ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Pacing the diaphragm: Patient selection, evaluation, implantation, and complications

Pacing the diaphragm: Patient selection, evaluation, implantation, and complications
Literature review current through: Jan 2024.
This topic last updated: Nov 07, 2023.

INTRODUCTION — Diaphragmatic pacing can be used in patients with ventilatory failure due to severe weakness or paralysis of the diaphragm as a means to eliminate or reduce the need for ventilatory support. Intact phrenic nerve function is required for effective pacing. The typical approach has been to pace the diaphragm via stimulation of the phrenic nerve at the level of the neck or thorax. However, pacing of the phrenic nerve at the level of the diaphragm may also be used in some patients.

Patient selection, evaluation for pacemaker candidacy, implantation technique, postoperative recovery, and complications of pacemaker placement will be reviewed here. The etiology, diagnosis, and management of patients with bilateral and unilateral diaphragmatic paralysis are discussed separately. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis" and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults" and "Treatment of bilateral diaphragmatic paralysis in adults" and "Diaphragmatic paralysis in the newborn".)

SELECTION OF POTENTIAL CANDIDATES — Diaphragmatic pacing is typically a second line therapy for patients with ventilatory failure due to bilateral paralysis or severe paresis of the diaphragm [1]. This population of patients has traditionally been ventilated invasively with a mechanical ventilator, or noninvasively with positive pressure support. However, diaphragmatic pacing can be used in a select group of patients who cannot tolerate, have a desire to be liberated from, or have a desire to delay the need for noninvasive or invasive ventilatory support, the details of which are discussed in the sections below. (See 'Upper cervical spinal cord injury (above C3)' below and 'Amyotrophic lateral sclerosis' below and 'Other patient populations' below.)

Importantly, paralysis/paresis of the diaphragm can be due to muscle, nerve, or central nervous system disease, and only patients with intact phrenic nerve function are amenable to pacing. Notably, diaphragmatic pacing should be avoided in patients with evidence of a denervated diaphragm. (See 'Upper cervical spinal cord injury (above C3)' below and 'Amyotrophic lateral sclerosis' below and 'Other patient populations' below.)

It should be recognized by physicians and patients that only small case series have demonstrated benefits from diaphragmatic pacing including a reduction or a delay in the need for ventilatory support. Randomized trials are needed to validate these and other clinically important outcomes, including the effect of pacing on lung function and overall survival, compared with standard forms of ventilatory support (invasive or noninvasive ventilation) [2]. (See "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction" and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Practical aspects of initiation" and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support" and "Tracheostomy: Rationale, indications, and contraindications" and "Management and prognosis of patients requiring prolonged mechanical ventilation" and 'Making the decision to pace' below.)

Upper cervical spinal cord injury (above C3) — Patients with apnea due to bilateral diaphragmatic paralysis from complete upper cervical spinal cord injury (SCI) above the third cervical level (C3; quadriplegia) are the most suitable candidates for diaphragmatic pacing. (See "Respiratory complications in the adult patient with chronic spinal cord injury" and "Respiratory physiologic changes following spinal cord injury".)

The biologic rationale for pacing in this population is that phrenic nerve function is usually intact and can be stimulated at the level of the neck, thorax, and diaphragm. The nerve cell bodies of the phrenic nerve are located in the anterior horns of C3 to C5. Thus, ideal candidates are those with injury above C3 (ie, a central cause for bilateral diaphragmatic paralysis). In contrast, patients with trauma to the mid-cervical spine (C3 through C5) or with concurrent direct trauma to the phrenic nerve (eg, ischemia or crush injury) are less suitable as candidates for phrenic nerve pacing because phrenic nerve function at the lower motor neuron level is disrupted. Importantly, the diaphragm cannot be paced if it is completely denervated. The assessment of phrenic nerve function is discussed separately. (See 'Intact phrenic nerve function' below.)

Traditionally, the diaphragm was paced in this population using phrenic nerve stimulation at the level of the neck (cervical approach) or thorax (thoracic approach). A more advanced technique of stimulating the phrenic nerve at the level of the diaphragm (direct diaphragmatic pacing stimulation; DPS) has since been reported in this population. Data that supports each of these approaches include the following (see 'Technique' below):

Cervical or thoracic approach – The efficacy of bilateral phrenic nerve stimulation at the cervical or thoracic level is derived from case reports and retrospective series [3-11]. As examples:

One center reviewed their experience with phrenic nerve stimulation in 22 children and young adults, most of whom had ventilatory failure secondary to high level SCI [8]. Successful pacing of the diaphragm was reported for 11 years in one patient, 10 years in four patients, and five years or less for 17 patients. Only two patients failed all efforts at diaphragmatic pacing.

Another single center study of 20 patients with posttraumatic quadriplegia reported that 18 patients were successfully weaned from mechanical ventilation with phrenic nerve stimulation performed by video-assisted thoracoscopic surgery (VATS) [6].

A 15-year retrospective analysis of 12 quadriplegic patients who underwent cervical or thoracic phrenic nerve pacemaker placement reported that, despite prior concerns, chronic pacing was not associated with progressive phrenic nerve damage or loss of diaphragmatic function over time [7]. Half of the patients were paced for 15 years with the remainder undergoing pacing for two years or more. Pacing was well tolerated, and reasons for discontinuation included intercurrent medical illness and lack of social support.

Diaphragmatic approach – Preliminary studies report successful phrenic nerve stimulation at the diaphragmatic level (ie, DPS) in patients with upper level SCI [12-16]. Stimulation at this level is directed to phrenic nerve branches at their points of insertion into the diaphragm; the muscle is not stimulated directly. As examples:

One multicenter prospective evaluation of a laparoscopic DPS system was conducted in 50 adults with upper level SCI [12]. Time from SCI to implantation ranged from three months to 27 years. There were no perioperative deaths or infections. DPS resulted in adequate diaphragmatic contraction in all patients and reduced the time spent on mechanical ventilation (decrease by four or more hours). Almost half of the group was weaned off ventilatory support completely.

A retrospective multicenter study of 22 patients with upper level SCI treated with DPS within 40 days of the original injury reported that most patients (76 percent) were ventilator-free after ten days [13]. One-third of patients had resumption of spontaneous breathing over a similar time period such that pacing was no longer required. These data should be interpreted with caution as most patients were paced within the first three months following injury, a period during which spontaneous recovery of phrenic nerve function may have occurred.  

A retrospective review of 92 patients with upper level SCI who were treated with DPS within an average of 47.5 months (6 days to 25 years) of their injury found that 60.8 percent used diaphragm pacing 24 hours a day [17]. In that cohort five patients had full recovery of breathing. Subgroup analysis revealed that earlier initiation of diaphragm pacing led to a greater likelihood of 24 hour use of diaphragm pacing.

A retrospective review of 101 patients with acute cervical SCI was done at a single level I trauma center [18]. Forty patients who had laparoscopic DPS were matched to 61 patients who did not. Hospital length of stay and mortality were significantly lower in the DPS patients, though this may in part be related to improved critical care during that time the patients were treated.

Phrenic nerve stimulation has been combined with intercostal nerve stimulation as a means to augment inspiratory effort in quadriplegic patients with bilateral diaphragmatic paralysis who have only one functionally intact phrenic nerve (ie, only one diaphragm can be paced). One case series studied unilateral phrenic nerve stimulation (using the thoracic approach) combined with bilateral intercostal nerve stimulation in four quadriplegic patients who only had one functionally intact phrenic nerve [19]. The combination resulted in increased maximum inspired volume such that all patients could be maintained off mechanical ventilation for 16 to 24 hours a day. Intercostal muscle pacing requires intact intercostal nerve function and a hemilaminectomy to access the thoracic spinal cord where the nerve roots are located. Intercostal muscle pacing with or without concurrent phrenic nerve stimulation remains investigational.

