152: Diaphragm Pacing

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).

The fourth and newest device, the NeuRx DPS, was approved by the Food and Drug Administration under a humanitarian device exemption in 2008. It is available in the United States and many other countries. This technology takes advantage of the phrenic nerve motor point at the level of the diaphragm which is mapped for direct intramuscular electrode implantation. Although it is not fully implantable in its current form, only a few tiny electrode leads exit the skin from a subcutaneous tunnel which serves as a barrier to infection.

Implantation and Pacing with the Avery Mark IV Phrenic Pacemaker

Cervical approach: The Avery pacing device can be implanted in the neck via a cervical approach (Fig. 152-2A) or in the chest (Fig. 152-2B) by either open or video-assisted thoracic surgical technique. Technically speaking, cervical implantation fails to capture all of the potential nerve branches, since some accessory phrenic nerve fibers may join the main trunk lower down at the thoracic inlet. This is mainly of theoretical consequence, however, as it does not translate into noticeable differences in pacing abilities between the two levels. The principal advantage of cervical implantation is the possibility of avoiding general anesthesia and double lumen intubation, as the procedure can be performed under conscious sedation or with standard general endotracheal anesthesia. There is a slight increased risk of infection incurred by placing the incision close to a tracheostomy site, which is present in many of these patients.

A 3- to 4-cm transverse incision is made close to the base of the neck with the sternocleidomastoid muscle retracted medially. Dissection is carried down laterally to the phrenic nerve, which can be identified superficial to the anterior scalene muscle. Proper identification is done with a nerve stimulator to visualize ipsilateral diaphragm contraction. The platinum electrode is passed beneath the nerve, and the cuff is anchored with fine polypropylene sutures such that the nerve sits in the cradle with full contact. The lead is then tunneled under the skin above the clavicle and connected to the receiver pocket on the anterior chest wall.

Thoracic approach: A thoracotomy incision can generally be avoided by using minimally invasive access techniques (Fig. 152-2B). The video-assisted thoracic surgical approach can be performed bilaterally in one sitting with double lumen ventilation, but a staged approach is occasionally preferable. A small utility mini-thoracotomy incision is made in the second intercostal space with two thoracoscopic ports inserted in the fifth intercostal space along the midaxillary line and seventh intercostal space along the anterior axillary line. The phrenic nerve is again dissected circumferentially such that the electrode is passed around it and secured to ensure good contact with the nerve. On the right side, the ideal level for insertion is between the azygos junction with the superior vena cava and the cavoatrial junction. On the left side, the preferred site is between the aortic arch and the pulmonary artery.

Regardless of approach, precautions should be taken to prevent devascularization of the phrenic nerve during the dissection. For this reason, one should leave a 2- to 3-mm rim of perineural tissue at the level of the nerve dissection. The wire lead from the thoracic electrode exits via a port incision and then is tunneled to the subcutaneous receiver pocket on the anterior chest wall. A coil of slack lead should be left in the chest to account for lung re-expansion and patient growth, especially in younger children. Diaphragmatic contraction is confirmed and pacing thresholds are determined before closure. In patients with congenital hypoventilation syndrome who are ambulatory, the receiver pocket is often placed overlying the abdominal wall laterally, whereas in tetraplegic patients the chest wall is more commonly used.

With the DPS system, the leads are inserted at the phrenic nerve motor point on the underside of the diaphragm (Fig. 152-3). Inadvertent nerve injury caused by the necessity of implanting the lead directly on the phrenic nerve is thus avoided. The procedure is currently performed laparoscopically. Four ports are used including two 10-mm ports in the supraumbilical and epigastric regions in addition to two lateral 5-mm ports. A portion of the falciform ligament is taken down to improve exposure of both hemidiaphragms. The motor point is then mapped to determine the location of the optimal diaphragm contraction both visually and via pressure measurements using a transducer connected to one of the ports. Once two points of maximal contraction have been mapped on each side for redundancy, a laparoscopic insertion device is used to implant the electrodes (Fig. 152-4A,B).

Each lead is loaded into the shaft of the inserter such that the lead is released into the muscle at the mapped motor point when the device needle tip is pulled back and out. If the needle crosses into the pleural space, it is important to assess for capnothorax. If proper hemodynamics are maintained, treatment may be unnecessary. Otherwise, aspiration and/or temporary chest tube insertion may be required. The leads are each tested with train stimulations to confirm proper capture and then tunneled out the epigastric port to the right upper quadrant with a fifth subcutaneous lead serving as the ground electrode. The leads are then connected to the stimulator via a small switchboard adapter. Stimulus parameters are programmed into the primary and backup stimulator units using the clinical workstation console. Although the DPS is not completely implantable, as in the case of the phrenic nerve pacemakers, the tunneling serves as a good barrier for infection and the device can be implanted in the outpatient setting with laparoscopic technique. Currently, the NeuRx device is FDA approved only for patients 18 years and older, although clinical trials are being conducted in children aged 5 to 17 years, with encouraging results.

Setup and Perioperative Planning

When embarking on placement of a diaphragm pacer, it is wise for the surgeon to establish a multidisciplinary team to help in the perioperative assessment and planning. This assembly of clinicians can include a pulmonologist, rehabilitation physician, respiratory therapist, neurologist, electromyelography technician, physician assistant/nurse practitioner and nursing aides, as well as the patient and family members. There is an important educational component for the various team members in the operating room, ward, and rehab units that can be taken for granted if not considered ahead of time. Communication between these team members after implantation will help the weaning process significantly. There is also a lot of behind the scenes work that goes into the scheduling process from an administrative standpoint between the hospital, purchasing unit, biomedical engineering, insurance company, and institutional review board.

