Diagnostic evaluation of adults with bilateral diaphragm paralysis

INTRODUCTION — The dome-shaped diaphragm is the chief muscle of inspiration and the most powerful of the inspiratory muscles [1-3]. The diaphragm also serves as a mechanical barrier and maintains the pressure gradient between the abdominal and thoracic cavities.

Diaphragm paralysis can be unilateral or bilateral. Although less commonly encountered, bilateral diaphragmatic paralysis is a severe form of respiratory muscle weakness that needs prompt evaluation and management. The causes and diagnostic evaluation of bilateral diaphragmatic paralysis in adults will be reviewed here. The evaluation of respiratory muscle weakness due to neuromuscular disease, the evaluation and management of unilateral diaphragm paralysis, and the management of bilateral diaphragm paralysis are reviewed separately.

●(See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation".)

●(See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults".)

●(See "Treatment of bilateral diaphragmatic paralysis in adults".)

ETIOLOGY — The causes of bilateral diaphragmatic paralysis are similar to those of unilateral involvement (table 1). However, the proportional likelihood of each of the causes is different.

The most common causes of bilateral diaphragmatic paralysis are conditions that affect the spinal cord and motor neurons (eg, amyotrophic lateral sclerosis), systemic conditions associated with generalized weakness (eg, Guillain Barré, myasthenia gravis), and primary myopathies (eg, polymyositis, dermatomyositis, muscular dystrophy) [4-7]. Some cases are idiopathic. While in most settings, the underlying systemic illness is evident, sometimes, the diaphragm is the initial or only muscle involved [8,9].

●Spinal cord disease – Permanent diaphragmatic paralysis occurs in patients with destructive processes involving the cervical spine (C3 through C5), such as large tumors and spinal cord transection due to trauma. (See "Respiratory physiologic changes following spinal cord injury", section on 'Injury at C3 through C5'.)

●Motor neuron disease – The degree of diaphragm paralysis or paresis with motor neuron disease is generally in proportion to the degree of generalized muscle weakness (eg, amyotrophic lateral sclerosis). (See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease" and "Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease".)

●Neuropathy – A number of neuropathies are associated with bilateral diaphragmatic paralysis, including post-polio syndrome, Guillain-Barré syndrome, post-viral neuropathy, and thyroid and autoimmune diseases [10].

•Severe decompensation due to post-polio syndrome is unusual. However, some patients with post-polio syndrome do not develop new respiratory symptoms until many years after the initial infection. It is unclear whether such progression is due to motor neuron damage or reflects an axonal process. (See "Poliomyelitis and post-polio syndrome", section on 'Post-polio syndrome'.)

•In patients with Guillain-Barré syndrome, the consequences of diaphragmatic paralysis are often magnified by the coexistent weakness of other ventilatory muscles, but the condition is often reversible. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis".)

•Post-viral neuropathy can also cause reversible diaphragmatic paralysis [10,11].

•Thyroid disease (hyper- and hypothyroidism) can cause reversible respiratory muscle weakness through both neuropathic and myopathic mechanisms. (See "Respiratory function in thyroid disease", section on 'Respiratory muscle weakness'.)

•In some patients with systemic lupus erythematosus, the radiographic appearance of an elevated diaphragms, called the "shrinking lung syndrome," may be due to phrenic nerve involvement, although the precise etiology of this clinical disorder remains unknown and may be multifactorial. (See "Pulmonary manifestations of systemic lupus erythematosus in adults", section on 'Shrinking lung syndrome'.)

•Rare causes include critical care neuromyopathy where diaphragmatic weakness may be disproportionately worse than peripheral weakness and other rare neuropathic disorders. (See "Neuromuscular weakness related to critical illness".)

●Neuromuscular junction disease – Respiratory failure due to diaphragm weakness can occur in myasthenia gravis [12,13]. Eaton Lambert syndrome [14] and systemic botulism are presynaptic neuromuscular junction disorders which can also cause severe bilateral weakness or paralysis of the diaphragm. (See "Clinical manifestations of myasthenia gravis", section on 'Respiratory function' and "Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis" and "Botulism", section on 'Clinical manifestations'.)

●Muscle disease – A number of myopathies are associated with bilateral diaphragmatic paralysis, including the following:

•Polymyositis, dermatomyositis, and inclusion body myopathy comprise the inflammatory myopathies, which can all be associated with diaphragmatic weakness. Diaphragmatic weakness is generally in proportion to the degree of skeletal muscle weakness. However, occasionally the diaphragm is disproportionately affected. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation" and "Tests of respiratory muscle strength".)

•Certain forms of muscular dystrophy, including limb-girdle muscular dystrophy, can cause diaphragm weakness as part of generalized progressive muscle disease. (See "Limb-girdle muscular dystrophy".)

•Adult patients with Pompe disease typically present with progressive proximal muscle weakness in a limb girdle distribution with associated diaphragm involvement leading to respiratory insufficiency. (See "Lysosomal acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II, acid maltase deficiency)", section on 'Late-onset form'.)