Others have combined phrenic nerve reconstruction with diaphragm pacemakers in cases where neither phrenic nerve is functionally intact. In one study of 14 male patients with bilateral diaphragmatic dysfunction, phrenic nerve reconstruction combined with diaphragm pacing was significantly more effective in improving respiratory physiology and diaphragm contractions than pacing alone [20]. (See "Surgical treatment of phrenic nerve injury", section on 'Phrenic nerve reconstruction'.)

Pacing devices for each approach are approved by the US Food and Drug Administration in patients with upper level SCI who have ventilatory failure due to bilateral diaphragmatic paralysis.

The surgical implantation of cervical, thoracic, and diaphragmatic pacemakers are described separately. (See 'Technique' below.)

Other patient populations — There is less experience supporting diaphragmatic pacing in patients with ventilatory failure due to diaphragmatic paralysis/paresis from the following:

Central disorders other than upper level spinal cord injury (SCI) – Successful bilateral phrenic nerve stimulation at the cervical and thoracic level has been reported in patients with the following [8,10,21-28]:

Congenital central alveolar hypoventilation (see "Disorders of ventilatory control", section on 'Ondine curse' and "Congenital central hypoventilation syndrome and other causes of sleep-related hypoventilation in children", section on 'Congenital central hypoventilation syndrome')

Brainstem tumors or infarction (see "Focal brainstem glioma")

Basilar meningitis (see "Neurologic complications of bacterial meningitis in adults")

Arnold Chiari malformation (see "Chiari malformations")

Meningomyelocele (see "Myelomeningocele (spina bifida): Management and outcome")

Incomplete fractures of C3 through C5 (see "Respiratory complications in the adult patient with chronic spinal cord injury" and "Respiratory physiologic changes following spinal cord injury")

Syringomyelia (see "Disorders affecting the spinal cord", section on 'Syringomyelia')

Pompe disease

The feasibility of diaphragmatic pacing patients with central disorders as a cause for their diaphragmatic paralysis was best studied in six patients (mostly children) with central alveolar hypoventilation who underwent phrenic nerve stimulation using the thoracic approach [21]. All children were weaned successfully from mechanical ventilation during the day and led independent lives at school or work.

The biologic rationale for bilateral diaphragmatic pacing in this population is the same as that for patients with upper level SCI who typically have functionally intact phrenic nerves that are amenable to pacing. Such patients are also theoretically candidates for direct diaphragmatic pacing stimulation (DPS) but published evidence is lacking to support feasibility of this form of pacing in this population. (See 'Upper cervical spinal cord injury (above C3)' above.)

Lower motor neuron disorders other than ALS – Preliminary evidence from small case series also report successful DPS in patients with bilateral and unilateral diaphragmatic paralysis due to the following [29,30]:

Idiopathic or trauma-related phrenic nerve paralysis (see "Diagnostic evaluation of adults with bilateral diaphragm paralysis" and "Treatment of bilateral diaphragmatic paralysis in adults")

Polio (see "Poliomyelitis and post-polio syndrome", section on 'Poliomyelitis' and "Poliomyelitis and post-polio syndrome")

Charcot Marie Tooth (see "Charcot-Marie-Tooth disease: Genetics, clinical features, and diagnosis")

Spinal muscle atrophy (see "Spinal muscular atrophy")

Diaphragmatic flutter or hiccups (see "Hiccups")

Acute flaccid myelitis [31]

In support of DPS in these populations, successful diaphragmatic contraction was reported in one prospective series of 27 patients who had DPS for unilateral or bilateral diaphragmatic paralysis associated with the disorders listed above [29]. Additionally, one-third of patients weaned from ventilatory support, either completely or partially.

The biologic rationale for DPS in these populations is based upon the observation that the phrenic nerve may be stimulated using residual functioning motor fibers at the level of the diaphragm. However, these patients are not suitable candidates for any type of pacing if the diaphragm is completely denervated.

The surgical approach and implantation of direct diaphragmatic pacemakers are described separately. (See 'Diaphragmatic approach' below.)

PATIENTS WITH UNCLEAR BENEFIT — Patients with amyotrophic lateral sclerosis (ALS) are not suitable candidates for pacing via the cervical or thoracic approach. We do not recommend direct diaphragmatic pacing stimulation (DPS) in patients with ALS since randomized trials have reported no benefit and potential harm in this population. Importantly, diaphragmatic pacing (cervical, thoracic, DPS) should be avoided in ALS patients with evidence of a denervated diaphragm.  

Amyotrophic lateral sclerosis — The hallmark of ALS is the combination of upper and lower motor neuron weakness. With disease progression, the lower motor neurons that innervate the diaphragm via the phrenic nerve degenerate, resulting in muscle denervation and diaphragmatic paresis and paralysis. Thus, this population is not suitable for diaphragmatic pacing via the thoracic or cervical approach since the phrenic nerve conduction is not fully intact. (See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease".)

Use of direct diaphragmatic pacing stimulation (DPS) in patients with ALS is controversial. We believe that patients with ALS are not suitable candidates for DPS. This belief is based upon the rationale that not only is it not a viable strategy if the number of innervated muscle fibers is insufficient to drive contraction of the diaphragm, data derived from two randomized trials have reported potential harm in association with its use. Data that describe the use of DPS in patients with ALS include the following [12,29,32-34]:

Three uncontrolled randomized trials showed no benefit or harm associated with DPS:

One multicenter randomized trial of 74 patients with respiratory failure from ALS reported reduced survival when DPS was used in combination with NIV compared with patients treated with NIV alone (11 versus 23 months) [33]. In addition, a higher rate of adverse events was seen with pacing plus NIV such that the trial was stopped early (5.9 versus 2.5 events per person-year).

Another multicenter randomized trial of 74 patients with ALS who had early respiratory impairment (forced vital capacity 60 to 80 percent) not requiring NIV, reported increased mortality in patients undergoing DPS (49 versus 19 percent), compared to those who underwent sham pacing [34]. In addition, DPS did not delay the time to noninvasive ventilation (ventilation-free survival six versus nine months). Adverse events were similar (65 versus 59 percent). This trial was also terminated early.

A single center prospective evaluation of a laparoscopic DPS system was conducted in 34 patients with ALS with the goal to define clinical and functional characteristics of the ALS patients that were of prognostic significance [35]. There were no complications related to the surgery, and 28 of the 34 patients survived two years after their surgery. Compared with those who did not survive two years, thickness of the hemidiaphragms was again found to be strongly predictive of survival.

Two uncontrolled trials suggested benefit associated with DPS:

One multicenter prospective evaluation of a laparoscopic DPS system was conducted in 38 patients with ALS [12]. DPS was well tolerated without deaths or infections. DPS slowed the decline in forced vital capacity (FVC) when compared with rates of FVC decline (-0.9 versus -2.4 percent predicted per month) prior to pacemaker placement. When these rates were extrapolated over time, it was estimated that the need for mechanical ventilation could potentially be delayed by two years (ie, a two year increase in ventilation-free survival).  

Sixteen of these 38 patients were followed for up to two years [36]. There were no device-related major adverse events, and DPS resulted in thicker diaphragms (3.9 versus 4.8 mm) and a slower decline in FVC (-2.4 versus -1.3 percent predicted per month). Indirect comparison with historical controls treated with noninvasive ventilation (NIV) suggested that treatment with DPS extended the survival of ALS patients by 16 months.

While some centers may continue to perform DPS in this population, we prefer to avoid DPS until further trials, which are in progress, show a clear benefit.