Ample support from the device manufacturers has always seemed available throughout the entire perioperative period. Additionally, in the surgical community, an experienced person is usually approachable for questions and personal support. Irrespective of device, the initial settings are made in the operating room with a specialist from the company present to assist with programming. Pacing thresholds and tidal volumes are determined for each patient to optimize performance. The conduct of pacing initiation and ventilator weaning is patient-dependent and can vary with pacer device and indication. Long-term results seem comparable between devices, but the NeuRx patients are able to pace sooner and wean faster. If there is substantial atrophy of the diaphragm, a common occurrence with spinal cord injury patients, a longer period of conditioning may be needed before full-time pacing can be instituted. The necessity for conditioning results from the conversion of type I fatigue-resistant slow twitch muscle fibers to the less efficient type II fast twitch fibers during prolonged periods of ventilator dependence. For these patients, progress with conditioning by electrical stimulation is monitored by clinical observation of the respiratory work of breathing along with measurements of pulse oximetry, end-tidal CO₂ values, or even arterial blood gases, before weaning is attempted.

All of these efforts are worthwhile in getting a return on investment that can be seen within 3 years of pacing when taking into account the costs of the devices against the costs of mechanical ventilation, its disposables and monitored care personnel wages. From a clinical standpoint, the patients benefit from natural breathing with successful pacing by simplified nursing care, reduced ventilator-associated pneumonia, improved speech patterns and olfactory sensations, physical freedom from mechanical ventilation and eventual conversion to a button or outright decannulation.

Results

An early report of results using the Avery device showed that in 165 patients out of 477 implanted for spinal cord injury who had detailed follow-up, 47% were pacing completely with 35% pacing part-time and 17% not pacing.¹⁸ The unsuccessful patients were not pacing largely due to socioeconomic reasons as opposed to device malfunction. In a more recent study, Elefteriades found that 6 out of 12 tetraplegic patients were pacing full time 10 years out from implantation and that thresholds had not increased over time.¹⁹ No patient lost the ability to pace, and pathology specimens showed that there was no evidence of nerve injury on microscopic analysis, demonstrating that the electrode does not cause damage to the nerve despite direct implantation.

In a study of 50 spinal cord patients implanted with the NeuRx system followed for 2 years, 50% of those implanted over 6 months were completely off mechanical ventilation while 66% were pacing over 12 hours a day without the need of an attendant.²⁰ No patient was on the ventilator full time. The longest patient with the device was pacing out a 8 years and another was weaned from mechanical ventilation 28 years after injury. The latter patient took longer to wean from the ventilator, but the case demonstrates that it was still possible effectively pace despite this long period due to the intact phrenic nerves.

In its application to ALS patients, the DPS has been shown by Onders to be an effective means of delaying the inevitable need for mechanical ventilation in this patient population by up to 2 years.⁷ In the first 16 ALS patients, the decline in FVC with pacing was 0.9% per month compared to controls of 2.4% per month. Ultrasound studies in several patients showed thickening with improved excursion on fluoroscopy.

Procedure-Specific Complications

By virtue of the differences in implantation schemes, the Avery unit puts the phrenic nerve at greater risk for devascularization or mechanical injury during the dissection and insertion of the electrode. This risk is largely avoided with NeuRx system, which implants at the neuromuscular motor point. While each system is susceptible to device-related infection, the risks are lower with the Avery system, which is completely implantable making percutaneous infection theoretically less likely. Capnothorax is a known complication for the NeuRx system since the electrode is inserted from the underside of the diaphragm and the needle may inadvertently puncture the pleura during insertion. The condition may be symptomatic requiring treatment or occult requiring additional close observation.

Each device is quite durable from a mechanical standpoint, but both may require electrode or electrode component replacement due to wear and tear over time. The Avery electrode on the nerve cannot be removed easily or safely, but the end attached to the receiver can be replaced should the receiver malfunction. The NeuRx electrodes can fray or be damaged outside the body, but are easily spliced back together at the bedside with experience. Additionally, these electrodes implanted in the diaphragm can be simply cut similar to epicardial pacing wires or perhaps carefully pulled out if necessary.

Conclusion

Diaphragm pacing is an uncommon procedure in thoracic surgery. Many patients with unilateral diaphragm paralysis are referred for diagnostic evaluation, but few will be suitable for pacing. Others will have idiopathic, viral, or traumatic etiology that can be managed surgically with diaphragm plication, if clinically warranted. For patients with high cervical spinal cord injury or central hypoventilation (congenital or acquired), the integrity of the phrenic nerve must be carefully evaluated, including full review of the neurologic and pulmonary systems, and careful assessments conducted via diagnostic procedures. During implantation, the ability of the phrenic nerve or motor point to conduct a signal is retested on-the-spot before proceeding to full implantation of the device. All four devices mentioned in this chapter are suitable for pacing. However, the author's experience is limited to the Avery Mark IV and the NeuRx DPS, as these are the only two approved for implantation in the United States. Nevertheless, the surgical access techniques and technical principles are all very similar. Recently, it has been shown that diaphragm pacing may play a valuable role in patients with acute respiratory insufficiency and with the neuromuscular disease, ALS. This expanded indication may benefit patients by promoting weaning long-term result. Future applications of this technique in patients with marginal pulmonary function following high-risk resection, after lung transplantation, or for temporary pacing in the intensive care unit for difficult to wean patients may prove viable but will require further exploration. Thoracic surgeons should keep this enabling technology in their armamentarium.

Pacing technology has been available for many decades. Unfortunately, only a few thoracic surgeons have developed expertise in this area. A large population of patients can benefit from diaphragmatic pacing. This chapter clearly maps out patient selection, operative technique, and available hardware for use. The specific details provided by Dr. Ducko on available hardware are a particularly valuable resource. The operative intervention is straightforward, and this field can be expected to dramatically expand in the next few years.