is the major inspiratory muscle, adequate levels of ventilation can be maintained by diaphragm contraction alone. In fact, patients with lower cervical

Advantages of phrenic nerve pacing

Positive pressure mechanical ventilation is a useful life sustaining modality for patients with acute and chronic respiratory failure, including those with cervical spinal cord injury. While some patients can be managed with noninvasive mechanical ventilation, most are managed with standard positive pressure ventilators via tracheostomy. These machines provide a high degree of reliability and have multiple alarm systems to alert health care providers of respiratory system abnormalities or

Patient selection and evaluation

Patients considering PNP should be highly motivated to improve their functional capacity and degree of independence. Optimal candidates and their caregivers anticipate the benefits of improved mobility and speech with the ultimate goals of greater social interaction, greater participation in rehabilitation programs and possibly improving their occupational potential (DiMarco, 1999, Elefteriades et al., 2002, DiMarco et al., 2005a).

The initial physical evaluation of patients contemplating PNP

Equipment and methods of application

Details of the various PNP systems have been discussed in recent papers and therefore will be reviewed only briefly (DiMarco, 2004, DiMarco, 2005). Commercially available manufacturers include Avery Laboratories (Commack, NY, USA), Atrotech OY (Tampere, Finland), MedImplant Biotechnisches Labor (Vienna, Austria) and Synapse BioMedical (Oberlin, OH, USA). The Avery and Synapse systems are FDA-approved and available in the USA.

All PNP systems are similar in design consisting of both implanted

Combined intercostal and phrenic nerve pacing

A significant number of patients with ventilator-dependent cervical spinal cord injury have suffered damage to the phrenic motoneuron pools and/or phrenic nerves and therefore are not candidates for PNP (DiMarco, 1999, Oo et al., 1999, DiMarco et al., 1994, DiMarco et al., 2005b). The upper thoracic nerves, which innervate the inspiratory intercostal muscles, a muscle group which contributes ∼35% of the inspiratory capacity, however, are usually functional. Moreover, previous studies have shown

Implementation of PNP

The different surgical techniques required for implantation of the various PNP systems are well described in previous reviews (Glenn et al., 1973, Glenn et al., 1980, Onders et al., 2004, Onders et al., 2007) and are beyond the scope of this article.

Phrenic nerve pacing should be started ∼2 weeks following surgical implantation of the system to allow for resolution of inflammation and edema at the electrode/nerve interface and initial wound healing (Glenn and Phelps, 1985). Attention to

Effect of PNP on patient outcomes

Several clinical studies have established that PNP is an effective method of providing ventilator support in patients with ventilator-dependent tetraplegia (Glenn et al., 1984, Glenn et al., 1986, Elefteriades et al., 2002, DiMarco et al., 2005a). In fact, in many patients requiring full-time ventilator support, PNP can be utilized as the sole mode of respiration. Moreover, there are several reports of successful long-term pacing for 10 years or longer (Glenn et al., 1986, Elefteriades et al.,

Complications and side effects

With proper use of stimulus parameters, adequate patient monitoring and appropriate patient selection, the incidence of serious complications and side effects (Table 2) of commercially available PNP systems is very low (Weese-Mayer et al., 1996). While failure of PNP systems is very uncommon, inspiratory muscle pacing is a life support system. Therefore, back-up mechanical ventilation or other means of providing ventilator support, e.g. use of an Ambu bag, should always be available.

Direct

Monitoring of the pacing system

Phrenic nerve pacing systems do not have alarms signaling inadequate ventilation. Tetraplegics, however, can adequately detect small changes in tidal volume and will alert caregivers in the event of changes in ventilation (DiMarco et al., 1982). When caregivers are not in direct attendance, however, use of external pulse oximeters with alarm systems may be useful.

Caregivers with knowledge of the PNP system should perform routine evaluations of pacemaker function and maintain a log of inspired

Future directions

Optimal design of a PNP system would result in the complete restoration of normal inspiratory muscle function. Currently available systems, however, have significant disadvantages and limitations and therefore fall short of this goal.

Since all PNP systems employ an open-loop design, the electrical signals which activate the diaphragm occur independent of the spontaneous generation of electrical signals from the respiratory centers in the medulla. Consequently, upper airway muscle activation can

Acknowledgement

The author would like to acknowledge the assistance of Dana Hromyak, BS, RRT for her assistance in the preparation of this chapter.

