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Phrenic Nerve and Diaphragmatic Stimulation

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Electrical stimulation options for the restoration of inspiratory muscle function in subjects with spinal cord injuries include bilateral phrenic nerve pacing, bilateral diaphragmatic pacing and combined intercostal muscle stimulation with unilateral phrenic pacing (DiMarco et al. 2005b).

Intact phrenic nerves are required for successful stimulation. Phrenic nerve function is generally assessed through phrenic nerve conduction studies and fluoroscopic observation of diaphragmatic movement with phrenic nerve stimulation. Subjects with injuries at C3, C4 and C5 may have compromised diaphragmatic function, but are unlikely to be candidates for pacing due to inadequate phrenic nerve function.

Bilateral phrenic nerve stimulation was first reported by Glenn and colleagues in the 1970s.  The original surgery involved a thoracotomy and inpatient hospital stay to place the electrodes on the phrenic nerves in the neck or thorax. Potential risks included direct injury to the phrenic nerves during surgery. The original protocols applied intermittent high frequency stimulation to the diaphragms in an alternating pattern, but were revised to a continuous lower frequency stimulation to decrease diaphragmatic fatigue (Glenn et al. 1984; Elefteriades et al. 2002).

In recent years, the laparoscopic placement of intramuscular diaphragmatic electrodes has eliminated the need for more extensive thoracotomy surgery and associated hospital stays. The approach has also decreased the risk of phrenic nerve injury (DiMarco et al. 2005a). The electrodes are placed laparoscopically as a day surgery procedure with optimum placement of the electrodes being mapped to the phrenic nerve motor point (Onders et al. 2004).

Most patients with diaphragmatic pacemakers continue to have tracheostomies and mechanical ventilators as a back-up to their pacemakers. It is important to note that diaphragmatic pacemakers only improve inspiratory function and do not target expiratory functions such as coughing and clearing secretions. Given the small number of controlled trials and large number of pre-post trials, the full data extraction and scoring are only shown for the controlled trials with a briefer summary of the level 4 evidence.

Table 17: Phrenic Nerve Stimulation – Controlled Trials

Table 18: Phrenic Nerve Stimulation – Level 4 Evidence

Discussion

Recent studies show higher success rates with long-term implantation (Hirschfeld et al. 2013); 77% of patients had stable threshold currents for an average of 6.3 yr.  An earlier report by the same first author (Hirschfeld et al. 2008) prospectively compared subjects receiving phrenic nerve stimulation and those receiving mechanical ventilation. Although they show decreased rates of respiratory infections and increased social participation in the phrenic nerve stimulation group, they acknowledge that the mechanical ventilation group is not a comparable group as these subjects were not usually candidates for phrenic nerve stimulation.

A retrospective case control study suggests a higher survival rate in a phrenic nerve paced group compared to a mechanically ventilated group (Carter 1993). The prospective study by Hirschfeld et al. (2008) shows no difference in duration of life between the phrenic nerve paced group and mechanically ventilated group.

Hirschfeld et al. (2008) comment on decreased costs of care, improved quality of speech and higher rates of social participation in the phrenic nerve group. The increased rates of return to work and school may have been influenced by the lower ages seen in the phrenic nerve group.  In another retrospective case control study, Esclarin et al. (1994) reports higher rates of power wheelchair management, phonation success, patient satisfaction and hospital discharge in paced subjects compared to mechanically ventilated subjects. A basic cost analysis in that study suggested increased costs of 50 hours per year for ventilatory management in the mechanically ventilated group (Esclarin et al. 1994). However, the small numbers, the difficulty in comparing baseline statistics in the two groups, the potential for selection bias in the subjects receiving pacemakers and the overall high rate of death in the high lesion spinal cord injury population make this data very difficult to interpret. Prospective comparison studies looking at morbidity, mortality, quality of life and costs related to phrenic and diaphragmatic pacing are lacking.

