The Journal of Family Practice

The American Diabetes Association describes what diabetes is, the differences between Types 1 and 2, and what causes Type 2 in “The Diabetes Advisor: Type 2 Diabetes,” available at http://professional.diabetes.org/content/PML/Type_2_03a577ec-a58b-4ecd-a88f-72a29c46e32c/Type_2.pdf. The resource describes available treatments and explains the ABCs (A1C, Blood pressure, and Cholesterol levels) of diabetes to help patients understand how well their treatment is working.

The American Diabetes Association describes what diabetes is, the differences between Types 1 and 2, and what causes Type 2 in “The Diabetes Advisor: Type 2 Diabetes,” available at http://professional.diabetes.org/content/PML/Type_2_03a577ec-a58b-4ecd-a88f-72a29c46e32c/Type_2.pdf. The resource describes available treatments and explains the ABCs (A1C, Blood pressure, and Cholesterol levels) of diabetes to help patients understand how well their treatment is working.

The American Diabetes Association describes what diabetes is, the differences between Types 1 and 2, and what causes Type 2 in “The Diabetes Advisor: Type 2 Diabetes,” available at http://professional.diabetes.org/content/PML/Type_2_03a577ec-a58b-4ecd-a88f-72a29c46e32c/Type_2.pdf. The resource describes available treatments and explains the ABCs (A1C, Blood pressure, and Cholesterol levels) of diabetes to help patients understand how well their treatment is working.

An online resource from the American Heart Association can help reinforce the teaching you’ve done in your office about anticoagulation. “A Patient’s Guide to Warfarin,” which is available at http://www.heart.org/HEARTORG/Conditions/Arrhythmia/PreventionTreatmentofArrhythmia/A-Patients-Guide-to-Taking-Warfarin_UCM_444996_Article.jsp, describes how the anticoagulant works, drugs that interact with it, adverse effects to watch for, and the importance of wearing a medical alert bracelet. It also offers an easy-to-understand explanation of several anticoagulation concepts, such as prothrombin time and the International Normalized Ratio, and provides a list of patient do’s and don’ts.

An online resource from the American Heart Association can help reinforce the teaching you’ve done in your office about anticoagulation. “A Patient’s Guide to Warfarin,” which is available at http://www.heart.org/HEARTORG/Conditions/Arrhythmia/PreventionTreatmentofArrhythmia/A-Patients-Guide-to-Taking-Warfarin_UCM_444996_Article.jsp, describes how the anticoagulant works, drugs that interact with it, adverse effects to watch for, and the importance of wearing a medical alert bracelet. It also offers an easy-to-understand explanation of several anticoagulation concepts, such as prothrombin time and the International Normalized Ratio, and provides a list of patient do’s and don’ts.

An online resource from the American Heart Association can help reinforce the teaching you’ve done in your office about anticoagulation. “A Patient’s Guide to Warfarin,” which is available at http://www.heart.org/HEARTORG/Conditions/Arrhythmia/PreventionTreatmentofArrhythmia/A-Patients-Guide-to-Taking-Warfarin_UCM_444996_Article.jsp, describes how the anticoagulant works, drugs that interact with it, adverse effects to watch for, and the importance of wearing a medical alert bracelet. It also offers an easy-to-understand explanation of several anticoagulation concepts, such as prothrombin time and the International Normalized Ratio, and provides a list of patient do’s and don’ts.

The FP originally thought the nodules were abscesses, but began to suspect that they might be metastases from her breast cancer. A punch biopsy was performed with local anesthesia. There was no abscess, fluid, or fatty tissue and the solid tissue was sent for pathology. Pathology came back and confirmed the FP’s suspicion.

The FP shared the results of the biopsy with the patient and referred her to an oncologist.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

The FP originally thought the nodules were abscesses, but began to suspect that they might be metastases from her breast cancer. A punch biopsy was performed with local anesthesia. There was no abscess, fluid, or fatty tissue and the solid tissue was sent for pathology. Pathology came back and confirmed the FP’s suspicion.

The FP shared the results of the biopsy with the patient and referred her to an oncologist.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

The FP originally thought the nodules were abscesses, but began to suspect that they might be metastases from her breast cancer. A punch biopsy was performed with local anesthesia. There was no abscess, fluid, or fatty tissue and the solid tissue was sent for pathology. Pathology came back and confirmed the FP’s suspicion.

The FP shared the results of the biopsy with the patient and referred her to an oncologist.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

The FP, who had palpated firm, matted nodes in the left axilla, immediately recognized the peau d’orange sign of breast cancer with lymphedema. (With this sign, the skin of the breast looks that of an orange as a consequence of lymphedema.)

The FP explained to the patient that she most likely had breast cancer and referred her to the local university breast center. While the prognosis appeared poor, the FP recognized the importance of making every effort to have the disease staged to determine the most appropriate therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

The FP, who had palpated firm, matted nodes in the left axilla, immediately recognized the peau d’orange sign of breast cancer with lymphedema. (With this sign, the skin of the breast looks that of an orange as a consequence of lymphedema.)

The FP explained to the patient that she most likely had breast cancer and referred her to the local university breast center. While the prognosis appeared poor, the FP recognized the importance of making every effort to have the disease staged to determine the most appropriate therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

The FP, who had palpated firm, matted nodes in the left axilla, immediately recognized the peau d’orange sign of breast cancer with lymphedema. (With this sign, the skin of the breast looks that of an orange as a consequence of lymphedema.)

The FP explained to the patient that she most likely had breast cancer and referred her to the local university breast center. While the prognosis appeared poor, the FP recognized the importance of making every effort to have the disease staged to determine the most appropriate therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux, EJ. Breast cancer. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:551-556.

To learn more about the Color Atlas of Family Medicine, see: http://www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: http://usatinemedia.com/

Ms. C says she sleeps well, getting more than 8 hours of sleep per night on weekends but fewer than 7 hours per night during the week. But no matter how long she sleeps, she never awakens feeling refreshed. Ms. C reports that she doesn’t smoke, has no more than 4 alcoholic drinks per month, and adheres to an “average” diet. She is too tired to exercise.

Ms. C is single, with no children. Although she says she has a strong network of family and friends, she increasingly finds she has no energy for socializing. If Ms. C were your patient, what would you do?

Patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, while those with fatigue that is not organ-based typically say that they're tired all the time.Fatigue is a common presenting symptom in primary care, accounting for about 5% of adult visits.¹ Defined as a generalized lack of energy, fatigue that persists despite adequate rest or is severe enough to disrupt an individual’s ability to participate in key social and/or occupational activities warrants a thorough investigation.

Because fatigue is a nonspecific symptom that may be linked to a number of medical and psychiatric illnesses or medications used to treat them, determining the cause can be difficult. In about half of all cases, no specific etiology is found.² This review, which includes the elements of a work-up and management strategies for patients presenting with ongoing fatigue, will help you arrive at the appropriate diagnosis and provide optimal treatment.

Chronic fatigue: Defining the terms

A definition of chronic fatigue syndrome (CFS) was initially published in 1988.³ In subsequent years, the term myalgic encephalomyelitis (ME) became popular. Although the terms are sometimes used interchangeably, ME often refers to patients whose condition is thought to have an infectious cause and for whom postexertional malaise is a hallmark symptom.⁴

CDC criteria. While several sets of diagnostic criteria for CFS have been developed, the most widely used is that of the Centers for Disease Control and Prevention (CDC), published in 1994 (TABLE 1).^5,6 A diagnosis of CFS is made on the basis of exclusion, subjective clinical interpretation, and patient self-report.

When the first 2 criteria—fatigue not due to ongoing exertion or other medical conditions that has lasted ≥6 months and is severe enough to interfere with daily activities—but fewer than 4 of the CDC’s 8 concurrent symptoms (eg, headache, unrefreshing sleep, and postexertion malaise lasting >24 hours) are present, idiopathic fatigue, rather than CFS, is diagnosed.⁶

International Consensus Criteria (ICC). In 2011, the ICC for ME were proposed in an effort to provide more specific diagnostic criteria (TABLE 2).⁷ The ICC emphasize fatigability, or what the authors identify as “post-exertional neuroimmune exhaustion.”

The ICC have not yet been broadly researched.  But an Australian study of patients with chronic fatigue found that those who met the ICC definition were sicker and more homogeneous, with significantly lower scores for physical and social functioning and bodily pain compared with those who fulfilled the CDC criteria alone.⁸

Chronic fatigue & neuropsychiatric conditions: Common threads

Recent research has made it clear that depression, somatization, and CFS share some biological underpinnings. These include biomarkers for inflammation, cell-mediated immune activation—which may be related to the symptoms of fatigue—autonomic dysfunction, and hyperalgesia.⁹ Evidence suggests that up to two-thirds of patients with CFS also meet the criteria for a psychiatric disorder.¹⁰ The most common psychiatric conditions are major depressive disorder (MDD), affecting an estimated 22% to 32% of those with CFS; anxiety disorder, affecting about 20%; and somatization disorder, affecting about 10%—at least double the incidence of the general population.¹⁰

Others point out, however, that up to half of those with CFS do not have a psychiatric disorder.¹¹ A diagnosis of somatization disorder, in particular, depends largely on a subjective interpretation of whether or not the presenting symptoms have a physical cause.¹⁰

CFS and MDD comorbidity. The most widely studied association between CFS and psychiatric disorders involves MDD. Observational studies have found patients with CFS have a lifetime prevalence of MDD of 65%,^12,13 which is higher than that of patients with other chronic diseases. Overlapping symptoms include fatigue, sleep disturbance, poor concentration, and memory problems. However, those with CFS have fewer symptoms related to anhedonia, poor self-esteem, guilt, and suicidal ideation compared with individuals with MDD.^12,13

There are several possible explanations for CFS and MDD comorbidity, which are not necessarily mutually exclusive.¹⁰ One theory is that CFS is an atypical form of depression; another holds that the disability associated with CFS leads to depression, as is the case with many other chronic illnesses; and a third points to overlapping pathophysiology.¹⁰

An emerging body of evidence suggests that CFS and MDD have some common oxidative and nitrosative biochemical pathways. Activated by infection, psychological stress, and immune disorders, they are believed to have damaging free radical and nitric oxide effects at the cellular level.¹⁴ The cellular effects can result in fatigue, muscle pain, and flu-like malaise.

Cortisol response differs

The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.CFS and MDD might be distinguishable by another pathway—the hypothalamic-pituitary-adrenal (HPA) axis. MDD is classically associated with activation and raised cortisol levels, while CFS is consistently associated with impaired HPA axis functioning and reduced cortisol levels.¹⁰ The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.¹⁵

A meta-analysis of 50 studies of patients with CFS showed deficits in attention, memory, and reaction time, but not in fine motor speed, vocabulary, or reasoning.¹⁶ Autonomic dysfunction has also been observed, including disordered sympathetic activity. The most frequently observed abnormalities on autonomic testing are postural hypotension, tachycardia syndrome, neurally mediated hypotension, and heart rate variability during tilt table testing.¹⁶

The link between infection and CFS

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus (EBV), herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.^8,17,18 Most agents that have been linked to ME/CFS are associated with persistent infection and thus incitement of the immune system.

Numerous observational studies^17,18 have documented postinfectious fatigue syndromes after acute viral and bacterial infections and symptoms suggestive of infection, such as fever, myalgias, and respiratory and gastrointestinal distress. In one prospective Australian study,¹⁹ investigators identified 253 cases of acute EBV, Ross River virus, and Q fever. Of those 253 patients, 12% went on to develop CFS, with a higher likelihood among those with more severe acute symptoms. No correlation with preexisting psychiatric disorders was found.