•Hypothyroidism and hyperthyroidism can impair diaphragm function as part of a generalized myopathy. Neuropathy may also contribute. (See "Respiratory function in thyroid disease".)

•Malnutrition generally affects all muscle groups but can predominantly affect the diaphragm [15]. This dysfunction is reversible with refeeding.

CLINICAL MANIFESTATIONS — Clinical manifestations due to bilateral diaphragm weakness are discussed in this section. Patients may also have clinical findings of the underlying disorder (table 1) and manifestations of generalized respiratory muscle weakness, the details of which are described elsewhere. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Clinical manifestations' and 'Find underlying cause' below.)

●Symptoms – Symptoms include the following:

•Orthopnea – Patients with chronic bilateral diaphragmatic paralysis typically present with dyspnea that worsens in the supine position (ie, orthopnea). In most patients it is an anticipated presentation associated with the presence of a known underlying disease while less commonly, it is the primary manifestation of an underlying disease [6,16].

Orthopnea is frequently misinterpreted as a sign of heart failure. However, the onset of orthopnea from bilateral diaphragm paralysis is dramatic, occurring within minutes of recumbency, and associated with tachypnea and rapid shallow breathing. In contrast, orthopnea due to heart failure usually develops more gradually over the course of the night. (See "Heart failure: Clinical manifestations and diagnosis in adults", section on 'Clinical presentation'.)

•Dyspnea – Patients with bilateral diaphragm paralysis may complain of dyspnea on exertion.

Progressive dyspnea is more likely to occur in patients with progressive disease (eg, amyotrophic lateral sclerosis) or with the development of pulmonary hypertension as a complication of bilateral diaphragm paralysis.

Acute dyspnea or dyspnea at rest may be present in those with severe impairment, acute disease (eg, Guillain Barré syndrome, transection of the spinal cord, or acute myasthenia gravis crisis) or an acute complication (eg, pneumonia). Acute dyspnea is often accompanied by frank ventilatory failure (ie, hypercapnic respiratory acidosis). (See "Approach to the patient with dyspnea".)

Bendopnea (dyspnea when bending over) is rare [17].

•Symptoms of nocturnal hypoventilation or sleep disturbance – Disruptive sleep, daytime fatigue, and early morning headaches may be present in those with nocturnal hypoventilation and sleep disordered breathing due to bilateral diaphragmatic paralysis. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Nocturnal hypoventilation'.)

•Symptoms of pulmonary hypertension – Symptoms of pulmonary hypertension including progressive dyspnea, exercise intolerance, and syncope may be present in those with severe chronic disease. (See "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Clinical manifestations'.)

•Failure to wean off mechanical ventilation – Patients with bilateral diaphragmatic paralysis may present with failure to wean from mechanical ventilation (eg, patients with transection of the spinal cord, critical illness myopathy and/or neuropathy). (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Discontinuing invasive mechanical ventilation' and "Management of the difficult-to-wean adult patient in the intensive care unit".)

Unlike patients with unilateral paralysis, patients with bilateral disease do not present with an incidental finding on chest radiography or without symptoms. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Clinical manifestations'.)

●Examination – Close observation of the breathing pattern typically shows tachypnea, short shallow breathing, and paradoxical abdominal wall retraction (instead of normal protrusion) during inspiration; the latter is due to elevation of the anterior rib cage by accessory muscles, best appreciated when the patient is supine. Air entry is limited in both lung fields and dullness to percussion may be noted at the lung bases.

The appearance of respiratory distress and accessory muscle use may be variable, depending on the severity of paralysis and co-existence of accessory muscle weakness. As an example, patients with severe paralysis and involvement of accessory muscles may not be able to generate sufficient respiratory rate or tidal volume to give the appearance of distress; therefore, the threshold to obtain arterial blood gas analysis should be low. (See 'Arterial blood gas analysis' below.)

Care must be taken in assessing abdominal wall motion in patients who are actively exhaling. In these individuals, contraction of the lateral oblique abdominal muscles during expiration and subsequent relaxation of these muscles during inspiration may give the appearance of outward motion of the anterior abdominal wall during inspiration. To observe this phenomenon, we palpate under the costal margins to look for poor or no caudad (ie, downward) motion of the upper quadrant organs during inspiration.

●Laboratory – There are no specific findings that suggest bilateral diaphragm weakness, but abnormal findings can be seen in association with the underlying cause (eg, elevated creatinine phosphokinase in patients with myositis) or complications (eg, erythrocytosis due to pulmonary hypertension, elevated bicarbonate due to nocturnal hypercapnia).

Acute, chronic, or acute on chronic hypoxemic, hypercapnic respiratory failure may be present depending on the degree of impairment and the presence of acute disease (eg, pneumonia). (See 'Find underlying cause' below and 'Arterial blood gas analysis' below.)

