The technique of applying electrical stimulation to the phrenic nerve to induce diaphragm pacing was first described by Cavallo in 1777.¹ Early proponents used this technique for a variety of conditions associated with impaired respiration, including asphyxia (Hufeland, 1783), cholera (Duchenne, 1849), apnea (Israel, 1927), and polio (Sarnoff, 1950).² Diaphragm pacing was introduced into contemporary thoracic surgical practice in the 1970s by Glenn, who pioneered its application in patients with central apnea (Glenn, 1966) and quadriplegia (Glenn, 1972).^2–4 With the standard pacing devices, the electrical stimulus is applied at the phrenic nerve, as originally described. However, a newer approach applies the stimulus directly into the muscle at the phrenic nerve motor point for more direct control.⁵ The primary conditions amenable to pacing are high cervical spinal cord injuries (i.e., C3–C5) and congenital or acquired central hypoventilation syndrome. Onders et al. have extended pacing via the motor point technique to other populations, including patients with the progressive neuromuscular degenerative disorder, amyotrophic lateral sclerosis (ALS), and other more transient problems, such as intensive care unit patients who demonstrate difficulty weaning from mechanical ventilation.^6,7

The successful application of diaphragm pacing requires a fundamental knowledge of the anatomy and physiology of the respiratory system. A full discussion of the neural control of breathing is beyond the scope of this chapter. Briefly, the major components of the respiratory system include respiratory centers in the brainstem that control voluntary and involuntary breathing through connections to the diaphragm and muscles of respiration via the phrenic and intercostal nerves. Respiratory sensors deliver feedback to the brain via mechanoreceptors and chemoreceptors, which help regulate ventilation based on oxygen and carbon dioxide levels, as well as neural reflexes from smooth muscles in the airways and chest wall. The three respiratory centers in the brainstem include the medullary, which controls rhythmic inspiration and expiration, the apneustic center in the lower pons, which controls the prolongation of inspiration, and the pneumotaxic center in the upper portion of the pons. The latter inhibits inspiration to prevent overexpansion of the lungs.

The diaphragm is innervated by the phrenic nerve bundle, which exits the spinal cord from the upper motor nerve centers in the brainstem at C3 to C5 and passes from the neck between the heart and respective lung to its most distal extent on the hemidiaphragm. The phrenic nerve can be accessed in the cervical region or in the chest. The nerve descends obliquely with the internal jugular vein across the anterior scalene deep to the prevertebral layer of the deep cervical fascia and the transverse cervical and suprascapular arteries. On the left, the phrenic nerve crosses anterior to the first part of the subclavian artery. On the right it lies on the anterior scalene muscle and crosses anterior to the second part of the subclavian artery. On both sides, the phrenic nerve runs posterior to the subclavian vein and anterior to the internal thoracic artery as it enters the thorax.

The right phrenic nerve passes over the innominate artery posterior to the subclavian vein. It then crosses the root of the right lung anteriorly and leaves the thorax by passing through the vena cava hiatus in the diaphragm at the level of T8. The right phrenic nerve passes over the right atrium. The left phrenic nerve passes over the pericardium of the left ventricle and penetrates the diaphragm separately. Within the diaphragm muscle are three branches that split from the main phrenic nerve. These include the anterior or sternal, lateral, and posterior trunks. The location of these branches is relevant to mapping for diaphragm pacer insertion at the motor point. The phrenic nerve must be identified along its course and preserved during thoracic procedures, since severing the nerve will cause paralysis of the corresponding hemidiaphragm. The nerve is easily identified as it passes anterior to the hilum of the corresponding lung.

Patients with diaphragmatic paralysis are occasionally referred for thoracic surgical evaluation. Most are found to have unilateral paralysis from idiopathic conditions that can be managed with diaphragmatic plication (see Chapters 150 and 151) if the clinical situation warrants. Select populations, however, may benefit from diaphragm pacing, where the goal is to wean the patient from mechanical ventilation or to avoid it altogether. Patients with partial or total ventilatory insufficiency typically are those with high cervical spinal cord injuries (above C3) and congenital or acquired central hypoventilation syndrome. Select patients with these disorders have an intact phrenic nerve, but the signal required to conduct an impulse from the respiratory centers in the brainstem to the diaphragm is disrupted as a result of injury or underlying disease, that is, axonal degeneration or idiopathic central disconnect, respectively. Diaphragm pacing can provide a significant benefit in this setting. It also may be indicated in other less common conditions including intracranial vascular lesions, tumors, central nervous system infections, syringomyelia, and poliomyelitis. Contrary to initial thoughts on diaphragm pacing, recently it has been shown that pacing may play a valuable role in patients with acute respiratory insufficiency as well as patients with neuromuscular disease, that is, ALS. This paradigm shift may benefit patients by promoting weaning from, or delaying the need for, mechanical ventilation. Careful patient selection is critical to a successful result.

