Non-REM Sleep

Non-REM sleep usually begins immediately after an individual dozes off. This phase consists of four separate stages, each progressing into a deeper sleep. During stages N1 and N2 the ventilatory rate and tidal volume continually increase and decrease, and brief periods of apnea may be seen. The electroencephalogram (EEG) shows increased slow-wave activity (slow-wave sleep) and loss of alpha rhythm. Alpha rhythm is defined as containing EEG signals at 8 to 13 Hz. Cheyne-Stokes respiration also is commonly seen in older male adults during non-REM sleep, especially at high altitudes.

During stage N3, ventilation becomes slow and regular. Minute ventilation is commonly 1 to 2 L/min less than during the quiet wakeful state. Typically, the Paco₂ levels are higher (4 to 8 mm Hg), the Pao₂ levels are lower (3 to 10 mm Hg), and the pH is lower (0.03 to 0.05 units) during stage N3. Normally, non-REM sleep lasts for 60 to 90 minutes. Although an individual typically moves into and out of all four stages during non-REM sleep, most of the time is spent in stage N2. An individual may move into REM sleep at any time directly from any of the three non-REM sleep stages, although the lighter stages (N1 and N2) are commonly the levels of sleep just before REM sleep.

REM Sleep

During REM sleep a burst of fast alpha rhythms occurs in the electroencephalographic tracing. During this period the ventilatory rate becomes rapid and shallow. Sleep-related hypoventilation and apnea frequently are demonstrated during this period. Apneic periods occur in normal adults as often as five times per hour. These apneas may last 15 to 20 seconds without producing any discernible effects. In the normal infant, apneas are shorter (approximately 10 seconds in length), although even these may be cause for concern. A marked reduction in both the hypoxic ventilatory response and the hypercapnic ventilatory response occurs during REM sleep. The heart rate also becomes irregular, and the eyes move rapidly. Dreaming occurs mainly during REM sleep, and profound atonia (paralysis) of movement occurs. The skeletal muscle paralysis primarily affects the arms, legs, and intercostal and upper airway muscles. The activity of the diaphragm is maintained during REM sleep.

The muscle paralysis that occurs during REM sleep can affect an individual’s ventilation in two major ways. First, because the muscle tone of the intercostal muscles is low during this period, the negative intrapleural pressure generated by the diaphragm often causes a paradoxic motion of the rib cage. In other words, during inspiration the tissues between the ribs move inward, and during expiration the tissues bulge outward. This paradoxic motion of the rib cage causes the functional residual capacity to decrease. During the wakeful state the intercostal muscle tone tends to stiffen the tissue between the ribs.

Second, the loss of muscle tone in the upper airway involves muscles that normally contract during each inspiration and hold the upper airway open. These muscles include the posterior muscles of the pharynx, the genioglossus (which normally causes the tongue to protrude), and the posterior cricoarytenoid (the major abductor of the vocal cords). The loss of muscle tone in the upper airway may result in airway obstruction. The negative pharyngeal pressure produced when the diaphragm contracts during inspiration tends to bring the vocal cords together, collapse the pharyngeal wall, and suck the tongue back into the oropharyngeal cavity.

REM sleep periods last 5 to 40 minutes and recur approximately every 60 to 90 minutes. The REM sleep periods lengthen and become more frequent toward the end of a night’s sleep. REM sleep constitutes about 20% to 25% of the total sleep time. Most studies show that it is more difficult to awaken a subject during REM sleep. Table 30-1 provides an overview of the electroencephalographic findings in the various stages of sleep.

Obstructive Sleep Apnea

It is estimated that more than 12 million people in the United States have OSA.

OSA is caused by an anatomic obstruction of the upper airway in the presence of continued ventilatory effort (see Figure 30-1). During periods of obstruction, patients commonly appear quiet and still, as though they are holding their breath, followed by increasingly desperate efforts to inhale. Often the apneic episode ends only after an intense struggle. A snorting sound called “fricative breathing” may be heard at the end of the apneic periods. In severe cases, the patient may suddenly awaken, sit upright in bed, and gasp for air. These events are called confusional arousals. Patients with OSA usually demonstrate perfectly normal and regular breathing patterns during the wakeful period.

In fact, a large number of patients with OSA demonstrate what is commonly called the Pickwickian syndrome (named after a character in Charles Dickens’s The Posthumous Papers of the Pickwick Club, published in 1837). Dickens’s description of Joe, “the fat boy” who snored and had excessive daytime sleepiness, included many of the classic features of what is now recognized as the sleep apnea syndrome. Box 30-1 provides common signs and symptoms associated with OSA. However, many patients with sleep apnea are not obese, and therefore clinical suspicion should not be limited to this group. Table 30-2 provides the more common risk factors associated with OSA.