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus, herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.Muscle mitochondria studies have demonstrated what appear to be acquired abnormalities in those with CFS.^20,21 Signs of increased oxidative stress have been found in both blood and muscle samples from patients with CFS, and longitudinal studies suggest that oxidative stress is greatest during periods of clinical exacerbation.²² Increased lactate levels suggest increased anaerobic metabolism in the central nervous system consistent with mitochondrial dysfunction. Several studies have demonstrated that exercise can precipitate oxidative stress in patients with CFS, in contrast with healthy controls and controls with other chronic illnesses, suggesting a physiologic basis for their postexertional symptoms.¹⁷

Autoinflammatory syndrome induced by adjuvants, a rare syndrome associated with vaccine administration, has been linked to postvaccination adverse events, exposure to silicone implants, Gulf War syndrome (related to multiple vaccinations), and macrophagic myofasciitis. All involve exposure to immune adjuvants and have similar clinical manifestations. The corresponding exposures appear to trigger an autoimmune response in susceptible individuals.  The hepatitis B vaccine is most often associated with CFS, with symptoms occurring within 90 days of administration.²³

The clinical work-up: Putting knowledge into practice

Familiarity with potential causes of and connections with ME/CFS will help you ensure that patients who say they’re always tired receive a thorough work-up. Start with a medical history, inquiring directly about medical and psychiatric disorders that may contribute to fatigue (TABLE 3).^5,24,25 Include a medication history, as well, to help determine whether the fatigue is drug-related (TABLE 4).^5,25 

What to ask. Determine the onset, course, duration, daily pattern, and impact of fatigue on the patient’s daily life. Inquire, too, about related symptoms of daytime sleepiness, dyspnea on exertion, generalized weakness, and depressed mood. The prominence of any of these rather than fatigue, per se, point to a diagnosis of a chronic illness other than ME/CFS.

Keep in mind, too, that patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, such as shopping or light housework. In contrast, those with fatigue that is not organ-based typically say that they’re tired all the time. Their fatigue is not necessarily related to exertion, nor does it improve with rest.²⁶

To address this distinction, take a sleep history, assessing both the quality and quantity of the patient’s sleep to determine how it affects symptoms.²⁷ Consider using a questionnaire designed to help distinguish between sleepiness—and a primary sleep disorder—and fatigue,²⁸ such as the Fatigue Severity Scale of Sleep Disorders (http://www.healthywomen.org/sites/default/files/FatigueSeverityScale.pdf).

What to rule out. In addition to a medical history, the physical examination should be oriented toward ruling out secondary causes of fatigue. In addition to a system-by-system approach to the differential diagnosis, carefully observe the patient’s general appearance, with attention to his or her level of alertness, grooming, and psychomotor agitation or retardation as possible signs of a psychiatric disorder.  To rule out neurologic causes, evaluate muscle bulk, tone, and strength; deep tendon reflexes; and sensory and cranial nerves, as well.²⁹

Lab tests to consider. In most cases of ME/CFS, basic studies—complete blood count with differential, erythrocyte sedimentation rate, blood chemistry, and thyroid-stimulating hormone (TSH) levels—are sufficient. When no medical or psychiatric cause has been found, additional tests may be ordered on a case-by-case basis, although laboratory analysis affects the management of fatigue in less than 5% of such patients.³⁰ Tests to consider include:

• Creatine kinase (for patients who report pain or muscle weakness)
• pregnancy test (for women of childbearing age)
• ferritin testing (for young women who might benefit from iron supplementation for levels <50 ng/mL even if anemia is not present)³¹
• hepatitis C screening (recommended by the US Preventive Services Task Force for those born between 1945 and 1965)³²
• human immunodeficiency virus screening and the purified protein derivative test for tuberculosis (based on patient history).

Forego routine testing for other infections

Routine testing for infectious diseases and conditions associated with fatigue, such as Epstein-Barr virus or Lyme disease, immune deficiency, and inflammatory disease, is unlikely to be helpful. Routine testing for infectious diseases and conditions associated with fatigue, such as EBV or Lyme disease, immune deficiency (eg, immunoglobulins), inflammatory disease (eg, antinuclear antibodies, rheumatoid factor), celiac disease, vitamin D deficiency, vitamin B₁₂ deficiency, or heavy metal toxicity, is unlikely to be helpful.²⁹ Additional testing simply to reassure a worried patient usually does not accomplish that objective.³³

Additional studies, referrals to consider. If you suspect that a patient has a sleep disorder, a referral to a sleep clinic to rule out idiopathic sleep disorders, obstructive sleep apnea, or movement disorders that interfere with sleep may be in order. Spirometry and echocardiography may be helpful for some patients. If you suspect peripheral muscle fatigue, a referral for neuromuscular testing is indicated.

CASE › Ms. C’s medical history reveals that she also suffers from irritable bowel syndrome, which she manages with diet and over-the-counter medication, as needed, for constipation or diarrhea. She denies having any other chronic conditions. Her only other symptoms, she reports, are mild upper back pain after spending long hours at the computer, and arthralgias in her left knee and both hands. She admits to being “somewhat depressed” in the last few months, but denies the presence of anhedonia.

The patient’s physical examination is normal, and her depression screen does not meet the criteria for MDD. Her metabolic chemistry panel, complete blood count, TSH, and sedimentation rate are all normal, as well.

Symptom management and coping strategies

When no specific cause of chronic fatigue is found, the focus shifts from diagnosis to symptom management and coping strategies.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.This requires engagement with the patient. It is important to acknowledge the existence of his or her symptoms and to reassure the patient that further investigation may be warranted later, should new symptoms emerge. Advise the patient, too, that periods of remission and relapse are likely.

Strategies designed to motivate patient self-management, as well as the formulation of patient-centered treatment plans, have been shown to reduce symptom scores.³⁴ Participation in a support group, as well as frequent follow-up visits with a primary care physician, a behavioral therapist, or both, may help to provide needed psychological support.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.³⁵ Exercise should be low intensity, such as walking or cycling for 30 minutes 3 times a week, with a gradual increase in duration and frequency over a period of weeks to months. Patients with cancer-related fatigue may benefit from yoga, group therapy, and stress management.³⁶

Associated mood and pain symptoms should be treated, as well. Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.

Other potentially beneficial approaches include a healthy diet, avoidance of more than nominal amounts of alcohol, relative avoidance of caffeine (no more than one cup of a caffeinated beverage in the morning), and stress reduction techniques.

Attention to good sleep hygiene may be especially beneficial, including a regular bedtime routine and sleep schedule, and elimination of bedroom light and noise. Pharmacologic treatments for insomnia should be used with caution, if at all.

Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.CASE › Ms. C receives a referral for CBT and is scheduled for a return visit in 4 weeks.

At the advice of both her primary care physician and the behavioral therapist, Ms. C gradually makes several lifestyle changes. She begins going to bed earlier on weeknights to ensure that she sleeps for at least 7 hours. She improves her diet, with increasing emphasis on vegetables, fruits, and whole grains. She also starts a walking program, increasing gradually to a total of 3 hours per week. After 4 months she adds a weekly trip to a gym, where she practices resistance training for about 40 minutes.

Ms. C also increases her social activities on weekends, and recently accepted an invitation to join a book club. Six months from her initial visit, Ms. C notes that although she is still more easily fatigued than most people, she has made significant improvement.

CORRESPONDENCE
Linda Speer, MD; University of Toledo, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; linda.speer@utoledo.edu

Ms. C says she sleeps well, getting more than 8 hours of sleep per night on weekends but fewer than 7 hours per night during the week. But no matter how long she sleeps, she never awakens feeling refreshed. Ms. C reports that she doesn’t smoke, has no more than 4 alcoholic drinks per month, and adheres to an “average” diet. She is too tired to exercise.

Ms. C is single, with no children. Although she says she has a strong network of family and friends, she increasingly finds she has no energy for socializing. If Ms. C were your patient, what would you do?

Patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, while those with fatigue that is not organ-based typically say that they're tired all the time.Fatigue is a common presenting symptom in primary care, accounting for about 5% of adult visits.¹ Defined as a generalized lack of energy, fatigue that persists despite adequate rest or is severe enough to disrupt an individual’s ability to participate in key social and/or occupational activities warrants a thorough investigation.

Because fatigue is a nonspecific symptom that may be linked to a number of medical and psychiatric illnesses or medications used to treat them, determining the cause can be difficult. In about half of all cases, no specific etiology is found.² This review, which includes the elements of a work-up and management strategies for patients presenting with ongoing fatigue, will help you arrive at the appropriate diagnosis and provide optimal treatment.

Chronic fatigue: Defining the terms

A definition of chronic fatigue syndrome (CFS) was initially published in 1988.³ In subsequent years, the term myalgic encephalomyelitis (ME) became popular. Although the terms are sometimes used interchangeably, ME often refers to patients whose condition is thought to have an infectious cause and for whom postexertional malaise is a hallmark symptom.⁴

CDC criteria. While several sets of diagnostic criteria for CFS have been developed, the most widely used is that of the Centers for Disease Control and Prevention (CDC), published in 1994 (TABLE 1).^5,6 A diagnosis of CFS is made on the basis of exclusion, subjective clinical interpretation, and patient self-report.

When the first 2 criteria—fatigue not due to ongoing exertion or other medical conditions that has lasted ≥6 months and is severe enough to interfere with daily activities—but fewer than 4 of the CDC’s 8 concurrent symptoms (eg, headache, unrefreshing sleep, and postexertion malaise lasting >24 hours) are present, idiopathic fatigue, rather than CFS, is diagnosed.⁶

International Consensus Criteria (ICC). In 2011, the ICC for ME were proposed in an effort to provide more specific diagnostic criteria (TABLE 2).⁷ The ICC emphasize fatigability, or what the authors identify as “post-exertional neuroimmune exhaustion.”

The ICC have not yet been broadly researched.  But an Australian study of patients with chronic fatigue found that those who met the ICC definition were sicker and more homogeneous, with significantly lower scores for physical and social functioning and bodily pain compared with those who fulfilled the CDC criteria alone.⁸

Chronic fatigue & neuropsychiatric conditions: Common threads

Recent research has made it clear that depression, somatization, and CFS share some biological underpinnings. These include biomarkers for inflammation, cell-mediated immune activation—which may be related to the symptoms of fatigue—autonomic dysfunction, and hyperalgesia.⁹ Evidence suggests that up to two-thirds of patients with CFS also meet the criteria for a psychiatric disorder.¹⁰ The most common psychiatric conditions are major depressive disorder (MDD), affecting an estimated 22% to 32% of those with CFS; anxiety disorder, affecting about 20%; and somatization disorder, affecting about 10%—at least double the incidence of the general population.¹⁰

Others point out, however, that up to half of those with CFS do not have a psychiatric disorder.¹¹ A diagnosis of somatization disorder, in particular, depends largely on a subjective interpretation of whether or not the presenting symptoms have a physical cause.¹⁰

CFS and MDD comorbidity. The most widely studied association between CFS and psychiatric disorders involves MDD. Observational studies have found patients with CFS have a lifetime prevalence of MDD of 65%,^12,13 which is higher than that of patients with other chronic diseases. Overlapping symptoms include fatigue, sleep disturbance, poor concentration, and memory problems. However, those with CFS have fewer symptoms related to anhedonia, poor self-esteem, guilt, and suicidal ideation compared with individuals with MDD.^12,13

There are several possible explanations for CFS and MDD comorbidity, which are not necessarily mutually exclusive.¹⁰ One theory is that CFS is an atypical form of depression; another holds that the disability associated with CFS leads to depression, as is the case with many other chronic illnesses; and a third points to overlapping pathophysiology.¹⁰

An emerging body of evidence suggests that CFS and MDD have some common oxidative and nitrosative biochemical pathways. Activated by infection, psychological stress, and immune disorders, they are believed to have damaging free radical and nitric oxide effects at the cellular level.¹⁴ The cellular effects can result in fatigue, muscle pain, and flu-like malaise.

Cortisol response differs

The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.CFS and MDD might be distinguishable by another pathway—the hypothalamic-pituitary-adrenal (HPA) axis. MDD is classically associated with activation and raised cortisol levels, while CFS is consistently associated with impaired HPA axis functioning and reduced cortisol levels.¹⁰ The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.¹⁵

A meta-analysis of 50 studies of patients with CFS showed deficits in attention, memory, and reaction time, but not in fine motor speed, vocabulary, or reasoning.¹⁶ Autonomic dysfunction has also been observed, including disordered sympathetic activity. The most frequently observed abnormalities on autonomic testing are postural hypotension, tachycardia syndrome, neurally mediated hypotension, and heart rate variability during tilt table testing.¹⁶

The link between infection and CFS

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus (EBV), herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.^8,17,18 Most agents that have been linked to ME/CFS are associated with persistent infection and thus incitement of the immune system.

Numerous observational studies^17,18 have documented postinfectious fatigue syndromes after acute viral and bacterial infections and symptoms suggestive of infection, such as fever, myalgias, and respiratory and gastrointestinal distress. In one prospective Australian study,¹⁹ investigators identified 253 cases of acute EBV, Ross River virus, and Q fever. Of those 253 patients, 12% went on to develop CFS, with a higher likelihood among those with more severe acute symptoms. No correlation with preexisting psychiatric disorders was found.

