Pathophysiology and Pulmonary Function Testing

Weakness of the respiratory muscles leads to the inability to generate or maintain normal respiratory pressures. Pulmonary function testing in patients with neuromuscular weakness typically reveals a restrictive ventilatory defect even if the lungs are normal. Vital capacity (VC), forced expiratory volume in 1 second (FEV₁), and total lung capacity (TLC) are decreased. Residual volume (RV) is normal or decreased, and diffusing capacity corrected for alveolar volume is normal or near-normal but has been reported to be decreased.¹ Comparison of spirometric results obtained with the patient in seated and supine positions can be useful in showing that orthopnea is caused by neuromuscular weakness. A decrease in VC or FEV₁ of greater than 20% when a patient moves from the seated to the supine position suggests diaphragmatic weakness (Table 29-2 and Figure 29-2). The inability to generate normal respiratory pressures is reflected in a decreased maximal inspiratory pressure (PImax). Expiratory muscle weakness is characterized by a decreased maximal expiratory pressure (PEmax).

Arterial blood gases in the setting of a rapid, shallow breathing pattern may show a decreased PaCO₂, although progressive inspiratory muscle weakness leads to hypoventilation and hypercapnia. Hypoxemia can occur in patients unable to take deep breaths and may be caused by microatelectasis, which leads to ventilation/perfusion mismatching within the lung and a resulting decrease in PaO₂ (Figure 29-3). Chronic hypoxemia in this situation may be protective against acute respiratory muscle failure. Experimental data suggest that when hypoxemia is chronic, it may increase diaphragm muscle endurance.² Hypoventilation that occurs with progressive neuromuscular disease may be a protective mechanism that avoids acute respiratory muscle fatigue. However, when hypoxemia is acute, it potentiates respiratory muscle fatigue, hastening respiratory failure.³

Clinical Signs and Symptoms

In the early stages of neuromuscular disease, patients with respiratory muscle weakness initially report exertional dyspnea and fatigue. As the disease process progresses, patients may complain of orthopnea or symptoms of cor pulmonale. These symptoms occur because the muscles involved with respiration can no longer generate or maintain normal ventilation. The response to hypoxemia and respiratory drive, measured with airway occlusion pressure (P0.1), is preserved in most patients with neuromuscular weakness.⁴ Because these patients do not have the strength to take deep breaths, they increase minute ventilation by increasing respiratory rate and adopting a rapid, shallow breathing pattern, which uses less respiratory muscle strength but provides less efficient ventilation. Patients with poor inspiratory muscle function (especially diaphragm weakness) may have marked orthopnea and prefer to sleep in a seated position. They may also experience a decline in the volume and power of voice or voice quality. Progressive muscle weakness can progress to the point where adequate ventilation is no longer maintained, and hypercapnia occurs.

Monitoring and Assessing Patients With Muscle Weakness for Respiratory Insufficiency

If respiratory muscle weakness progresses and cannot be stopped, the eventual result is respiratory failure. The onset of respiratory failure is acute or chronic depending on the time course of the disease process and the circumstances of the patient. When this progression toward respiratory failure is noted, careful follow-up and monitoring of symptoms and pulmonary function are necessary for assessment of the need for mechanical ventilation.

Monitoring the ventilatory function of a patient with neuromuscular weakness can involve repeated measurement of inspiratory pressure, VC, and arterial blood gas values. Depending on the condition, the need for mechanical support can be signaled by reaching either a critical value on testing or an overall clinical condition that does not allow unassisted ventilation to continue. Additional measurements that have been suggested to be more indicative of early respiratory insufficiency, at least in amyotrophic lateral sclerosis (ALS), include maximal sniff nasal inspiratory force⁵ and nocturnal oximetry.⁶

At least two caveats to this general approach should be mentioned. First, patients with myasthenia gravis having an acute myasthenic crisis may have normal test results within minutes of acute ventilatory failure because of the nature of the disorder.⁷ Second, the need to protect the upper airway from secretions and aspiration may not be clearly reflected in results of pulmonary function tests, which evaluate only the mechanical function of the ventilatory pump. Neuromuscular weakness may not manifest uniformly in all muscle groups. Ventilation may be only moderately reduced in patients with gross oropharyngeal dysfunction leading to aspiration. Patients with ventilatory weakness can have a high risk of acute respiratory failure if upper respiratory tract infection or pneumonia develops. In these patients, inability to clear secretions can increase the work of breathing; the results are muscle fatigue, hypoventilation, and acute respiratory failure.

Patients with significant weakness of the respiratory muscles can have a high risk of respiratory failure when any pulmonary process increases the work of breathing. Pulmonary edema, pneumonia, and mucous plugging are examples of clinical conditions that can precipitate respiratory failure rapidly in patients with significant neuromuscular weakness. Such patients may need observation of their respiratory status when they are in the hospital with these conditions. Although the underlying disease may not have progressed to the point that these patients need continual or routine ventilatory support, that support may be critical in the setting of acute, exacerbating illness.

