Treatment of bilateral diaphragmatic paralysis in adults

INTRODUCTION — Bilateral diaphragm paralysis is a severe form of respiratory muscle weakness that needs prompt evaluation and management.

An overview of the different therapies available for the treatment of bilateral diaphragmatic paralysis will be presented here. The diagnostic evaluation of patients with suspected bilateral diaphragmatic paralysis and the evaluation and treatment of patients with unilateral diaphragm 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".)

GENERAL APPROACH — In most patients with bilateral diaphragmatic paralysis, we suggest treatment of the underlying disorder, if feasible, and general supportive therapies. Select patients may benefit from antiviral therapy or phrenic nerve repair.

Treat the underlying cause

Reversible etiologies — For patients with an underlying cause (table 1), we suggest targeting therapy to that pathology. In some cases, the paralysis may be reversible with therapy, while in others it may be partially reversible, irreversible (eg, old poliomyelitis), or progressive (eg, amyotrophic lateral sclerosis).

Examples of targeted therapy where improvement is expected include the following:

●Patients with cervical compression due to tumors may respond to debulking or decompression. (See "Cervical spinal column injuries in adults: Evaluation and initial management", section on 'Further management and disposition'.)

●Patients with viral neuropathy may respond to targeted antiviral therapy with or without glucocorticoids. Patients with presumed viral neuropathy may benefit from empiric antiviral therapy. (See 'Empiric antiviral therapy for acute idiopathic disease' below.)

●Patients with inflammatory myopathies may respond to glucocorticoids. (See "Overview of and approach to the idiopathic inflammatory myopathies" and "Management of inclusion body myositis" and "Initial treatment of dermatomyositis and polymyositis in adults".)

●Patients with thyroid disease may respond to thyroid-targeted therapies. (See "Treatment of primary hypothyroidism in adults" and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Radioiodine in the treatment of hyperthyroidism" and "Surgical management of hyperthyroidism".)

●Patients with connective tissue disease may require glucocorticoids and/or immunosuppressive therapy. (See "Surgical management of hyperthyroidism" and "Overview of the management and prognosis of systemic lupus erythematosus in adults".)

●Immune checkpoint inhibitor-induced neuropathy may improve with drug cessation and immunosuppression that may include corticosteroids, intravenous immunoglobulins, and/or plasmapheresis [1]. (See "Toxicities associated with immune checkpoint inhibitors".)

●Patients with Guillain-Barré syndrome or myasthenia crisis may respond to immunomodulatory therapy. (See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Immunomodulatory therapy' and "Overview of the treatment of myasthenia gravis".)

●Select patients with acute traumatic transection of the phrenic nerve may be candidates for phrenic nerve repair, the details of which are provided separately. (See "Surgical treatment of phrenic nerve injury".)

Patients with severe or generalized disease or progressive disorders may be expected to not respond as well as those with reversible disorders. (See 'Prognosis' below.)

Special considerations

Empiric antiviral therapy for acute idiopathic disease — In patients with idiopathic bilateral diaphragmatic paralysis that is acute in onset, we typically treat with a one-week course of antiviral therapy (eg, valacyclovir 1000 mg twice daily for one week). Although data to support this approach are weak, our rationale is based upon the administration of a therapy that has potential benefit but with minimal harm.

One preliminary study examined the effect of valacyclovir 1000 mg twice daily for one week in three consecutive patients with recent-onset bilateral diaphragmatic paralysis (suggesting a viral etiology) and found recovery of diaphragmatic function over four to six weeks [2]. In another retrospective study of 16 such patients, 11 recovered function over an average of 14 months while the other five patients failed to respond to the therapy [3]. Whether recovery was specifically valacyclovir related or would have occurred spontaneously is unknown.

Repair of phrenic nerve injury — Combined surgical nerve reconstruction with or without diaphragm pacing is an investigational therapy that is performed at very few centers. It can be considered in select patients with phrenic nerve trauma (surgical or other) but requires immediate transfer to a specialized center, which is not universally available. Rarely, some patients can be considered for surgical repair at a later point in time. It is typically more suitable for patients with unilateral disease rather than bilateral paralysis. (See "Surgical treatment of phrenic nerve injury", section on 'Phrenic nerve reconstruction' and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults".)

