Case Study: Mrs. S is a 63-year-old retired teacher who returns to the office for breast cancer follow-up. She was diagnosed with intraductal carcinoma, and her treatment included a modified radial mastectomy followed by four cycles of doxorubicin and cyclophosphamide. Her tumor was estrogen receptor-positive,

progesterone receptor-positive, and human epidermal growth factor receptor 2-negative by fluorescence in-situ hybridization. Chemotherapy was completed nine months ago, and she is taking adjuvant tamoxifen. She has recovered quite well; her only complaint is fatigue. She states, "I expected to be tired during and immediately after chemotherapy, but I thought I would have all my energy back by now. I still feel the need to take a nap in the afternoon. In fact, I feel sleepy all the time!" Mrs. S's medical history is significant for moderate obesity and hypertension for 10 years, which is controlled with the angiotensin converting enzyme inhibitor lisinopril. She has not exercised since her breast cancer diagnosis but has been trying to lose weight with dietary changes. She believes that tamoxifen is hampering her weight-loss efforts. She takes no other medications.

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Fatigue may be caused by multiple physical and emotional factors. Common causes are depression, cancer-related fatigue, anemia, sleep disturbances, hypoxia, fluid or electrolyte imbalances, and medications. Other comorbid conditions, including hypothyroidism and immune system disorders, also should be considered because they may contribute to fatigue (National Comprehensive Cancer Network [NCCN], 2007) (see Figure 1). Before beginning to examine this patient, the advanced practice nurse (APN) should mentally review the typical causes of fatigue, which will guide the interview process and the physical examination.

Review of Systems

Likely causes of fatigue in patients treated for breast cancer in the previous year are depression, hypothyroidism, anemia, metabolic disorders, sleep disturbances, and medications. Cancer-related fatigue and tamoxifen should be considered as causes or contributing factors; however, other causes must be investigated and systematically eliminated. Nurses should inquire about comorbidities such as chronic anemia, unusual bleeding, endocrine deficiencies, immune system disorders, recent infections, and hepatic disorders because the conditions may contribute to fatigue. Patients should be questioned about emotional stressors. Ask the obvious question: "Have you ever been diagnosed with chronic fatigue syndrome?" Question patients specifically about sleep patterns (sound or restless) and the presence of snoring, which could indicate obstructive sleep apnea (OSA). Review a current list of medications, noting any new medications or changes in dosages (NCCN, 2007; Silverberg, Iaina, & Oksenberg, 2002; Victor, 2004).

Mrs. S denies any mood changes, feelings of sadness, loss of interest in usual activities, or early morning awakenings, all typical of depression. She also denies any hair, skin, or nail changes that might indicate altered thyroid function. She reports that she is asleep as soon as her head hits the pillow and feels that she sleeps well; however, she does not feel rested when she gets up in the morning. She is a widow, sleeps alone, and is unsure whether she snores. She notes that her mental processing seems to be a little slower when she is balancing her checkbook.

Physical Examination

The review of systems, Mrs. S's reports of slower mental processing, and prioritizing of likely diagnoses by the APN guide the physical examination. In addition to evaluation of the breasts, chest, and lymphatic system indicated by the diagnosis of breast cancer, the examination includes an evaluation of body habitus; head, eyes, ears, nose, and throat (HEENT); and cardiovascular, respiratory, neurologic, integumentary, and psychiatric systems, all of which are pertinent to the differential diagnosis of fatigue.

Given Mrs. S's history and review of systems, the APN determines that the likely causes of fatigue are OSA, cancer-related fatigue, hypothyroidism, and medication (tamoxifen).

General observation of the patient should include body habitus (size and shape) and weight. Visual cues, such as facial expressions and body language, should be noted. A HEENT examination should include the size of the airway and thyroid, as well as neck circumference. Airway size may be evaluated using the Mallampati airway scoring system (see Figure 2). Smaller airway size (class III or IV) correlates with the presence and severity of sleep apnea (Nuckton, Glidden, Browner, & Claman, 2006). Neck size of greater than 17 inches in men and greater than 16 inches in women is a predisposing factor for sleep apnea (Holman, 2005). A HEENT examination also includes inspection and palpation of the thyroid, noting the presence of nodules, enlargement, or asymmetry. Cardiovascular examination includes blood pressure and heartbeat rate and regularity. The presence of gallops, rubs, or murmurs should be noted. Examination of the pulmonary system encompasses the character and rate of respirations. Patients should be observed for conversational dyspnea, and oxygen saturation on room air should be documented if available. Integumentary system observations include skin changes, lesions, and abnormal pigmentations. Hair should be inspected for dryness and nails inspected for brittleness, fragility, and Beau lines, which may indicate injury or illness. The neurologic system examination should include the cranial nerves, reflexes, mental status, and coordination. Note changes in cognition, demonstrated by the inability to concentrate, short-term memory loss, or problems with word finding. Fundoscopic examination should be performed because the patient has a history of hypertension.

