Muscular dystrophy (MD) is a group of degenerative disorders of the skeletal muscles that develop secondary to abnormalities of dystrophin or dystrophin-associated proteins. Most muscular dystrophies follow a progressive clinical course, culminating in respiratory insufficiency. Some milder forms, however, may follow a static course or may even show functional improvement. As such, they do not lead to significant respiratory compromise.
This article summarizes normal respiratory mechanics both while awake and while sleeping, as well as the clinical presentation and routine management of patients with MD. The specific management of a child with MD during the perioperative period also is discussed.
NORMAL RESPIRATORY MECHANICS
The respiratory system comprises two anatomic components: the lungs, which are the gas exchange organs, and the pump, which ventilates the lungs. The respiratory pump consists of the chest wall, including the respiratory muscles, the respiratory controllers in the central nervous system, and the pathways connecting these controllers with the respiratory muscles (eg, spinal cord, peripheral nerves). Impaired respiratory muscle strength and altered intrinsic mechanical properties of the chest wall and the lung lead to suboptimal functioning of this system. Failure of the pump may lead to respiratory decompensation and development of hypercapnia and hypoxemia.
The muscles of respiration can be divided into those that participate mainly during inspiration and those that are predominantly expiratory in function (Sidebar 1). The most important muscle of inspiration is the diaphragm. In conditions of increased ventilatory demand, the accessory muscles of ventilation play a role. Abdominal muscle contraction helps in forceful exhalation, as well as in exhalation under conditions when the respiratory system is under stress.
Another important function of the respiratory system is to help clear respiratory secretions. The ability to perform this function is determined by effective cough. Coughing requires an initial deep inspiratory effort, followed by the closure of the glottis and a forceful contraction of the diaphragm and the abdominal muscles. The sudden opening of the upper airway results in an explosive expiratory effort that helps clear the airways.
EFFECTS OF DECREASED RESPIRATORY MUSCLE STRENGTH
Impaired respiratory muscle function results in reduction of lung volume. Reduction of inspiratory muscle strength causes a decrease in the inspiratory capacity and therefore a smaller total lung capacity. The characteristically measured abnormality of inspiratory muscle weakness is a low vital capacity (VC). The reduction in VC is greater than would be anticipated for the degree of respiratory muscle weakness. The disproportionate reduction in lung volume relative to the degree of muscle weakness is the result of the change in lung1 and chest wall2 mechanical properties. Diffusion capacity is normal, which distinguishes respiratory muscle weakness from alveolar disorders such as pulmonary fibrosis.
In addition to these effects on lung volumes, each of the components of a normal cough can be impaired in patients with neuromuscular weakness. When present, inspiratory muscle weakness limits the depth of the precough inspiration and bulbar weakness, while presence of a tracheostomy impairs glottic closure. Expiratory muscle weakness or chest wall distortion from scoliosis reduces intrathoracic expiratory pressures and flows. Respiratory complications of ineffective airway clearance include pneumonia, atelectasis, and altered gas exchange, resulting in supplemental oxygen dependency, and respiratory acidosis.3
Effect During Sleep
With sleep onset, there is a fall in ventilation,4 primarily due to a reduction in ventilatory drive5 and a fall in the functional residual capacity. Also, the upper airway resistance increases significantly.6
The sleep-related fall in postural muscle tone reaches its nadir during rapid eye movement (REM) sleep, with a shift from predominantly ribcage to predominately diaphragmatic breathing. As such, the degree of alveolar hypoventilation during sleep and the accompanying hypoxemia and hypercapnia are dependent on diaphragmatic functioa In patients with neuromuscular disorders, these changes are often exaggerated during sleep.7'8
Early evidence of respiratory muscle dysfunction is noted when muscles perform their function under conditions of stress, such as respiratory infection, recovery from general anesthesia, exercise, and sleep. In many instances, the onset of early respiratory insufficiency develops after the patient has lost ambulation. Detecting respiratory muscle dysfunction during exercise thus becomes unfeasible. In these patients, evaluation of breathing during sleep may enable the identification of the early stages of respiratory muscle dysfunction.
Figure 1 outlines the stages of hypercapnic respiratory failure in patients with progressive neuromuscular disorders. The gradual transition from stage 1 to stage 3 respiratory failure is characteristic of Bucherine MD, in which there is a gradual progression of respiratory muscle weakness during the course of approximately 2 decades. Patients with the Becker subtype have a slower rate of progression, not causing respiratory failure until the late 20s, and limb-girdle MD may not cause respiratory deterioration until the late 30s or 40s.
In some disorders, such as congenital MD, respiratory insufficiency, if present, might not progress beyond stage 1 or 2. In other disorders, respiratory muscle weakness is extremely severe, with patients presenting in stage 3 respiratory failure.
A history of prolonged cough with upper respiratory infections or need for frequent antibiotics to treat chest congestion reflects an inability to clear respiratory secretions effectively. Patients with impaired cough from involvement of bulbar and ventilatory muscles are at increased risk for aspiration, atelectasis, and pneumonia. These risks should be considered in the office evaluation of febrile illness in this group of patients. A history of disrupted sleep, daytime somnolence and impaired intellectual function can be secondary to nocturnal hypoventilation and obstructive sleep apnea.