Successful use of combined phrenic nerve repair and diaphragmatic pacing has been reported but is investigational. Patients who are ventilator dependent as a result of combined cervical spinal cord injury and phrenic nerve lesions are generally considered to be unsuitable candidates for diaphragmatic pacing due to loss of phrenic nerve integrity. However, two studies from the same group reported the outcome of such patients who were treated with simultaneous surgical phrenic nerve repair and diaphragm pacing [4,5]. All patients required, at minimum, nocturnal ventilation and over one-half were oxygen dependent. This procedure resulted in diaphragm electromyographic activity in the majority of patients. Two-thirds achieved sustainable periods (>1 hour/day) of ventilator weaning (mean = 10 hours/day). All eight oxygen-dependent patients were able to discontinue oxygen therapy following treatment. Two patients recovered voluntary control of diaphragm activity and regained the capacity for spontaneous respiration. More studies are needed to expand the acceptance of this procedure.

General and supportive therapies — Supportive therapies include the following:

●We treat patients with routine vaccinations, counsel against smoking and vaping, and administer oxygen, if indicated. We avoid administering oxygen alone due to the risk of worsening hypercapnia. (See "Standard immunizations for nonpregnant adults" and "Overview of smoking cessation management in adults" and "Long-term supplemental oxygen therapy" and "Adverse effects of supplemental oxygen", section on 'Accentuation of hypercapnia'.)

●Pulmonary rehabilitation with respiratory muscle strength training may facilitate symptoms of dyspnea, but data to support their use are lacking [6,7]. (See "Pulmonary rehabilitation", section on 'Ventilatory muscle training'.)

●We also maximize therapies for coexisting cardiopulmonary disease and sleep-disordered breathing. (See "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders".)

●Coughing aids may be required in this population. Tracheostomy is also sometimes required for troublesome secretion clearance. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Respiratory adjunctive therapy' and 'NIV failure or contraindications: Tracheostomy' below.)

●We ensure that electrolyte abnormalities and nutritional depletion are corrected and that sedating medications are avoided.

●Lifestyle modifications, such as sleeping with the head of the bed elevated and nonimmersive bathing, may help alleviate symptom exacerbation with sleeping and bathing.

VENTILATORY SUPPORT — Most patients with bilateral diaphragmatic paralysis have ventilatory failure (ie, hypercapnic respiratory failure) and are treated with ventilatory support (invasive or noninvasive).

Patients with early or mild disease: Observation — It is rare for patients to have mild disease or be asymptomatic. Examples include patients with mild stretch injury to the phrenic nerve or patients with progressive disease (eg, amyotrophic lateral sclerosis) who are early in the course of their condition and have paresis rather than paralysis. Such patients require clinical observation and monitoring to look for the development of symptoms or frank hypoventilation that warrant ventilatory support.

While there is no set protocol for observation, we monitor the patient's symptoms, pulmonary function tests, and respiratory muscle strength testing. The testing frequency depends upon the etiology and may range from daily (eg, acute Guillain-Barré syndrome or myasthenia gravis crisis) to weeks or months (eg, amyotrophic lateral sclerosis). (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Pulmonary function tests' and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Pulmonary tests'.)

Patients who need acute invasive or noninvasive ventilatory support — In patients with bilateral diaphragmatic paralysis who have acute respiratory failure, we evaluate the need for acute ventilatory support (invasive or noninvasive) [8]. The need for acute ventilatory support may be temporary. However, those who require invasive mechanical ventilation are at high risk of failing to wean off ventilatory support. Such patients may need to transition to a long-term solution such as tracheostomy or chronic noninvasive ventilation (NIV). (See 'Noninvasive ventilation' below and 'NIV failure or contraindications: Tracheostomy' below.)

Indications, weaning, and other issues that face patients with respiratory muscle weakness who need acute support are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Acute ventilatory support'.)

Patients who need chronic ventilatory support (including during sleep) — Most patients with bilateral diaphragmatic paralysis require some form of chronic ventilatory support during sleep and/or while awake during the day.