DIAGNOSTIC EVALUATION IN SPONTANEOUSLY BREATHING PATIENTS — In this section, we discuss investigative findings that pertain to the diagnosis of bilateral diaphragmatic paralysis itself. The approach listed in this section is ideal for patients who are spontaneously breathing and may need to be modulated for patients who are mechanically ventilated. Further details are provided below. (See 'Patients who are intubated' below.)

General approach — Bilateral diaphragmatic paralysis should be suspected in patients with known neuromuscular disease (table 1) who present with dyspnea and orthopnea. Bilateral diaphragmatic paralysis may also be suspected in patients without a known neuromuscular disorder when dyspnea or orthopnea is of unclear etiology. When suspected, we also inquire about sleep disturbance and early morning headaches that suggest nocturnal hypercapnia. We examine patients for supportive finding of diaphragmatic paralysis and obtain routine complete blood count and routine chemistries, the details of which are discussed above. (See 'Clinical manifestations' above.)

In suspected cases of bilateral diaphragmatic paralysis, we typically obtain the following:

●An upright anteroposterior and lateral chest radiograph. (See 'Imaging studies' below and 'Chest radiography' below.)

●Chest computed tomography (CT; typically with contrast). (See 'Chest computed tomography' below.)

●A sniff test. (See 'Sniff testing' below.)

●Sitting and supine pulmonary function tests with respiratory muscle strength testing. (See 'Pulmonary function tests' below and 'Supine and sitting spirometry, volumes, diffusion' below.)

●An arterial blood gas. (See 'Arterial blood gas analysis' below.)

For patients in whom the diagnosis is in question, specific diaphragm testing is generally necessary. (See 'Specific diaphragmatic tests' below.)

For those in whom there is no known underlying diagnosis of a neuromuscular disorder, we evaluate patients in search of a cause, once a diagnosis of bilateral diaphragm paralysis or respiratory muscle weakness is in place. (See 'Find underlying cause' below and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Investigating the underlying disorder'.)

Imaging studies — In patients with suspected bilateral diaphragmatic paralysis, we obtain an upright, inspiratory, anteroposterior and lateral chest radiograph and chest computed tomography (CT) to assess the position and contour of the diaphragm and to exclude parenchymal lung processes that might be causing the patient's symptoms. We also perform sniff testing to look for diaphragm movement with inspiration. However, these tests are less useful than in patients with unilateral disease. (See 'Chest radiography' below and 'Sniff testing' below and 'Chest computed tomography' below and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Imaging'.)

Dynamic magnetic resonance imaging of the thorax is a promising modality but is not part of the routine evaluation [18,19].

Chest radiography — Normally, the dome of the right hemidiaphragm projects anteriorly over the 5th or 6th rib and posteriorly over the 10th rib, and the dome of the left hemidiaphragm is up to one interspace lower than the right. In patients with bilateral diaphragmatic paralysis, smooth elevation of both hemidiaphragms and small lung volumes is usually seen. The costophrenic sulci are deep and narrow. The lateral view confirms a smooth contour and elevated diaphragmatic position with deep and narrow and costovertebral sulci. Plate-like atelectasis may also be present, usually at the lung bases (image 1).

Chest computed tomography — CT findings are similar to those seen on chest radiography but are seen in greater detail (eg, bilateral elevation of both hemidiaphragm leaflets, plate-like atelectasis). (See 'Chest radiography' above.)

Diaphragmatic paralysis leads to atrophy of the diaphragmatic crus which can be appreciated on CT. Measurement of the crus at the level of the L1 vertebra on CT has been shown to be helpful in the detection of unilateral diaphragmatic paralysis but there is limited information on its potential role in the diagnosis of bilateral paralysis [20]. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Chest computed tomography'.)

CT also helps to exclude other competing diagnoses that are associated with elevation of the diaphragm including sub-diaphragm or sub-pulmonic processes (eg, bilateral pleural effusion or thickening, ascites, bilateral lower lobe atelectasis, lobectomy, or pneumonia). (See 'Differential diagnosis' below.)

Chest CT may also reveal a potential etiology when an underlying cause for bilateral diaphragmatic paralysis is unknown. (See 'Find underlying cause' below.)

Sniff testing — This test involves fluoroscopic imaging of the diaphragm during a sniff maneuver. During rapid inspiration, no movement of the paralyzed hemidiaphragms supports the diagnosis of bilateral diaphragmatic paralysis.

However, fluoroscopic sniff testing can be misleading in this population because accessory muscle use during inspiration may result in the cephalad (upward) movement of the ribs to give the false appearance of caudad (downward) displacement of the diaphragm [18,21]. This limitation is not seen in unilateral diaphragmatic paralysis, where the sniff fluoroscopy test is positive in over 90 percent of cases. Thus, while a test that shows no caudad (ie, downward) movement of the diaphragm during inspiration is helpful, one that shows some movement does not rule of the possibility of bilateral diaphragmatic paralysis.

While ultrasonography during the sniff maneuver allows assessment of diaphragm movement (and thickness) in patients with bilateral diaphragm weakness, the same limitation as that listed for fluoroscopic sniff testing exists. In addition, the field of view may be limited, and the technique requires operator expertise. However, it may provide useful in patients who are intubated or severely impaired who cannot co-operate with fluoroscopic testing. (See "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Sniff test'.)

