US Pharm. 2015;40(1):30-33.
ABSTRACT: Obstructive sleep apnea (OSA) is a common chronic breathing disorder associated with reduced quality of life. Given the rising prevalence of obesity, the leading risk factor for this condition, OSA is an important public health concern. Noninvasive continuous positive airway pressure (CPAP) is first-line therapy for OSA. Despite the benefits of consistent CPAP use, adherence remains a challenge. CPAP machines and accessories are sold in community pharmacies and home healthcare settings. It is increasingly important that pharmacists understand the principles of OSA and CPAP therapy to optimize pharmacotherapy with this disorder and reinforce CPAP compliance.
Obstructive sleep apnea (OSA) is a chronic disorder characterized by frequent breathing pauses during sleep. It is a common condition that is associated with significant morbidity and mortality.1,2 The primary risk factor for OSA is obesity, and the incidence of OSA is predicted to rise as the obese population increases.3 A summary of risk factors is provided in TABLE 1.3,4 The gold standard treatment for OSA is continuous positive airway pressure (CPAP) therapy.5 Unfortunately, 30% of patients refuse CPAP therapy from the outset, and 25% discontinue therapy within the first year.6 Here, we summarize OSA, review CPAP therapy, and present pharmacist-implemented strategies to improve outcomes.
Obstructive Sleep Apnea
The clinical definition of OSA requires sleep-related symptoms (daytime sleepiness, loud snoring, witnessed breathing interruptions, or awakenings due to gasping or choking) with a formal sleep study documenting at least five obstructive respiratory events per hour of sleep. Respiratory events include apneas and hypopneas, or arousals related to respiratory efforts.7 Apnea refers to the complete cessation of breathing and may result from total airway obstruction. Hypopnea is the reduction of breathing defined as at least a 50% reduction in ventilation due to partial airway obstruction.8 OSA is graded according to the apnea-hypopnea index (AHI). The AHI value is calculated by dividing the total number of disordered breathing episodes by the number of hours slept, effectively reducing the sleep study to the number of sleep-related breathing events per hour.
The most serious immediate complication of OSA is motor vehicle accidents due to excessive daytime sleepiness. Patients with OSA can have impaired driving ability akin to that of a person with a blood alcohol level above the legal limit.9 Other possible consequences of OSA include cancer, hypertension, cardiovascular and cerebrovascular diseases, reduced cognitive function, and lipid dysregulation.2,4 Patients with moderate-to-severe OSA are three times more likely to die from cancer and 2.5 times likelier to develop cancer.10 OSA is associated with self-reported heart failure and stroke, systolic hypertension, and increased risk of heart failure and ischemic stroke in men.11-14 Patients with OSA are 2.6 times more likely to experience sudden cardiac death.15
The underlying mechanisms whereby OSA contributes to related comorbidities are not fully understood. Obesity narrows the airway. Rapid eye movement sleep relaxes pharyngeal muscles, also leading to airway obstruction. As a result, cessation of airflow, hypoxic events, increased respiratory efforts, and repeated arousals occur. These cyclic changes are associated with the release of various inflammatory mediators. Overall, explanations for the effect of OSA on cancer development are limited by study design. Murine models suggest that intermittent hypoxia can enhance tumor growth and progression.16
OSA has been shown to be associated with atherosclerosis, myocardial infarction, and stroke. The relationship between OSA and coronary atherosclerosis may involve oxidative stress, endothelial dysfunction, and inflammatory processes.17 Patients with OSA but without cardiovascular disease have been shown to have increased microcirculatory oxidant production independent of age, weight, or sex.18 Oxidative stress from the repeated hypoxia and reoxygenation characteristic of OSA can lead to vascular damage and enhanced lipid peroxidation.17,19 In addition, local activation of macrophages and T lymphocytes contributes to inflammation and further tissue injury.17
Continuous Positive Airway Pressure
Invasive ventilator support requires an artificial airway and is limited to inpatient use. In the outpatient setting, OSA is commonly treated using noninvasive ventilation via CPAP therapy. Small, bedside CPAP machines (FIGURE 1) are frequently available from community pharmacies and home healthcare companies. Patients will have frequent contact with pharmacists in these settings for medication refills as well as CPAP masks and accessories.
CPAP ventilation provides continuous positive pressure to the airway, acting as a pneumatic splint and maintaining airway patency during sleep. Pressure is delivered using a CPAP machine consisting of three parts: a motor that generates the required pressure, a tube that relays the pressurized air, and a mask with straps that creates the seal between the machine and the patient.20 Based on polysomnography, a patient-specific CPAP pressure is determined and the CPAP mask is custom-fitted. CPAP therapy can be attached to supplemental oxygen to provide up to 6 L/min of oxygen and may be adjusted by a physician.