Figure 1 .The stages of hypercapnic respiratory failure in patients with progressive neuromuscular disorders.
EVALUATION (SIDEBAR 2)
Pulmonary Function Testing
The measurement of forced vital capacity (FVC) is practical to evaluate, quantify, and follow patients suspected of having respiratory muscle weakness. An entirely normal VC makes significant respiratory muscle weakness unlikely. VC is normal, or minimally reduced, when respiratory muscle strength is more than 50% of what is predicted.9 With chronic respiratory muscle weakness, VC falls further because of reduced chest wall and lung compliance.
In longstanding conditions, FVC in the supine position decreases between 30% and 50% compared with upright value. This finding is almost pathognomonic of respiratory muscle paralysis.
Respiratory Muscle Strength Testing
To test respiratory muscle strength, the pressure generated can be measured either during a voluntary maneuver or during involuntary contractions, particularly in response to phrenic nerve stimulation. These tests require trained personnel and properly calibrated equipment and are thus performed optimally in a wellequipped pulmonary function laboratory.
The volitional tests of respiratory muscle strength include the following:
* Maximum static inspiratory and expiratory pressures.
* Maximum static transdiaphragmatic pressure.
* Maximum sniff pressure.
* Maximum cough pressure.
The nonvolitional tests of respiratory muscle strength include the following:
* Electrical phrenic nerve stimulation.
* Magnetic phrenic nerve stimulation.
* Twitch transdiaphragmatic pressure.
* Abdominal muscle stimulation.
We will discuss primarily volitional tests of respiratory muscle strength. These tests are dependent on the subject's cooperation, and the value obtained may underestimate the true strength of the respiratory muscles.
The tests most widely used to assess respiratory muscle strength are the maximal inspiratory (Pi1113x) and expiratory (Pe1113x) pressures. These tests have the advantage of being noninvasive, and several studies provide normal reference values.10'11
After the first year of life, normal values for Pi^sub max^ range between 80 and 120 cm H2O. Patients with maximal inspiratory force of less than 25 cm H2O are at high risk for developing ventilatory failure. Similarly, maximal expiratory force of less than 30 cm H2O at functional residual capacity is seen in patients with ineffective cough, which could lead to accumulation of bronchial secretions, possible atelectasis, pneumonia, and ventilatory failure.
The maximum flow generated during voluntary cough maneuver can be used to assess the strength of the respiratory muscles. Cough peak flows correlate with the ability to clear secretions from the respiratory tract. The normal value for cough peak flow in adults is 360 L/ min, and values below 160 L/min are associated with inadequate airway clearance. 12In the absence of normative data for children, these values are utilized in clinical decision making in children.
Another method of measuring the force generated by the contraction of the diaphragm and other inspiratory muscles is the "sniff test" A sniff is a short, sharp, voluntary, inspiratory maneuver performed through one or both unoccluded nostrils. The pressure in the obstructed nostril reflects the pressure in the nasopharynx, which is a reasonable indication of alveolar pressure. The sniff test is easily performed by most patients, requires little practice, and is relatively reproducible.13
The maximal transdiaphragmatic pressure (Pdi^sub max^) test provides measurement of the strength of the diaphragm. It requires the simultaneous measurement of esophageal (Pes, to represent pleural) and gastric (Pga, to represent abdominal) pressures using balloon catheters placed in the esophagus and stomach, respectively. Transdiaphragmatic pressure is calculated as the difference between Pga and Pes and is the best index of diaphragmatic intramuscular tension and pressure developed across the diaphragm. However, it is not used routinely in clinical practice.
The polysomnogram involves monitoring of the patient's electroencephalographic (EEG) and cardiorespiratory parameters during sleep.Abnormal sleep architecture with reduced sleep efficiency, increase in stage 1 sleep, and reduction in REM sleep has been described.14 Sleep-disordered breathing manifesting as hypoventilation is the most common presentatioa Increased frequencies of both obstructive and central events have been reported.
The central hypopneas are more frequent and prolonged in REM sleep, particularly phasic REM. The degree of oxygen desaturation is related to the severity of diaphragmatic weakness.15 Inspiratory vital capacity and peak inspiratory pressure, but not symptom score, have been shown to correlate with sleep disordered breathing and severity of nocturnal hypercapnic hypoventilation.16 The apnea:hypopnea index and the degree of nocturnal desaturation are greater in myotonic dystrophy than in nonmyotonic neuromuscular disease with a similar degree of respiratory muscle weakness.17
Routine pulmonary management of the patient with MD should include measures to ensure adequate airway clearance and correction of impaired ventilation.