Mrs. S's physical examination reveals blood pressure of 135/84 mmHg, pulse 86 and regular, and respirations of 16 breaths per minute. Her weight is 220 pounds, height 65 inches, and body mass index (BMI) 35. She has gained eight pounds since her last visit three months ago. HEENT examination is unremarkable, except for the notation of a class III oropharyngeal airway. Her neck circumference is 16 inches. Thyroid abnormalities are not palpable. Skin, hair, and nails are unremarkable. Cardiovascular and respiratory system examinations are negative. Examination of the remaining breast is within normal limits. Her abdomen is obese with apple shape and without any tenderness or organomegaly. The neurologic system examination is within normal limits. Mrs. S is attentive and exhibits a positive attitude in her interactions. Her affect is that of a nondepressed patient.

The most revealing clues ascertained from the physical examination are BMI of 35 with central obesity, class III (small) airway, and recent weight gain. Interpretation of the review of systems and the physical examination findings thus far suggest sleep disturbance from OSA as a potential cause of the patient's complaint of fatigue. However, gathering additional information to rule out other causes such as anemia, metabolic imbalances, and hypothyroidism is indicated (Holman, 2005; NCCN, 2007).

Laboratory Testing and Imaging Studies

Laboratory testing may cover any or all of the following: complete blood count (CBC), thyroid stimulating hormone (TSH), free T4, complete 18-item metabolic panel (CMP), and lactic dehydrogenase (LDH). A thyroid ultrasound or scan should be considered if the TSH, free T4, or thyroid examination is abnormal (NCCN, 2007). Laboratory testing for Mrs. S, including CBC, TSH, free T4, CMP, and LDH, is within normal limits.

Diagnosis

The APN has methodically eliminated anemia, hypothyroidism, and metabolic imbalance as sources of fatigue. Although cancer-related fatigue and tamoxifen-related fatigue still are possible causes or comorbid contributors, OSA is the diagnosis of exclusion.

An estimated 18 million Americans have OSA, but only 10%-20% of cases are actually diagnosed. Approximately one-half of patients with OSA have comorbid essential hypertension, and OSA has been implicated as an independent cause of hypertension and cardiovascular disease. Evidence exists of an independent association between OSA and fasting insulin levels, supporting a link with diabetes mellitus (Holman, 2005). Studies have shown that patients with OSA may have increased platelet activation, increased C-reactive protein, decreased fibrinolytic activity, and enhanced leukocyte adhesion and endothelial function (Bounhoure, Galinier, Didier, & Leophonte, 2005). OSA is associated with metabolic syndrome and obesity, although not all patients with OSA are obese (Holman; Silverberg et al., 2002).

OSA is characterized by repetitive episodes of airway obstruction that occur during sleep and is associated with a decrease in oxygen saturation. The etiology is a narrowed upper airway secondary to obesity, tonsillar or adenoid hypertrophy, muscular weakness, craniofacial deformities, or use of sedatives or alcohol at bedtime. Repetitive desaturation from apnea or hypopnea causes multiple rousings from third-stage rapid-eye-movement sleep, resulting in daytime drowsiness and fatigue. Patients may be unaware of sleep disturbances (Holman, 2005).

Mrs. S is at high risk for OSA because of her long-standing hypertension, obesity, and small oropharyngeal airway. Her symptoms of daytime drowsiness, not feeling rested, mental slowing, and fatigue are typical findings in patients with OSA. Weight gain is not a usual finding in patients with OSA; however, Mrs. S's weight gain may have accelerated the severity of her symptoms.

Treatment

The plan for Mrs. S includes an overnight polysomnography (i.e., sleep study). If the first night's polysomnography is positive for significant OSA, a second-night study to titrate continuous positive airway pressure (CPAP) will be needed. Alternatively, a split-night study may be ordered. If OSA is detected during the first half of the study, CPAP is applied during the second half of the study, with titration of the level of pressure needed to keep the airway open. Mrs. S's visit must include education about OSA and the test used to diagnose it. The relationship among fatigue, sleep apnea, hypertension, obesity, and diabetes also should be discussed and weight loss recommended.

Overnight polysomnography is the gold standard for diagnosing OSA and the only diagnostic modality recommended by the American Academy of Sleep Medicine (Holman, 2005). It also may be known and ordered as nocturnal polysomnographic diagnostic testing, or NPSG. A positive sleep study reveals the presence of five or more apneic or hypopneic episodes, oxygen desaturations of 4% or more, and/or a respiratory disturbance index (RDI) of 4 or greater. RDI also is known as apnea/hypopnea index, or AHI.

OSA is classified as mild in patients with an RDI from 5-15, moderate in those with an RDI from 15-30, and severe in patients with an RDI greater than 30. Adjunctive treatment for all classifications of OSA includes aggressive weight loss and elimination of sedatives and hypnotics, which may be the only treatment needed for mild OSA. CPAP is the recommended treatment for moderate or severe OSA accompanied by preexisting cardiovascular disease or significant quality-of-life disturbances. Patients with severe OSA may require surgical procedures, such as septal deviation repair, polypectomy, or turbinectomy. Resection of the uvula and soft palate also is an option for some patients (Ferri, 2006; Holman, 2005).