Further details on sniff testing are provided separately. (see "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Sniff test').

Pulmonary function tests — In spontaneously breathing patients with suspected bilateral diaphragm paralysis, we perform pulmonary function tests (PFTs) (with spirometry in the sitting and supine position) and tests of respiratory muscle strength.

Supine and sitting spirometry, volumes, diffusion — In spontaneously breathing patients with suspected bilateral diaphragmatic paralysis, we perform spirometry (in the supine and sitting positions), lung volumes, and diffusing capacity for carbon monoxide (DLCO). We do not routinely obtain maximum voluntary ventilation (MVV), unless needed for cardiopulmonary exercise testing.

When bilateral diaphragm paralysis is present, a pattern of restriction is typically seen on spirometry, provided no other physiologic or abnormal lung or pleural pathology is present. A reduced forced vital capacity (FVC), vital capacity (VC), and total lung capacity (TLC) are typically seen; forced expiratory volume in one second (FEV₁)/FVC ratio (greater than 70 percent of predicted) and DLCO are often preserved. (See "Overview of pulmonary function testing in adults" and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Pulmonary function testing'.)

The most important pulmonary function test is measurement of the FVC and/or VC in the upright and supine positions. The FVC and VC in the upright sitting position can be decreased to values lower than 70 percent of predicted. Patients with bilateral diaphragmatic paralysis show a 50 percent decrease in the FVC or VC when they are supine (normal is a 10 percent reduction) [22,23]. This is due to cephalad (ie, upward) displacement of abdominal contents without the normal concomitant increase in diaphragmatic tone that occurs during supination.

Tests of respiratory muscle strength — We also obtain tests of respiratory muscle strength, maximal inspiratory pressure (MIP; PImax) and maximal expiratory pressure (MEP; PEmax). We do not routinely perform sniff nasal pressure (SNIP), since it provides no real additional information other than that provided by MIP; however, other experts use this test as a supplement to MIP [24].

The MIP is usually decreased to values lower than 60 percent of predicted (normal values are more negative than -60 cm H₂O) [25]. The MEP is usually normal but may be mildly reduced, as it is measured at full inspiration and patients with bilateral diaphragmatic paralysis are unable to achieve full inspiration. In one study, a MEP to MIP ratio (MEP/MIP) >3.0 had a sensitivity and specificity of 85 and 84 percent respectively, for bilateral diaphragm paralysis [26].

Further details regarding performance and interpretation of respiratory muscle strength tests and details of how to address difficulties in patients who are unable to obtain a tight seal at the mouth are provided separately. (See "Tests of respiratory muscle strength".)

Arterial blood gas analysis — In patients with suspected bilateral diaphragmatic paralysis, we obtain arterial blood gases to assess for elevation in the partial pressure of carbon dioxide (PaCO₂) due to alveolar hypoventilation (algorithm 1). (See "Arterial blood gases", section on 'Ventilation' and "Measures of oxygenation and mechanisms of hypoxemia", section on 'Hypoventilation'.)

Hypoxemia may also be present, reflecting the alteration in ventilation-perfusion matching due to poor ventilation of the lung bases.

Since oxygenation may also be worsened in the supine position, we also measure oxygen saturation in the sitting and supine position as tolerated (some patients cannot tolerate being supine even for short periods).

Differential diagnosis — The differential diagnosis of bilateral diaphragmatic elevation on the chest radiograph includes the following:

●Obesity (eg, body mass index >40 kg_/m²). (See "Overweight and obesity in adults: Health consequences", section on 'Respiratory system'.)

●Bilateral subdiaphragmatic processes such as ascites, ileus, and organomegaly. (See "Evaluation of adults with ascites".)

●Bilateral subpulmonic pleural effusions, thickening, or masses. (See "Pleural fluid analysis in adults with a pleural effusion".)

●Bilateral lobar atelectasis (eg, due to pain or abdominal surgery) or lobectomy. (See "Atelectasis: Types and pathogenesis in adults" and "Radiologic patterns of lobar atelectasis" and "Overview of pulmonary resection".)

●Bilateral diaphragm eventration or hernia (rare). (See "Eventration of the diaphragm in adults" and "Congenital diaphragmatic hernia in the neonate".)

●Bilateral pleural adhesions resulting in tenting of the diaphragm (image 2).

The differential diagnosis that we consider in patients with respiratory muscle weakness is also considered in patients with suspected bilateral diaphragm paralysis. This differential includes the following and is discussed in detail separately (see "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Differential diagnosis'):

●Restrictive lung disorders (for patients with restriction on PFTs). (See "Overview of pulmonary function testing in adults", section on 'Restrictive ventilatory defect'.)

●Poor effort (for patients with reduced respiratory muscle strength testing). (See "Tests of respiratory muscle strength", section on 'Poor patient effort, technique, and repeatability'.)