Airway clearance is compromised at cough peak flows of less than 160 L/ min.12 Baseline cough peak flow values of greater than 160 L/min also may be insufficient for patients with MD during a respiratory infection, as these patients can experience decreased respiratory muscle function during respiratory illnesses.18 Thus, at cough peak flows less than 270 L/min, assisted cough techniques are recommended.3'19
Measures to improve airway clearance can minimize or prevent life-threatening conditions that typically require hospital admission for a patient with MD. Both manually3 and mechanically assisted20 cough, with or without insufflation, have been used successfully to avoid pulmonary morbidity and mortality in patients with MD. There are, however, limitations to manually assisted cough. It may not be effective in patients with chest wall distortion from scoliosis because of the difficulty in establishing optimal hand placement on the chest to enhance expiratory flows. Manual techniques also are time-intensive and require special training to optimize caregiver-patient coordination.
The indications for insufflator-exsufflator (cough assist) are summarized in Sidebar 3 (see page 542). The frequency of airway clearance techniques should be individualized. However, an increase in airway clearance with upper respiratory infections is recommended.
The goal of mechanical ventilation is to correct chronic respiratory insufficiency. This option is thus presented when it is believed that the patient is unable to maintain adequate lung inflation and ventilation without support. The patient may present with a history of recurrent atelectasis, evidence of sleep-disordered breathing on the polysomnogram, or ventilatory impairment manifested as abnormal blood gas analysis. The decision to use mechanical ventilation and the method of ventilatory support remain the personal decision of patients and their families. Methods of mechanical ventilation fall into two classifications, invasive and noninvasive (Sidebar 4).
Invasive mechanical ventilation can be achieved via a permanent tracheostomy. As a general principle, patients with chronic respiratory failure who require mechanical ventilation 24 hours per day most often are treated with a permanent tracheotomy and positive-pressure ventilation.
Noninvasive positive-pressure ventilation (NIPPV) may be provided by a nasal or full-face mask; however, a fullface mask carries the risk of pulmonary aspiration or gastric perforation. This mode of ventilation has several advantages, including the avoidance of a tracheotomy, portability, and the simplicity of the equipment and the setup. The drawbacks of noninvasive positive-pressure ventilation using a bilevel ventilator include patient-ventilator asynchrony and the potential risk that the patient will rebreathe carbon dioxide and develop secondary hypercapnia.
The mechanisms by which chronic nocturnal ventilation contributes to clinical improvement are multifactorial and include respiratory muscle rest with improved inspiratory muscle strength as well as reexpansion of areas of atelectasis. Also, the respiratory control center is reset by lowered PCO2 during the period of noninvasive ventilation.
Several studies have found respiratory failure in Duchenne MD responds well to the initiation of NIPPV, with resolution of symptoms and good quality of life, improvement in physiological parameters, and increased survival rates.21'22 However, the optimal timing for initiation of positive pressure ventilation is not clear. With the increasing use of screening polysomnography,19 it is expected that objective nocturnal monitoring will determine the timing for initiation of ventilatory support.23 A titration polysomnogram is recommended to assess for mouth leaks and patientventilator asynchrony.
Figure 2. Respiratory events in a child with muscular dystrophy and sleep-disordered breathing.
Figures 2 and 3 depict the effects of optimal positive pressure on sleepdisordered breathing in a patient with Duchenne MD. Long-term follow up in several studies shows that nocturnal ventilation (either NIPPV or by tracheostomy, depending on local experience) is very effective treatment for respiratory failure in Duchenne MD, and that often nocturnal use alone provides very good stabilization for many years.3 Patients commonly notice that the frequency of chest infections falls with ventilator use and that, when infections do occur, they are managed effectively in an outpatient setting. With the use of ventilation as the major variable, the mean age of death in the Newcastle Centre has risen from 19 to at least 25.14
Patients with respiratory muscle weakness are at increased risk for postoperative respiratory morbidity. Optimization of respiratory status in the preoperative period can help reduce the frequency and severity of these complications. At Cincinnati Children's Hospital Medical Center, preoperative admission for optimization of airway clearance and positive pressure ventilation (if indicated) is recommended routinely.
Figure 3. Effects of initiation of bilevel positive airway pressure initiation in a child with sleep-disordered breathing (Figure 2). The results illustrate resolution of tachypnea, normal oxygen saturation, and absence of apnea or hypopnea.
Aggressive airway clearance in the postoperative period should be emphasized. Use of positive-pressure ventilation in the immediate postoperative period also should be considered.
It is important to mention that these recommendations are based on clinical practice at several centers that provide multidisciplinary care to children with neuromuscular disorders. Unfortunately, there is a paucity of literature supporting these practices.
Pulmonary involvement is common in patients with muscular dystrophy, and routine screening for evidence of respiratory muscle dysfunction should be performed. Testing for respiratory muscle strength, as well as an assessment for sleep-disordered breathing, should be obtained in consultation with a specialist. Adequate airway clearance and correction of impaired ventilation are the key components of pulmonary management in this group of patients. Also, special emphasis on airway clearance is recommended during upper respiratory infections, as well as in the postoperative period. Early initiation of ventilatory support has been shown to result in longer life expectancy.
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