Several different devices for phrenic nerve pacing have been developed. Many of the reported studies are level 4 case series or pre-post study designs looking at the feasibility of phrenic nerve stimulation devices. Reported benefits to subjects include improved sense of smell, mobility, quality of speech and overall sense of well-being (DiMarco et al. 2005b). Long-term partial or total independence from mechanical ventilation can generally be interpreted as a successful intervention with these devices.

There are several small level 4 studies to show that bilateral phrenic nerve pacing and bilateral diaphragmatic pacing can be used successfully for the ventilation of subjects with SCI (Baer et al. 1990, DiMarco et al. 2005a, Elefteriades et al. 2002, Glenn et al. 1976, Sharkey et al. 1989, Mayr et al. 1993, Oakes et al. 1980, Miller et al. 1990, Nakajima and Sharkey 1990, Onders et al. 2004).  More recent studies have included large sample sizes including the study by Alshekhlee et al. (2008) (n = 26).

For subjects without intact bilateral phrenic nerves, there is one small level 4 study to show that unilateral phrenic pacing in combination with intercostals stimulation can be used successfully for the ventilation of subjects with SCI with only one intact phrenic nerve (DiMarco et al. 2005b). In addition, there is one small level 4 study reporting on successful phrenic nerve stimulation following intercostal nerve to phrenic nerve transfer in a case series of 6 subjects with C3-C5 injuries (Krieger and Krieger 2000). There is level 4 evidence to show that intercostal muscle pacing via upper thoracic ventral root stimulation alone has not succeeded in supporting ventilation for prolonged periods (DiMarco et al. 1994).

There are high complication rates reported with these devices. Many of these are likely due to the learning curve involved in successful subject selection, surgical technique development and the “prototype” or single unit design of the devices themselves with a higher inherent risk of technical failure (Baer et al. 1990). There is at least one case report of the successful off label use of a spinal cord stimulator (rather than a purpose built phrenic nerve stimulator) being used to stimulate the phrenic nerves in subjects with SCI (Taira and Hori 2007).

Potential complications of phrenic pacing include wires breaking, wires or receivers becoming displaced, devices failing, aspiration of food during inspiration, shoulder or abdominal pain and infections (Baer et al. 1990, DiMarco et al. 2005a, 2005b). With the laparoscopic approach for diaphragm pacing, subjects may develop pneumothoraces or subcutaneous emphysema (DiMarco et al. 2005a).

Conclusion

There is level 3 evidence (from 1 case control study) (Carter 1993) that suggests a higher survival rate in a phrenic nerve paced group compared to a mechanically ventilated group.

There is level 3 evidence (from 1 case control study) (Esclarin et al. 1994) that suggests better power wheelchair management, phonation success, patient satisfaction and hospital discharge in phrenic paced subjects compared to mechanically ventilated subjects.

There is level 4 evidence (from 8 pre-post studies) (see Table 18) that phrenic nerve stimulation can be used as a long-term alternative to mechanical ventilation for subjects with injuries at C2 or above.

There is level 4 evidence from (1 pre-post study) (Alshekhlee et al. 2008) that diaphragm pacing system (DPS) can help cervical SCI patients breathe without a mechanical ventilator.

There is level 4 evidence (Tedde et al. 2012; DiMarco et al. 2005a; Onders et al. 2004) that diaphragmatic stimulation via laparoscopic placement of electrodes can be used as a long-term alternative to mechanical ventilation for subjects with high cervical spinal cord injuries.

There is level 4 evidence from 1 study (DiMarco el al. 2005b) that unilateral phrenic stimulation in combination with intercostals stimulation can be used as an alternative to mechanical ventilation for subjects with a single intact phrenic nerve.

There is level 4 evidence from 1 study (DiMarco et al. 1994) to show that intercostal muscle pacing via upper thoracic ventral root stimulation cannot be used as a long-term alternative to mechanical ventilation (DiMarco et al. 1994).

  • There is some evidence that suggests a higher survival rate, as well as better power wheelchair management, phonation success, and patient satisfaction in phrenic paced subjects compared to mechanically ventilated subjects.
  • Phrenic nerve or diaphragmatic stimulation may be used as a long-term alternative to mechanical ventilation for subjects with injuries at C2 or above.