Conclusion

Mrs. S underwent a sleep study, which revealed an RDI of 20. The findings were communicated to her primary-care physician, who assumed long-term management of Mrs. S's OSA. She was started on a CPAP machine with self-regulating automatic pressures of 5-20 cm. She was referred to a dietician to assist her in planning low-calorie meals for a single person; a weight-loss goal of two pounds per week was recommended. At her next oncology office visit one month later, she reported that she was feeling significantly better. She had lost six pounds, and her fatigue and daytime sleepiness were much improved. Her blood pressure control was improved, with a reading of 120/76 mmHg. Because she was improved, no changes were made to her tamoxifen treatment, and cancer-related fatigue was eliminated as a comorbid consideration.

Detecting and treating OSA can lead to dramatic improvements in quality of life (Silverberg et al., 2002). OSA is not a problem usually discovered in oncology; however, oncology APNs should be aware of typical diagnoses in primary-care practices as well as oncology diagnoses.

For demonstration purposes, this article followed the patient's problem through to completion. Most APNs in oncology do not proceed with the workup of OSA but rather communicate their concerns and refer back to primary-care providers. Professionalism and courtesy demand excellent communication with primary-care providers.

References

Bounhoure, J.P., Galinier, M., Didier, A., & Leophonte, P. (2005). Sleep apnea syndromes and cardiovascular disease. Bulletin de l'Academie Nationale de Medecine, 189, 445-459. Retrieved January 12, 2007, from http://www.medscape.com/ medline/abstract/16149210

Darrow, M.D. (2001). Hypokalemia. In M.R. Dambro (Ed.), Griffith's five-minute clinical consult (9th ed, pp. 544-545). Philadelphia: Lippincott Williams and Wilkins.

Ferri, F. (2006). Ferri's clinical advisor: Instant diagnosis and treatment. Philadelphia: Elsevier Mosby.

Holman, M.L. (2005). Obstructive sleep apnea syndrome: Implications for primary care. Nurse Practitioner, 30(9), 38-43.

Iredell County EMS. (2007). Difficult airway assessment guide. Retrieved September 9, 2007, from http://www.iredellems.com/ protocols

National Comprehensive Cancer Network. (2007). Cancer-related fatigue. Retrieved June 25, 2007, from http://www.nccn.org/ professionals/physician_gls/PDF/fatigue .pdf

Nuckton, T.J., Glidden, D.V., Browner, W.S., & Claman, D.M. (2006). Physical examination: Mallampati score as an independent predictor of obstructive sleep apnea. Sleep, 2, 903-908.

Silverberg, D.S., Iaina, A., & Oksenberg, A. (2002). Treating obstructive sleep apnea improves essential hypertension and quality of life. American Family Physician, 65, 229-236. Retrieved January 12, 2007, from http://www.medscape.com/ medline/abstract/11820487

Strickland, P.L., & Recabaren, J. (2002). Are preoperative serum calcium, parathyroid hormone, and adenoma weight predictive of postoperative hypocalcemia? American Surgeon, 68,1080-1083.

Victor, L.D. (2004). Treatment of obstructive sleep apnea in primary care. American Family Physician, 69, 561-568. Retrieved January 12, 2007, from http://www.med scape.com/medline/abstract/14971838

Figure 1. Differential Diagnoses
and Comorbidities for Fatigue

Cardiovascular disorders

* Bradycardia

* Congestive heart failure

* Hypotension

Endocrine disorders

* Adrenal insufficiency

* Hypogonadism

* Hypothyroidism

Hematologic disorders

* Anemia

* Hypokalemia

Hepatic disorders

* Cirrhosis

* Hepatitis

Immune system disorders

* Recent infection

* Rheumatoid arthritis

* Systemic lupus erythematosus

Medications

* Alpha adrenergic blockers

* Beta blockers

* Calcium channel blockers

* Sedatives and hypnotics

* Antineoplastic agents

Metabolic disorders

* Hypocalcemia

* Hypokalemia

Psychiatric disorders

* Depression

* Depressive phase of manic-depressive
disorder

* Seasonal affective disorder

Pulmonary disorders

* Chronic obstructive pulmonary disease

* Emphysema

* Obstructive sleep apnea

Sleep disorders

* Obstructive sleep apnea

* Restless leg syndrome

Note. Based on information from Darrow,
2001; National Comprehensive Cancer Network,
2007; Strickland & Recabaren, 2002.

Figure 2. Mallampati Airway
Scoring System

* Class I: Soft palate, fauces, uvula, and
pillars are visible.

* Class II: Soft palate, fauces, and uvula
are visible.

* Class III: Only the soft palate and base
of uvula are visible.

* Class IV: Soft palate is not visible.

Note. Based on information from Iredell
County EMS, 2007.

Author Contact: Kathy Sharp, MSN, APRN-BC, AOCNP[R], can be reached at mulekat@charter.net, with copy to editor at CJONEditor@ons.org.

Kathy Sharp, MSN, APRN-BC, AOCNP[R], is an oncology nurse practitioner at Blue Ridge Medical Specialists in Bristol, TN.