Cardiopulmonary and Other Conditions Associated with Obstructive Sleep Apnea

The morbidity associated with OSA is increased by an increased incidence of the following cardiovascular conditions: nocturnal angina and heart attacks, atrial fibrillation and other cardiac arrhythmias, hypertension, and congestive heart failure. The metabolic syndrome associated with OSA is composed of hypertension, hyperlipidemia, and centripetal (truncal) obesity. The neuropsychiatric complications of sleep apnea include morning headaches, cerebrovascular accidents, nocturnal seizures, depression, and short-term memory loss.

Central Sleep Apnea

CSA occurs when the respiratory centers of the medulla fail to send signals to the respiratory muscles. It is characterized by cessation of airflow at the nose and mouth along with cessation of inspiratory efforts (absence of diaphragmatic excursions), as opposed to OSA, which is characterized by the presence of heightened inspiratory efforts during apneic periods.

CSA is associated with cardiovascular, metabolic, and central nervous system disorders. A few brief central apneas normally occur with the onset of sleep or the onset of REM sleep. CSA, however, is diagnosed when the frequency of the apnea or hypopnea episodes is excessive (more than 30 in a 6-hour period). Box 30-2 provides a listing of clinical disorders associated with CSA.

Mixed Sleep Apnea

Mixed sleep apnea is a combination of obstructive and CSAs. It usually begins as central apnea followed by the onset of ventilatory effort without airflow (obstructive apnea). Clinically, patients with predominantly mixed apnea are classified (and treated) as having OSA.

Figure 30-2 illustrates the patterns of airflow, respiratory effort (reflected through the esophageal pressure), and arterial oxygen saturation in central, obstructive, and mixed apneas.

Continuous Positive Airway Pressure Compliance

Despite the fact that CPAP efficiency is determined in the CPAP titration polysomnogram, its effectiveness over the long term (i.e., in the patient’s home) is not without problems. The American Association of Sleep Medicine’s suggestion for optimal CPAP compliance is only 5 hours per night. The patient’s use of the device is both critical and problematic. There certainly is a “learning” curve for the patient to get used to the CPAP device, but once this critical acclimatization phase is over, the respiratory care practitioner must verify that the device is, indeed, being used as prescribed. Today, many CPAP devices have downloadable compliance features that provide periodic updates of patient compliance. Objective documentation of the patient’s CPAP compliance is increasingly being required by third-party insurance agencies if payment for the CPAP device is to be made.

Management of Central Sleep Apnea

VPAP Adapt SV and Adaptive Servo-Ventilation*

With the recent development of the adaptive servo-ventilation algorithm and variable positive airway pressure (VPAP), the ResMed VPAP Adapt SV provides ventilatory support to treat all forms of CSA, mixed apnea, and periodic breathing (Cheyne-Stokes respirations). The VPAP Adapt SV responds to apnea by increasing pressure support. To determine the degree of pressure support needed to hold the patient’s upper airway open, the VPAP Adapt SV algorithm continuously calculates a target ventilation. The algorithm uses the following three factors to achieve synchronization between the needed pressure support and the patient’s breathing pattern:

The VPAP Adapt SV ensures that ventilatory support is synchronized with the patient’s ventilatory efforts by means of numbers 1 and 2 in this list. When the patient experiences an episode of central apnea or hypopnea, the pressure support initially works to reflect the patient’s recent ventilatory pattern. However, if the apnea or hypopnea persists, the VPAP Adapt SV increasingly uses the backup respiratory rate (number 3 in the list). Figure 30-5 illustrates this.

The VPAP Adapt SV has been widely accepted as a first-line treatment modality for CSA patients. Most patients with CSA do not tolerate conventional bilevel positive airway pressure (BiPAP) ventilatory support. This is because the pressure must be adjusted to a constant high pressure to adequately support the patient during periods of apnea and hypopnea. As a result, the patient is overventilated during periods of normal breathing or hyperpnea. This causes arousals and discomfort. It can even cause more CSA events. The VPAP Adapt SV (1) ventilates the patient appropriately during apnea and hypopnea periods, and (2) decreases ventilatory support during periods of hyperventilation or normal breathing. These features minimize the discomfort and arousals commonly associated with BiPAP ventilatory support.

Therapeutic Strategies Used to Treat Sleep Apnea

Over the past few decades, it has become apparent that many pathologic conditions are associated with sleep apnea, including hypoxemia, fragmented sleep, cardiac arrhythmias, and neurologic and psychiatric disorders. In general, the prognosis is more favorable for obstructive and mixed apneas than for CSA. Table 30-3 provides an overview of the various therapeutic strategies used for sleep apnea. Table 30-4 summarizes the major therapeutic modalities described in this chapter for obstructive and central apnea and their effectiveness.