The reasons for conflicting data are unclear but may include the degree of diaphragm thickness or atrophy, diaphragmatic denervation, and/or upper relative to lower motor neuron disease. For example, when compared with patients with upper level SCI, DPS-induced diaphragmatic contraction is typically weaker in patients with ALS because of progressive muscle atrophy, suggesting that this population is less responsive to pacing [12]. One study also reported a higher mortality in ALS patients with a diaphragm thickness <3.5 mm who underwent DPS, when compared with those who had a thicker diaphragm [37].

Mechanically ventilated patients — Temporary transvenous phrenic nerve pacing has recently been introduced as a means to limit diaphragm atrophy or improve diaphragm strength for conditions such as acute respiratory failure, or bilateral lung transplantation, where prolonged mechanical ventilation may be necessary [38-42]. Transvenous pacing catheters are placed through the subclavian vein into the superior vena cava with the electrodes located near the phrenic nerves in the chest. This form of temporary pacing has been shown to help wean the patient from mechanical ventilation [40]. However, a higher level of electrical stimulation is required for transvenous phrenic nerve stimulation and this can cause hiccups, discomfort or chest pain in some patients [41].

EVALUATION

Requirements for successful pacing — Once patients have been selected as potential candidates, several clinical parameters need to be in place to ensure successful diaphragmatic pacing. These include the demonstration of apnea or severe hypoventilation from diaphragmatic paralysis or paresis, as well as the demonstration of intact phrenic nerve function. (See 'Apnea or severe hypoventilation due to diaphragmatic dysfunction' below and 'Intact phrenic nerve function' below.)

In addition, patients should be assessed for medical issues that may increase surgical complications or limit the potential benefit from pacing. (See 'General medical issues' below.)

The timing of the evaluation should be individualized according to the population studied. In general, patients with upper level spinal cord injury are evaluated three months or more following the initial injury because spontaneous phrenic nerve recovery may occur during this period. Patients with amyotrophic lateral sclerosis should be evaluated early in the course of ventilatory failure because phrenic nerve function declines over time. (See 'Timing of evaluation' below.)

Most patients are evaluated at specialized centers with expertise in diaphragmatic pacing. The investigations are frequently performed simultaneously, and a final assessment made once the evaluation is completed.

Apnea or severe hypoventilation due to diaphragmatic dysfunction — A diagnosis of apnea or severe hypoventilation due to bilateral diaphragmatic paralysis/paresis should be sought, if not already in place.

Diaphragmatic paralysis/paresis – The diagnosis of bilateral diaphragmatic paralysis/paresis is presented elsewhere in detail; briefly, the diagnosis is made using a combination of the following tests in the appropriate clinical setting (eg, neuromuscular disease, spinal cord injury) (see "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Diagnostic evaluation in spontaneously breathing patients' and 'Intact phrenic nerve function' below):

Sitting and supine pulmonary function tests that demonstrate an exaggerated reduction in vital capacity when lying supine, and reduced maximal inspiratory pressure (regardless of posture).

Diaphragmatic imaging studies (eg, fluoroscopy) that demonstrate severely limited or absent diaphragmatic contraction with voluntary effort and/or with phrenic nerve stimulation.

Diaphragmatic electromyography (EMG) and measurement of transdiaphragmatic pressure (Pdi) are more definitive diagnostically, especially when performed in conjunction with phrenic nerve stimulation. However, they are invasive tests that require local expertise. Absence of an EMG signal, or a negative Pdi during peak tidal inspiration is highly suggestive of diaphragmatic paralysis.

Ventilatory failure – The demonstration of ventilatory failure depends upon the underlying etiology of diaphragmatic paralysis/paresis. As an example, patients with complete upper level spinal cord injury (SCI) present for evaluation while on mechanical ventilation because they cannot voluntarily breathe; they are therefore, apneic and ventilator-dependent. Thus, the identification of ventilatory failure in this population is obvious by the absence of respiratory effort and tidal volume on minimal ventilatory support (eg, flow-by).

As the injury resolves, some patients recover but are left with hypoventilation due to severe paresis of the diaphragm. In this population, measurement of bedside vital capacity (VC; less than 10 mL/kg) and maximum inspiratory pressure (MIP; less than -20 cm H2O) may identify those who cannot sustain spontaneous breathing. (See "Respiratory physiologic changes following spinal cord injury" and 'Timing of evaluation' below.)

Intact phrenic nerve function — Patients should be assessed for intact phrenic nerve function, if not already performed. Viability of both phrenic nerves (right and left) is a fundamental requirement for successful bilateral diaphragmatic pacing. Conversely, when phrenic nerve function is not intact (ie, denervated diaphragm), the diaphragm cannot be paced.

The phrenic nerves should be accessed preoperatively at the level of the neck (using percutaneous noninvasive stimulation) and intraoperatively (using invasive stimulation). (See 'Percutaneous nerve conduction studies' below and 'Intraoperative nerve stimulation' below.)

The nerve is stimulated using an electrical impulse and the following is examined:

Conductance of the impulse – Conductance is measured by recording the amplitude and duration of the action potential, preferably with the concurrent demonstration of diaphragmatic contraction in response to the stimulus. (See "Overview of nerve conduction studies".)

Diaphragmatic contraction – Diaphragmatic contraction can be detected using image guidance (usually fluoroscopy, rarely ultrasound), direct visualization, measurement of diaphragmatic electromyography and/or transdiaphragmatic pressure [43-47]. It can be characterized on image guidance as strong (descends ≥3 cm), weak (descends <3 cm), or absent; unilateral or bilateral. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Diagnostic evaluation in spontaneously breathing patients'.)  

Percutaneous nerve conduction studies — In patients that are being considered for diaphragmatic pacing, phrenic nerve conduction studies (PNCS) should be performed by percutaneously stimulating the phrenic nerve in the neck where it passes over the scalene muscle (ie, noninvasive stimulation). Although percutaneous testing is generally considered less reliable than intraoperative testing (invasive stimulation), it is generally performed because it is less invasive and safer. PNCS are ideally performed together with image guidance, electromyography, and/or measurement of transdiaphragmatic pressures to enhance diagnostic sensitivity. (See "Overview of nerve conduction studies" and "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Diagnostic evaluation in spontaneously breathing patients'.)

PNCS are insensitive with false negative testing often recorded due to the following:

Persistent inflammation following injury.

Technical difficulties accessing the nerve (eg, thick neck, additional hardware in place, malpositioning of the probe).

Incomplete stimulation of the phrenic nerve. Only the upper components of the phrenic nerve are accessible percutaneously while the lower branches of the nerve join at the thoracic level. Partial stimulation of the phrenic nerve at the cervical level may result in limited amplitude potential recordings and reduced stimulation of the diaphragm.

Insensitivity of the nerve to the stimulus (eg, patients with lower motor neuron diseases may require higher stimulating impulses).

We suggest the following approach to PNCS test results:

A positive test result is one in which a signal is recorded and there is concurrent demonstration of corresponding diaphragmatic leaflet contraction.

Patients with positive testing in both right and left phrenic nerves are suitable candidates for bilateral diaphragmatic pacing but should also receive confirmatory intraoperative testing.  

Patients with positive testing on one side only are candidates for unilateral pacing. However, unilateral pacing is not typically performed in patients with bilateral diaphragmatic paralysis as improvement in ventilation is considered suboptimal when compared to bilateral pacing [19]. Unless there is a penetrating trauma or some other reason for unilateral phrenic nerve injury, a false negative test should be considered, and the PNCS test repeated at a later date.

A negative test result is one in which no signal is recorded and/or there is no concurrent demonstration of corresponding diaphragmatic leaflet contraction. Patients with negative testing in both right and left phrenic nerves are, in general, not suitable candidates for bilateral diaphragmatic pacing. However, patients in whom false negative testing is suspected (eg, technically difficult studies) may undergo repeat PNCS at a later date.