References (77)

  • G.C. Sieck

    Diaphragm muscle: structural and functional organization

    Clin. Chest Med.

    (1988)
  • G.C. Sieck

    Physiological effects of diaphragm muscle denervation and disuse

    Clin. Chest Med.

    (1994)
  • D.E. Weese-Mayer et al.

    Diaphragm pacing in infants and children

    J. Pediatr.

    (1992)
  • D. Adler et al.

    Diaphragm pacing restores olfaction in tetraplegia

    Eur. Respir. J.

    (2009)
  • R. Brown et al.

    Respiratory dysfunction and management in spinal cord injury

    Respir. Care

    (2006)
  • R.E. Carter et al.

    Comparative study of electrophrenic nerve stimulation and mechanical ventilatory support in traumatic spinal cord injury

    Paraplegia

    (1987)
  • J. Chae et al.

    Neuromuscular electrical stimulation in spinal cord injury

  • T.E. Ciesielski et al.

    Response of the diaphragm muscle to electrical stimulation of the phrenic nerve, a histochemical and ultrastructural study

    J. Neurosurg.

    (1983)
  • A.R. Claxton et al.

    Predictors of hospital mortality and mechanical ventilation in patients with cervical spinal cord injury

    Can. J. Anaesth.

    (1998)
  • G. Creasey et al.

    Electrical stimulation to restore respiration

    J. Rehabil. Res. Dev.

    (1996)
  • M.J. DeVivo et al.

    Long-term survival and causes of death

  • T.E. Dick et al.

    Recruitment order of diaphragmatic motor units obeys Henneman's size principle

  • A.F. DiMarco

    Diaphragm pacing in patients with spinal cord injury

    Top. Spinal Cord Inj. Rehabil.

    (1999)
  • A.F. DiMarco

    Neural prostheses in the respiratory system

    J. Rehabil. Res. Dev.

    (2001)
  • A.F. DiMarco

    Respiratory muscle stimulation in patients with spinal cord injury

  • A.F. DiMarco et al.

    Activation of intercostal muscles by electrical stimulation of the spinal cord

    Am. Rev. Respir. Dis.

    (1987)
  • A.F. DiMarco et al.

    Artificial ventilation by means of electrical activation of intercostal/accessory muscles alone in anesthetized dogs

    Am. Rev. Respir. Dis.

    (1989)
  • A.F. DiMarco et al.

    Gas exchange during separate diaphragm and intercostal muscle breathing

    J. Appl. Physiol.

    (2004)
  • A.F. DiMarco et al.

    High-frequency spinal cord stimulation of inspiratory muscles in dogs: a new method of inspiratory muscle pacing

    J. Appl. Physiol.

    (2009)
  • A.F. DiMarco et al.

    Inspiratory muscle pacing in spinal cord injury: case report and clinical commentary

    J. Spinal Cord Med.

    (2006)
  • A.F. DiMarco et al.

    Phrenic nerve pacing in a tetraplegic patient via intramuscular diaphragm electrodes

    Am. J. Respir. Crit. Care Med.

    (2002)
  • A.F. DiMarco et al.

    Evaluation of intercostal pacing to provide artificial ventilation in quadriplegics

    Am. J. Respir. Crit. Care Med.

    (1994)
  • A.F. DiMarco et al.

    Sensation of inspired volume in normal subjects and quadriplegic patients

    J. Appl. Physiol.

    (1982)
  • W.H. Dobelle et al.

    200 cases with a new breathing pacemaker dispel myths about diaphragm pacing

    ASAIO J.

    (1994)
  • J.A. Elefteriades et al.

    Diaphragm pacing

    Chest Surg. Clin. N. Am.

    (1998)
  • J.A. Elefteriades et al.

    Long-term follow-up of pacing of the conditioned diaphragm in quadriplegia

    Pacing Clin. Electrophysiol.

    (2002)
  • A. Esclarin et al.

    Tracheostomy ventilation versus diaphragmatic pacemaker ventilation in high spinal cord injury

    Paraplegia

    (1994)
  • M.J. Fishburn et al.

    Atelectasis and pneumonia in acute spinal cord injury

    Arch. Phys. Med. Rehabil.

    (1990)
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    This paper is part of a special issue entitled “Spinal Cord Injury”, guest-edited by “Gary C. Sieck and Carlos B. Mantilla”.

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