CPAP AND BEYOND: Medical Treatment Options for Sleep Apnea

Nirupam Singh, MD

A few years ago, while still in fellowship training for pulmonary and critical care, I went to my sleep-medicine attending complaining of excessive daytime sleepiness. Despite being in great health, with a normal BMI, my need for sleep was a running joke among all who knew me. The attending told me, “You are a fellow, what do you expect? You will get better once this fellowship ends.“

My fog-like state extended for a few more years, until I got fed up and insisted on a sleep study. I was diagnosed with mild sleep apnea and was prescribed a continuous positive airway pressure machine. After the first night of CPAP use, I bounced off the walls with energy. I kept thinking, “Oh my God! This is how the rest of the world sleeps.” That transformative experience led me to a mid-career sabbatical and a sleep fellowship.

Sleep apnea is a uniquely human condition. Other than brachi-ocephalic dogs, such as English bulldogs, no other mammal has sleep apnea. Sleep apnea is the price we pay for speech.¹ As ancient hominids evolved to speak, their larynx moved down and their epiglottis no longer covered their uvula. From an evolutionary standpoint, the benefits of speech were immediate—but as hominids evolved into humans, the problems associated with sleep apnea began to appear in late middle age, far beyond the lifespan of our ancient ancestors.

Depending on how sleep apnea is defined, it is estimated to have a prevalence rate of 20–30% in males and 10–15% in females. While sleep apnea does occur in thin people, obesity is a major risk factor. In one Brazilian cohort, 63% of obese men were found to have sleep apnea.² Other predisposing factors include increasing age, race (Asian, African American), cranial pharyngeal abnormalities (tonsillar hypertrophy, abnormal maxillary size, micrognathia) and medical conditions (congestive heart failure, chronic lung disease, stroke, hypothyroidism, polycystic ovarian syndrome, acromegaly).

The cardiovascular consequences of untreated sleep apnea (hypertension, risk of stroke, pulmonary hypertension, coronary artery disease) have been known for a while. Now there is convincing data linking sleep apnea to diabetes and cancer. The repeated oxidative stress, catecholamine release and interrupted sleep all predispose to diabetes. Hypoxia-induced angiogenesis is the proposed mechanism for cancer. The most severe cohort of obstructive sleep apnea associated with hypoxia had almost five times the adjusted relative risk for cancer mortality.3 In addition to the neurocognitive and quality-of-life impacts, motor vehicle accidents are the other major contributor to morbidity and mortality among patients with sleep apnea, many of whom fall asleep at the wheel.

Diagnosis of sleep apnea is quickly migrating from the inpatient lab to the outpatient clinic. In keeping with this move, the cost of sleep apnea testing has dropped substantially, from $1,200–$1,500 to about $200. Even with rapidly improving technology, outpatient sleep testing has a low negative predictive value and a high positive predictive value. In other words, a negative outpatient sleep test still needs to be followed up with an inpatient test if the pretest probability of the disease was high. Overnight oximetry is neither sensitive nor specific and has no role in the diagnosis of OSA.

With the diagnostic test having become so cheap and easily accessible, the threshold of testing should be dropped. Patients complaining of sleepiness, nonrestorative sleep, fatigue, chronic insomnia, gasping, choking, snoring, hypertension, mood disorder, stroke, CHF, diabetes, atrial fibrillation and cognitive dysfunction should all be considered for testing. A significant proportion of ADD and ADHD patients actually have underlying OSA and are misdiagnosed.

CPAP remains the mainstay of treatment for obstructive sleep apnea (OSA) but is a tough therapy to get used to. Long-term compliance rates are in the 50–70% range. Alternative therapies for apnea tend to work best in the mild to moderate non-obese OSA patient, as they typically decrease the apnea hypoxia index by a factor of 10–20. These therapies tend to be effective for patients with an AHI of less than 30, but they are much less effective for obese patients who start with an AHI of 100 and are hypoxic.

The effectiveness of CPAP can be correlated with patient demographics:
Mild asymptomatic patients without comorbidities. No long-term morbidity and mortality data currently exist. Behavioral interventions can be effective for this group.
Moderate asymptomatic men. Some data suggest increased risk of stroke.
Moderate asymptomatic women. Minimal data suggest adverse outcomes, but Medicare and specialty societies still recommend treatment.
Mild to moderate symptomatic patients. This group tends to have worse outcomes and should be treated. Alternatives to CPAP therapy work well in this group.
Thin patients with OSA. Hypothyroidism should be ruled out for this group.
Patients with severe OSA and/or obesity. These patients tend to respond best to CPAP.

The only effective surgery for curing OSA in the obese severe cohort is maxillary-mandibular advancement. (Surgical options for sleep apnea are covered elsewhere in this issue.)

Behavioral interventions, including positional therapy and limiting alcohol, are effective in a certain subset of patients. Alcohol can turn a snorer into an OSA patient and transform mild to moderate sleep apnea to severe with desaturation. Decreasing the amount of alcohol consumed can be very effective. If positional therapy or behavioral interventions alone are chosen, repeat sleep testing for efficacy should be done with these measures in place. Weight loss has huge implications: a 10–20% weight loss can sometimes lead to cure of OSA. Even if the sleep apnea is not cured by weight loss, alternative therapies become available again because the degree of sleep apnea usually improves.

CPAP has mostly been supplanted by auto-adjusting machines, or APAP. (I will use the terms interchangeably for the remainder of this article.) An in-lab titration is usually not required for garden-variety sleep apnea because the current machines have become quite sophisticated in picking up events and increasing pressure as needed.