Nocturnal oximetry or formal sleep testing with polysomnography may be suggested in some clinical settings when patients have cor pulmonale, sleep disturbance, or excessive daytime somnolence that is otherwise unexplained.

Management of Respiratory Muscle Weakness

Respiratory insufficiency and failure to clear secretions are the major consequences of inspiratory and expiratory muscle weakness. Treatment of these patients involves consideration of mechanical ventilation via face mask or other noninvasive interfaces or via tracheostomy. Although often overlooked, therapies to augment secretion clearance and assist with cough are important in these patients (see Chapters 39 and 40). Used together, these interventions can decrease hospitalizations secondary to respiratory complications in patients with neuromuscular disease.⁸ These measures may also be useful in delaying or preventing the need for intubation or tracheostomy, although severe bulbar muscle weakness may limit a patient’s ability to avoid invasive ventilatory support.⁹ In addition to these interventions, general rehabilitation focusing on aerobic conditioning, muscle strengthening, and respiratory muscle training can often delay the need for ventilatory support and improve the overall quality of life for patients with muscle weakness.¹⁰

Noninvasive ventilation is being used increasingly for short-term and intermittent ventilatory support of patients with neuromuscular disease.¹¹ Acute deterioration, such as during a pneumonia, and surgical procedures such as gastrostomy tube insertion are situations where noninvasive ventilation is safe and effective if used carefully.^9,12 If a patient needs long-term ventilatory support on an intermittent basis, such as at night only, noninvasive ventilation may be appropriate.¹³ Decisions to begin mechanical ventilation in some patients with neuromuscular weakness have varied greatly among physicians¹⁴ and may be motivated by many different patient factors.¹⁵ No uniform guidelines exist for the use of long-term mechanical ventilation for patients with neuromuscular weakness. However, it is considered a standard option for patients who have reached the point of respiratory failure. Starting a patient on long-term mechanical ventilation requires careful planning and consideration of various issues related to respiratory care in alternative settings. These issues have been addressed in consensus statements^16,17 and are discussed in Chapter 51.

Diaphragm pacing in patients with spinal cord injury has been described for some time using direct stimulation of an intact phrenic nerve to contract the diaphragm and produce negative intrathoracic pressure and inspiration.¹⁸ This technique usually requires a thoracotomy, with its associated risks and high cost, and carries some risk of phrenic nerve injury. These objections have led to the development of an alternative system for diaphragm pacing using direct pacing of the diaphragm employing intramuscular electrodes implanted laparoscopically.¹⁹ When the electrodes can be placed in the diaphragm muscle at an electrophysiologically mapped motor point, the result is often elimination of the need for mechanical ventilation in patients with spinal cord injury and delay in the need to start mechanical ventilation in patients with ALS and other neuromuscular diseases.²⁰

Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic muscle-wasting disorder caused by mutations in the dystrophin gene.²¹ Because it is an X-linked recessive disorder, it affects mostly males. The diagnosis is made when a dystrophin mutation is found in DNA from peripheral white blood cells or when dystrophin is found to be absent or abnormal in muscle biopsy tissue.

DMD manifests early in life with proximal muscle weakness that leads to a waddling gait, exaggerated lumbar curvature (lordosis), and frequent falls. Most affected children need a wheelchair by 12 years of age. Death generally occurs by 20 years of age, usually as a result of declining respiratory muscle strength and subsequent infection. Becker muscular dystrophy, a milder form of DMD, also is associated with dysregulation of the dystrophin gene and manifests later in life.

Other systemic effects of DMD include scarring of the left ventricle and decreased bowel motility (intestinal pseudoobstruction). The progressive decline in respiratory function in patients with DMD parallels limb weakness and typically occurs at the point of wheelchair dependence. Respiratory weakness is primarily due to loss of muscle strength and leads to a lower PImax at all lung volumes than is present in healthy persons.

Progressive scoliosis is associated with DMD and can contribute further to respiratory insufficiency. Many patients undergo spine fusion surgery, and often the procedure allows greater comfort and ease in maintaining an upright posture. Although no randomized trials have proven any benefit of surgery on pulmonary function,²² observational data suggest that the rate of respiratory decline is slower after fusion surgery.²³

Obstructive sleep apnea has been described in a significant proportion of patients with DMD, prompting some authors to recommend formal polysomnography in patients with symptoms of obstructive sleep apnea or at the stage of becoming wheelchair-bound.²⁴ Institution of positive pressure ventilation (PPV) is a decision most patients face at some point in the disease. The point at which to begin different stages of ventilatory support depends on both test results and clinical condition. Nocturnal PPV is usually indicated when FVC reaches 30% of predicted with signs of hypoventilation.^25,26

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