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus, herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.Muscle mitochondria studies have demonstrated what appear to be acquired abnormalities in those with CFS.^20,21 Signs of increased oxidative stress have been found in both blood and muscle samples from patients with CFS, and longitudinal studies suggest that oxidative stress is greatest during periods of clinical exacerbation.²² Increased lactate levels suggest increased anaerobic metabolism in the central nervous system consistent with mitochondrial dysfunction. Several studies have demonstrated that exercise can precipitate oxidative stress in patients with CFS, in contrast with healthy controls and controls with other chronic illnesses, suggesting a physiologic basis for their postexertional symptoms.¹⁷

Autoinflammatory syndrome induced by adjuvants, a rare syndrome associated with vaccine administration, has been linked to postvaccination adverse events, exposure to silicone implants, Gulf War syndrome (related to multiple vaccinations), and macrophagic myofasciitis. All involve exposure to immune adjuvants and have similar clinical manifestations. The corresponding exposures appear to trigger an autoimmune response in susceptible individuals.  The hepatitis B vaccine is most often associated with CFS, with symptoms occurring within 90 days of administration.²³

The clinical work-up: Putting knowledge into practice

Familiarity with potential causes of and connections with ME/CFS will help you ensure that patients who say they’re always tired receive a thorough work-up. Start with a medical history, inquiring directly about medical and psychiatric disorders that may contribute to fatigue (TABLE 3).^5,24,25 Include a medication history, as well, to help determine whether the fatigue is drug-related (TABLE 4).^5,25 

What to ask. Determine the onset, course, duration, daily pattern, and impact of fatigue on the patient’s daily life. Inquire, too, about related symptoms of daytime sleepiness, dyspnea on exertion, generalized weakness, and depressed mood. The prominence of any of these rather than fatigue, per se, point to a diagnosis of a chronic illness other than ME/CFS.

Keep in mind, too, that patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, such as shopping or light housework. In contrast, those with fatigue that is not organ-based typically say that they’re tired all the time. Their fatigue is not necessarily related to exertion, nor does it improve with rest.²⁶

To address this distinction, take a sleep history, assessing both the quality and quantity of the patient’s sleep to determine how it affects symptoms.²⁷ Consider using a questionnaire designed to help distinguish between sleepiness—and a primary sleep disorder—and fatigue,²⁸ such as the Fatigue Severity Scale of Sleep Disorders (http://www.healthywomen.org/sites/default/files/FatigueSeverityScale.pdf).

What to rule out. In addition to a medical history, the physical examination should be oriented toward ruling out secondary causes of fatigue. In addition to a system-by-system approach to the differential diagnosis, carefully observe the patient’s general appearance, with attention to his or her level of alertness, grooming, and psychomotor agitation or retardation as possible signs of a psychiatric disorder.  To rule out neurologic causes, evaluate muscle bulk, tone, and strength; deep tendon reflexes; and sensory and cranial nerves, as well.²⁹

Lab tests to consider. In most cases of ME/CFS, basic studies—complete blood count with differential, erythrocyte sedimentation rate, blood chemistry, and thyroid-stimulating hormone (TSH) levels—are sufficient. When no medical or psychiatric cause has been found, additional tests may be ordered on a case-by-case basis, although laboratory analysis affects the management of fatigue in less than 5% of such patients.³⁰ Tests to consider include:

• Creatine kinase (for patients who report pain or muscle weakness)
• pregnancy test (for women of childbearing age)
• ferritin testing (for young women who might benefit from iron supplementation for levels <50 ng/mL even if anemia is not present)³¹
• hepatitis C screening (recommended by the US Preventive Services Task Force for those born between 1945 and 1965)³²
• human immunodeficiency virus screening and the purified protein derivative test for tuberculosis (based on patient history).

Forego routine testing for other infections

Routine testing for infectious diseases and conditions associated with fatigue, such as Epstein-Barr virus or Lyme disease, immune deficiency, and inflammatory disease, is unlikely to be helpful. Routine testing for infectious diseases and conditions associated with fatigue, such as EBV or Lyme disease, immune deficiency (eg, immunoglobulins), inflammatory disease (eg, antinuclear antibodies, rheumatoid factor), celiac disease, vitamin D deficiency, vitamin B₁₂ deficiency, or heavy metal toxicity, is unlikely to be helpful.²⁹ Additional testing simply to reassure a worried patient usually does not accomplish that objective.³³

Additional studies, referrals to consider. If you suspect that a patient has a sleep disorder, a referral to a sleep clinic to rule out idiopathic sleep disorders, obstructive sleep apnea, or movement disorders that interfere with sleep may be in order. Spirometry and echocardiography may be helpful for some patients. If you suspect peripheral muscle fatigue, a referral for neuromuscular testing is indicated.

CASE › Ms. C’s medical history reveals that she also suffers from irritable bowel syndrome, which she manages with diet and over-the-counter medication, as needed, for constipation or diarrhea. She denies having any other chronic conditions. Her only other symptoms, she reports, are mild upper back pain after spending long hours at the computer, and arthralgias in her left knee and both hands. She admits to being “somewhat depressed” in the last few months, but denies the presence of anhedonia.

The patient’s physical examination is normal, and her depression screen does not meet the criteria for MDD. Her metabolic chemistry panel, complete blood count, TSH, and sedimentation rate are all normal, as well.

Symptom management and coping strategies

When no specific cause of chronic fatigue is found, the focus shifts from diagnosis to symptom management and coping strategies.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.This requires engagement with the patient. It is important to acknowledge the existence of his or her symptoms and to reassure the patient that further investigation may be warranted later, should new symptoms emerge. Advise the patient, too, that periods of remission and relapse are likely.

Strategies designed to motivate patient self-management, as well as the formulation of patient-centered treatment plans, have been shown to reduce symptom scores.³⁴ Participation in a support group, as well as frequent follow-up visits with a primary care physician, a behavioral therapist, or both, may help to provide needed psychological support.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.³⁵ Exercise should be low intensity, such as walking or cycling for 30 minutes 3 times a week, with a gradual increase in duration and frequency over a period of weeks to months. Patients with cancer-related fatigue may benefit from yoga, group therapy, and stress management.³⁶

Associated mood and pain symptoms should be treated, as well. Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.

Other potentially beneficial approaches include a healthy diet, avoidance of more than nominal amounts of alcohol, relative avoidance of caffeine (no more than one cup of a caffeinated beverage in the morning), and stress reduction techniques.

Attention to good sleep hygiene may be especially beneficial, including a regular bedtime routine and sleep schedule, and elimination of bedroom light and noise. Pharmacologic treatments for insomnia should be used with caution, if at all.

Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.CASE › Ms. C receives a referral for CBT and is scheduled for a return visit in 4 weeks.

At the advice of both her primary care physician and the behavioral therapist, Ms. C gradually makes several lifestyle changes. She begins going to bed earlier on weeknights to ensure that she sleeps for at least 7 hours. She improves her diet, with increasing emphasis on vegetables, fruits, and whole grains. She also starts a walking program, increasing gradually to a total of 3 hours per week. After 4 months she adds a weekly trip to a gym, where she practices resistance training for about 40 minutes.

Ms. C also increases her social activities on weekends, and recently accepted an invitation to join a book club. Six months from her initial visit, Ms. C notes that although she is still more easily fatigued than most people, she has made significant improvement.

CORRESPONDENCE
Linda Speer, MD; University of Toledo, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; linda.speer@utoledo.edu

Ms. C says she sleeps well, getting more than 8 hours of sleep per night on weekends but fewer than 7 hours per night during the week. But no matter how long she sleeps, she never awakens feeling refreshed. Ms. C reports that she doesn’t smoke, has no more than 4 alcoholic drinks per month, and adheres to an “average” diet. She is too tired to exercise.

Ms. C is single, with no children. Although she says she has a strong network of family and friends, she increasingly finds she has no energy for socializing. If Ms. C were your patient, what would you do?

Patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, while those with fatigue that is not organ-based typically say that they're tired all the time.Fatigue is a common presenting symptom in primary care, accounting for about 5% of adult visits.¹ Defined as a generalized lack of energy, fatigue that persists despite adequate rest or is severe enough to disrupt an individual’s ability to participate in key social and/or occupational activities warrants a thorough investigation.

Because fatigue is a nonspecific symptom that may be linked to a number of medical and psychiatric illnesses or medications used to treat them, determining the cause can be difficult. In about half of all cases, no specific etiology is found.² This review, which includes the elements of a work-up and management strategies for patients presenting with ongoing fatigue, will help you arrive at the appropriate diagnosis and provide optimal treatment.

Chronic fatigue: Defining the terms

A definition of chronic fatigue syndrome (CFS) was initially published in 1988.³ In subsequent years, the term myalgic encephalomyelitis (ME) became popular. Although the terms are sometimes used interchangeably, ME often refers to patients whose condition is thought to have an infectious cause and for whom postexertional malaise is a hallmark symptom.⁴

CDC criteria. While several sets of diagnostic criteria for CFS have been developed, the most widely used is that of the Centers for Disease Control and Prevention (CDC), published in 1994 (TABLE 1).^5,6 A diagnosis of CFS is made on the basis of exclusion, subjective clinical interpretation, and patient self-report.

When the first 2 criteria—fatigue not due to ongoing exertion or other medical conditions that has lasted ≥6 months and is severe enough to interfere with daily activities—but fewer than 4 of the CDC’s 8 concurrent symptoms (eg, headache, unrefreshing sleep, and postexertion malaise lasting >24 hours) are present, idiopathic fatigue, rather than CFS, is diagnosed.⁶

International Consensus Criteria (ICC). In 2011, the ICC for ME were proposed in an effort to provide more specific diagnostic criteria (TABLE 2).⁷ The ICC emphasize fatigability, or what the authors identify as “post-exertional neuroimmune exhaustion.”

The ICC have not yet been broadly researched.  But an Australian study of patients with chronic fatigue found that those who met the ICC definition were sicker and more homogeneous, with significantly lower scores for physical and social functioning and bodily pain compared with those who fulfilled the CDC criteria alone.⁸

Chronic fatigue & neuropsychiatric conditions: Common threads

Recent research has made it clear that depression, somatization, and CFS share some biological underpinnings. These include biomarkers for inflammation, cell-mediated immune activation—which may be related to the symptoms of fatigue—autonomic dysfunction, and hyperalgesia.⁹ Evidence suggests that up to two-thirds of patients with CFS also meet the criteria for a psychiatric disorder.¹⁰ The most common psychiatric conditions are major depressive disorder (MDD), affecting an estimated 22% to 32% of those with CFS; anxiety disorder, affecting about 20%; and somatization disorder, affecting about 10%—at least double the incidence of the general population.¹⁰

Others point out, however, that up to half of those with CFS do not have a psychiatric disorder.¹¹ A diagnosis of somatization disorder, in particular, depends largely on a subjective interpretation of whether or not the presenting symptoms have a physical cause.¹⁰

CFS and MDD comorbidity. The most widely studied association between CFS and psychiatric disorders involves MDD. Observational studies have found patients with CFS have a lifetime prevalence of MDD of 65%,^12,13 which is higher than that of patients with other chronic diseases. Overlapping symptoms include fatigue, sleep disturbance, poor concentration, and memory problems. However, those with CFS have fewer symptoms related to anhedonia, poor self-esteem, guilt, and suicidal ideation compared with individuals with MDD.^12,13

There are several possible explanations for CFS and MDD comorbidity, which are not necessarily mutually exclusive.¹⁰ One theory is that CFS is an atypical form of depression; another holds that the disability associated with CFS leads to depression, as is the case with many other chronic illnesses; and a third points to overlapping pathophysiology.¹⁰

An emerging body of evidence suggests that CFS and MDD have some common oxidative and nitrosative biochemical pathways. Activated by infection, psychological stress, and immune disorders, they are believed to have damaging free radical and nitric oxide effects at the cellular level.¹⁴ The cellular effects can result in fatigue, muscle pain, and flu-like malaise.