Intraoperative nerve stimulation — Repeat testing of phrenic nerve function is routinely performed intraoperatively in patients undergoing pacemaker placement.  

For patients undergoing pacemaker placement in the neck or thorax, phrenic nerve stimulation using a handheld or laparoscopic nerve stimulator can confirm that the nerve is functionally intact by demonstrating diaphragmatic contraction (with fluoroscopy) in response to stimulation.

For patients undergoing direct diaphragm pacing stimulation, phrenic nerve stimulation is performed using an intra-abdominal laparoscopic stimulator. The nerve is quickly stimulated at its points of insertion into the diaphragm (usually three to four points), after which diaphragm contraction is visualized:

If diaphragmatic contraction is visualized, then phrenic nerve function is intact and DPS is feasible.

If no contraction is seen, intra-abdominal pressure is reduced and the procedure is repeated.

If diaphragmatic contraction is visualized, then phrenic nerve function is intact and DPS is feasible.

If no contraction is visualized, then the abdominal wall musculature (transversus abdominis) is stimulated to test the system and the thoracic nerve roots.

-If there is contraction of the abdominal wall, but not the diaphragm, phrenic nerve function is not intact, the diaphragm is denervated, and DPS is not feasible.

-Absence of contraction of the abdominal wall identifies a system failure and equipment which needs to be replaced.

General medical issues — Several additional clinical factors should be in place to ensure candidacy for diaphragmatic pacing. They include the following:

Normal cognitive function – Patients should be assessed clinically for neurocognitive function because the major goals of pacing are less likely to be achieved in patients with poor neurocognitive function. As an example, benefits such as phonation and olfaction are not feasible in patients who are severely neurocognitively impaired, in a coma, or obtunded. (See "Mental status scales to evaluate cognition".)

Absence of severe underlying primary pulmonary disease – Diaphragmatic pacing is contraindicated in patients with severe underlying lung disease because ventilatory impairment in this population is typically not responsive to this intervention. Patients should be assessed for evidence of prior pulmonary disease by performing a thorough history and examination, obtaining prior and current chest imaging, and pulmonary function testing (when feasible). (See "Overview of pulmonary function testing in adults" and "Respiratory physiologic changes following spinal cord injury", section on 'Assessment of pulmonary function'.)

Good chest wall mechanics – Cases have been reported of failure of diaphragmatic pacing due to rib cage stiffening from ankylosing spondylitis. Patients should be assessed to assure normal chest wall movement. Obesity leading to excessive mechanical inspiratory loads also has been cited as a cause for DPS failure, and some suggest that obesity should be considered a contraindication to pacing [26,48].

Absence of contraindications to surgery – A comprehensive history and examination should be performed to evaluate patients for medical and/or surgical contraindications to cervical, thoracic, or laparoscopic abdominal surgery when choosing cervical, thoracic, or direct diaphragmatic pacing, respectively. Each approach has an associated risk, the details of which are discussed separately. (See "Evaluation of perioperative pulmonary risk" and "Overview of minimally invasive thoracic surgery" and 'Complications' below.)

Patient age is not considered an exclusion criterion, such that children and adults may be candidates for pacing [8]. Similarly, a lengthy period of time from injury to pacing (among those with spinal cord injury) is not considered an absolute contraindication. Clinical experience and case reports demonstrate phrenic nerve recovery by two to three years following injury as well as successful pacing in those in whom injury occurred many years prior (up to 27 years) [3,49].

Although the presence of a cardiac pacemaker or a feeding tube may make pacemaker placement technically more challenging, neither are considered a contraindication to pacing [12,15].

Timing of evaluation — The optimal timing of the evaluation is unknown. For patients with upper level spinal cord injury, most experts agree that a minimum of three months should elapse following the initial injury before performing a formal evaluation, particularly for functional testing of the phrenic nerve. The rationale for this approach is that phrenic nerve function may partially or completely recover in the weeks following injury in conjunction with recovery of the patient’s medical condition [3,50-53]. Some patients may resume spontaneous breathing and reduce or eliminate the need for mechanical ventilation during this period. Clinical experience and small case series also suggest that some patients may benefit from periodic retesting of the phrenic nerve up to two or three years after the injury to determine whether or not late recovery has occurred, but this is rare [3]. If the phrenic nerve is damaged, or there is damage or atrophy of the lower motor neurons below C3, the phrenic nerves will atrophy.

MAKING THE DECISION TO PACE — Assuming suitable candidacy, which is discussed in the section above (see 'Evaluation' above), the decision to pace the diaphragm is a shared one, and often dependent upon multiple variables including the following:

Ability of the patient to reach the goals of diaphragmatic pacing – The major goal of diaphragmatic pacing is to increase ventilator-free survival by reducing the time spent on, or eliminating the need for, ventilatory support (eg, in patients with upper level cervical spinal cord injury)

In most patients, achieving these goals is associated with an improved quality of life, sense of independence, cosmetic appearance, quality of sleep, verbal communication, and olfaction, especially when compared with invasive or noninvasive ventilation [3,54-56].

The ability of patients to achieve such benefits should be taken into consideration when making the decision to pace the diaphragm. For example, these goals may not be achieved in patients with bilateral diaphragmatic paralysis who are only eligible for unilateral phrenic nerve stimulation, or in patients with severe malnutrition, multiple comorbidities (eg, aphasic stroke), poor motivation, or poor psychosocial support.

Patient values and preferences – For patients and clinicians to make an informed decision, the benefits of diaphragmatic pacing listed above (eg, independence and phonation) should be weighed against the disadvantages of pacing which include the following:

Complications of the surgery and the pacemaker (see 'Complications' below)

Potential for catastrophic effects of sudden hardware malfunction, and consequently, the continued need in many patients for a tracheostomy (see "Tracheostomy: Rationale, indications, and contraindications")

Continued need for assistance with cough and secretion clearance (diaphragmatic pacing improves inspiratory effort but it has no effect on the muscles of expiration) [36] (see 'Complications' below and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support" and "Noninvasive ventilatory support and mechanical insufflation-exsufflation for patients with respiratory muscle dysfunction", section on 'Types of expiratory aids for cough assistance' and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support", section on 'Adjunctive therapy (cough supplementation, nutrition)')

The cost

SURGICAL TECHNIQUE — There are three locations for phrenic nerve stimulation: the neck (cervical approach), the chest (thoracic approach), and the diaphragm (diaphragmatic approach; diaphragmatic pacing stimulation [DPS]). For cervical and thoracic approaches, two electrodes are needed, one for the right and the other for the left phrenic nerve. For the diaphragmatic approach, typically four electrodes are needed (one for each point of insertion on the diaphragm). Patient selection for specific approaches and details of each surgical technique are discussed in the sections below.

Selection of approach/pacemaker type

Patients with upper level spinal cord injury — Patients with upper level spinal cord injury (ie, above the third cervical level) are suitable candidates for all three approaches (cervical, thoracic, diaphragmatic). The rationale and data that support the efficacy of pacing in this population are discussed separately. (See 'Upper cervical spinal cord injury (above C3)' above.)

Choosing among the options is usually individualized and dependent upon institutional expertise. The advantages and disadvantages associated with each approach can be used to facilitate this choice. As examples:

The advantage of the cervical approach is that it avoids the morbidity and mortality associated with chest surgery that are required for the thoracic approach. In addition, bilateral phrenic nerve electrodes can be placed with one operative procedure, rather than the two procedures that are needed for thoracic pacemaker implantation. The second procedure is usually performed two weeks later after recovery from the first procedure.

The disadvantage of the cervical approach is that, in a small proportion of patients, the amplitude of current necessary to stimulate the phrenic nerve results in transmission of current through the soft tissues. This stimulates the functioning portions of the brachial plexus, leading to rhythmic jerking motions of the upper extremities. (See 'Complications of cervical pacemakers' below.)