CPAP is the mainstay of therapy for sleep apnea and is effective for a vast majority of patients. However, having the mask strapped to the face while the machine pushes in air is not the easiest thing to get used to. The technology has come a long way in recent years, with much quieter and smaller machines. Newer masks have a smaller footprint with significantly better seals and fitting. Hundreds of different masks are available, and proper fitting of the interface device can substantially improve compliance.

From personal experience, use of CPAP is difficult with nasal congestion. Simple solutions such as a saline rinse and nasal steroids can have an impact. Desensitization to the mask by gradually increasing the time on the machine and doing activities such as watching TV with the mask on are some of the other techniques routinely used for claustrophobic patients.

From a long-term cost perspective, CPAP is one of the cheaper therapies. A CPAP machine with mask and tubing costs about $500–$800. The mask and tubing usually need to be upgraded at 3–6 month intervals.

Patients with central sleep apnea (most common causes being opiates and congestive heart failure) occasionally worsen with CPAP alone. In such cases an adaptive servo ventilation (ASV) machine is indicated.

The Pickwickian patient with obesity hypoventilation syndrome tends to have nocturnal hypercarbia and hypoxia. These patients have the worst outcomes and very high mortality.⁴ Options for therapy include CPAP with oxygen, bilevel ventilation and average volume assured pressure support (AVAPS), which is essentially a nocturnal noninvasive ventilation. Bilevel and AVAPS are the preferred modes for correcting nocturnal hypoventilation. All patients with a BMI greater than 40 should be screened for obesity hypoventilation, especially if their bicarb on Chem-7 is greater than 28.

In the pediatric population, obesity and adenotonsillar hypertrophy are the major risk factors. Children tend to present mostly with behavioral issues, ADHD and poor school performance. Tonsillectomy is the treatment of choice if hypertrophy is present. Surprisingly, CPAP is quite well tolerated in the pediatric population. Rapid maxillary expansion can be effective in select patients. In milder pediatric sleep apnea, nasal steroids are also effective.

Alternatives to CPAP include the following therapies.

Mandibular advancement device. A custom-crafted treatment device designed to advance the lower jaw and maintain an open airway during sleep. There are multiple manufacturers of these devices, but comparative efficacy data are lacking. Exclusion criteria for these devices include temporomandibular joint disorder, periodontal disease, or incomplete dentition (missing many teeth). Dental devices may cause TMJ disorder and misalignment of teeth and may be uncomfortable for some patients. Costs can vary widely from approximately $1,000 to $3,000. Given the issues with TMJ and jaw pain, I recommend having the device fabricated by a dentist experienced with the device or one who has been certified by the American Academy of Dental Sleep Medicine (aadsm.org).

Provent. A disposable nasal device that uses positive pressure generated with exhaled air to hold the airway open during sleep. Provent, a differential valve, is secured to the nostrils with hypoallergenic adhesive. It tends to be most effective in patients with mild to moderate sleep apnea, and it costs approximately $2 per night. Patients must have unobstructed sinus passages. Unfortunately, most patients who cannot tolerate CPAP have had difficulty using Provent as well.

Winx. A small bedside device that uses suction to pull the soft palate and tongue forward and open the airway during sleep. Even though the device is FDA-approved, outcome studies are lacking. Patients can’t have obstructed sinuses. Winx treatment may cause dental, oral and TMJ discomfort. It costs approximately $1,000, but the company does offer a two-week trial. It is not covered by most insurances.

Circular breathing exercises. Limited studies have shown that practicing circular breathing (exhaling through the mouth while simultaneously inhaling through the nose) or regularly playing the didgeridoo may help strengthen supporting tissues in the throat and possibly reduce snoring or sleep apnea severity. Improvement may occur with several months of practice.

Hypoglossal nerve stimulation. Highly selective non-obese patients (BMI less than 32) with mild-to-moderate disease did have significant improvement in sleep apnea with hypoglossal nerve stimulation via an implantable neurostimulator device.5 The device is not yet available clinically. In the largest trial to date, the most significant adverse events were discomfort related to the stimulation, tongue soreness, and transient weakness after surgery. Since I am a sleep patient and have seen multiple complications of infected pacers, the only reason anyone is putting a pacer in my body is for a complete heart block.

I started my sleep apnea journey with CPAP. While I was a lot more awake in the morning, it was painful to have a mask on my face every night. It would rain in the mask if the humidity was too high, or I would wake up with dry cotton mouth if the humidity was not high enough. I eventually migrated to the dental device, which worked well except for a persistent clicking in the jaw.

Seeing the TMJ writing on the wall, back to the CPAP I went. In spite of knowing what I know and being an experienced CPAP user, it took me 2–3 weeks to get used to the machine again. The newer machine does come with heated tubing, eliminating the rain-in-the-face issue. It is also much quieter, and the newer mask fits better. It is my new best friend.

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Dr. Singh is a pulmono-logist and sleep-medicine physician at Kaiser Permanente San Rafael.

Email: nirupam.singh@kp.org

References
1.  Davidson TM, “The great leap forward: the anatomic basis for the acquisition of speech and OSA,” Sleep Med, 4:185-194 (2003).
2.  Tufik S, et al, “Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study,” Sleep Med, 11:441-446 (2010).
3.  Nieto FJ, et al, “Sleep-disordered breathing and cancer mortality,” Am J Resp Crit Care Med, 15:190-194 (2012).
4.  Marik PE, “Malignant obesity hypoventilation syndrome,” Obes Rev, 13:902-909 (2012).
5.  Strollo PJ, et al, “Upper-airway stimulation for obstructive sleep apnea,” NEJM, 370:139-149 (2014).