●In most patients, we prefer NIV (daytime and/or nocturnal), provided there are no contraindications (table 2) [9]. However, a tracheostomy may be needed temporarily (eg, during weaning from mechanical ventilation) or permanently (eg, failure of chronic NIV). (See 'Noninvasive ventilation' below and 'NIV failure or contraindications: Tracheostomy' below.)

●Pacing of the diaphragm may appropriate in a select few. (See 'Intact phrenic nerve: Evaluate eligibility for diaphragm pacing' below.)

Noninvasive ventilation — NIV is the most common form of ventilatory support used in patients with bilateral diaphragmatic paralysis, typically bilevel positive airway pressure. We generally avoid continuous positive airway pressure, as it has been associated with a high failure rate [10].

●Indications for NIV – Indications for and application of NIV are listed in the table and algorithm, respectively (table 3 and algorithm 1).

These indications and alternative modes of chronic ventilatory support are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Chronic ventilatory support' and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Noninvasive positive pressure ventilation' and "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Patient selection and alternative modes of ventilatory support".)

For patients with a significant coexistent sleep-related disorder of breathing, an alternate approach to NIV may be needed and is dictated by the events detected on overnight polysomnography (eg, obstructive or central events, nocturnal hypoventilation). However, overnight polysomnography should not delay initiation of NIV, if needed; empiric settings can be used and adjusted during polysomnography. (See "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders".)

●Outcomes associated with NIV – In patients with neuromuscular disease, NIV is a supportive therapy that can improve gas exchange, symptoms, and in some cases, survival. However, the outcome is largely dependent upon the patient's willingness to tolerate and comply with NIV and the nature of the underlying disorder (eg, progressive or reversible). Efforts targeted at improving tolerance are key to the success of NIV. Efficacy and outcomes in association with NIV and efforts needed to target adherence are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Efficacy' and "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Outcomes' 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: Adaptation and follow-up after initiation".)

NIV failure or contraindications: Tracheostomy — Tracheostomy is generally reserved for patients who fail noninvasive ventilation (NIV), those in whom NIV is contraindicated (table 2) or declined, patients who fail to wean from mechanical ventilation, and patients who need aggressive secretion clearance. These indications and placement of tracheostomy are discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Tracheostomy' and "Tracheostomy: Rationale, indications, and contraindications".)

Intact phrenic nerve: Evaluate eligibility for diaphragm pacing — The diaphragm can be paced by stimulating the phrenic nerve at the level of the neck (or lower branches) and, therefore, requires intact phrenic nerve function and a muscularized diaphragm for success. Patients who have denervated diaphragms cannot be paced. Importantly, pacing is generally a supplementary therapy that allows liberation from or reduction in time spent on mechanical ventilation.

Typical candidates include patients with high-level cervical cord injury who have apnea or severe hypoventilation due to bilateral diaphragmatic paralysis. Pacing is generally considered late after spinal cord injury (eg, three months) to maximize natural recovery of phrenic nerve function.

The selection of suitable candidates, evaluation, implantation, and complications of diaphragm pacing are discussed separately. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications".)

Others (eg, plication) — While diaphragmatic plication has been described in bilateral paralysis, it is less effective than in unilateral paralysis and is typically not used [11,12]. However, it may be an option in younger patients with no underlying lung disease, or as a supplement to other therapies. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Surgical plication'.)

Patients who prefer palliation — Some patients in whom ventilatory support is declined or inconsistent with their preferences may be suitable candidates for palliation or hospice level of care. Further details are provided separately. (See "Assessment and management of dyspnea in palliative care" and "Approach to symptom assessment in palliative care" and "Symptom-based management of amyotrophic lateral sclerosis", section on 'Management of other associated symptoms'.)

MONITORING RESPONSE TO THERAPY — In general, patients are followed clinically for a response to therapy. Principles are similar among therapies (eg, noninvasive ventilation, tracheostomy, pacing) and involve following patients clinically as well as performing pulmonary function testing and respiratory strength testing. Further details are provided separately. (See "Noninvasive ventilation in adults with chronic respiratory failure from neuromuscular and chest wall diseases: Adaptation and follow-up after initiation".)

PROGNOSIS — The prognosis of patients with bilateral diaphragmatic paralysis depends upon the reversibility of the underlying disorder, the severity of the paralysis, the presence of comorbidities, and complications of paralysis or other therapies (eg, pneumonia, sepsis, pulmonary embolism).