●Heart failure (for patients who present with orthopnea) and sleep apnea (for those with symptoms of sleep disordered breathing [SDB]). (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Clinical presentation and diagnosis of obstructive sleep apnea in adults", section on 'Diagnostic evaluation'.)

●Disorders that cause hypercapnia (table 2). (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure" and "Mechanisms, causes, and effects of hypercapnia".)

The differential can be narrowed significantly by history, examination, and chest computed tomography (CT). Although PFT findings in patients with obesity may be similar to those seen in patients with respiratory muscle weakness, obesity may be distinguished by examination.

With the exception of diaphragmatic eventration, most of the remaining conditions are not associated with PFT abnormalities, respiratory muscle weakness, or abnormal sniff testing.

Echocardiography and polysomnography may be needed to distinguish heart failure and SDB from bilateral diaphragmatic paralysis.

Further discussion on distinguishing these etiologies is provided separately. (See "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Differential diagnosis' and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Unilateral elevation of the hemidiaphragm'.)

PATIENTS WITH EQUIVOCAL FINDINGS — Many patients are diagnosed with bilateral diaphragmatic paralysis with standard testing including history and examination, plain chest radiography, chest computed tomography (CT), sniff testing, pulmonary function tests (PFTs), tests of respiratory muscle strength, and arterial blood gas analysis. However, in patients with equivocal findings in whom a diagnosis cannot be confidently made, we perform specific diaphragmatic testing that is targeted at measuring diaphragm function and innervation. (See 'Specific diaphragmatic tests' below and 'Diagnostic evaluation in spontaneously breathing patients' above and 'Diagnosis' below.)

Patients with suspected bilateral diaphragmatic paralysis are more likely to require specific diaphragmatic testing compared with patients with suspected unilateral disease because noninvasive tests are less helpful diagnostically in the setting of bilateral disease. Furthermore, patients with bilateral disease are more likely to be evaluated for diaphragmatic pacing, for which preoperative diaphragmatic testing is mandatory. (See "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications".)

Magnetometers or inductance plethysmographic coils placed around the abdomen and chest may also provide diagnostic insight by revealing paradoxical chest wall motion during the respiratory cycle, although this technology is rarely used outside a research setting (waveform 1).

Specific diaphragmatic tests — Specific diaphragmatic tests include transdiaphragmatic pressure measurement (Pdi), diaphragm electromyography (EMG), and phrenic nerve conduction studies (PNCS).

These tests are more specific for the diagnosis of diaphragmatic paralysis but are not routinely performed since the diagnosis can frequently be made without them, they are generally more invasive and therefore come with risk (eg, pneumothorax, lung or esophageal perforation), and their performance can be technically difficult, requiring significant expertise, which is not universally available.

If indicated, in many patients, specific diaphragmatic tests can be combined with each other to provide complimentary information regarding diaphragm contraction and innervation and to help distinguish neuropathic from myopathic causes of paralysis (table 1). Choosing among the options is largely dependent upon available expertise.

Measurement of transdiaphragmatic pressure — The objective measurement of Pdi is considered the gold standard for the diagnosis of diaphragmatic paralysis. In experienced hands, measurement of the Pdi can be extremely useful in differentiating diaphragmatic paralysis from other causes of respiratory failure.

●Technique – This test is performed via the transnasal placement of two thin-walled balloon-tipped catheters. One is placed in the lower third of the esophagus above the diaphragm to assess changing pleural pressure (Ppl); the location is adjusted to avoid cardiac contraction signals that can modify the tracing [27]. The second balloon is placed in the stomach, to reflect changing abdominal or gastric pressure (Pga) (waveform 1). In adults, the distance between the nostril and the tip of the balloon is approximately 35 to 40 cm for the esophageal balloon and 50 to 60 cm for the gastric balloon [27].

●Interpretation – The Pdi is the difference between Pga and Ppl (Pdi = Pga – Ppl). The Pdi is generally measured during tidal breathing (Pdi) at end inspiration and is negative in patients with bilateral diaphragm paralysis, but positive if the diaphragm is working normally (waveform 1). Thus, a negative value with a paradoxical downward displacement of the gastric wave (ie, negative deflection) provides support for the diagnosis of bilateral diaphragmatic paralysis. There are no reference values and Pdi cannot distinguish right- from left-sided involvement.

Pdi can also be measured at rest, during tidal breathing at end expiration, as well as with voluntary maneuvers such as a deep breath [28], a sniff maneuver (sniff Pdi) [24,29], or a maximal inspiratory force maneuver with airflow limited by a partially closed shutter, that guarantees no airflow (Pdi-max) [5,30].

Additionally, Pdi can be measured independent of the patient's effort by electrically stimulating the phrenic nerve (eg, at the level of the neck) and measuring the Pdi (twitch Pdi) [31]. The twitch Pdi can also help to distinguish neuropathic from myopathic causes of diaphragm paralysis. (See 'Phrenic nerve conduction studies' below and "Overview of nerve conduction studies".)