CPAP therapy has been reported to have positive associations with neurobehavioral and cardiovascular outcomes. Randomized placebo-controlled trials have shown that optimal CPAP therapy helps relieve sleepiness and improves vigilance and productivity.21 A meta-analysis evaluating automobile crashes among OSA patients indicated that CPAP therapy alleviated daytime sleepiness after one night of therapy and improved simulated driving performance within 2 to 7 days of treatment.22
CPAP may reduce cardiovascular risk and cardiovascular outcomes (fatal and nonfatal), such as stroke mortality, type 2 diabetes mellitus, hypertension, and cardiovascular mortality in the elderly (TABLE 2).23-38 A greater reduction in mean blood pressure and a stronger dose-response relationship between CPAP use and severity of OSA have been demonstrated.23 The long-term effect of CPAP therapy in nonsleepy OSA patients was shown to be a small decrease in blood pressure.24 This finding contributes to the growing evidence that CPAP therapy improves blood pressure. Among patients with OSA and resistant hypertension, improvements in 24-hour blood pressure and nighttime blood pressure pattern were observed with 12 weeks of CPAP treatment.25 Similarly, a reduced daytime blood pressure was seen in patients with resistant hypertension treated with CPAP and antihypertensive medications compared to blood pressure in patients treated with medications alone.26 Prehypertensive patients may also benefit from CPAP therapy by reductions in both daytime and nighttime blood pressure.27
In patients with congestive heart failure (CHF), CPAP therapy may improve ejection fraction, nocturnal oxygenation, 6-minute walk distance, New York Heart Association functional class, blood pressure, and sleepiness, but it has not shown a survival benefit.28-31 Patients with CHF treated with 2 weeks of daily CPAP experienced better pulmonary function and greater tolerance for physical activities, suggesting that CPAP may be an effective adjunct therapy in CHF.32 Similarly, patients with asthma crises have clinically improved pulmonary function with CPAP therapy, and patients with stable asthma have reduced airway reactivity after 7 days of CPAP.33,34 Patients with chronic obstructive pulmonary disease (COPD) who are adherent to their CPAP regimen are reported to have increased inspiratory capacity.35
The benefits of CPAP on blood glucose control have been less clearly delineated. Studies have shown mixed results for improved nighttime blood glucose control in patients with type 2 diabetes mellitus and OSA.36,37 Recently, CPAP therapy combined with weight-loss intervention for 24 weeks produced greater reductions in insulin resistance and serum triglyceride levels than CPAP treatment alone.38
Adherence, the primary obstacle associated with CPAP therapy, involves patient-specific characteristics, healthcare conditions, and social factors. Challenges to CPAP therapy include mask-related problems (air leakage, skin abrasion, mask discomfort), treatment-related side effects (nasal congestion, dry throat, frequent awakenings), patient attitudes, knowledge, and perceived benefits and risks.5 Poor adherence has been observed in patients who are black, have lower socioeconomic status, or are claustrophobic.39 Smoking, nocturia, and benign prostatic hyperplasia may also complicate adherence to CPAP.40
Role of the Pharmacist
As front-line healthcare professionals, pharmacists can increase OSA awareness and improve adherence with CPAP use.41 Pharmacologic therapy is typically not a primary treatment recommendation for OSA. However, pharmacists are well positioned to counsel on adjunctive medications, such as modafinil. Modafinil is FDA-approved for residual daytime sleepiness despite optimal use of CPAP.42 Drug utilization review focusing on appropriately avoiding benzodiazepines, opioids, and opioid combination products in patients with OSA (these products can worsen carbon dioxide retention and lead to respiratory distress or even require ventilation) who use CPAP can be integrated into a pharmacist’s daily practice. In addition, pharmacists can also promote wellness through education about smoking cessation, exercise maintenance, proper diet and nutrition, effective sleep habits, and compliance with medications and CPAP therapy.
Optimizing CPAP therapy outcomes may be improved using a patient-centered approach. Patients new to CPAP have longer-lasting success if they achieve adherence early. Patients who communicate to healthcare providers any difficulty with autotitrating CPAP use are more likely to remain adherent than those patients who do not report problems.43 Thus, pharmacists who are aware that a patient is initiating CPAP therapy can inquire about the patient’s experiences. For patients who report discomfort with the CPAP device, the pharmacist can help identify the source of discomfort, discuss the importance of a custom fit, and refer the patient to a respiratory therapist or pulmonary medicine specialist.
Patients’ perceived benefit and other psychological variables have stronger associations with CPAP adherence than disease-related factors.44 This suggests that support is integral to successful treatment. Explanations describing the behavioral and cardiovascular benefits of CPAP therapy can help patients understand the purpose of and gains from CPAP treatment.
For patients who report nasal irritation or rhinitis, a common side effect of CPAP therapy, pharmacists can suggest a saline spray or nasal rinses. This strategy is low-risk, relatively inexpensive, safe, and efficacious. Sedative hypnotics (prescribed or OTC) are not generally recommended. In addition, pharmacists can also identify factors associated with poor CPAP adherence.40 For patients seeking smoking cessation support, the pharmacist can recommend follow-up with a physician and educate them about nonprescription agents, such as the nicotine patch, gum, and lozenge. Pharmacists can also discuss prescription medications for smoking cessation.
OSA is a significant medical and public health problem that is increasingly being recognized. Although CPAP treatment is first-line therapy for OSA, consistent adherence remains a challenge. Strategies to optimize CPAP outcomes involve recognizing patients who use home CPAP, maintaining an open dialogue with them about CPAP therapy, especially during the initiation phase, and helping with side-effect management. Given their access to patients, pharmacists are a well-positioned but underutilized resource to help patients achieve success with CPAP therapy.
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