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2025 PACUPrep BCCCP Preparatory Course

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  1. Pulmonary

    ARDS
    4 Topics
    |
    1 Quiz
  2. Asthma Exacerbation
    4 Topics
    |
    1 Quiz
  3. COPD Exacerbation
    4 Topics
    |
    1 Quiz
  4. Cystic Fibrosis
    6 Topics
    |
    1 Quiz
  5. Drug-Induced Pulmonary Diseases
    3 Topics
    |
    1 Quiz
  6. Mechanical Ventilation Pharmacotherapy
    5 Topics
    |
    1 Quiz
  7. Pleural Disorders
    5 Topics
    |
    1 Quiz
  8. Pulmonary Hypertension (Acute and Chronic severe pulmonary hypertension)
    5 Topics
    |
    1 Quiz
  9. Cardiology
    Acute Coronary Syndromes
    6 Topics
    |
    1 Quiz
  10. Atrial Fibrillation and Flutter
    6 Topics
    |
    1 Quiz
  11. Cardiogenic Shock
    4 Topics
    |
    1 Quiz
  12. Heart Failure
    7 Topics
    |
    1 Quiz
  13. Hypertensive Crises
    5 Topics
    |
    1 Quiz
  14. Ventricular Arrhythmias and Sudden Cardiac Death Prevention
    5 Topics
    |
    1 Quiz
  15. NEPHROLOGY
    Acute Kidney Injury (AKI)
    5 Topics
    |
    1 Quiz
  16. Contrast‐Induced Nephropathy
    5 Topics
    |
    1 Quiz
  17. Drug‐Induced Kidney Diseases
    5 Topics
    |
    1 Quiz
  18. Rhabdomyolysis
    5 Topics
    |
    1 Quiz
  19. Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
    5 Topics
    |
    1 Quiz
  20. Renal Replacement Therapies (RRT)
    5 Topics
    |
    1 Quiz
  21. Neurology
    Status Epilepticus
    5 Topics
    |
    1 Quiz
  22. Acute Ischemic Stroke
    5 Topics
    |
    1 Quiz
  23. Subarachnoid Hemorrhage
    5 Topics
    |
    1 Quiz
  24. Spontaneous Intracerebral Hemorrhage
    5 Topics
    |
    1 Quiz
  25. Neuromonitoring Techniques
    5 Topics
    |
    1 Quiz
  26. Gastroenterology
    Acute Upper Gastrointestinal Bleeding
    5 Topics
    |
    1 Quiz
  27. Acute Lower Gastrointestinal Bleeding
    5 Topics
    |
    1 Quiz
  28. Acute Pancreatitis
    5 Topics
    |
    1 Quiz
  29. Enterocutaneous and Enteroatmospheric Fistulas
    5 Topics
    |
    1 Quiz
  30. Ileus and Acute Intestinal Pseudo-obstruction
    5 Topics
    |
    1 Quiz
  31. Abdominal Compartment Syndrome
    5 Topics
    |
    1 Quiz
  32. Hepatology
    Acute Liver Failure
    5 Topics
    |
    1 Quiz
  33. Portal Hypertension & Variceal Hemorrhage
    5 Topics
    |
    1 Quiz
  34. Hepatic Encephalopathy
    5 Topics
    |
    1 Quiz
  35. Ascites & Spontaneous Bacterial Peritonitis
    5 Topics
    |
    1 Quiz
  36. Hepatorenal Syndrome
    5 Topics
    |
    1 Quiz
  37. Drug-Induced Liver Injury
    5 Topics
    |
    1 Quiz
  38. Dermatology
    Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
    5 Topics
    |
    1 Quiz
  39. Erythema multiforme
    5 Topics
    |
    1 Quiz
  40. Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS)
    5 Topics
    |
    1 Quiz
  41. Immunology
    Transplant Immunology & Acute Rejection
    5 Topics
    |
    1 Quiz
  42. Solid Organ & Hematopoietic Transplant Pharmacotherapy
    5 Topics
    |
    1 Quiz
  43. Graft-Versus-Host Disease (GVHD)
    5 Topics
    |
    1 Quiz
  44. Hypersensitivity Reactions & Desensitization
    5 Topics
    |
    1 Quiz
  45. Biologic Immunotherapies & Cytokine Release Syndrome
    5 Topics
    |
    1 Quiz
  46. Endocrinology
    Relative Adrenal Insufficiency and Stress-Dose Steroid Therapy
    5 Topics
    |
    1 Quiz
  47. Hyperglycemic Crisis (DKA & HHS)
    5 Topics
    |
    1 Quiz
  48. Glycemic Control in the ICU
    5 Topics
    |
    1 Quiz
  49. Thyroid Emergencies: Thyroid Storm & Myxedema Coma
    5 Topics
    |
    1 Quiz
  50. Hematology
    Acute Venous Thromboembolism
    5 Topics
    |
    1 Quiz
  51. Drug-Induced Thrombocytopenia