Diaphragmatic electromyography — Diaphragmatic electromyography (EMG) is recorded with either esophageal or surface electrodes placed bilaterally below the lower frontal and dorsal ribs [6,32,33]. An absent EMG signal supports diaphragm paralysis but does not distinguish a neuropathic from myopathic cause. Esophageal electrodes are most reliable but do not distinguish right from left-sided disease while surface electrodes allow distinction between right and left but can be contaminated by extra-diaphragmatic inspiratory muscle activity.

EMG may be complemented by examining the response following bilateral phrenic nerve stimulation to distinguish neuropathic (ie, phrenic nerve abnormality) from myopathic etiologies and right-sided from left-sided disease [34]. (See 'Phrenic nerve conduction studies' below and "Overview of nerve conduction studies".)

Phrenic nerve conduction studies — The phrenic nerve can be stimulated (eg, at the level of the neck where it passes over the scalene muscle) using percutaneous noninvasive stimulation (typically preoperatively) or using invasive stimulation techniques (typically intraoperatively); the latter is more accurate.

Following stimulation, the ability of the phrenic nerve to conduct a signal (eg, amplitude and duration) and induce diaphragm contraction is assessed. Reduced amplitude and prolongation of phrenic nerve conduction may support a neuropathy while normal amplitude and conduction time supports a myopathy.

PNCS can be combined with diaphragmatic EMG, fluoroscopy, ultrasonography, direct visualization, and Pdi to assess the contractile response to stimulation. Further data on nerve conduction studies are provided separately. (See "Overview of nerve conduction studies" and "Pacing the diaphragm: Patient selection, evaluation, implantation, and complications", section on 'Intact phrenic nerve function'.)

PATIENTS WHO ARE INTUBATED — Patients with bilateral diaphragmatic weakness who are mechanically ventilated often present with failure to wean rather than other findings discussed above. (See 'Clinical manifestations' above.)

In patients who are mechanically ventilated, we adopt a diagnostic approach that is, in principle, similar to that in patients who are spontaneously breathing (see 'Diagnostic evaluation in spontaneously breathing patients' above). However, we modify or delay testing (provided partial or full recovery is expected [eg, pneumonia]) or make a presumptive diagnosis based upon a constellation of clinical findings. In addition, interpreting abnormal test results should take into account the potential impact of mechanical ventilation itself on reducing diaphragm function. The diagnostic value of this approach has not been rigorously studied.

Examples of test modifications include the following:

●The sniff maneuver may not be easily performed with fluoroscopy in an intensive care unit (ICU) setting since transport is generally required but may be performed using bedside ultrasonography, provided expertise is available. The sniff maneuver should not be performed during mechanically delivered or pressure-supported breaths to avoid false positive testing. In addition, the patient should be alert enough to follow commands needed for the maneuver. (See 'Sniff testing' above and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Sniff test'.)

●Performing a full set of pulmonary function tests (PFTs) in the supine and sitting position and comprehensive respiratory muscle strength testing are not feasible in a ventilated patient. As an alternative, a hand-held bedside spirometer can be used to obtain a rudimentary forced vital capacity. A handheld manometer can also be used to record negative inspiratory pressure (NIF) during a maximal forced inspiratory maneuver; values less negative than -60 cm H₂O (eg, -10 cm H₂O) are supportive of inspiratory weakness. Similar to the sniff maneuver, an alert patient is necessary to follow the commands needed to obtain NIF. Supine and sitting values are not typically feasible.

●Specific diaphragm studies (eg, transdiaphragmatic pressure, diaphragmatic electromyography, phrenic nerve conduction studies) may be feasible in intubated patients. However, the same limitations as in spontaneously breathing patients exist and the interpretation is hindered by many interfering signals and neuromechanical uncoupling. For example, measurements of transdiaphragmatic pressure should not be taken during a ventilator-delivered breath. (See 'Specific diaphragmatic tests' above.)

Due to these limitations, making a diagnosis can be challenging. (See 'Diagnosis' below.)

Discontinuing mechanical ventilation in this population is discussed separately. (See "Respiratory muscle weakness due to neuromuscular disease: Management", section on 'Discontinuing invasive mechanical ventilation'.)

DIAGNOSIS — For patients who are spontaneously breathing, the diagnosis of bilateral diaphragmatic paralysis is usually made by a constellation of typical findings that includes all of the following in a patient with an underlying disorder known to be associated with bilateral diaphragmatic paralysis:

●Symptoms and gas exchange parameters supportive of inspiratory muscle weakness (eg, dyspnea, orthopnea, hypercapnic respiratory failure). (See 'Clinical manifestations' above and 'Arterial blood gas analysis' above.)

●Bilateral elevated hemidiaphragms on upright chest radiograph or chest computed tomography. (See 'Chest radiography' above and 'Chest computed tomography' above.)

●No movement of both hemidiaphragms on sniff testing using fluoroscopy or ultrasonography. (See 'Sniff testing' above.)