Cortisol response differs

The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.CFS and MDD might be distinguishable by another pathway—the hypothalamic-pituitary-adrenal (HPA) axis. MDD is classically associated with activation and raised cortisol levels, while CFS is consistently associated with impaired HPA axis functioning and reduced cortisol levels.¹⁰ The majority of patients with CFS report symptoms of cognitive decline, with the acquisition of new verbal learning and information-processing speed particularly likely to be impaired.¹⁵

A meta-analysis of 50 studies of patients with CFS showed deficits in attention, memory, and reaction time, but not in fine motor speed, vocabulary, or reasoning.¹⁶ Autonomic dysfunction has also been observed, including disordered sympathetic activity. The most frequently observed abnormalities on autonomic testing are postural hypotension, tachycardia syndrome, neurally mediated hypotension, and heart rate variability during tilt table testing.¹⁶

The link between infection and CFS

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus (EBV), herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.^8,17,18 Most agents that have been linked to ME/CFS are associated with persistent infection and thus incitement of the immune system.

Numerous observational studies^17,18 have documented postinfectious fatigue syndromes after acute viral and bacterial infections and symptoms suggestive of infection, such as fever, myalgias, and respiratory and gastrointestinal distress. In one prospective Australian study,¹⁹ investigators identified 253 cases of acute EBV, Ross River virus, and Q fever. Of those 253 patients, 12% went on to develop CFS, with a higher likelihood among those with more severe acute symptoms. No correlation with preexisting psychiatric disorders was found.

Several infectious agents have been associated with ME/CFS, including the Epstein-Barr virus, herpes simplex virus 6, parvovirus, Q fever, and Lyme disease.Muscle mitochondria studies have demonstrated what appear to be acquired abnormalities in those with CFS.^20,21 Signs of increased oxidative stress have been found in both blood and muscle samples from patients with CFS, and longitudinal studies suggest that oxidative stress is greatest during periods of clinical exacerbation.²² Increased lactate levels suggest increased anaerobic metabolism in the central nervous system consistent with mitochondrial dysfunction. Several studies have demonstrated that exercise can precipitate oxidative stress in patients with CFS, in contrast with healthy controls and controls with other chronic illnesses, suggesting a physiologic basis for their postexertional symptoms.¹⁷

Autoinflammatory syndrome induced by adjuvants, a rare syndrome associated with vaccine administration, has been linked to postvaccination adverse events, exposure to silicone implants, Gulf War syndrome (related to multiple vaccinations), and macrophagic myofasciitis. All involve exposure to immune adjuvants and have similar clinical manifestations. The corresponding exposures appear to trigger an autoimmune response in susceptible individuals.  The hepatitis B vaccine is most often associated with CFS, with symptoms occurring within 90 days of administration.²³

The clinical work-up: Putting knowledge into practice

Familiarity with potential causes of and connections with ME/CFS will help you ensure that patients who say they’re always tired receive a thorough work-up. Start with a medical history, inquiring directly about medical and psychiatric disorders that may contribute to fatigue (TABLE 3).^5,24,25 Include a medication history, as well, to help determine whether the fatigue is drug-related (TABLE 4).^5,25 

What to ask. Determine the onset, course, duration, daily pattern, and impact of fatigue on the patient’s daily life. Inquire, too, about related symptoms of daytime sleepiness, dyspnea on exertion, generalized weakness, and depressed mood. The prominence of any of these rather than fatigue, per se, point to a diagnosis of a chronic illness other than ME/CFS.

Keep in mind, too, that patients with an organ-based medical illness tend to associate their fatigue with activities that they are unable to complete, such as shopping or light housework. In contrast, those with fatigue that is not organ-based typically say that they’re tired all the time. Their fatigue is not necessarily related to exertion, nor does it improve with rest.²⁶

To address this distinction, take a sleep history, assessing both the quality and quantity of the patient’s sleep to determine how it affects symptoms.²⁷ Consider using a questionnaire designed to help distinguish between sleepiness—and a primary sleep disorder—and fatigue,²⁸ such as the Fatigue Severity Scale of Sleep Disorders (http://www.healthywomen.org/sites/default/files/FatigueSeverityScale.pdf).

What to rule out. In addition to a medical history, the physical examination should be oriented toward ruling out secondary causes of fatigue. In addition to a system-by-system approach to the differential diagnosis, carefully observe the patient’s general appearance, with attention to his or her level of alertness, grooming, and psychomotor agitation or retardation as possible signs of a psychiatric disorder.  To rule out neurologic causes, evaluate muscle bulk, tone, and strength; deep tendon reflexes; and sensory and cranial nerves, as well.²⁹

Lab tests to consider. In most cases of ME/CFS, basic studies—complete blood count with differential, erythrocyte sedimentation rate, blood chemistry, and thyroid-stimulating hormone (TSH) levels—are sufficient. When no medical or psychiatric cause has been found, additional tests may be ordered on a case-by-case basis, although laboratory analysis affects the management of fatigue in less than 5% of such patients.³⁰ Tests to consider include:

• Creatine kinase (for patients who report pain or muscle weakness)
• pregnancy test (for women of childbearing age)
• ferritin testing (for young women who might benefit from iron supplementation for levels <50 ng/mL even if anemia is not present)³¹
• hepatitis C screening (recommended by the US Preventive Services Task Force for those born between 1945 and 1965)³²
• human immunodeficiency virus screening and the purified protein derivative test for tuberculosis (based on patient history).

Forego routine testing for other infections

Routine testing for infectious diseases and conditions associated with fatigue, such as Epstein-Barr virus or Lyme disease, immune deficiency, and inflammatory disease, is unlikely to be helpful. Routine testing for infectious diseases and conditions associated with fatigue, such as EBV or Lyme disease, immune deficiency (eg, immunoglobulins), inflammatory disease (eg, antinuclear antibodies, rheumatoid factor), celiac disease, vitamin D deficiency, vitamin B₁₂ deficiency, or heavy metal toxicity, is unlikely to be helpful.²⁹ Additional testing simply to reassure a worried patient usually does not accomplish that objective.³³

Additional studies, referrals to consider. If you suspect that a patient has a sleep disorder, a referral to a sleep clinic to rule out idiopathic sleep disorders, obstructive sleep apnea, or movement disorders that interfere with sleep may be in order. Spirometry and echocardiography may be helpful for some patients. If you suspect peripheral muscle fatigue, a referral for neuromuscular testing is indicated.

CASE › Ms. C’s medical history reveals that she also suffers from irritable bowel syndrome, which she manages with diet and over-the-counter medication, as needed, for constipation or diarrhea. She denies having any other chronic conditions. Her only other symptoms, she reports, are mild upper back pain after spending long hours at the computer, and arthralgias in her left knee and both hands. She admits to being “somewhat depressed” in the last few months, but denies the presence of anhedonia.

The patient’s physical examination is normal, and her depression screen does not meet the criteria for MDD. Her metabolic chemistry panel, complete blood count, TSH, and sedimentation rate are all normal, as well.

Symptom management and coping strategies

When no specific cause of chronic fatigue is found, the focus shifts from diagnosis to symptom management and coping strategies.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.This requires engagement with the patient. It is important to acknowledge the existence of his or her symptoms and to reassure the patient that further investigation may be warranted later, should new symptoms emerge. Advise the patient, too, that periods of remission and relapse are likely.

Strategies designed to motivate patient self-management, as well as the formulation of patient-centered treatment plans, have been shown to reduce symptom scores.³⁴ Participation in a support group, as well as frequent follow-up visits with a primary care physician, a behavioral therapist, or both, may help to provide needed psychological support.

Evidence of the effectiveness of specific therapies for ME/CFS is limited; however, the best-studied approaches are cognitive behavioral therapy (CBT) and graded exercise therapy.³⁵ Exercise should be low intensity, such as walking or cycling for 30 minutes 3 times a week, with a gradual increase in duration and frequency over a period of weeks to months. Patients with cancer-related fatigue may benefit from yoga, group therapy, and stress management.³⁶

Associated mood and pain symptoms should be treated, as well. Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.

Other potentially beneficial approaches include a healthy diet, avoidance of more than nominal amounts of alcohol, relative avoidance of caffeine (no more than one cup of a caffeinated beverage in the morning), and stress reduction techniques.

Attention to good sleep hygiene may be especially beneficial, including a regular bedtime routine and sleep schedule, and elimination of bedroom light and noise. Pharmacologic treatments for insomnia should be used with caution, if at all.

Bupropion, which is somewhat stimulating, may be considered as an initial treatment for patients with depression and clinically significant fatigue.CASE › Ms. C receives a referral for CBT and is scheduled for a return visit in 4 weeks.

At the advice of both her primary care physician and the behavioral therapist, Ms. C gradually makes several lifestyle changes. She begins going to bed earlier on weeknights to ensure that she sleeps for at least 7 hours. She improves her diet, with increasing emphasis on vegetables, fruits, and whole grains. She also starts a walking program, increasing gradually to a total of 3 hours per week. After 4 months she adds a weekly trip to a gym, where she practices resistance training for about 40 minutes.

Ms. C also increases her social activities on weekends, and recently accepted an invitation to join a book club. Six months from her initial visit, Ms. C notes that although she is still more easily fatigued than most people, she has made significant improvement.

CORRESPONDENCE
Linda Speer, MD; University of Toledo, 3000 Arlington Avenue, MS 1179, Toledo, OH 43614; linda.speer@utoledo.edu

A young mother in your practice wants her toddler to begin swimming lessons because her family loves water activities. How would you advise her? In fielding an urgent call about a drowning incident, what priorities would you urge regarding resuscitation at the scene? For a stabilized patient following a drowning episode, when might antibiotics be indicated? This article covers these issues as well as follow-up matters such as assisted ventilation and tiered hypothermia intervention.

Drowning likely occurs more often than is reported

Worldwide, drowning accounts for more than 388,000 deaths annually and is the third leading cause of unintentional injury death. Low- and middle-income countries represent 96% of the yearly total.¹ As reported in the United States, nearly 6000 individuals are hospitalized and nearly 4000 die from drowning events annually.² But these figures likely underestimate the true rate, as many drowning fatalities are officially attributed to floods, boating accidents, or other associated events. Nonfatal drownings often go unreported.

Children under the age of 5 years have the highest drowning mortality worldwide, and drowning is the leading cause of unintentional injury death for this age group in many countries, including the United States.^1,2 Men are nearly 4 times as likely to die from drowning than women.² Predictably, in the United States most drowning happens on the weekend and during summer months. More than half of drownings in children younger than 4 years occur in swimming pools; with increasing age, drowning is more likely to occur in natural bodies of water.² With adults in higher income countries, alcohol is a significant contributor to drowning events during recreational activities.^3-5

Much effort has been made in recent years to standardize the nomenclature and treatment of drowning episodes. The International World Congress on Drowning met in the Netherlands in 2002, and established the definition of drowning as “the process of experiencing respiratory impairment from submersion/immersion in liquid.”⁶ Submersion refers to the complete submergence of the victim under the water, while immersion implies that the victim’s airway remains above the water.

CPR should begin, if possible, the moment the victim is out of the water.The Congress recommended that terms such as “wet-drowning,” “dry-drowning,” and “near-drowning” be discontinued in favor of the outcome classifications “death,” “no morbidity,” and “morbidity.” The “morbidity” subgroup was further characterized as “moderately disabled,” “severely disabled,” “vegetative state/coma,” and “brain death.” This meeting established guidelines on the treatment of drowning victims in addition to outlining points for future research.⁶

Physiologic chain of events in drowning

An unexpected immersion in water, particularly cold water, causes a reflexive inspiratory gasp, and some degree of aspiration occurs in most, if not all, cases of drowning. Aspiration further impairs victims’ ability to hold their breath or breathe normally.^5,7,8 It decreases lung compliance due to surfactant washout or intrapulmonary shunting and thereby leads to hypoxia. Aspiration-induced severe laryngospasm can also lead to hypoxia. Pulmonary edema and acute respiratory distress syndrome (ARDS) can follow.

