Disturbed Sleep in a Patient with Duchenne Muscular Dystrophy

A 17-year-old white male with Duchenne muscular dystrophy presented to the pediatric pulmonary clinic for a follow-up evaluation after being hospitalized for pneumonia. During the hospital stay he was noted to have nocturnal desaturation intermittently during sleep. The patient has been wheelchair bound since age 12 years. His father's two current concerns include the patient's difficulty swallowing and difficulty breathing during sleep.

Physical Examination: The patient is a thin young man sitting in a wheelchair with decreased breath sounds at his lung bases. He exhibits a weak cough. Auscultation of his heart reveals a regular rate and rhythm with a rapid rate and a S3 gallop. No pedal edema is present.

Pulmonary Function Testing: He is unable to perform testing

Chest Radiograph: Scoliosis and elevation of both hemidiaphragms with no focal infiltrates or atelectasis.

Polysomnography was requested due to the history of nocturnal desaturation and difficulty breathing during sleep.

A representative 60-sec tracing of the patient's sleep is shown below (Figure 1).

Figure 1.

A tracing from NREM sleep while patient breathed room air. These epochs show continued respiratory effort with decreased oxygen saturation to 88%-94% and increased ETCO ₂ to 47 to 57 torr. The CO₂ tracings do not show a clear plateau therefore the end-tidal CO₂ value probably underestimates the true alveolar/arterial PCO₂. The depicted derivations include left and right electro-oculographic tracings; frontal, central, and occipital EEG tracings; chin EMG tracing; ECG; heart rate derived from the oximeter; snore, nasal pressure, nasal-oral airflow by a thermal device; chest and abdomen by piezoelectric belts; pulse oximetry; end-tidal CO₂; and an exhaled CO₂ tracing.

Q: What is the appropriate therapy for this young man's gas exchange abnormalities during sleep?

A: Nocturnal positive pressure ventilation, not oxygen therapy alone.

Duchenne muscular dystrophy (DMD) is an X-linked trait occurring in 1:3000 male births.¹ The disease results from a mutation of the dystrophin gene and leads to progressive decrease in muscle strength. This results in loss of ambulation and respiratory muscle weakness. Progressive deterioration in respiratory muscle strength results in hypoventilation. Death is due to respiratory failure in greater than 80% of cases.² The earliest signs of respiratory insufficiency are seen in sleep as shown by Suresh et al.³ They examined 34 patients with DMD ranging in age from 1 to 15 years. They found that almost two-thirds had sleep symptoms. On polysomnography, one-third had hypoventilation and one-third had obstructive sleep apnea. Others have reported an increased risk of sleep related breathing disorders including hypoventilation, central apnea, and obstructive apnea and hypopnea.¹

The ATS consensus statement on the respiratory care of patients with DMD recommends a regular review of the sleep history with a focus on symptoms of sleep related breathing disorders at every visit.¹ Patients should have an annual evaluation of their sleep when they become wheelchair bound or sooner as clinically indicated. Most develop problems with scoliosis when they become wheelchair bound.⁴ The preferred method for evaluation of sleep in DMD patients is polysomnography (PSG) with continuous CO₂ monitoring.¹ Other methods, though less optimal, include oximetry with CO₂ monitoring or capillary blood gas upon arising in the morning. Simple oximetry alone will provide a direct measure of nocturnal arterial oxygen saturation but only indirect information on the adequacy of nocturnal ventilation or the presence of obstructive apnea and hypopnea.

Nocturnal arterial PCO₂ can be estimated by the value of the end tidal CO₂ obtained by measuring exhaled CO₂. During a sleep study the exhaled CO₂ is typically measured by the sidestream method with a device that continually samples (suctions) air from a nasal cannula worn by the patient. With each breath, the CO₂ tracing rises and then exhibits a plateau (the end-tidal CO₂ value). The actual arterial PCO₂ exceeds the end-tidal CO₂ (except in rare circumstances). The difference between the arterial and end-tidal CO₂ values depends on the physiology of the patient's lung and the CO₂ monitoring device. Ideally, both the end-tidal value and a CO₂ versus time tracing should be recorded. If the CO₂ versus time tracing does not show a plateau (Fig. 1), the actual end-tidal CO₂ is higher than the measured value. Lack of a plateau can occur with rapid or shallow breaths. One can monitor exhaled CO₂ during nocturnal non-invasive ventilation using either a connection to the mask or via a small nasal cannula worn under the mask. In either case, the measured value may not reflect the true end-tidal CO₂. In this circumstance, measurement of transcutaneous CO₂ can be useful.