●Evidence of reduced forced vital capacity and/or vital capacity (on spirometry) and inspiratory muscle weakness (on respiratory muscle strength testing). (See 'Pulmonary function tests' above.)

●Reasonable exclusion of other etiologies that can cause elevated hemidiaphragms or mimic respiratory muscle weakness. (See 'Differential diagnosis' above.)

In many patients with neuromuscular disorders known to be associated with bilateral diaphragmatic paralysis, there is sufficient information from the clinical history, chest radiography, sniff testing, spirometry, arterial blood gas analysis, and respiratory muscle strength testing that a diagnosis can be confidently made without further testing. However, further testing may be needed for the following:

●For patients in whom the diagnosis is in doubt (eg, equivocal test results) or in whom surgery is planned, we typically require specific diaphragm testing to make the diagnosis. A negative value for transdiaphragmatic pressures (Pdi) at end inspiration and an absent signal on diaphragm electromyography (EMG) support the diagnosis of bilateral diaphragm paralysis. Bilateral phrenic nerve conduction studies (PNCS) can further support the diagnosis and may help distinguish a neuropathic (abnormal PNCS) or myopathic (normal PNCS) reason for diaphragmatic paralysis. (See 'Specific diaphragmatic tests' above.)

●For patients in whom other etiologies of elevated hemidiaphragms or conditions that mimic respiratory neuromuscular weakness need to be confidently excluded, we perform additional testing (eg, chest computed tomography for interstitial lung disease, echocardiography for heart failure, polysomnography for sleep disordered breathing). (See 'Differential diagnosis' above and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Differential diagnosis'.)

In patients who are intubated and in whom only limited testing can be performed, we sometimes make a provisional diagnosis of bilateral diaphragmatic paralysis based upon an appropriate clinical setting (eg, transection of the cervical cord, Guillain Barré syndrome, and acute myasthenia gravis) together with one or more rudimentary bedside tests (ultrasonography, spirometry, negative inspiratory pressure [NIF]) and an inability to wean from mechanical ventilation. Further details are described above. (See 'Patients who are intubated' above.)

FOLLOW-UP TESTING

Find underlying cause — For most patients with a diagnosis of bilateral diaphragmatic paralysis, the underlying etiology is already known (table 1). However, in some cases an underlying diagnosis is not known. In such patients, we perform further testing to discover an underlying etiology. Further testing is variable and directed by the suspicion for an underlying disorder. This evaluation is best done in conjunction with a subspecialist, typically a neurologist.

●We inquire about any history of childhood poliomyelitis or other serious viral illnesses (eg, Lyme disease), diabetes, neurological illnesses, remote history of trauma, previous cardiothoracic surgery chest, neck, or cervical spine injury, cervical manipulation therapy, or irradiation. We enquire about upper extremity weakness, known chest or neck pathology, and shoulder pain or paresthesia of the arm. We also ask about symptoms that might suggest lung or other cancer (eg, weight loss, cough, hemoptysis). (See "Clinical manifestations of lung cancer".)

●Depending on the suspicion, we obtain additional laboratory tests such as thyroid function tests, creatine phosphokinase, aldolase, aspartate aminotransferase, alanine aminotransferase, and a connective tissue screen (eg, antinuclear antibody), especially when generalized muscle weakness is present.

●We also obtain cervical spine imaging to rule out cervical spine conditions (eg, computed tomography, magnetic resonance imaging).

As a general principle, we try to rule out structural pathologies using imaging and then focus on common etiologies associated with bilateral diaphragmatic paralysis including motor neuron disease (eg, amyotrophic lateral sclerosis) and systemic conditions (eg, Guillain Barré, myasthenia gravis, polymyositis, dermatomyositis, muscular dystrophy) (table 1).

The approach to assessment of a patient with generalized muscle weakness is provided separately. (See "Approach to the patient with muscle weakness".)

Polysomnography — In many patients with bilateral paralysis (particularly those who have manifestations of sleep disorder while on mechanical ventilation), we perform polysomnography to look for sleep disordered breathing that can complicate paralysis, so that the specific disorder can be identified and treated accordingly.

Since most patients with bilateral diaphragmatic paralysis are at risk of or have clinical manifestations of sleep disordered breathing and need ventilatory support (eg, noninvasive ventilation), we typically obtain overnight polysomnography (table 3) prior to or at the same time as initiating noninvasive ventilation (NIV). Additional rationale for polysomnography is that ventilatory support during sleep may require an alternative approach than that required during the day (eg, continuous positive pressure during sleep and bilevel positive pressure during the day). (See "Evaluation of sleep-disordered breathing in adult patients with neuromuscular and chest wall disorders" and "Treatment of bilateral diaphragmatic paralysis in adults".)

We do not perform home sleep apnea testing (HSAT) since HSAT has a low sensitivity for the detection of central events, which are more likely in this population.

We do not perform overnight pulse oximetry since it is not an adequate test to screen for or diagnose sleep-disordered breathing in these patients, as it underestimates the degree of hypoventilation and sleep disturbance.