The main advantage of the thoracic approach is that it avoids brachial plexus stimulation associated with the cervical approach. It is also thought that the pacing stimulus is more effective when using the thoracic approach because a lower branch of the phrenic nerve joins the main nerve trunk only after it enters the chest cavity. As a result, a larger portion of the phrenic nerve may be stimulated by the thoracic approach.

The disadvantage of the thoracic approach is the greater associated morbidity and mortality, particularly if an open thoracotomy needs to be performed. (See 'Complications of thoracic pacemakers' below.)

The main advantages of direct diaphragmatic pacing (DPS) are that it is performed laparoscopically, device implantation can be performed in one procedure, and it avoids brachial plexus stimulation as well as the potential for phrenic nerve damage that is associated with both the cervical and thoracic approaches.

However, compared to the cervical and thoracic approach, patients are at risk of the complications of laparoscopy including viscus and diaphragmatic perforation. In addition, expertise with this approach is limited to a small number of centers. (See 'Complications of direct diaphragmatic pacemakers' below.)

Other patient populations — Similar to patients with upper level spinal cord injury, patients with a central cause for their diaphragmatic paralysis are suitable candidates for cervical and thoracic pacing systems, and theoretically for diaphragmatic pacemakers. Similarly, patients with lower motor neuron diseases other than ALS (eg, idiopathic or trauma-related phrenic nerve neuropathy) may be candidates for direct diaphragm pacing stimulation. However, there is a paucity of evidence to support these indications. (See 'Other patient populations' above.)

In patients with amyotrophic lateral sclerosis (ALS), cervical and thoracic phrenic nerve stimulation is not effective. Direct diaphragmatic pacing (DPS) may be feasible if there are a sufficient number of functional phrenic nerve motor fibers at their points of insertion into the diaphragm. However, DPS is potentially harmful in patients with ALS and not recommended at this time. (See 'Amyotrophic lateral sclerosis' above and 'Complications' below.)

Hardware — Unlike cardiac pacemakers, which have a completely internalized system, all diaphragmatic pacemakers have both internal and external components [57]:

An internal electrode – The electrode is secured to the phrenic nerve (cervical or thoracic) or to diaphragmatic muscle at the point of insertion of the phrenic nerve (direct diaphragmatic pacing [DPS]). It is connected using pacing wires to a receiving unit which is placed under the skin (figure 1).

An external transmitting box – The transmitting box is connected to an antenna that is taped over the surface of the skin, just above the subcutaneous receiver. The transmitting box, which emits radiofrequency signals, is battery powered and contains controls for pulse duration, pulse frequency, pulse ramp, amplitude of the current, as well as respiratory rate and inspiratory time.

Technique

Cervical approach — A skin incision is made in the midportion of the neck, just lateral to the sternocleidomastoid muscle, which is retracted medially and the lateral border of the scalene muscles are identified. The phrenic nerve is identified beneath the scalene fat pad crossing the anterior scalene muscle (figure 2 and figure 3). A hand-held nerve stimulator identifies the phrenic nerve and confirms a functionally intact nerve by demonstrating diaphragmatic contraction in response to stimulation as visualized using fluoroscopy.

Once identified, the phrenic nerve is carefully dissected free of its investing fascia; care should be taken to avoid damaging the nerve intraoperatively from undue stretching, tension, transection, or ischemia. The U-shaped electrode is hooked under the nerve and secured to the surrounding connective tissue with sutures. The connecting wire from the electrode is then tunneled subcutaneously over the clavicle to a receiver that is created in a subcutaneous pocket on the ipsilateral anterior chest. The connections are made and the pacemaker is tested to ensure that there is excellent contact with the nerve and that stimulation through the receiver results in good diaphragmatic contraction. The wounds are then closed.

Thoracic approach — Implantation of thoracic phrenic nerve pacemakers can be performed thoracoscopically (video-assisted thoracoscopic surgery [VATS]), or less commonly via an open thoracotomy [6,49,58]. Details of the technical aspects of VATS are discussed separately. (See "Overview of minimally invasive thoracic surgery".)

The phrenic nerve on the right side is located along the mediastinum just posterior or lateral to the esophagus, and on the left side lying lateral to the pericardium (figure 2). The nerve is freed of its fibrous investments at approximately the mid-thoracic vertebra level (T6-8) (figure 4); the electrode is hooked under it and secured to the adjacent connective tissue with sutures. The connecting wire from the electrode is brought through chest just below the clavicle and then tunneled subcutaneously to a receiver that is created in a subcutaneous pocket on the ipsilateral chest wall. The connections are made, the pacemaker is tested to ensure good diaphragmatic contraction, and wounds are closed. Similar to the cervical approach, care should be taken to avoid damaging the nerve intraoperatively. Traditionally, after one pacemaker has been placed, most experts will wait for a period of two weeks before inserting the second pacemaker on the opposing side.  

Diaphragmatic approach — Implantation of diaphragmatic pacemakers is performed laparoscopically. Details of the techniques and instruments used in intra-abdominal laparoscopic surgery are discussed separately. (See "Abdominal access techniques used in laparoscopic surgery" and "Instruments and devices used in laparoscopic surgery".)

Following the intraoperative demonstration of viable phrenic nerve function as discussed above (see 'Intraoperative nerve stimulation' above), the ligaments attaching the superior margin of the liver (coronary, left triangular) are divided to increase exposure of the right diaphragm (figure 5). The diaphragm is then formally ‘mapped’ to identify rapid motor points of maximal contraction for optimal placement of the stimulating electrodes. Mapping involves both qualitative (ie, direct visualization) and quantitative (changes in abdominal pressure) assessment of diaphragm contraction. In addition, identifying motor points for posterior leaflet contraction is important for the avoidance of postoperative lobar collapse and atelectasis. Once the sites are identified, two electrodes are placed on each diaphragmatic leaflet (anterior and posterior) (figure 6). Connecting wires are brought out through the epigastric port and tunneled to a receiver that is created in a subcutaneous pocket located in the chest or abdomen. The connections are made, the pacemaker is tested to ensure good diaphragmatic contraction, and wounds are closed.

Intraoperative anesthesia — Because visualization or imaging of diaphragmatic contraction is required intraoperatively, neuromuscular blocking agents (eg, succinylcholine, vecuronium) and long acting muscle relaxants (eg, valium) should be avoided in most patients during diaphragmatic pacemaker surgery [59-62]. Typically, agents including etomidate, propofol, and remifentanil are used for induction, and agents such as desflurane are used for maintenance anesthesia.  

Additional issues in spinal cord injury patients that require attention intraoperatively include autonomic dysreflexia that may temporarily require vasopressor support, and poor vascular access that may require central intravenous catheter placement. (See "Chronic complications of spinal cord injury and disease", section on 'Autonomic dysreflexia' and "Perioperative management of hypertension" and "Overview of post-anesthetic care for adult patients".)

Specific aspects of anesthesia including lung isolation techniques and one lung ventilation that are necessary for placement of thoracic pacemakers are discussed separately. (See "Lung isolation techniques" and "One lung ventilation: General principles".)

Immediate postoperative period — Patients should be monitored routinely in the postoperative period for complications of anesthesia and surgery (eg, pain, atelectasis, lobar collapse, hemorrhage, infection, hypotension). (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children".)  

Patients with spinal cord injury are invariably ventilator-dependent prior to surgery, and will need full ventilatory support in the immediate postoperative period. In contrast, most patients with amyotrophic lateral sclerosis can be extubated postoperatively, although some will require short periods of mechanical ventilation or noninvasive pressure support in the immediate postoperative period.

