Fatigue resident survival guide

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Resident Survival Guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]Mounika Lakhmalla, MBBS[3]Ramyar Ghandriz MD[4]

Synonyms and keywords:Approach to weakness, Approach to tiredness, Approach to lethargy, Approach to debility


Fatigue is a common nonspecific symptom due to a wide range of etiologies. Patients often use this term to describe a range of issues such as difficulty initiating activity, decreased capacity to maintain activity, trouble with concentration, memory, and emotional stability; or sleepiness or an uncontrollable need to sleep. The term fatigue can sometimes be used synonymously with tiredness. Fatigue can present alone as a primary symptom or in association with other localizing symptoms.


Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

Common Causes

  • Multiple sclerosis
  • After malignancy treatment, patients can experience different patterns of fatigue from chemotherapy, radiation treatment, or surgery.


The approach to the diagnosis of fatigue is based on a step-wise testing strategy. Below is an algorithm summarizing the identification and laboratory diagnosis of fatigue.

  • Diagnostic evaluation of fatigue when it presents as a predominant symptom includes a detailed history and physical examination, basic laboratory studies, and updated cancer screening interventions.
  • Additional diagnostic testing depends on associated localized findings.
  • Extensive laboratory studies without a suggestive history or physical exam findings is of limited diagnostic utility while evaluating chronic fatigue.

Seek proper history, ask patients to describe in their own words, what do they mean by fatigue?
This will help distinguish fatigue from
muscle weakness
The history should also determine the characteristics, severity, and temporal pattern of fatigue:
❑ Onset – Abrupt or gradual, relationship to illness or life event
❑ Course – Stable, improving, or worsening
❑ Duration and daily pattern
❑ Factors that alleviate or exacerbate it
❑ Impact on daily life – Ability to work, socialize, participate in family activities
❑ Accommodations that the patient/family has had to make to deal with symptom
Characterize the cardiac symptoms:
Dyspnea on exertion
❑ Leg swelling
Characterize the pulmonary symptoms:
❑ Dyspnea
❑ Chronic cough
❑ Sputum production
❑ Snoring
❑ Interrupted breathing during sleep
Characterize the endocrinologic / metabolic symptoms:
Cold intolerance
Weight gain
❑ Dry skin
Heat intolerance
Weight loss
❑ Diarrhea
❑ Moist skin
❑ Nausea/vomiting
❑ Mental status changes
❑ Decreased urine
❑ Abdominal distention
❑ Gastrointestinal bleeding
❑ Salt craving
❑ Gastrointestinal complaints
❑ Malaise
❑ Cognitive dysfunction
Characterize the hematologic / neoplastic symptoms:
❑ Dizziness
❑ Weakness
❑ Weight loss
Characterize the Infectious diseases symptoms:
❑ Fever/chills
❑ Sore throat
❑ Tender lymph nodes
❑ Nausea/vomiting
❑ Abdominal discomfort
Weight loss
Night sweats
❑ Myalgias
Characterize the rheumatologic symptoms:
❑ Chronic diffuse muscle pain
❑ Aching/morning stiffness of shoulders, neck, and hips
Characterize the psychological symptoms:
❑ Sad mood
❑ Altered sleep
❑ Cognitive dysfunction
❑ Generalized nervousness
Panic attacks
❑ Multiple chronic constitutional and localized complaints
Examine the patient:
❑ Elevated jugular venous distension
❑ Peripheral edema
❑ S3 gallop
❑ Inspiratory rales
Examine the patient:
❑ Evidence of hyperinflation
❑ Hypertension
Examine the patient:
❑ Slow deep tendon reflex relaxation phase
❑ Ophthalmopathy
❑ Hypertension
❑ Peripheral edema
Palmar erythema
❑ Evidence of ascites
❑ Hypotension
❑ Hyperpigmentation
❑ Vitiligo
Examine the patient:
Examine the patient:
❑ Exudate pharyngitis
❑ Tender cervical adenopathy
❑ Tender hepatomegaly
❑ New (regurgitant) murmur
Chest pain
❑ Dyspnea
Examine the patient:
❑ Multiple "tender points" on palpation
❑ Decreased range of motion of shoulders, neck, and hips
Examine the patient:
❑ Tachycardia
❑ Muscle tension
Diagnostic work-up:
❑ Chest radiograph
❑ Echocardiogram
Diagnostic work-up:
❑ Chest radiograph
❑ Sleep study
Diagnostic work-up:
Thyroid function tests
Renal function tests/ serum electrolytes
Hepatic function tests
❑ Morning cortisol/ACTH, ACTH stimulation test
❑Serum sodium level
❑Serum calcium level
Diagnostic work-up:
Complete blood count
Diagnostic work-up:
❑ Complete blood/differential count
❑ Monospot
Hepatic function tests
❑ Viral hepatitis serologies
HIV serology
❑ Blood cultures
❑ PPD/gamma-interferon assay
❑ Chest radiograph
Diagnostic work-up:
Erythrocyte sedimentation rate
Diagnostic work-up:
❑ Screening tests (eg, PHQ-2, PHQ-9, GAD-7, SSS-8
Consider differential diagnosis:
Congective heart failure
Atypical angina [1]
Consider differential diagnosis:
Chronic obstructive pulmonary disease [2]
Sleep apnea [3]
Consider differential diagnosis:
Hypothyroidism [4]
Hyperthyroidism [5]
❑ Inflammatory bowel disease [6]
Chronic renal disease [7]
Chronic hepatic disease [8]
Adrenal insufficiency [9]
Hyponatremia [10]
Hypercalcemia [11]
Consider differential diagnosis:
Anemia [11]
Occult malignancy [12]
Consider differential diagnosis:
Depression [20]
Anxiety disorder [21]
Somatization disorder [22]