SUMMARY AND RECOMMENDATIONS

●Etiology – The diaphragm is the most powerful of the inspiratory muscles. The most common conditions associated with bilateral diaphragmatic paralysis are those that affect the spinal cord and motor neurons (eg, amyotrophic lateral sclerosis) and systemic conditions (eg, Guillain Barré, myasthenia gravis, polymyositis, dermatomyositis, muscular dystrophy); some cases are idiopathic (table 1). While in most settings, the underlying systemic illness is evident, sometimes, the diaphragm is the initial or only muscle involved and an underlying cause may not be apparent. (See 'Introduction' above and 'Etiology' above.)

●Diagnostic evaluation

•Presentation – Patients with acute bilateral diaphragmatic paralysis (eg, due to transection of the spinal cord, Guillain Barré syndrome, or myasthenia gravis crisis) present with acute dyspnea and frank ventilatory failure, while patients who are intubated may present with failure to wean from mechanical ventilation. (See 'Clinical manifestations' above.)

Patients with chronic bilateral diaphragmatic paralysis (eg, due to systemic neuromuscular disorders) classically present with orthopnea (occurring within minutes of recumbency) and dyspnea.

Examination may reveal paradoxical abdominal wall retraction (during inspiration).

•Testing – When suspected, we obtain an upright, inspiratory, anteroposterior and lateral chest radiograph, chest computed tomography (preferably with contrast) and sniff test, as well as sitting and supine pulmonary function tests with respiratory muscle strength testing, and arterial blood gases.

•Diagnosis – A clinical diagnosis can be made in many patients if all of the following are present:

-Symptoms and gas exchange parameters supportive of inspiratory muscle weakness (eg, dyspnea, orthopnea, hypercapnic respiratory failure). (See 'Clinical manifestations' above and 'Arterial blood gas analysis' above.)

-Chest imaging shows smooth elevation of both hemidiaphragms. (See 'Chest radiography' above and 'Chest computed tomography' above.)

-No movement of both hemidiaphragms on sniff testing (may be misleading if accessory muscles result in cephalad [ie, upward] movement of the ribs during inspiration, giving the deceptive appearance of downward displacement of the diaphragm). (See 'Sniff testing' above.)

-Evidence of reduced forced vital capacity (FVC) and/or vital capacity (VC) (eg, <70 percent predicted in the upright position, decrease in FVC >10 percent in the supine position [often >50 percent]), and reduced maximal inspiratory pressure (eg, <60 percent predicted). (See 'Pulmonary function tests' above and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Pulmonary function testing' and "Respiratory muscle weakness due to neuromuscular disease: Clinical manifestations and evaluation", section on 'Respiratory muscle strength testing' and "Tests of respiratory muscle strength".)

-Reasonable exclusion of other etiologies that can cause bilateral diaphragm elevation (eg, obesity, subpulmonic or subdiaphragmatic disorders, diaphragm eventration, pleural adhesions) or mimic respiratory muscle weakness (eg, restrictive lung disorders, poor effort, heart failure, disorders associated with hypercapnia). Further testing including chest computed tomography (CT) and echocardiography may be needed to distinguish these conditions. (See 'Differential diagnosis' above.)

●Special populations – Additional testing or a different approach may be needed in the following:

•Diagnosis in doubt or considering diaphragm pacing – For patients in whom the diagnosis is in question or in whom diaphragm pacing is being considered, we perform specific diaphragm testing that is targeted at measuring diaphragm function and innervation. This includes transdiaphragmatic pressure measurement (Pdi), diaphragm electromyography (EMG), and phrenic nerve conduction studies (PNCS). (See 'Diagnostic evaluation in spontaneously breathing patients' above and 'Specific diaphragmatic tests' above and 'Patients with equivocal findings' above.)

These tests are generally more invasive and therefore come with risk (eg, pneumothorax, lung or esophageal perforation), and their performance can be technically difficult, requiring significant expertise, which is not universally available.

In many patients, these tests can be combined with each other by providing complimentary information regarding diaphragm contraction and distinguishing neuropathic from myopathic causes and left-sided from right-sided disease.

•Patients who are intubated – In patients who are invasively mechanically ventilated, we adopt a diagnostic approach that is similar to that in patients who are spontaneously breathing. However, ventilator-dependence may interfere with the performance and interpretation of standard tests that are typically used to make the diagnosis. Modifying testing (eg, use of bedside ultrasonography, spirometry, and negative inspiratory forced maneuver) or delaying testing (ie, resolution of pneumonia) or making a presumptive diagnosis based upon a constellation of clinical findings are reasonable alternatives. (See 'Patients who are intubated' above.)

●Follow-up – For those in whom an underlying etiology is unknown, we advise additional further testing directed by the suspicion for an underlying disorder. We also typically obtain overnight polysomnography prior to or at the same time as initiating nocturnal noninvasive ventilation (NIV), since patients with ventilatory disorders may have coexistent sleep disturbances that require an alternate therapeutic approach (table 3). (See 'Polysomnography' above.)