After two weeks, patients can begin an escalating regimen of diaphragmatic pacing to strengthen and condition the diaphragm, the details of which are discussed below.

CONDITIONING OF THE DIAPHRAGM — Every patient should undergo a period of diaphragmatic conditioning. Conditioning is required because in patients with diaphragmatic paralysis/paresis, the diaphragm undergoes disuse atrophy, a feature that is particularly prominent in those who have had paralysis/paresis for prolonged periods.

Initial pacemaker settings — In patients with upper level spinal cord injury, an initial amplitude setting of three to six milliamps (mA) is usually required to provide a tidal volume that is 15 percent above basal need, particularly if the patient has had no diaphragmatic function for six months or more (basal need is typically 5 to 7 mL/kg).

In patients with amyotrophic lateral sclerosis, there is less disuse atrophy, and therefore higher initial amplitudes can be tolerated. We suggest an initial amplitude setting of 25 mA, a frequency below 20 Hertz, and pulse width below 200 microseconds.  

Settings can be altered to optimize ventilation and gas exchange while simultaneously avoiding patients discomfort during the diaphragmatic conditioning period, the details of which are discussed below. (See 'Conditioning of the diaphragm' above.)

Conditioning regimen — Conditioning may begin immediately after surgery but we typically wait for a period of healing around the nerve to occur for one to two weeks prior to starting a conditioning regimen. Conditioning takes weeks to months but may be prolonged (six months to one year) in those in whom diaphragmatic paralysis was present for two years or more prior to pacing [4,63,64]. Pacemaker settings are adjusted according to parameters that indicate adequate minute ventilation (tidal volume x respiratory rate), adequate gas exchange, and comfort level. Conditioning can occur at home or as an inpatient in a rehabilitation facility depending upon the comfort level of staff and caregivers with the equipment.

The regimen for diaphragm conditioning should be individualized as it varies from patient to patient and with the population studied. As examples:

For patients with spinal cord injury, we use the following regimen:

Pacing should commence slowly with a set duration of pacing time allocated to each hour during waking hours (eg, five minutes per hour while awake followed by 10 to 12 hours of nocturnal rest on mechanical ventilation). The pacing duration is extended on a daily or weekly basis (eg, 10 minutes per hour, 15 minutes per hour, etc) during waking hours until the patient is ventilator-free for the maximum amount of time that it is tolerated. The goal is to be ventilator-free for at least the awake period of the day and preferably for 24 hours a day.  

The patient should be monitored during pacing for respiratory rate, heart rate, blood pressure, oxygen saturation, as well as for comfort level and pain. The tidal volume of a paced breath should also be followed intermittently to ensure that the minimum target goal of 15 percent above the basal tidal volume is reached (basal tidal volume is usually 5 to 7 mL/kg).

Pulse oximetry and arterial blood gases are monitored frequently (eg, initially daily and eventually weekly). In our experience, hypercapnia is one of the more common problems encountered during the conditioning period and may be responsible for the feeling of dyspnea during the transition period. It can usually be avoided by adjusting the ventilatory rate on the pacemaker. Alternatively, some experts will reduce the respiratory rate and tidal volume on the mechanical ventilator for several days prior to the initiation of pacing. This allows mild permissive hypercapnia and bicarbonate buffering, which resets central chemoreceptors, thereby avoiding acute hypercapnic acidosis during pacing hours and reducing the sensation of dyspnea.

Although many patients may be weaned off ventilatory support for 24 hours a day, some only partially meet this goal and still require a tracheostomy for supplementary ventilation. For those who successfully wean off completely, many need a tracheostomy as a backup in the event of equipment failure. For those who choose to remove their tracheostomy, an Ambu bag should be available for the same reason. Once a plateau is reached settings can be altered according to planned daily activities.

COMPLICATIONS — Complications of diaphragmatic pacing include those related to the surgery and those related to the pacing system. Complications are infrequent (<1 percent) and can be prevented by meticulous surgical technique, paying attention to alarms and settings on pacing devices, and vigilant education of caregivers and staff so that patients can be adequately monitored following pacemaker placement.

Obstructive sleep apnea is not uncommon in patients with congenital central hypoventilation syndrome who have diaphragmatic pacing, and in one study was found to be improved by decreasing the pacer amplitude settings without compromising gas exchange [65].

General complications of pacemaker surgery — General complications specific to pacemaker surgery include the following:

Infection of the skin or pacemaker site

Dislodgement of the pacemaker electrode, which necessitates a second surgery

Malfunction of hardware (typically battery failure, antenna wire breakage, receiver failure), which may require wire and/or electrode removal or replacement

Upper airway obstruction during sleep, which in some patients can be ameliorated by ramping up the pulse-width setting or treated using nocturnal ventilatory support (noninvasively or invasively through a tracheostomy) [64]

Complications of cervical pacemakers — Complications specific to cervical pacemaker placement include the following:

Transmission of pacemaker impulses to the brachial plexus, with rhythmic jerking of the upper extremity

Phrenic nerve damage

Local vascular injury

Complications of thoracic pacemakers — Complications specific to thoracic pacemaker placement include the following:

Phrenic nerve injury

Complications of thoracic and mediastinal surgery including infection (in particular, pneumonia), acute lung injury, as well as vascular or lymphatic injury, prolonged air leaks, esophageal or pericardial injury, and cardiac arrhythmias

Complications of direct diaphragmatic pacemakers — Complications specific to the placement of diaphragmatic pacing stimulators (DPS systems) include the following:

Capnothorax (carbon dioxide accumulation in the thoracic cavity)

Diaphragmatic perforation

Complications of laparoscopic surgery (eg, viscus perforation, peritonitis) (see "Complications of laparoscopic surgery")

Patients with amyotrophic lateral sclerosis undergoing DPS implantation may have an increased risk of postprocedural venous thromboembolism [66]

SUMMARY AND RECOMMENDATIONS

Diaphragmatic pacing is a second line therapy for patients with ventilatory failure due to bilateral paralysis or severe paresis of the diaphragm who cannot tolerate, have a desire to be liberated from, or have a desire to delay the need for noninvasive or invasive ventilatory support. Importantly, paralysis/paresis of the diaphragm can be due to muscle, nerve, or central system disease, and only patients with intact phrenic nerve function are amenable to pacing. (See 'Selection of potential candidates' above.)  

The diaphragm can be paced using phrenic nerve stimulation at the level of the neck (cervical approach), thorax (thoracic approach), or diaphragm (direct diaphragmatic pacing stimulation [DPS]). (See 'Surgical technique' above.)

Patients with apnea due to bilateral diaphragmatic paralysis from complete upper cervical spinal cord injury (SCI, above the third cervical level) are the most suitable candidates for diaphragmatic pacing. Traditionally, cervical or thoracic pacemakers have been used in this population; however, DPS is also feasible. (See 'Upper cervical spinal cord injury (above C3)' above and 'Selection of approach/pacemaker type' above.)

Patients with central causes for bilateral diaphragmatic paralysis other than upper level SCI, or patients with select lower motor neuron disorders (with the exception of ALS) may be candidates for diaphragmatic pacing (cervical, thoracic, diaphragmatic) or for DPS, respectively. Data to support pacing in these populations are limited. (See 'Other patient populations' above and 'Selection of approach/pacemaker type' above.)

Patients with amyotrophic lateral sclerosis (ALS) who have ventilatory failure due to severe bilateral paresis of the diaphragm are not suitable candidates for diaphragmatic pacing (cervical, thoracic, diaphragmatic). Some trials have suggested harm in association with DPS in this population and until future trials show clear benefit we prefer to avoid DPS in this population. (See 'Amyotrophic lateral sclerosis' above and 'Selection of approach/pacemaker type' above.)