For example, patients with bilateral diaphragmatic paralysis due to Guillain-Barré syndrome, hypo- or hyperthyroidism, or inflammation from blunt trauma [13] may expect full or partial recovery with supportive therapy, while patients with amyotrophic lateral sclerosis may expect progressive decline despite therapy. Patients with transection of the spinal cord may have mixed outcomes, and prognosis may additionally depend upon the severity of trauma elsewhere (eg, those with coexisting severe traumatic brain injury may have a worse outcome than those with coexistent extremity fracture). (See "Guillain-Barré syndrome in adults: Treatment and prognosis", section on 'Prognosis' and "Disease-modifying treatment of amyotrophic lateral sclerosis" and "Symptom-based management of amyotrophic lateral sclerosis" and "Acute traumatic spinal cord injury" and "Chronic complications of spinal cord injury and disease" and "Respiratory physiologic changes following spinal cord injury".)

SUMMARY AND RECOMMENDATIONS

●General therapies – General measures for patients with bilateral diaphragmatic paralysis include (see 'General approach' above):

•Treatment of the underlying disorder if a treatable etiology is identified (eg, spinal cord tumor debulking, glucocorticoids for steroid-responsive diseases). For those with traumatic transection of the phrenic nerve, surgical repair is feasible but unusual for patients with bilateral compared with unilateral involvement. (See 'Treat the underlying cause' above and 'Repair of phrenic nerve injury' above.)

•Empiric antiviral therapy – For patients with acute onset of bilateral diaphragmatic paralysis without an identified etiology despite a comprehensive evaluation, we suggest empiric antiviral therapy for treatment of presumed viral neuropathy (Grade 2C). We typically treat with valacyclovir 1000 mg twice daily for one week. (See 'Empiric antiviral therapy for acute idiopathic disease' above.)

•General supportive therapies (eg, routine vaccinations, counseling against smoking and vaping, and supplemental oxygen as needed) should be provided. (See 'Empiric antiviral therapy for acute idiopathic disease' above.)

●Ventilatory support – Most patients with bilateral diaphragmatic paralysis have ventilatory failure and are treated with ventilatory support (invasive or noninvasive; nocturnal and/or daytime). Although rare, patients with mild disease (eg, mild stretch injury to the phrenic nerve or patients who are early in the course of their condition) require clinical observation and monitoring to look for the development of symptoms or frank hypoventilation that warrant ventilatory support. (See 'Ventilatory support' above and 'Patients with early or mild disease: Observation' above.)

•Noninvasive – Noninvasive ventilation (NIV) is the most common form of ventilatory support used in the acute and chronic setting (table 3). Indications, weaning, and other issues that face patients with respiratory muscle weakness who need acute or chronic support are discussed separately. (See 'Ventilatory support' above and "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Acute ventilatory support' and 'Noninvasive ventilation' above.)

•Invasive – Intubation and mechanical ventilation may be required in the acute setting. Tracheostomy is generally reserved for patients who fail NIV, those in whom NIV is contraindicated (table 2) or declined, patients who fail to wean from mechanical ventilation, and patients who need aggressive secretion clearance. These and other issues surrounding tracheostomy are discussed separately. (See 'NIV failure or contraindications: Tracheostomy' above and "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Tracheostomy' and "Tracheostomy: Rationale, indications, and contraindications".)

•Diaphragm pacing – For many patients with bilateral diaphragmatic paralysis in whom phrenic nerve function is intact and in whom no spontaneous recovery of nerve or diaphragm function is expected, we suggest diaphragmatic pacing (Grade 2C). This requires evaluation at a specialized center. The best candidates for diaphragmatic pacing are those with high-level spinal cord injury (above the third cervical level). Further details are provided separately. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications".)

●Prognosis – The prognosis depends upon the reversibility of the underlying disorder, the severity of the paralysis, the presence of comorbidities, and complications of paralysis or other therapies (eg, pneumonia, sepsis, pulmonary embolism). Patients with paralysis due to reversible pathologies (eg, Guillain-Barré syndrome) have a better prognosis than those due to irreversible or progressive conditions (eg, amyotrophic lateral sclerosis). (See 'Prognosis' above.)