    5 Topics
    |
    1 Quiz
  52. Anemia of Critical Illness
    5 Topics
    |
    1 Quiz
  53. Drug-Induced Hematologic Disorders
    5 Topics
    |
    1 Quiz
  54. Sickle Cell Crisis in the ICU
    5 Topics
    |
    1 Quiz
  55. Methemoglobinemia & Dyshemoglobinemias
    5 Topics
    |
    1 Quiz
  56. Toxicology
    Toxidrome Recognition and Initial Management
    5 Topics
    |
    1 Quiz
  57. Management of Acute Overdoses – Non-Cardiovascular Agents
    5 Topics
    |
    1 Quiz
  58. Management of Acute Overdoses – Cardiovascular Agents
    5 Topics
    |
    1 Quiz
  59. Toxic Alcohols and Small-Molecule Poisons
    5 Topics
    |
    1 Quiz
  60. Antidotes and Gastrointestinal Decontamination
    5 Topics
    |
    1 Quiz
  61. Extracorporeal Removal Techniques
    5 Topics
    |
    1 Quiz
  62. Withdrawal Syndromes in the ICU
    5 Topics
    |
    1 Quiz
  63. Infectious Diseases
    Sepsis and Septic Shock
    5 Topics
    |
    1 Quiz
  64. Pneumonia (CAP, HAP, VAP)
    5 Topics
    |
    1 Quiz
  65. Endocarditis
    5 Topics
    |
    1 Quiz
  66. CNS Infections
    5 Topics
    |
    1 Quiz
  67. Complicated Intra-abdominal Infections
    5 Topics
    |
    1 Quiz
  68. Antibiotic Stewardship & PK/PD
    5 Topics
    |
    1 Quiz
  69. Clostridioides difficile Infection
    5 Topics
    |
    1 Quiz
  70. Febrile Neutropenia & Immunocompromised Hosts
    5 Topics
    |
    1 Quiz
  71. Skin & Soft-Tissue Infections / Acute Osteomyelitis
    5 Topics
    |
    1 Quiz
  72. Urinary Tract and Catheter-related Infections
    5 Topics
    |
    1 Quiz
  73. Pandemic & Emerging Viral Infections
    5 Topics
    |
    1 Quiz
  74. Supportive Care (Pain, Agitation, Delirium, Immobility, Sleep)
    Pain Assessment and Analgesic Management
    5 Topics
    |
    1 Quiz
  75. Sedation and Agitation Management
    5 Topics
    |
    1 Quiz
  76. Delirium Prevention and Treatment
    5 Topics
    |
    1 Quiz
  77. Sleep Disturbance Management
    5 Topics
    |
    1 Quiz
  78. Immobility and Early Mobilization
    5 Topics
    |
    1 Quiz
  79. Oncologic Emergencies
    5 Topics
    |
    1 Quiz
  80. End-of-Life Care & Palliative Care
    Goals of Care & Advance Care Planning
    5 Topics
    |
    1 Quiz
  81. Pain Management & Opioid Therapy
    5 Topics
    |
    1 Quiz
  82. Dyspnea & Respiratory Symptom Management
    5 Topics
    |
    1 Quiz
  83. Sedation & Palliative Sedation
    5 Topics
    |
    1 Quiz
  84. Delirium Agitation & Anxiety
    5 Topics
    |
    1 Quiz
  85. Nausea, Vomiting & Gastrointestinal Symptoms
    5 Topics
    |
    1 Quiz
  86. Management of Secretions (Death Rattle)
    5 Topics
    |
    1 Quiz
  87. Fluids, Electrolytes, and Nutrition Management
    Intravenous Fluid Therapy and Resuscitation
    5 Topics
    |
    1 Quiz
  88. Acid–Base Disorders
    5 Topics
    |
    1 Quiz
  89. Sodium Homeostasis and Dysnatremias
    5 Topics
    |
    1 Quiz
  90. Potassium Disorders
    5 Topics
    |
    1 Quiz
  91. Calcium and Magnesium Abnormalities
    5 Topics
    |
    1 Quiz
  92. Phosphate and Trace Electrolyte Management
    5 Topics
    |
    1 Quiz
  93. Enteral Nutrition Support
    5 Topics
    |
    1 Quiz
  94. Parenteral Nutrition Support
    5 Topics
    |
    1 Quiz
  95. Refeeding Syndrome and Specialized Nutrition
    5 Topics
    |
    1 Quiz
  96. Trauma and Burns
    Initial Resuscitation and Fluid Management in Trauma
    5 Topics
    |
    1 Quiz
  97. Hemorrhagic Shock, Massive Transfusion, and Trauma‐Induced Coagulopathy
    5 Topics
    |
    1 Quiz
  98. Burns Pharmacotherapy
    5 Topics
    |
    1 Quiz
  99. Burn Wound Care
    5 Topics
    |
    1 Quiz
  100. Open Fracture Antibiotics
    5 Topics
    |
    1 Quiz