A thorough and careful preoperative evaluation is performed with particular attention to the neurologic and pulmonary systems. Before assessing the status of the patient’s phrenic nerve and diaphragm, preexisting conditions must be systematically excluded, particularly any condition that would preclude effective signal conductance or proper oxygenation and ventilation.⁸ Patients with advanced neuromuscular disorders, underlying restrictive lung disease, or extensive parenchymal processes, for example, would not be suitable for diaphragm pacing. A detailed survey of the cervical spine, neck, and chest by CT is recommended to rule out underlying mass lesion or organic pathology. Elevated unilateral hemidiaphragm on chest radiography is suggestive of phrenic nerve paralysis, and diaphragm plication should be considered.⁹

The purpose of the preoperative assessment is to verify the integrity of the phrenic nerve, neuromuscular junction, and diaphragm without which diaphragm pacing will not succeed. The current gold standard for phrenic nerve function testing is percutaneous cervical electrical stimulation.^10–12 This study is performed by placing an electrode at the lateral edge of the clavicular head of the sternocleidomastoid muscle. The muscle is retracted medially, and the current is directed posteriorly toward the phrenic nerve. An obvious contraction of the diaphragm should occur after stimulation, if the nerve is intact. Any failure to conduct the nerve evidenced by absence of contraction or prolonged latency of response is a sign of phrenic nerve compromise.

Magnetic stimulation is a noninvasive alternative to percutaneous cervical electrical stimulation, but results of this test must be interpreted with caution, since the body can lateralize function with unilateral nerve injury by activating accessory muscles of respiration and the contralateral diaphragm.¹³ An appropriate interval should pass between the time of injury and testing, since the nerves may initially be unresponsive to stimulation. Likewise, patients who fail nerve conduction early after spinal cord injury may show recovery up to 2 years later.¹⁴

The “sniff test” relies on the fluoroscopic visualization of radioopaque markers that are strategically placed to measure the maximal excursion of the diaphragm on inspiration. The patient in supine position sniffs through his or her nose. This maneuver elicits a brisk downward deflection of the diaphragm if the phrenic nerve is intact. The test is deemed positive when a paradoxical upward shift of the diaphragm is visualized fluoroscopically. Ultrasound and MRI imaging of the diaphragm is an emerging option for visualizing the diaphragm, but is somewhat limited in availability.

For ALS patients, proper patient selection is critical because of the increased risks associated with general anesthesia in patients with neuromuscular degeneration. It is imperative to demonstrate that the diaphragm is capable of stimulation and that the patient has clear evidence of chronic hypoventilation before pacing can be considered. Patients must be 21 years of age or older and cannot have progressed to a forced vital capacity (FVC) of less than 45% predicted. A variety of metrics can be used to document chronic hypoventilation including FVC greater than 50% predicted; maximum inspiratory pressure (MIP) less than 60 cm H₂O; pCO₂ greater than 45 mmHg; and oxygen saturation less than 88% for 5 consecutive minutes during sleep. Phrenic nerve function can be assessed by neurophysiologic testing with EMG, by visualizing diaphragm contraction with full-motion fluoroscopy or by other radiologic techniques including ultrasound or MRI.

The pacing electrode of most phrenic nerve pacemakers is implanted directly on the phrenic nerve either in the chest or in the cervical neck region. In a more recent approach to pacing, the electrode is implanted in the muscle at the phrenic nerve motor point. Most patients with phrenic nerve or diaphragm pacemakers can be successfully weaned from mechanical ventilation for a substantial time each day, if not completely. Even transitory periods of ventilator independence can have a significant impact on the patient’s quality of life and significantly reduce overall healthcare costs. The potential exists for expanding this technology to other types of respiratory failure. Application of this technique to ALS or temporary scenarios in difficult-to-wean intensive care unit patients may grow as investigative experience emerges. Although diaphragm pacing is appropriate for only a few select conditions, it is a useful tool and worth mastering. Ample assistance is available online to get started, and the diaphragm pacing manufacturers are knowledgeable and can assist the surgeon through the learning curve. Websites for the two companies available in the United States can be found at www.averybiomedical.com and www.synapsebiomedical.com.

Four pacing systems are available worldwide. These include the Vienna Phrenic Pacemaker (Medimplant, Vienna, Austria), the Atrostim (Atrotech, Ltd., Tampere, Finland), the Avery Mark IV Phrenic Pacemaker (Avery Biomedical, Commack, NY, USA), and the NeuRx Diaphragm Pacing System (DPS; Synapse Biomedical Inc., Oberlin, OH, USA). The first three systems are implanted directly on the phrenic nerve and use an external transmitter with antenna to transmit radiofrequency signals transcutaneously to a receiver implanted subcutaneously.^15–17 The receiver translates the signal into electrical impulses which are delivered to the phrenic nerve electrode to generate contraction of the diaphragm. Diaphragm stimulation and muscle fatigue can be affected by the electrode type which may be unipolar, bipolar, or quadripolar. All three systems seem to rely on the same concept and implantation strategies. Of these three only the Avery device with its monopolar electrode is available in the United States (Fig. 152-1).