Most patients are evaluated at specialized centers with expertise in diaphragmatic pacing. In order to ensure successful pacing, clinicians should demonstrate apnea/severe hypoventilation from diaphragmatic paralysis/paresis and a functionally intact phrenic nerve. Clinicians should also identify medical conditions that may limit the potential benefit of pacing. (See 'Evaluation' above.)

In most patients, pacing improves diaphragmatic function. In some patients it reduces the time spent on mechanical ventilation (eg, patients with spinal cord injury) thereby allowing phonation and improving quality of life. However, it has not been conclusively shown to improve survival. (See 'Making the decision to pace' above and 'Selection of potential candidates' above.)

During surgery, an internal electrode is secured to the phrenic nerve (cervical and thoracic approach) or to the phrenic nerve branches at their points of insertion into the diaphragm (diaphragmatic approach). The electrode is connected to a subcutaneous receiver. An external transmitting box emits radiofrequency signals to the receiver via an antenna that is taped over the surface of the skin (figure 1). (See 'Hardware' above and 'Technique' above.)

In most patients undergoing pacemaker surgery, neuromuscular blocking agents (eg, succinylcholine, vecuronium) and long acting muscle relaxants (eg, valium) should be avoided because visualization or imaging of diaphragmatic contraction is required intraoperatively. (See 'Intraoperative anesthesia' above.)

Every patient should undergo diaphragmatic conditioning beginning two weeks after pacemaker implantation. Pacemaker settings are adjusted according to parameters that indicate adequate minute ventilation (tidal volume x respiratory rate), adequate gas exchange, and comfort level. Pacing should commence slowly with a set duration of pacing time allocated to each hour during waking hours. The pacing duration is extended on a daily or weekly basis during waking hours until the patient is ventilator-free for the maximum amount of time that it is tolerated. (See 'Conditioning of the diaphragm' above.)

Complications of diaphragmatic pacing include infection, hardware malfunction, and electrode dislodgement, as well as specific complications of each approach including brachial plexus stimulation (cervical approach), phrenic nerve injury (cervical and thoracic approach), and diaphragmatic or viscus perforation (diaphragmatic approach). (See 'Complications' above.)