Surgery Some nonobese patients with obstructive sleep apnea benefit from surgical correction or bypass of the anatomic defect or obstruction that is responsible for the apneic episodes.  Uvulopalatopharyngoplasty Uvulopalatopharyngoplasty (UPPP) is the surgical procedure most commonly used to treat snoring and sleep apnea. During this surgery, the soft palate tissue is shortened by removing the posterior third, including the uvula. The pillars of the palatoglossal arch and the palatopharyngeal arch are tied together, and the tonsils are removed if they are still present. As much excess lateral posterior wall tissue is removed as possible. The success rate of this type of surgery is 30% to 50%.  Laser-assisted uvulopalatoplasty Laser-assisted uvulopalatoplasty (LAUP) is performed to eliminate snoring. This surgical procedure entails using a laser to remove tissue from the back of the throat.  Nasal surgery Nasal surgery may be performed to remove nasal polyps or straighten a deviated nasal septum.  Tracheostomy Tracheal intubation with or without tracheostomy is often the treatment of choice in emergency situations and in patients who do not respond satisfactorily to drug therapy or other treatment interventions.  Mandibular advancement surgery Approximately 6% of patients with obstructive sleep apnea have a mandibular malformation. For example, patients who have obstructive sleep apnea because of retrognathia or mandibular micrognathia may benefit from surgical mandibular advancement. The surgery is not often performed and carries considerable risks. Mechanical ventilation    Continuous mechanical ventilation Intubation and continuous mechanical ventilation may be used for short-term therapy when acute ventilatory failure develops in central or obstructive sleep apnea.  Negative-pressure ventilation In patients with central sleep apnea, negative-pressure ventilation without an endotracheal tube may be useful. For example, a negative-pressure cuirass, which is applied to the patient’s chest and upper portion of the abdomen, may effectively control ventilation throughout the night. A negative-pressure cuirass is convenient for home use. It is contraindicated in obstructive sleep apnea. Phrenic nerve pacemaker An external phrenic nerve pacemaker may be useful in patients with central sleep apnea resulting from the absence of a signal from the central nervous system to the diaphragm by way of the phrenic nerve. This procedure has not received wide application. Medical devices Oral appliances that optimally position the tongue and jaw are the most successful alternatives to surgery and continuous positive airway pressure (CPAP) by mask or “nasal pillows.” The devices are best used in patients with mild- to-moderate obstructive sleep apnea. Patients who have mandibular overbites, who clench or grind their teeth (bruxism), and who have temporomandibular joint (TMJ) dysfunction may benefit from these devices as well. Neck collar A small number of patients have used a collar (similar to those used to stabilize cervical fractures) to increase the diameter of the airway and reduce the apnea. The therapeutic success of this procedure is questionable. Other therapeutic approaches Patients should be advised to avoid alcohol and drugs that depress the central nervous system. Alcohol and sedatives have been shown to increase the severity and frequency of sleep apnea. All obese patients with sleep apnea should be encouraged to lose weight.

Physical Examination

On observation in the Emergency Room, the man appeared to be in severe respiratory distress. He was 5 feet 11 inches tall. He was obese, weighing more than 160 kg (355 lb) and was perspiring profusely. His Basal Metabolic Index (BMI) (BMI = weight [kg]/height [m²]) was 50. His skin appeared cyanotic, and his neck veins were distended. He had +4 edema of his feet and legs, extending to midcalf. His blood pressure was 164/100, heart rate was 78 bpm, respiratory rate was 22/min, and temperature was normal. Although the man was in obvious discomfort, he stated that he was breathing “OK.” His wife quickly piped up, “There’s that damn Marine coming out again!”

The man’s breath sounds were normal but diminished. The diminished breath sounds were believed to result primarily from the patient’s obesity. Palpation of the chest was unremarkable, and percussion was unreliable because of the obesity. A chest x-ray film showed cardiomegaly; the lungs appeared unremarkable. To treat the presumed cor pulmonale, the treating physician immediately started the patient on diuretics. His awake arterial blood gas values (ABGs) on room air were as follows: pH 7.54, Paco₂ 58, 48, and Pao₂ 52. His oxygen saturation measured by pulse oximetry (Spo₂) was 86%.

Because of the patient’s history and present clinical manifestations, the respiratory therapist on duty suspected that the man had obstructive sleep apnea. The therapist suggested this possibility to the emergency room physician, who requested a polysomnographic study. The physician asked the respiratory therapist to document her assessment. The following SOAP was charted.