The cardiovascular effects of drowning mirror those seen in hypoxia. Initially, apnea leads to decreased oxygen saturation and precipitates tachycardia and hypertension. Bradycardia and hypotension follow and blood is shunted to vital organs, such as the brain, heart, and lungs.⁹ This phenomenon is accelerated in cold water and leads to “swimming failure,” the impaired ability of the victim to swim because of decreased perfusion of the extremities.^5,7,8,10

“Autonomic conflict” has been proposed as an additional mechanism for morbidity and mortality from drowning episodes. Breath holding and immersion in cold water each can induce cardiac arrhythmias. When combined, these events may increase the risk of an arrhythmogenic state secondary to opposing chronotropic effects: the diving reflex (bradycardia via parasympathetic activation), and the cold shock response (tachycardia via sympathetic activation). This is thought to be an underreported cause of death in drowning, as arrhythmias are undetectable during autopsy.^8,11

Drowning prevention

The American Academy of Pediatrics (AAP) recommends swimming lessons for most children ages 4 years and older.¹² Previously, swimming lessons were not recommended for children ages 1 to 4 because evidence of benefit was lacking, and there was some concern that it might reduce children’s caution around water and reduce parents’ perceived level of need for supervision. Although data are still conflicting, some reports have since shown benefit in early swimming lessons for
toddlers.^13,14

As of 2010, the AAP acknowledges that training may be beneficial for children in this age group, but cautions that not all children will be ready for swimming by this age.¹² Infant water safety programs for children under the age of 1 are not recommended because evidence of benefit is lacking.¹²

Evidence is growing to support teaching basic water survival skills in low- to middle-income countries where water sources are abundant, particularly in Southeast Asia. Specifically, the SwimSafe survival swimming program has yielded impressive results in Bangladesh.¹⁵ This program targets children starting at age 5, and involves 20 lessons teaching basic water survival and rescue skills.

Results have shown a 93% reduction in drowning rates for children enrolled in the program, compared with those not enrolled.¹⁵ Subsequent analyses have proposed that swimming lessons for children in these parts of the world would be as cost effective as current attempts to prevent diarrheal and respiratory diseases in the same areas.¹⁶

Additional preventive measures that are effective in the United States include 4-sided pool fencing, use of personal flotation devices, and bystander cardiopulmonary
resuscitation (CPR).^2,5,17

On-scene evaluation and treatment

CPR for victims of drowning should always involve rescue breathing in addition to chest compressions.Drowning victims can appear mottled and have minimal or no peripheral pulses despite a heartbeat. Rescuers may assume the victim is dead when, in fact, there is cardiac function. Because initial assessment in this situation is difficult, CPR should begin, if possible, the moment the victim is out of the water. Successful on-scene resuscitation is the surest predictor of survival.^9,18 In fact, delay of CPR until the arrival of emergency personnel lessens the likelihood of survival.¹⁹

CPR applied to drowning. For cardiogenic cardiac arrest, chest compressions alone may be better than compressions with rescue breathing. For victims of drowning, though, coordinated compressions and rescue breathing are recommended.²⁰ The
2010 revision of the American Heart Association Guidelines for CPR and Emergency Cardiovascular Care emphasize “compression first” for CPR in cases of cardiogenic cardiac arrest, but continue to support the traditional Airway-Breathing-Chest Compressions sequence for drowning victims in its Special Situations section.²¹

Ventricular fibrillation (VF) is rare after submersion injury. An external defibrillator should be used when available, but it is unlikely to play a significant role in initial resuscitation.⁹

Don’t attempt to remove water from the victim’s mouth before resuscitation. The volume of fluid in the oral cavity is usually insignificant, and trying to remove it by abdominal thrusts or Heimlich maneuver will delay CPR and may injure the patient.²¹

Cervical spine injury is uncommon in drowning episodes, making cervical spine immobilization unnecessary unless the mechanism of injury is known or if there are clinical signs suggesting such injury. Needless cervical spine immobilization can interfere with adequate ventilation.^22,23 However, concern for head or cervical spine injury is warranted when recovering an unconscious victim from shallow water, where such injuries are more likely to result from falling or diving into the water.²⁴

Unless the mechanism of injury is known, cervical spine immobilization is typically unnecessary; needless c-spine immobilization can interfere with adequate ventilation.Administer oxygen supplementation when available to all spontaneously breathing individuals. Individuals who respond well to initial resuscitation and who don’t require intubation tend to have a very good prognosis overall.²⁵

Total time of submersion and the temperature of the water have bearing on the likelihood of survival. Only in rare cases have victims survived submersion lasting longer than 30 minutes. Ten minutes generally is considered the “point of no return.”^9,26 This is consistent with data suggesting 10 minutes of hypoxic insult causes irreversible neurologic damage, with each additional minute rapidly leading to coma.²⁰ However, to complicate matters, unlike cardiac arrest victims, drowning victims can lose cerebral blood flow slowly after respiratory impairment, which makes duration of submersion a potentially unreliable predictor of neurologic outcome.^20,26

Does hypothermia have a protective effect? Hypothermia can occur in water 85°F (30°C) or cooler.¹⁰ It has been hypothesized that resuscitation can be achieved after longer periods of submersion in cold water. However, the considerable debate on this topic has been based on little more than case reports.

For hypothermia to have a protective effect on neurologic function, cooling must take place rapidly and, ideally, before any hypoxic insult. The water would have to be exceptionally cold, likely less than 50°F (10°C).²⁷ The greater surface-to-volume ratio in children enables more rapid cooling and quicker onset of hypothermia, which may explain why they seem to have better neurologic outcomes than adults after prolonged submersion.²⁸

Hypothermia can also be protective if the victim is breathing when cooling begins, such as while floating or swimming in cold water before drowning.²⁹ This was the likely scenario in a reported case of a Norwegian kayaker who called for help after capsizing in 38°F (3.3°C) seawater. Despite having been in cardiac arrest for over 3 hours, the individual experienced a spontaneous return of circulation and was discharged after 32 days with no neurologic deficits.²⁹

Correcting hypothermia after rescue. Conscious patients with no cardiovascular or respiratory compromise should have wet clothing removed at the scene in exchange for blankets, towels, or warm dry clothing. Advise rescuers to attempt no further rewarming at the scene. With unconscious patients, take only simple measures to prevent further heat loss, and focus on transport and resuscitative efforts.²⁴

Hospital management

Attempts have been made to create a prognostic or predictive scoring system for drowning victims presenting to the emergency department. Factors thought to have bearing on mortality include duration of submersion, victim’s age, Glasgow Coma Scale (GCS) score, pupillary reactivity, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score.^23,30,31 Other measurements, such as core temperature, blood pH, and response to painful stimuli, correlate poorly with mortality.³¹ Hyperkalemia is repeatedly mentioned as a predictor of a poor neurologic outcome, as it is thought to indicate hypoxia before the onset of cooling.^8,26,32 The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.⁴

Continued ventilation assistance is critical. As with prehospital resuscitation efforts, ventilation is critical to in-hospital management. For patients who are breathing spontaneously, continuous positive airway pressure or bi-level positive airway pressure can reduce hypoxia in pulmonary edema. Standard indications of the need for intubation include decreased level of consciousness or concern for ability to protect the airway, hypoxia despite a high fraction of inspired oxygen (FiO₂), or persistent hypercapnia even with adequate noninvasive ventilatory support.³³

Victims may swallow large amounts of liquid during drowning; for intubated patients, advise orogastric tube placement to prevent aspiration of gastric contents. The reliability of pulse oximetry has been called into question in this setting and may be less accurate for victims who are hypothermic or who have been submerged in cold water.^23,34

Tiered intervention for hypothermia. In the hospital setting, passive rewarming is indicated for individuals with a body core temperature of 89.6°F to 95°F (32°C-35°C). Remove wet clothing; cover the victim with warm, dry towels or blankets; and give warm oral fluids and urge movement.

Individuals with core temperatures between 82.4°F to 89.6°F (28°C-32°C) require active external rewarming by applying heat directly to the skin via hot packs, warm blankets, and insulation. These patients should remain in a horizontal position with little movement, if possible, to avoid cold peripheral blood rapidly shifting to the core and precipitating an arrhythmia. Warmed intravenous fluids are appropriate as well.

With a core temperature less than 82.4°F (28°C), aggressive rewarming with extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) may be warranted as this individual will likely have unstable or absent vital signs (TABLE).^35,36 Some authorities advise that drowning victims with severe hypothermia and cardiac arrest should be resuscitated at facilities with CPB capability.^27,28,37

Inducing hypothermia therapeutically is still unproven. Although not tested specifically on drowning victims, therapeutic hypothermia would seem to have theoretical benefit for their resuscitation. In cardiogenic cardiac arrest, good evidence exists for improved neurologic outcomes with therapeutic hypothermia,³⁸ and this benefit might extend to drowning victims given their similar neurologic injury. No specific pharmacologic therapies have shown benefit in preventing loss of cerebral function.⁹

Monitor for clinical worsening. The concept of “secondary drowning,” a term now abandoned, referred to the phenomenon of clinical worsening hours after the initial drowning episode and resuscitation. This occurrence is now thought to be due to laryngospasm or to the progressive development of pulmonary edema from the aspiration of small amounts of water. Evidence supports monitoring asymptomatic patients; however, the period of suggested monitoring varies between 4 and 24 hours after the incident.^8,22,24

Imaging, if delayed, may be useful. Imaging immediately after a drowning episode is an unreliable predictor of outcome and should be sought only if trauma or symptoms dictate. Cranial computed tomography (CT) has yielded normal findings in drowning victims with a GCS score as low as 4.

If CT is performed, any abnormality detected within 2 to 3 days of injury is a strong predictor of a poor neurologic outcome.³⁹ Magnetic resonance imaging can be beneficial when performed more than 24 hours after resuscitation, preferably within a 4- to 7-day window.²⁰ Lung ultrasound has been used as a bedside tool to monitor progression of pulmonary edema, and could serve the same purpose in drowning recovery.⁴⁰

Anticipate respiratory complications. Since only a small amount of water is usually aspirated during a drowning event, the salinity of the aspirate is unlikely to cause significant disruption in hemodynamic or electrolyte balance.^17,20 However, even a small amount of aspirated water, particularly fresh water, can disrupt gas exchange by washing out surfactant. This can rapidly precipitate ARDS. Not surprisingly, the use of exogenous surfactant has been studied in limited case reports and has had positive results.^41-43 However, large trials have not yet been conducted, mostly because of the significant cost associated with surfactant therapy.

Antibiotics are rarely indicated prophylactically. Pneumonia after a drowning event is potentially fatal. It is more common in patients who have been intubated, and is therefore thought to be a hospital-acquired infection rather than a direct result of the drowning event.

The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.Frequently, pneumonia after drowning is caused by pathogens native to the upper airway, when a victim is unable to protect his or her upper airway.⁴⁴ In these cases, start broad spectrum antibiotics, with particular concern for organisms of the upper oropharynx. Also take into consideration species native to the body of water in which the victim was immersed.⁴⁴

Routine prophylaxis with antibiotics, although common, is not recommended. Exceptions may be victims of drowning in known contaminated water or victims with high volumes of water aspiration.²⁵ Some experts recommend blood cultures for victims who have aspirated, regardless of the presence or absence of infection.²⁴ However, this recommendation seems to be based on opinion.

CORRESPONDENCE
Sean C. Engel, MD, 6600 Excelsior Boulevard Suite 100, St. Louis Park, MN 55426; enge0289@umn.edu

A young mother in your practice wants her toddler to begin swimming lessons because her family loves water activities. How would you advise her? In fielding an urgent call about a drowning incident, what priorities would you urge regarding resuscitation at the scene? For a stabilized patient following a drowning episode, when might antibiotics be indicated? This article covers these issues as well as follow-up matters such as assisted ventilation and tiered hypothermia intervention.

Drowning likely occurs more often than is reported

Worldwide, drowning accounts for more than 388,000 deaths annually and is the third leading cause of unintentional injury death. Low- and middle-income countries represent 96% of the yearly total.¹ As reported in the United States, nearly 6000 individuals are hospitalized and nearly 4000 die from drowning events annually.² But these figures likely underestimate the true rate, as many drowning fatalities are officially attributed to floods, boating accidents, or other associated events. Nonfatal drownings often go unreported.

Children under the age of 5 years have the highest drowning mortality worldwide, and drowning is the leading cause of unintentional injury death for this age group in many countries, including the United States.^1,2 Men are nearly 4 times as likely to die from drowning than women.² Predictably, in the United States most drowning happens on the weekend and during summer months. More than half of drownings in children younger than 4 years occur in swimming pools; with increasing age, drowning is more likely to occur in natural bodies of water.² With adults in higher income countries, alcohol is a significant contributor to drowning events during recreational activities.^3-5

Much effort has been made in recent years to standardize the nomenclature and treatment of drowning episodes. The International World Congress on Drowning met in the Netherlands in 2002, and established the definition of drowning as “the process of experiencing respiratory impairment from submersion/immersion in liquid.”⁶ Submersion refers to the complete submergence of the victim under the water, while immersion implies that the victim’s airway remains above the water.