The treatment of choice for OSA and hypoventilation in DMD patients is positive pressure ventilation which can be delivered using nasal mask noninvasively (NIPPV) or with a mechanical ventilator through a tracheotomy. Benefits of treatment with NIPPV include improved sleep quality, improved quality of life, decreased daytime sleepiness, improved daytime gas exchange and a slower decline in the pulmonary function.^1,3 The level of therapeutic support needs should be determined in the sleep laboratory. Oxygen saturation and carbon dioxide status should be monitored in addition to patient tolerance of the mask and pressure. Pressure levels should be adjusted to maintain oxygen saturation above 94% with attention to carbon dioxide status as well. Carbon dioxide can be monitored using ETCO₂; however this can be difficult to interpret with nasal ventilation if a nasal ETCO₂ cannula is used. In this case, transcutaneous carbon dioxide monitoring can be useful. The carbon dioxide level that can be achieved will depend on the starting CO₂ and effectiveness of the positive pressure. Using bilevel pressure with an inspiratory to expiratory pressure difference of greater than 6 cm is often effective. A back up rate can also be helpful to stabilize the ventilatory pattern, provide respiratory muscle rest and improve ventilation. Blood gas determination during the study will help correlate arterial or venous CO₂ levels with ETCO₂ or TcPCO₂. Serial evaluation should be performed to evaluate changing needs with disease progression or other changes in clinical status.

Complications of positive pressure have included gastric distention and issues related to the CPAP mask. There is one case report of a pneumothorax in a patient with DMD and subpleral blebs.⁵ DMD patients treated with NIPPV may need an oximeter with an alarm at home to monitor their status at night as displacement of the positive pressure mask may result in severe hypoxemia and hypercarbia. Another consideration for treatment of hypoxemia due to hypoventilation is tracheotomy with volume ventilation. Treatment with oxygen alone should be avoided without ventilatory support as these patients may develop worsening of their hypoventilation and hypercarbia.

In the current patient after sleep onset, the SpO₂ fell to 88%-91% without events, with ETCO₂ 47-57 torr (Fig. 1). With respiratory events, ETCO₂ increased to a high of 69 torr with oxygen desaturation as low as 83%. He would not tolerate placement of a mask for CPAP and his father requested a trial of oxygen therapy. On oxygen at 0.5 liters/min his baseline saturation increased to 95%-98%, but ETCO₂ increased as high as 95 torr (Fig. 2). His oxygen flow rate was decreased using a pediatric flow meter that can deliver oxygen in increments of 0.1 liters/min to 0.2 liters/min. At this flow rate his saturation ranged from 88% to 91% with ETCO₂ 50 to 60 torr. ABG in the morning on 0.2 liters/min showed: pH 7.34, PaCO₂ 75.6, PaO₂ 77, HCO₃ 40.8. The patient underwent a program of mask desensitization at home and eventually had a PAP titration in the sleep laboratory.

Figure 2.

A tracing from NREM sleep while patient breathed supplemental oxygen at 0.5 liters/minute. He has continued respiratory effort during these epochs with no discrete respiratory events. Gas exchange parameters show increased arterial oxygen saturation to 95%–98% with a concomitant significant rise in the ETCO₂ to 83–95 torr. The depicted derivations include left and right electro-oculographic tracings; frontal, central, and occipital EEG tracings; chin EMG tracing; ECG; heart rate derived from the oximeter; snore, nasal pressure, nasal-oral airflow by a thermal device; chest and abdomen by piezoelectric belts; pulse oximetry; end-tidal CO₂; and a CO₂ tracing.

See Figure 2.

Clinical Pearls

1. Patients with Duchenne muscular dystrophy (DMD) are at risk for sleep related breathing disorders including obstructive sleep apnea and alveolar hypoventilation.

2. Nocturnal oximetry will detect arterial oxygen desaturation (hypoxemia) but will not reflect the degree of hypoventilation. Polysomnography with monitoring of end-tidal CO₂ or transcutaneous CO₂ is more informative.

3. The earliest signs of respiratory failure in DMD patients are generally detectable during sleep.

4. Yearly evaluation for sleep related breathing disorders should be performed in patients with DMD starting when they are confined to a wheelchair or sooner for clinical symptoms. The test of choice is PSG with CO₂ monitoring.

5. Sleep related hypoventilation and/or OSA should be treated with ventilatory assistance by NIPPV. Another option is tracheotomy and volume ventilation.

6. Oxygen alone should not be used to treat nocturnal hypoxemia as it is usually due to hypoventilation. Oxygen may worsen nocturnal hypoventilation and lead to significant hypercarbia.

Table 1.

PSG Findings

Total sleep time:	380 min
Sleep efficiency	71%
Sleep latency	70 min
Sleep stages as (%TST)
Stage W	32%
Stage N1 + N2	51%
Stage N3	13%
Stage R	4%
AHI (#/hour)	9.6
REM AHI	22.7
Events:	30 obstructive apneas, 31 hypopneas
Min SpO2	83%
Awake Baseline SpO2	97%-98%
Awake ETCO2	45-47 torr