Respiratory Assessment and Plan

Over the Next 72 Hours

A clinical diagnosis of severe obstructive sleep apnea was quickly established. Along with the patient’s classic history of obstructive sleep apnea, the polysomnogram documented more than 325 periods of obstructive apnea or hypopnea in the study night. The continuous positive airway pressure (CPAP) titration study indicated that 12 cm H₂O CPAP was required to effectively treat the apneic syndrome. In addition to the patient’s short, muscular neck and extreme obesity, an oropharyngeal examination revealed a small mouth and large tongue for his body size. The free margin of the soft palate hung low in the oropharynx, nearly obliterating the view behind it. The uvula was widened (4+) and elongated; the tonsillar pillars were widened (3+). Air entry through the nares was reduced bilaterally. The patient’s hematocrit was 51%, and hemoglobin level was 17 g/dL.

A complete pulmonary function test (PFT) showed that the man had a severe restrictive disorder. In addition, a saw-toothed pattern was seen in the maximal inspiratory and expiratory flow-volume loops. A chest x-ray film obtained on the patient’s second day of hospitalization showed reduction in heart size, and the lungs were clear. A brisk diuresis was in process. The patient stated that he was breathing much better.

On inspection the patient no longer appeared short of breath. Although he still appeared flushed, he did not look as cyanotic as he had on admission. His neck veins were no longer distended, and the peripheral edema of his legs and feet had improved. His breath sounds were clear but diminished. His room air ABGs were as follows: pH 7.38, Paco₂ 82, 48, and Pao₂ 66. His Spo₂ was 91%. The physician again called for a respiratory care evaluation. On the basis of these clinical data, the following SOAP was recorded.

Respiratory Assessment and Plan

Discussion

Although the diagnosis of obstructive sleep apnea is made most frequently in the outpatient setting, experience has shown that it often may be diagnosed in the course of an acute hospitalization. In the case under discussion, although the patient was first seen in the emergency room, it soon became clear that he was ill enough to be admitted, and his workup proceeded from there.

In the first assessment the therapist needed to perform a careful examination of the patient’s nasopharynx and oropharynx, as well as his chest. The typical upper airway anatomy of obstructive sleep apnea was visible. While the patient’s polysomnogram and CPAP titration study were in progress, the therapist appropriately ensured the patient’s oxygenation (Fio₂ = 0.28 venturi oxygen mask) while attempting to prevent alveolar hypoventilation. In as classic a case as this, a split night study (half standard polysomnography, half CPAP titration) may be in order. Use of an autotitrating CPAP may be helpful in this setting. The autotitrating CPAP device senses the patient’s airway resistance and up-regulates or down-regulates the CPAP pressure to optimize airflow during the apneic episode.

The patient’s neck vein distention, polycythemia, cardiomegaly, and peripheral edema all suggested cor pulmonale. This condition would improve once the patient’s overall hypoventilation and oxygenation were treated. Many physicians would go ahead and give the patient a bicarbonate-losing diuretic, watching for metabolic acidosis while this step were being done. The therapist (in the first assessment) correctly analyzed the situation as being potentially hazardous, and this assessment included impending ventilatory failure, which was a real possibility.

After the second assessment the diagnosis was made. Pulmonary function tests showed upper airway obstruction and a restrictive disorder. Based on the pH value of 7.38, the patient’s Paco₂ appeared to be at its normal baseline level. It is not uncommon for patients with severe obstructive sleep apnea to have chronic ventilatory failure (compensated respiratory acidosis). The therapist elected to have the patient refrain from sleeping on his back and to sleep in the head-up position instead. In addition, the physician would likely ask for a nutrition consultation at that time because the patient needed to begin a drastic weight-loss program.

At the end of the case the patient’s condition still was not markedly improved, and he awaited the benefits of CPAP therapy. Indeed, the CPAP therapy was eventually helpful. The patient had a 9-kg (20-lb) diuresis during the first week of its use, and good oxygenation was achieved with 10 cm H₂O CPAP pressure.

A diagnosis of obstructive sleep apnea often can complicate other primary respiratory disorders, such as chronic obstructive pulmonary disease (COPD), pneumonia, atelectasis, or chest wall deformity. In these settings, the care is more complicated and, if anything, should be even more data-driven, with careful examination of all subjective and objective data.

Patients with obstructive sleep apnea have a significant risk of cardiovascular and central nervous system morbidity and mortality (myocardial infarctions, arrhythmias, hypertension, and cerebrovascular accidents). Psychiatric effects such as depression, sleep-related job malperformance, and daytime motor vehicle accidents also are seen. Current evidence suggests that such patients need not experience these effects if the sleep disorder–related breathing problem is treated effectively. Compliance with CPAP therapy is important but difficult to achieve. Close clinical monitoring is important if good therapeutic outcomes are to be achieved consistently.