CPR should begin, if possible, the moment the victim is out of the water.The Congress recommended that terms such as “wet-drowning,” “dry-drowning,” and “near-drowning” be discontinued in favor of the outcome classifications “death,” “no morbidity,” and “morbidity.” The “morbidity” subgroup was further characterized as “moderately disabled,” “severely disabled,” “vegetative state/coma,” and “brain death.” This meeting established guidelines on the treatment of drowning victims in addition to outlining points for future research.⁶

Physiologic chain of events in drowning

An unexpected immersion in water, particularly cold water, causes a reflexive inspiratory gasp, and some degree of aspiration occurs in most, if not all, cases of drowning. Aspiration further impairs victims’ ability to hold their breath or breathe normally.^5,7,8 It decreases lung compliance due to surfactant washout or intrapulmonary shunting and thereby leads to hypoxia. Aspiration-induced severe laryngospasm can also lead to hypoxia. Pulmonary edema and acute respiratory distress syndrome (ARDS) can follow.

The cardiovascular effects of drowning mirror those seen in hypoxia. Initially, apnea leads to decreased oxygen saturation and precipitates tachycardia and hypertension. Bradycardia and hypotension follow and blood is shunted to vital organs, such as the brain, heart, and lungs.⁹ This phenomenon is accelerated in cold water and leads to “swimming failure,” the impaired ability of the victim to swim because of decreased perfusion of the extremities.^5,7,8,10

“Autonomic conflict” has been proposed as an additional mechanism for morbidity and mortality from drowning episodes. Breath holding and immersion in cold water each can induce cardiac arrhythmias. When combined, these events may increase the risk of an arrhythmogenic state secondary to opposing chronotropic effects: the diving reflex (bradycardia via parasympathetic activation), and the cold shock response (tachycardia via sympathetic activation). This is thought to be an underreported cause of death in drowning, as arrhythmias are undetectable during autopsy.^8,11

Drowning prevention

The American Academy of Pediatrics (AAP) recommends swimming lessons for most children ages 4 years and older.¹² Previously, swimming lessons were not recommended for children ages 1 to 4 because evidence of benefit was lacking, and there was some concern that it might reduce children’s caution around water and reduce parents’ perceived level of need for supervision. Although data are still conflicting, some reports have since shown benefit in early swimming lessons for
toddlers.^13,14

As of 2010, the AAP acknowledges that training may be beneficial for children in this age group, but cautions that not all children will be ready for swimming by this age.¹² Infant water safety programs for children under the age of 1 are not recommended because evidence of benefit is lacking.¹²

Evidence is growing to support teaching basic water survival skills in low- to middle-income countries where water sources are abundant, particularly in Southeast Asia. Specifically, the SwimSafe survival swimming program has yielded impressive results in Bangladesh.¹⁵ This program targets children starting at age 5, and involves 20 lessons teaching basic water survival and rescue skills.

Results have shown a 93% reduction in drowning rates for children enrolled in the program, compared with those not enrolled.¹⁵ Subsequent analyses have proposed that swimming lessons for children in these parts of the world would be as cost effective as current attempts to prevent diarrheal and respiratory diseases in the same areas.¹⁶

Additional preventive measures that are effective in the United States include 4-sided pool fencing, use of personal flotation devices, and bystander cardiopulmonary
resuscitation (CPR).^2,5,17

On-scene evaluation and treatment

CPR for victims of drowning should always involve rescue breathing in addition to chest compressions.Drowning victims can appear mottled and have minimal or no peripheral pulses despite a heartbeat. Rescuers may assume the victim is dead when, in fact, there is cardiac function. Because initial assessment in this situation is difficult, CPR should begin, if possible, the moment the victim is out of the water. Successful on-scene resuscitation is the surest predictor of survival.^9,18 In fact, delay of CPR until the arrival of emergency personnel lessens the likelihood of survival.¹⁹

CPR applied to drowning. For cardiogenic cardiac arrest, chest compressions alone may be better than compressions with rescue breathing. For victims of drowning, though, coordinated compressions and rescue breathing are recommended.²⁰ The
2010 revision of the American Heart Association Guidelines for CPR and Emergency Cardiovascular Care emphasize “compression first” for CPR in cases of cardiogenic cardiac arrest, but continue to support the traditional Airway-Breathing-Chest Compressions sequence for drowning victims in its Special Situations section.²¹

Ventricular fibrillation (VF) is rare after submersion injury. An external defibrillator should be used when available, but it is unlikely to play a significant role in initial resuscitation.⁹

Don’t attempt to remove water from the victim’s mouth before resuscitation. The volume of fluid in the oral cavity is usually insignificant, and trying to remove it by abdominal thrusts or Heimlich maneuver will delay CPR and may injure the patient.²¹

Cervical spine injury is uncommon in drowning episodes, making cervical spine immobilization unnecessary unless the mechanism of injury is known or if there are clinical signs suggesting such injury. Needless cervical spine immobilization can interfere with adequate ventilation.^22,23 However, concern for head or cervical spine injury is warranted when recovering an unconscious victim from shallow water, where such injuries are more likely to result from falling or diving into the water.²⁴

Unless the mechanism of injury is known, cervical spine immobilization is typically unnecessary; needless c-spine immobilization can interfere with adequate ventilation.Administer oxygen supplementation when available to all spontaneously breathing individuals. Individuals who respond well to initial resuscitation and who don’t require intubation tend to have a very good prognosis overall.²⁵

Total time of submersion and the temperature of the water have bearing on the likelihood of survival. Only in rare cases have victims survived submersion lasting longer than 30 minutes. Ten minutes generally is considered the “point of no return.”^9,26 This is consistent with data suggesting 10 minutes of hypoxic insult causes irreversible neurologic damage, with each additional minute rapidly leading to coma.²⁰ However, to complicate matters, unlike cardiac arrest victims, drowning victims can lose cerebral blood flow slowly after respiratory impairment, which makes duration of submersion a potentially unreliable predictor of neurologic outcome.^20,26

Does hypothermia have a protective effect? Hypothermia can occur in water 85°F (30°C) or cooler.¹⁰ It has been hypothesized that resuscitation can be achieved after longer periods of submersion in cold water. However, the considerable debate on this topic has been based on little more than case reports.

For hypothermia to have a protective effect on neurologic function, cooling must take place rapidly and, ideally, before any hypoxic insult. The water would have to be exceptionally cold, likely less than 50°F (10°C).²⁷ The greater surface-to-volume ratio in children enables more rapid cooling and quicker onset of hypothermia, which may explain why they seem to have better neurologic outcomes than adults after prolonged submersion.²⁸

Hypothermia can also be protective if the victim is breathing when cooling begins, such as while floating or swimming in cold water before drowning.²⁹ This was the likely scenario in a reported case of a Norwegian kayaker who called for help after capsizing in 38°F (3.3°C) seawater. Despite having been in cardiac arrest for over 3 hours, the individual experienced a spontaneous return of circulation and was discharged after 32 days with no neurologic deficits.²⁹

Correcting hypothermia after rescue. Conscious patients with no cardiovascular or respiratory compromise should have wet clothing removed at the scene in exchange for blankets, towels, or warm dry clothing. Advise rescuers to attempt no further rewarming at the scene. With unconscious patients, take only simple measures to prevent further heat loss, and focus on transport and resuscitative efforts.²⁴

Hospital management

Attempts have been made to create a prognostic or predictive scoring system for drowning victims presenting to the emergency department. Factors thought to have bearing on mortality include duration of submersion, victim’s age, Glasgow Coma Scale (GCS) score, pupillary reactivity, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score.^23,30,31 Other measurements, such as core temperature, blood pH, and response to painful stimuli, correlate poorly with mortality.³¹ Hyperkalemia is repeatedly mentioned as a predictor of a poor neurologic outcome, as it is thought to indicate hypoxia before the onset of cooling.^8,26,32 The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.⁴

Continued ventilation assistance is critical. As with prehospital resuscitation efforts, ventilation is critical to in-hospital management. For patients who are breathing spontaneously, continuous positive airway pressure or bi-level positive airway pressure can reduce hypoxia in pulmonary edema. Standard indications of the need for intubation include decreased level of consciousness or concern for ability to protect the airway, hypoxia despite a high fraction of inspired oxygen (FiO₂), or persistent hypercapnia even with adequate noninvasive ventilatory support.³³

Victims may swallow large amounts of liquid during drowning; for intubated patients, advise orogastric tube placement to prevent aspiration of gastric contents. The reliability of pulse oximetry has been called into question in this setting and may be less accurate for victims who are hypothermic or who have been submerged in cold water.^23,34

Tiered intervention for hypothermia. In the hospital setting, passive rewarming is indicated for individuals with a body core temperature of 89.6°F to 95°F (32°C-35°C). Remove wet clothing; cover the victim with warm, dry towels or blankets; and give warm oral fluids and urge movement.

Individuals with core temperatures between 82.4°F to 89.6°F (28°C-32°C) require active external rewarming by applying heat directly to the skin via hot packs, warm blankets, and insulation. These patients should remain in a horizontal position with little movement, if possible, to avoid cold peripheral blood rapidly shifting to the core and precipitating an arrhythmia. Warmed intravenous fluids are appropriate as well.

With a core temperature less than 82.4°F (28°C), aggressive rewarming with extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) may be warranted as this individual will likely have unstable or absent vital signs (TABLE).^35,36 Some authorities advise that drowning victims with severe hypothermia and cardiac arrest should be resuscitated at facilities with CPB capability.^27,28,37

Inducing hypothermia therapeutically is still unproven. Although not tested specifically on drowning victims, therapeutic hypothermia would seem to have theoretical benefit for their resuscitation. In cardiogenic cardiac arrest, good evidence exists for improved neurologic outcomes with therapeutic hypothermia,³⁸ and this benefit might extend to drowning victims given their similar neurologic injury. No specific pharmacologic therapies have shown benefit in preventing loss of cerebral function.⁹

Monitor for clinical worsening. The concept of “secondary drowning,” a term now abandoned, referred to the phenomenon of clinical worsening hours after the initial drowning episode and resuscitation. This occurrence is now thought to be due to laryngospasm or to the progressive development of pulmonary edema from the aspiration of small amounts of water. Evidence supports monitoring asymptomatic patients; however, the period of suggested monitoring varies between 4 and 24 hours after the incident.^8,22,24

Imaging, if delayed, may be useful. Imaging immediately after a drowning episode is an unreliable predictor of outcome and should be sought only if trauma or symptoms dictate. Cranial computed tomography (CT) has yielded normal findings in drowning victims with a GCS score as low as 4.

If CT is performed, any abnormality detected within 2 to 3 days of injury is a strong predictor of a poor neurologic outcome.³⁹ Magnetic resonance imaging can be beneficial when performed more than 24 hours after resuscitation, preferably within a 4- to 7-day window.²⁰ Lung ultrasound has been used as a bedside tool to monitor progression of pulmonary edema, and could serve the same purpose in drowning recovery.⁴⁰

Anticipate respiratory complications. Since only a small amount of water is usually aspirated during a drowning event, the salinity of the aspirate is unlikely to cause significant disruption in hemodynamic or electrolyte balance.^17,20 However, even a small amount of aspirated water, particularly fresh water, can disrupt gas exchange by washing out surfactant. This can rapidly precipitate ARDS. Not surprisingly, the use of exogenous surfactant has been studied in limited case reports and has had positive results.^41-43 However, large trials have not yet been conducted, mostly because of the significant cost associated with surfactant therapy.

Antibiotics are rarely indicated prophylactically. Pneumonia after a drowning event is potentially fatal. It is more common in patients who have been intubated, and is therefore thought to be a hospital-acquired infection rather than a direct result of the drowning event.

The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.Frequently, pneumonia after drowning is caused by pathogens native to the upper airway, when a victim is unable to protect his or her upper airway.⁴⁴ In these cases, start broad spectrum antibiotics, with particular concern for organisms of the upper oropharynx. Also take into consideration species native to the body of water in which the victim was immersed.⁴⁴

Routine prophylaxis with antibiotics, although common, is not recommended. Exceptions may be victims of drowning in known contaminated water or victims with high volumes of water aspiration.²⁵ Some experts recommend blood cultures for victims who have aspirated, regardless of the presence or absence of infection.²⁴ However, this recommendation seems to be based on opinion.