  1. Hill TM, Onugha O. Diaphragmatic Pacing: Is There a Benefit? Surg Technol Int 2019; 35:265.
  2. McDermott CJ, Maguire C, Cooper CL, et al. Protocol for diaphragm pacing in patients with respiratory muscle weakness due to motor neurone disease (DiPALS): a randomised controlled trial. BMC Neurol 2012; 12:74.
  3. Elefteriades JA, Hogan JF, Handler A, Loke JS. Long-term follow-up of bilateral pacing of the diaphragm in quadriplegia. N Engl J Med 1992; 326:1433.
  4. Glenn WW, Hogan JF, Loke JS, et al. Ventilatory support by pacing of the conditioned diaphragm in quadriplegia. N Engl J Med 1984; 310:1150.
  5. Elefteriades JA, Quin JA. Diaphragm pacing. Ann Thorac Surg 2002; 73:691.
  6. Le Pimpec-Barthes F, Gonzalez-Bermejo J, Hubsch JP, et al. Intrathoracic phrenic pacing: a 10-year experience in France. J Thorac Cardiovasc Surg 2011; 142:378.
  7. Elefteriades JA, Quin JA, Hogan JF, et al. Long-term follow-up of pacing of the conditioned diaphragm in quadriplegia. Pacing Clin Electrophysiol 2002; 25:897.
  8. Garrido-Garcia H, Mazaira Alvarez J, Martín Escribano P, et al. Treatment of chronic ventilatory failure using a diaphragmatic pacemaker. Spinal Cord 1998; 36:310.
  9. Morgan JA, Morales DL, John R, et al. Endoscopic, robotically assisted implantation of phrenic pacemakers. J Thorac Cardiovasc Surg 2003; 126:582.
  10. Khong P, Lazzaro A, Mobbs R. Phrenic nerve stimulation: the Australian experience. J Clin Neurosci 2010; 17:205.
  11. Romero FJ, Gambarrutta C, Garcia-Forcada A, et al. Long-term evaluation of phrenic nerve pacing for respiratory failure due to high cervical spinal cord injury. Spinal Cord 2012; 50:895.
  12. Onders RP, Elmo M, Khansarinia S, et al. Complete worldwide operative experience in laparoscopic diaphragm pacing: results and differences in spinal cord injured patients and amyotrophic lateral sclerosis patients. Surg Endosc 2009; 23:1433.
  13. Posluszny JA Jr, Onders R, Kerwin AJ, et al. Multicenter review of diaphragm pacing in spinal cord injury: successful not only in weaning from ventilators but also in bridging to independent respiration. J Trauma Acute Care Surg 2014; 76:303.
  14. Onders RP, Ponsky TA, Elmo M, et al. First reported experience with intramuscular diaphragm pacing in replacing positive pressure mechanical ventilators in children. J Pediatr Surg 2011; 46:72.
  15. Onders RP, Khansarinia S, Weiser T, et al. Multicenter analysis of diaphragm pacing in tetraplegics with cardiac pacemakers: positive implications for ventilator weaning in intensive care units. Surgery 2010; 148:893.
  16. Onders RP, Elmo MJ, Ignagni AR. Diaphragm pacing stimulation system for tetraplegia in individuals injured during childhood or adolescence. J Spinal Cord Med 2007; 30 Suppl 1:S25.
  17. Bose R, Banerjee AD, Brajesh V, et al. Phrenic nerve stimulation for diaphragmatic pacing in chronic ventilator-dependent patients. Neurol India 2018; 66:1834.
  18. Kerwin AJ, Yorkgitis BK, Ebler DJ, et al. Use of diaphragm pacing in the management of acute cervical spinal cord injury. J Trauma Acute Care Surg 2018; 85:928.
  19. DiMarco AF, Takaoka Y, Kowalski KE. Combined intercostal and diaphragm pacing to provide artificial ventilation in patients with tetraplegia. Arch Phys Med Rehabil 2005; 86:1200.
  20. Kaufman MR, Bauer T, Onders RP, et al. Treatment for bilateral diaphragmatic dysfunction using phrenic nerve reconstruction and diaphragm pacemakers. Interact Cardiovasc Thorac Surg 2021; 32:753.
  21. Ali A, Flageole H. Diaphragmatic pacing for the treatment of congenital central alveolar hypoventilation syndrome. J Pediatr Surg 2008; 43:792.
  22. Lassman AB, Mayer SA. Paroxysmal apnea and vasomotor instability following medullary infarction. Arch Neurol 2005; 62:1286.
  23. Yasuma F, Sakamoto M, Okada T, Abe K. Eight-year follow-up study of a patient with central alveolar hypoventilation treated with diaphragm pacing. Respiration 1998; 65:313.
  24. Brouillette RT, Ilbawi MN, Hunt CE. Phrenic nerve pacing in infants and children: a review of experience and report on the usefulness of phrenic nerve stimulation studies. J Pediatr 1983; 102:32.
  25. Sardenberg RA, Secaf LB, Pinotti AC, et al. Diaphragmatic pacing: unusual indication with successful application. J Bras Pneumol 2011; 37:697.
  26. Diep B, Wang A, Kun S, et al. Diaphragm Pacing without Tracheostomy in Congenital Central Hypoventilation Syndrome Patients. Respiration 2015; 89:534.
  27. Smith BK, Fuller DD, Martin AD, et al. Diaphragm Pacing as a Rehabilitative Tool for Patients With Pompe Disease Who Are Ventilator-Dependent: Case Series. Phys Ther 2016; 96:696.
  28. Maloney MA, Kun SS, Keens TG, Perez IA. Congenital central hypoventilation syndrome: diagnosis and management. Expert Rev Respir Med 2018; 12:283.
  29. Onders RP, Elmo M, Kaplan C, et al. Extended use of diaphragm pacing in patients with unilateral or bilateral diaphragm dysfunction: a new therapeutic option. Surgery 2014; 156:776.
  30. Taslimuddin M, Islam Q, Islam S. Breathing pacemakers in poliomyelitis - A case report. Indian J Physical Med and Rehab 2003; 14:1.
  31. Edmiston TL, Elrick MJ, Kovler ML, et al. Early use of an implantable diaphragm pacing stimulator for a child with severe acute flaccid myelitis-a case report. Spinal Cord Ser Cases 2019; 5:67.
  32. Onders RP, Carlin AM, Elmo M, et al. Amyotrophic lateral sclerosis: the Midwestern surgical experience with the diaphragm pacing stimulation system shows that general anesthesia can be safely performed. Am J Surg 2009; 197:386.
  33. DiPALS Writing Committee, DiPALS Study Group Collaborators, McDermott CJ, et al. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol 2015; 14:883.
  34. Gonzalez-Bermejo J, Morélot-Panzini C, Tanguy ML, et al. Early diaphragm pacing in patients with amyotrophic lateral sclerosis (RespiStimALS): a randomised controlled triple-blind trial. Lancet Neurol 2016; 15:1217.
  35. Şanlı A, Şengün IŞ, Karaçam V, et al. Preoperative parameters and their prognostic value in amyotrophic lateral sclerosis patients undergoing implantation of a diaphragm pacing stimulation system. Ann Indian Acad Neurol 2017; 20:51.
  36. Onders RP, Elmo M, Kaplan C, et al. Final analysis of the pilot trial of diaphragm pacing in amyotrophic lateral sclerosis with long-term follow-up: diaphragm pacing positively affects diaphragm respiration. Am J Surg 2014; 207:393.
  37. Sanli A, Sengun IS, Tertemiz KC, et al. Importance of diaphragm thickness in amyotrophic lateral sclerosis patients with diaphragm pacing system implantation. Surg Endosc 2016; 30:154.
  38. Onders RP, Markowitz A, Ho VP, et al. Completed FDA feasibility trial of surgically placed temporary diaphragm pacing electrodes: A promising option to prevent and treat respiratory failure. Am J Surg 2018; 215:518.
  39. Testelmans D, Nafteux P, Van Cromphaut S, et al. Feasibility of diaphragm pacing in patients after bilateral lung transplantation. Clin Transplant 2017; 31.
  40. Reynolds S, Ebner A, Meffen T, et al. Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic Nerve Pacing Catheter. Crit Care Med 2017; 45:e691.
  41. Dekker LR, Gerritse B, Scheiner A, Kornet L. Mapping for Acute Transvenous Phrenic Nerve Stimulation Study (MAPS Study). Pacing Clin Electrophysiol 2017; 40:294.
  42. Reynolds SC, Meyyappan R, Thakkar V, et al. Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve Stimulation. Am J Respir Crit Care Med 2017; 195:339.
  43. Shaw RK, Glenn WW, Hogan JF, Phelps ML. Electrophysiological evaluation of phrenic nerve function in candidates for diaphragm pacing. J Neurosurg 1980; 53:345.
  44. Alshekhlee A, Onders RP, Syed TU, et al. Phrenic nerve conduction studies in spinal cord injury: applications for diaphragmatic pacing. Muscle Nerve 2008; 38:1546.
  45. McCauley RG, Labib KB. Diaphragmatic paralysis evaluated by phrenic nerve stimulation during fluoroscopy or real-time ultrasound. Radiology 1984; 153:33.
  46. DiMarco AF. Diaphragm pacing in patients with spinal cord injury. Top Spinal Cord Inj Rehabil 1999; 5:6.
  47. Boon AJ, Sekiguchi H, Harper CJ, et al. Sensitivity and specificity of diagnostic ultrasound in the diagnosis of phrenic neuropathy. Neurology 2014; 83:1264.
  48. Layachi L, Georges M, Gonzalez-Bermejo J, et al. Diaphragm pacing failure secondary to deteriorated chest wall mechanics: When a good diaphragm does not suffice to take a good breath in. Respir Med Case Rep 2015; 15:20.
  49. Shaul DB, Danielson PD, McComb JG, Keens TG. Thoracoscopic placement of phrenic nerve electrodes for diaphragmatic pacing in children. J Pediatr Surg 2002; 37:974.
  50. DiMarco AF. Phrenic nerve stimulation in patients with spinal cord injury. Respir Physiol Neurobiol 2009; 169:200.
  51. Carter RE, Donovan WH, Halstead L, Wilkerson MA. Comparative study of electrophrenic nerve stimulation and mechanical ventilatory support in traumatic spinal cord injury. Paraplegia 1987; 25:86.
  52. Lieberman JS, Corkill G, Nayak NN, et al. Serial phrenic nerve conduction studies in candidates for diaphragm pacing. Arch Phys Med Rehabil 1980; 61:528.
  53. Versteegh MI, Braun J, Voigt PG, et al. Diaphragm plication in adult patients with diaphragm paralysis leads to long-term improvement of pulmonary function and level of dyspnea. Eur J Cardiothorac Surg 2007; 32:449.
  54. Bach JR, O'Connor K. Electrophrenic ventilation: a different perspective. J Am Paraplegia Soc 1991; 14:9.
  55. Adler D, Gonzalez-Bermejo J, Duguet A, et al. Diaphragm pacing restores olfaction in tetraplegia. Eur Respir J 2009; 34:365.
  56. Gonzalez-Bermejo J, Morélot-Panzini C, Salachas F, et al. Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2012; 13:44.
  57. Breathing pacemakers. http://www.averylabs.com (Accessed on March 20, 2012).
  58. Morgan JA, Ginsburg ME, Sonett JR, et al. Advanced thoracoscopic procedures are facilitated by computer-aided robotic technology. Eur J Cardiothorac Surg 2003; 23:883.
  59. Story D, Mariampillai E, Nikfarjam M, et al. Anaesthetic aspects of implanting diaphragmatic pacing in patients with spinal cord injury. Anaesth Intensive Care 2010; 38:740.
  60. Tedde ML, Vasconcelos Filho P, Hajjar LA, et al. Diaphragmatic pacing stimulation in spinal cord injury: anesthetic and perioperative management. Clinics (Sao Paulo) 2012; 67:1265.
  61. Niazi AU, Mocon A, Varadi RG, et al. Ondine's curse: anesthesia for laparoscopic implantation of a diaphragm pacing stimulation system. Can J Anaesth 2011; 58:1034.
  62. Devine A, Watt JW. Anaesthesia and diaphragmatic pacing in patients with tetraplegia. A review of peri-operative management in patients over a 10-year period. Eur J Anaesthesiol 1996; 13:553.
  63. Chervin RD, Guilleminault C. Diaphragm pacing for respiratory insufficiency. J Clin Neurophysiol 1997; 14:369.
  64. Onders RP. Functional electrical stimuation: Restoration of respiratory function. In: Handbook of clinical neurology: Spinal cord injury, 3rd ed, Verhaagen J, Mc Donald J (Eds), Elsevier BV, 2012. Vol 109, p.275.
  65. Wang A, Kun S, Diep B, et al. Obstructive Sleep Apnea in Patients With Congenital Central Hypoventilation Syndrome Ventilated by Diaphragm Pacing Without Tracheostomy. J Clin Sleep Med 2018; 14:261.
  66. Rezania K, Gottlieb O, Guralnick A, et al. Venous thromboembolism after diaphragm pacing in amyotrophic lateral sclerosis. Muscle Nerve 2014; 50:863.
Topic 5117 Version 29.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