Treat the underlying causes
Fatigue due to heart failure[23][24][25][26] :
❑Vasodilator Therapy
❑Inotropic Therapy
❑Vasopressor Support
❑ACE Inhibition
❑Beta Blockers
❑Aldosterone Antagonism
Fatigue due to stable angina[27]:
❑Antiplatelet agents
❑Antianginal agents
❑ACEI/RAAS Blockers
Ftigue due to Chronic obstructive pulmonary disease[28][29][30].:
❑Beta Adrenergic Receptor Agonists
❑Long Acting Beta-2 Adrenergic Receptor Agonist
❑Phosphodiesterase Inhibitor
Fatigue due to sleep apnea:[31].[32][33][34][35]
❑Weight loss
❑Continuous positive airway pressure
❑Oral appliances
❑Modafinil 200-400 mg per day
Fatigue due to hypothyroidism:.[36][37]
❑Synthetic T4(Levothyroxin)
Fatigue due to hyperthyroidism:[39]
❑Beta blockers
Fatigue due to Chronic Renal Failure:[40]
❑Blood pressure management
❑Kidney Transplant
Fatigue due to anemia:[41][42] [43]
❑Blood transfusion,
❑Iron transfusion
❑Folate therapy
❑Vit B12
Fatigue due to Mononucleosis[44]
❑Intravenous corticostreoid
❑Opioid analgesics
Fatigue due to Viral Hepatitis.[51][52][53][54]:
❑Interferon-α 2b
Fatigue due to Endocarditis[55]:
❑Empiric antibiotics
❑Antithrombotic therapy
Fatigue due to Fibromyalgia:[56]; [57][58]
Fatigue due to Polymyalgia:[59][59]
Fatigue due to Rheumatoid arthritis:[60][61]

Fatigue due to Sjögren's syndrome[63][64][65]

Fatigue due to Mood disorders:[67]
❑Anti depresant therapy
❑Anxiolytic therapy


  • Though most of the conditions presenting with fatigue have the luxury of time for appropriate evaluation & treatment, a few may require immediate diagnosis & treatment to prevent death or serious sequelae.
  • In case of Cardiovascular emergencies: In symptomatic Heart failure secondary to atrial fibrillation, hemodynamically unstable patients require urgent direct-current cardioversion.
  • Endocrine disorders: Diabetic ketoacidosis or nonketotic hyperglycemic states require urgent correction of blood sugar levels, acidosis, electrolyte & Fluid imbalances.
  • Infectious disease
    • Untreated tuberculosis: respiratory failure and systemic spread of disease in immunocompromised individuals.
    • HIV, if not diagnosed or treated appropriately with antiretroviral drugs, may result in overt AIDS and eventually death.
    • Coronavirus disease 2019 (COVID-19)
      • Patients may develop severe viral pneumonia leading to acute respiratory distress syndrome that is potentially fatal.
      • Suspected COVID-19 infection should be isolated from others, along with contact and droplet precautions, airborne precautions if performing aerosol-generating procedures.


  • Extensive laboratory work-up is rarely helpful in the absence of suggestive signs and symptoms.
  • Mannitol is contraindicated in fatigue treatment.


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