CORRESPONDENCE
Sean C. Engel, MD, 6600 Excelsior Boulevard Suite 100, St. Louis Park, MN 55426; enge0289@umn.edu

A young mother in your practice wants her toddler to begin swimming lessons because her family loves water activities. How would you advise her? In fielding an urgent call about a drowning incident, what priorities would you urge regarding resuscitation at the scene? For a stabilized patient following a drowning episode, when might antibiotics be indicated? This article covers these issues as well as follow-up matters such as assisted ventilation and tiered hypothermia intervention.

Drowning likely occurs more often than is reported

Worldwide, drowning accounts for more than 388,000 deaths annually and is the third leading cause of unintentional injury death. Low- and middle-income countries represent 96% of the yearly total.¹ As reported in the United States, nearly 6000 individuals are hospitalized and nearly 4000 die from drowning events annually.² But these figures likely underestimate the true rate, as many drowning fatalities are officially attributed to floods, boating accidents, or other associated events. Nonfatal drownings often go unreported.

Children under the age of 5 years have the highest drowning mortality worldwide, and drowning is the leading cause of unintentional injury death for this age group in many countries, including the United States.^1,2 Men are nearly 4 times as likely to die from drowning than women.² Predictably, in the United States most drowning happens on the weekend and during summer months. More than half of drownings in children younger than 4 years occur in swimming pools; with increasing age, drowning is more likely to occur in natural bodies of water.² With adults in higher income countries, alcohol is a significant contributor to drowning events during recreational activities.^3-5

Much effort has been made in recent years to standardize the nomenclature and treatment of drowning episodes. The International World Congress on Drowning met in the Netherlands in 2002, and established the definition of drowning as “the process of experiencing respiratory impairment from submersion/immersion in liquid.”⁶ Submersion refers to the complete submergence of the victim under the water, while immersion implies that the victim’s airway remains above the water.

CPR should begin, if possible, the moment the victim is out of the water.The Congress recommended that terms such as “wet-drowning,” “dry-drowning,” and “near-drowning” be discontinued in favor of the outcome classifications “death,” “no morbidity,” and “morbidity.” The “morbidity” subgroup was further characterized as “moderately disabled,” “severely disabled,” “vegetative state/coma,” and “brain death.” This meeting established guidelines on the treatment of drowning victims in addition to outlining points for future research.⁶

Physiologic chain of events in drowning

An unexpected immersion in water, particularly cold water, causes a reflexive inspiratory gasp, and some degree of aspiration occurs in most, if not all, cases of drowning. Aspiration further impairs victims’ ability to hold their breath or breathe normally.^5,7,8 It decreases lung compliance due to surfactant washout or intrapulmonary shunting and thereby leads to hypoxia. Aspiration-induced severe laryngospasm can also lead to hypoxia. Pulmonary edema and acute respiratory distress syndrome (ARDS) can follow.

The cardiovascular effects of drowning mirror those seen in hypoxia. Initially, apnea leads to decreased oxygen saturation and precipitates tachycardia and hypertension. Bradycardia and hypotension follow and blood is shunted to vital organs, such as the brain, heart, and lungs.⁹ This phenomenon is accelerated in cold water and leads to “swimming failure,” the impaired ability of the victim to swim because of decreased perfusion of the extremities.^5,7,8,10

“Autonomic conflict” has been proposed as an additional mechanism for morbidity and mortality from drowning episodes. Breath holding and immersion in cold water each can induce cardiac arrhythmias. When combined, these events may increase the risk of an arrhythmogenic state secondary to opposing chronotropic effects: the diving reflex (bradycardia via parasympathetic activation), and the cold shock response (tachycardia via sympathetic activation). This is thought to be an underreported cause of death in drowning, as arrhythmias are undetectable during autopsy.^8,11

Drowning prevention

The American Academy of Pediatrics (AAP) recommends swimming lessons for most children ages 4 years and older.¹² Previously, swimming lessons were not recommended for children ages 1 to 4 because evidence of benefit was lacking, and there was some concern that it might reduce children’s caution around water and reduce parents’ perceived level of need for supervision. Although data are still conflicting, some reports have since shown benefit in early swimming lessons for
toddlers.^13,14

As of 2010, the AAP acknowledges that training may be beneficial for children in this age group, but cautions that not all children will be ready for swimming by this age.¹² Infant water safety programs for children under the age of 1 are not recommended because evidence of benefit is lacking.¹²

Evidence is growing to support teaching basic water survival skills in low- to middle-income countries where water sources are abundant, particularly in Southeast Asia. Specifically, the SwimSafe survival swimming program has yielded impressive results in Bangladesh.¹⁵ This program targets children starting at age 5, and involves 20 lessons teaching basic water survival and rescue skills.

Results have shown a 93% reduction in drowning rates for children enrolled in the program, compared with those not enrolled.¹⁵ Subsequent analyses have proposed that swimming lessons for children in these parts of the world would be as cost effective as current attempts to prevent diarrheal and respiratory diseases in the same areas.¹⁶

Additional preventive measures that are effective in the United States include 4-sided pool fencing, use of personal flotation devices, and bystander cardiopulmonary
resuscitation (CPR).^2,5,17

On-scene evaluation and treatment

CPR for victims of drowning should always involve rescue breathing in addition to chest compressions.Drowning victims can appear mottled and have minimal or no peripheral pulses despite a heartbeat. Rescuers may assume the victim is dead when, in fact, there is cardiac function. Because initial assessment in this situation is difficult, CPR should begin, if possible, the moment the victim is out of the water. Successful on-scene resuscitation is the surest predictor of survival.^9,18 In fact, delay of CPR until the arrival of emergency personnel lessens the likelihood of survival.¹⁹

CPR applied to drowning. For cardiogenic cardiac arrest, chest compressions alone may be better than compressions with rescue breathing. For victims of drowning, though, coordinated compressions and rescue breathing are recommended.²⁰ The
2010 revision of the American Heart Association Guidelines for CPR and Emergency Cardiovascular Care emphasize “compression first” for CPR in cases of cardiogenic cardiac arrest, but continue to support the traditional Airway-Breathing-Chest Compressions sequence for drowning victims in its Special Situations section.²¹

Ventricular fibrillation (VF) is rare after submersion injury. An external defibrillator should be used when available, but it is unlikely to play a significant role in initial resuscitation.⁹

Don’t attempt to remove water from the victim’s mouth before resuscitation. The volume of fluid in the oral cavity is usually insignificant, and trying to remove it by abdominal thrusts or Heimlich maneuver will delay CPR and may injure the patient.²¹

Cervical spine injury is uncommon in drowning episodes, making cervical spine immobilization unnecessary unless the mechanism of injury is known or if there are clinical signs suggesting such injury. Needless cervical spine immobilization can interfere with adequate ventilation.^22,23 However, concern for head or cervical spine injury is warranted when recovering an unconscious victim from shallow water, where such injuries are more likely to result from falling or diving into the water.²⁴

Unless the mechanism of injury is known, cervical spine immobilization is typically unnecessary; needless c-spine immobilization can interfere with adequate ventilation.Administer oxygen supplementation when available to all spontaneously breathing individuals. Individuals who respond well to initial resuscitation and who don’t require intubation tend to have a very good prognosis overall.²⁵

Total time of submersion and the temperature of the water have bearing on the likelihood of survival. Only in rare cases have victims survived submersion lasting longer than 30 minutes. Ten minutes generally is considered the “point of no return.”^9,26 This is consistent with data suggesting 10 minutes of hypoxic insult causes irreversible neurologic damage, with each additional minute rapidly leading to coma.²⁰ However, to complicate matters, unlike cardiac arrest victims, drowning victims can lose cerebral blood flow slowly after respiratory impairment, which makes duration of submersion a potentially unreliable predictor of neurologic outcome.^20,26

Does hypothermia have a protective effect? Hypothermia can occur in water 85°F (30°C) or cooler.¹⁰ It has been hypothesized that resuscitation can be achieved after longer periods of submersion in cold water. However, the considerable debate on this topic has been based on little more than case reports.

For hypothermia to have a protective effect on neurologic function, cooling must take place rapidly and, ideally, before any hypoxic insult. The water would have to be exceptionally cold, likely less than 50°F (10°C).²⁷ The greater surface-to-volume ratio in children enables more rapid cooling and quicker onset of hypothermia, which may explain why they seem to have better neurologic outcomes than adults after prolonged submersion.²⁸

Hypothermia can also be protective if the victim is breathing when cooling begins, such as while floating or swimming in cold water before drowning.²⁹ This was the likely scenario in a reported case of a Norwegian kayaker who called for help after capsizing in 38°F (3.3°C) seawater. Despite having been in cardiac arrest for over 3 hours, the individual experienced a spontaneous return of circulation and was discharged after 32 days with no neurologic deficits.²⁹

Correcting hypothermia after rescue. Conscious patients with no cardiovascular or respiratory compromise should have wet clothing removed at the scene in exchange for blankets, towels, or warm dry clothing. Advise rescuers to attempt no further rewarming at the scene. With unconscious patients, take only simple measures to prevent further heat loss, and focus on transport and resuscitative efforts.²⁴

Hospital management

Attempts have been made to create a prognostic or predictive scoring system for drowning victims presenting to the emergency department. Factors thought to have bearing on mortality include duration of submersion, victim’s age, Glasgow Coma Scale (GCS) score, pupillary reactivity, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score.^23,30,31 Other measurements, such as core temperature, blood pH, and response to painful stimuli, correlate poorly with mortality.³¹ Hyperkalemia is repeatedly mentioned as a predictor of a poor neurologic outcome, as it is thought to indicate hypoxia before the onset of cooling.^8,26,32 The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.⁴

Continued ventilation assistance is critical. As with prehospital resuscitation efforts, ventilation is critical to in-hospital management. For patients who are breathing spontaneously, continuous positive airway pressure or bi-level positive airway pressure can reduce hypoxia in pulmonary edema. Standard indications of the need for intubation include decreased level of consciousness or concern for ability to protect the airway, hypoxia despite a high fraction of inspired oxygen (FiO₂), or persistent hypercapnia even with adequate noninvasive ventilatory support.³³

Victims may swallow large amounts of liquid during drowning; for intubated patients, advise orogastric tube placement to prevent aspiration of gastric contents. The reliability of pulse oximetry has been called into question in this setting and may be less accurate for victims who are hypothermic or who have been submerged in cold water.^23,34

Tiered intervention for hypothermia. In the hospital setting, passive rewarming is indicated for individuals with a body core temperature of 89.6°F to 95°F (32°C-35°C). Remove wet clothing; cover the victim with warm, dry towels or blankets; and give warm oral fluids and urge movement.

Individuals with core temperatures between 82.4°F to 89.6°F (28°C-32°C) require active external rewarming by applying heat directly to the skin via hot packs, warm blankets, and insulation. These patients should remain in a horizontal position with little movement, if possible, to avoid cold peripheral blood rapidly shifting to the core and precipitating an arrhythmia. Warmed intravenous fluids are appropriate as well.

With a core temperature less than 82.4°F (28°C), aggressive rewarming with extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass (CPB) may be warranted as this individual will likely have unstable or absent vital signs (TABLE).^35,36 Some authorities advise that drowning victims with severe hypothermia and cardiac arrest should be resuscitated at facilities with CPB capability.^27,28,37

Inducing hypothermia therapeutically is still unproven. Although not tested specifically on drowning victims, therapeutic hypothermia would seem to have theoretical benefit for their resuscitation. In cardiogenic cardiac arrest, good evidence exists for improved neurologic outcomes with therapeutic hypothermia,³⁸ and this benefit might extend to drowning victims given their similar neurologic injury. No specific pharmacologic therapies have shown benefit in preventing loss of cerebral function.⁹

Monitor for clinical worsening. The concept of “secondary drowning,” a term now abandoned, referred to the phenomenon of clinical worsening hours after the initial drowning episode and resuscitation. This occurrence is now thought to be due to laryngospasm or to the progressive development of pulmonary edema from the aspiration of small amounts of water. Evidence supports monitoring asymptomatic patients; however, the period of suggested monitoring varies between 4 and 24 hours after the incident.^8,22,24

Imaging, if delayed, may be useful. Imaging immediately after a drowning episode is an unreliable predictor of outcome and should be sought only if trauma or symptoms dictate. Cranial computed tomography (CT) has yielded normal findings in drowning victims with a GCS score as low as 4.

If CT is performed, any abnormality detected within 2 to 3 days of injury is a strong predictor of a poor neurologic outcome.³⁹ Magnetic resonance imaging can be beneficial when performed more than 24 hours after resuscitation, preferably within a 4- to 7-day window.²⁰ Lung ultrasound has been used as a bedside tool to monitor progression of pulmonary edema, and could serve the same purpose in drowning recovery.⁴⁰

Anticipate respiratory complications. Since only a small amount of water is usually aspirated during a drowning event, the salinity of the aspirate is unlikely to cause significant disruption in hemodynamic or electrolyte balance.^17,20 However, even a small amount of aspirated water, particularly fresh water, can disrupt gas exchange by washing out surfactant. This can rapidly precipitate ARDS. Not surprisingly, the use of exogenous surfactant has been studied in limited case reports and has had positive results.^41-43 However, large trials have not yet been conducted, mostly because of the significant cost associated with surfactant therapy.

Antibiotics are rarely indicated prophylactically. Pneumonia after a drowning event is potentially fatal. It is more common in patients who have been intubated, and is therefore thought to be a hospital-acquired infection rather than a direct result of the drowning event.

The best predictor of a good outcome is consciousness at the time of arrival at the emergency department.Frequently, pneumonia after drowning is caused by pathogens native to the upper airway, when a victim is unable to protect his or her upper airway.⁴⁴ In these cases, start broad spectrum antibiotics, with particular concern for organisms of the upper oropharynx. Also take into consideration species native to the body of water in which the victim was immersed.⁴⁴

Routine prophylaxis with antibiotics, although common, is not recommended. Exceptions may be victims of drowning in known contaminated water or victims with high volumes of water aspiration.²⁵ Some experts recommend blood cultures for victims who have aspirated, regardless of the presence or absence of infection.²⁴ However, this recommendation seems to be based on opinion.

CORRESPONDENCE
Sean C. Engel, MD, 6600 Excelsior Boulevard Suite 100, St. Louis Park, MN 55426; enge0289@umn.edu

CASE › Your patient, Bob G, age 47, has a body mass index of 33, hypertension (blood pressure 150/85 mm Hg), and elevated cholesterol (low-density lipoprotein level, 187 mg/dL) and glucose levels (fasting glucose 122 mg/dL, with an HbA1c of 6.1%). He gets out of breath when he plays with his 2 children. His father has diabetes and had a myocardial infarction (MI) at age 55; Mr. G tells you he is concerned he will develop similar health problems. Mr. G frequents fast food restaurants and eats high-calorie snacks after work, especially when he feels stressed. During a recent office visit, he expresses his desire to “be there” for his children and says he is motivated to lose weight to prevent diabetes and/or an MI.

How would you proceed?

Most health conditions in the United States are directly or indirectly the result of patients’ health-related behaviors.¹ Fortunately, family physicians (FPs) and primary care teams are in an excellent position to help their patients make healthy behavior changes by using brief, evidence-based interventions that can be implemented during the typical office visit.

Specifically, the use of the following 7 techniques can build on patients’ own motivations, successes, and life circumstances to improve their satisfaction and self-efficacy:

• the 5 As (Ask, Advise, Assess, Assist, Arrange)
• the FRAMES protocol (Feedback, Responsibility, Advice, Menu, Empathy, and Self-efficacy)
• teachable moments (TM)
• solution-focused brief therapy (SFBT)
• cognitive behavioral therapy (CBT)
• narrative techniques (NT)
• motivational interviewing (MI).

But before we describe the practical application of these 7 techniques, we’ll begin by explaining a few underlying concepts for helping patients change their health-related behaviors.

Understanding what does—and doesn’t—help patients change

Research from the field of psychology and other social sciences has described several important concepts that affect how FPs can best help their patients change to healthier behaviors.^2-9 First, several “common factors” have been found to reliably predict behavior change. The likelihood of change is strongly tied to the patient’s strengths, the environment, and the quality of the physician-patient relationship. The patient’s expectations and the techniques a physician uses also predict behavior change, but to a lesser extent.¹⁰

Second, patients seldom become motivated to change ingrained behaviors solely by being provided with information about the risks and benefits associated with those behaviors. People overcome ambivalence and develop motivation for change when they align their behaviors with their core values and goals. FPs can help patients link their motivation to change to specific plans and environments. This can then facilitate small changes that can yield large returns by increasing a patient’s self-efficacy and sense of control.^2-9

Third, willpower is a finite but renewable resource that increases or decreases based on an individual’s internal and external environments. Reliance on willpower alone to make changes is unlikely to be successful without shaping the environment to support the new behavior.¹¹

A patient’s readiness to change affects choice of technique

Knowing how ready a patient is to change is important for determining which approaches are likely to be effective at a given visit.Knowing how ready a patient is to change is important for determining which approaches are likely to be effective at a given visit. Prochaska and DiClemente developed a model that defines 6 stages of change: Precontemplation (patient does not intend to change in the next 6 months), Contemplation (patient intends to change within the next 6 months), Preparation (patient intends to change within the next month), Action (patient has made specific changes within the past 6 months), Maintenance (patient works to prevent relapse), and Relapse (patient returns to an earlier stage) (TABLE).¹²

Patients who identify change as important and are ready to make changes benefit from collaborative work with an FP or other clinicians on the how, when, where, and who (eg, the patient, his or her significant other, family, and friends) of the new behaviors. These individuals are in the Preparation or Action stages of change, which comprise roughly 20% of patients.¹³ In these circumstances, techniques such as the 5 As, FRAMES, TM, SFBT, and CBT can be effective.

For the estimated 80% of patients who are in the Precontemplation or Contemplation stages and are unsure about the relative importance of changing behaviors and/or lack confidence to make changes, these directive techniques can cause defensiveness, which can make both the patient and the FP uncomfortable. For such patients, approaches that build on the patient’s own motivations and stories, such as MI and NT, may be preferred.

3 techniques that overlap

The FRAMES protocol and TM are based on behavior change theories, and each mixes directive techniques with relationship building to facilitate health behavior change. There is overlap in concepts across the 5 As, FRAMES, and TM, and some evidence suggests these approaches can be adapted for use in primary care settings.^14-16

The 5 As is a brief intervention in which the FP sets an agenda and provides advice at the outset. This technique has been shown to improve smoking cessation rates in pregnant women compared with physician recommendations alone.¹⁷ It may also help with weight loss for patients who are ready to change and are given support for their
efforts.¹⁸

Putting the 5 As into action

CASE › An FP who wants to use the 5 As technique to assist Mr. G might proceed as follows: Ask: “How often do you exercise and follow a diet?” Advise: “I recommend that you start exercising 30 minutes each day and start following a healthier diet. It is one of the most important things you can do for your health.” Assess: “Are you willing to start exercising and trying a diet in the next month?” Assist: “Here is a list of local recreation centers and some information about a healthy diet.” Arrange: “I’d like to have one of the nurses call you in a week to see how things are going and have you return in a month for a follow-up appointment.”

The 6 components of the FRAMES protocol overlap with the 5 As.¹⁴ FRAMES utilizes relationship-building by explicitly reinforcing patient autonomy, offering a menu of choices, and acknowledging patient strengths.¹⁴

Putting the FRAMES protocol into action

CASE › Using the FRAMES protocol for Mr. G might consist of the following: Feedback: “Your eating habits and lack of exercise have contributed to your weight, high glucose and cholesterol levels, and shortness of breath.” Responsibility: “The decision to lose weight is a choice only you can make.” Advice: “I recommend that you start regularly exercising and eating healthily.” Menu: “Here are some options that many people find helpful when they try to lose weight.” Empathy: “It is challenging to change the way we eat and exercise.” Self-efficacy: “You have been able to overcome a lot of difficult things in your life already and it seems very important to you to make these changes.”

TM begins with the FP linking a patient concern, such as shortness of breath, to a physician concern, such as obesity.¹⁵ The FP then provides advice, assesses readiness, and responds based on the patient’s stage of change.¹⁶

Putting TM into action

CASE › Using the TM approach to help Mr. G might work as follows: Link a patient concern with specific behavioral change: “I think that your shortness of breath is caused by your weight.” Recommend change, offer support, and ask for commitment: “I recommend that you lose 15 pounds. I’m confident that you can do this, and am here to help you. Are you ready to talk about some specific ways you can do this?” Respond based on the patient’s readiness to change: “All right, let’s talk about healthy food choices and exercise.” (This statement would be appropriate if Mr. G was in the Preparation or Action stage of change.)

Solution-focused brief therapy

In solution-focused brief therapy, the FP helps the patient explore solutions and/or exceptions to problems that have worked for the patient in the past.SFBT highlights a patient’s previous successes and strengths, as opposed to exploring problems and past failures.^19,20 The FP fosters behavior change by using strategic questions to develop an intervention with the patient.²¹ SFBT involves encouraging patients to find exceptions to current problems and increasing the occurrence of current beneficial behaviors.¹⁹ This approach begins with the patient identifying a problem for which he or she would like help. The FP helps the patient explore solutions and/or exceptions to this problem that have worked for the patient previously (or solutions/exceptions that the patient can imagine). The FP does not offer suggestions to solve the patient’s problem. Instead, the patient and FP collaboratively identify and support the patient’s strengths, and they develop a behavioral task to try based on these patient-derived solutions.²²

Putting SFBT into action

CASE › A physician who wants to use SFBT to help Mr. G might start by asking an “exception” question (“When have you been able to eat in a more healthy way?”) and following up with a “difference” question (“What was different about those times?”). Perhaps Mr. G remembers that previously he had improved his diet by buying and keeping a bag of apples in the car to snack on. He additionally recalls that he ate less at night if he brushed his teeth right after dinner.

Mr. G decides to revisit the apple and brushing strategies. Mr. G’s physician commends him for wanting to be there for his kids and identifying the apple and brushing strategies. She helps him design a small “experiment” in which he would use these strategies and observe the outcomes. They arrange to speak in one month to discuss how things are going.

Cognitive behavioral therapy

CBT is a practical, goal-directed, action-oriented treatment that focuses on helping patients make changes in their thinking and behavior.^23-28 A basic premise of CBT is that emotions are difficult to change directly, so CBT targets distressing emotions by focusing on changing thoughts and/or behaviors that contribute to those emotions. CBT can be useful when the patient and FP can find a link between the patient’s thoughts and a troubling behavior. After thoroughly assessing situations that bother the patient, the FP provides the patient with an empathic summary that captures the essence of the problem. CBT practitioners typically conceptualize problems and plan treatment by working with the patient to gather information on the patient’s thoughts, feelings, and behaviors.

By exploring patterns of thinking that lead to self-destructive behaviors, an FP can help the patient understand and challenge strongly held but often limited patterns of thinking. For example, a patient with depression-related overeating might think, “I am worthless. Nothing ever goes right for me.” A patient with anxiety-related smoking may believe, “I am in danger.” Through a collaborative, respectful relationship, patients learn to test their “hypotheses,” challenge their thoughts, and experiment with alternate ways of thinking and behaving. Patients are given homework assignments, such as tracking their thoughts and behaviors, practicing relaxation techniques, and challenging automatic ways of viewing themselves and the world around them.

Putting CBT into action

CASE › An FP who wants to implement CBT to help Mr. G would begin by trying to understand his patient’s view: “Tell me how your weight is a part of your life.” Next, he would offer Mr. G an empathic summary: “You’re worried that your weight could cause some of the same health problems your dad has and that will prevent you from being the kind of active father you want to be. You sometimes eat when you are feeling stressed and tired, but then you feel worse afterwards.” He would assign Mr. G homework: “Notice and write down your thoughts when you are eating due to stress rather than hunger. Bring this in and we can look at it together.” The FP might also teach Mr. G relaxation breathing, and encourage him to try doing 5 relaxation breaths when he feels stressed and wants to eat.

Narrative techniques

Narrative techniques avoid unsolicited advice and interpretations and rarely impose the FP’s agenda on the patient.NT can be effective for patients who are in the Precontemplation or Contemplation stages of change.^29-33 NT focuses on the patient’s story, context, and language. FPs explore connections, discuss hypotheses, strategize, share power with the patient, and offer reflections in order to understand the patient’s illness experience. This approach fits well with the complex way that many behaviors are woven into the concerns that patients bring to their FPs. As a patient’s story unfolds, the diagnosis and treatment can occur simultaneously. The FP involves the patient in choices about how to proceed and what to focus on together.