Participants 432

  • Allison Clemens
  • April
  • ababaabhay
  • achoi2392
  • adhoward1
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Lesson 95, Topic 1
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Foundational Principles: Pathophysiology, Epidemiology, and Risk Factors of Refeeding Syndrome

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Refeeding Syndrome: Pathophysiology, Epidemiology, and Risk Factors

Refeeding Syndrome: Pathophysiology, Epidemiology, and Risk Factors

Objectives Icon A checkmark inside a circle, symbolizing achieved goals.

Objective

Understand the epidemiology, metabolic derangements, and patient-specific and social risk factors underlying refeeding syndrome (RFS) to enable early recognition and prevention in critically ill and malnourished populations.

1. Epidemiology and Incidence

The incidence of refeeding syndrome (RFS) varies widely across clinical studies due to inconsistent diagnostic definitions and screening practices. However, it is consistently recognized as a significant threat in critically ill and malnourished patient populations.

Prevalence in High-Risk Groups

Reported Incidence of Refeeding Syndrome in Various High-Risk Populations
High-Risk Population Reported Incidence / Key Finding
Adult ICU Cohorts 8% to 40%, highly dependent on diagnostic criteria and initial caloric load.
Pediatric ICU ~7.4% experience significant electrolyte shifts within 72 hours of nutrition initiation.
Anorexia Nervosa 20% to 30% develop features of RFS upon re-nourishment.
Cancer Cachexia 15% to 25% are at risk during chemotherapy or post-treatment refeeding.

Diagnostic Criteria and Screening

  • Definition Variability: Historically, definitions ranged from isolated hypophosphatemia to a constellation of electrolyte abnormalities plus clinical sequelae. The 2020 ASPEN consensus provides a standardized definition based on the magnitude of electrolyte drops (phosphate, potassium, or magnesium) and the presence of organ dysfunction.
  • High-Risk Screening Criteria (Any one):
    • Body Mass Index (BMI) < 16 kg/m²
    • Minimal or no nutritional intake for >5 days
    • >10% unintentional weight loss in the last 3 months
    • Pre-existing low levels of phosphate, potassium, or magnesium before feeding

Key Takeaway: Routine screening for RFS risk on ICU admission can identify over 75% of at-risk patients. Adopting standardized definitions, such as those from ASPEN or NICE, is crucial for improving clinical research and ensuring consistent patient care.

Case Vignette Icon A clipboard with a document, representing a patient case.

Case Vignette: A Preventable Complication

A 58-year-old patient with cirrhosis, who has been nil per os (NPO) for 7 days, is started on nutritional support at a rate of 25 kcal/kg/day. By the second day, his serum phosphate plummets to 0.5 mmol/L (severe hypophosphatemia), and he develops new-onset atrial fibrillation. This severe manifestation of RFS could likely have been prevented by initiating nutrition at a more conservative rate (e.g., 10 kcal/kg/day) along with proactive thiamine and electrolyte supplementation.

2. Pathophysiology of Refeeding Syndrome

The core pathophysiologic event in RFS is the abrupt metabolic switch from a catabolic (starvation) state to an anabolic (fed) state. The reintroduction of carbohydrates triggers a cascade of hormonal and metabolic changes that lead to dangerous intracellular electrolyte shifts and thiamine depletion, while fluid retention compounds the clinical risk.

Pathophysiology of Refeeding Syndrome A flowchart showing the metabolic cascade of refeeding syndrome. It starts with a starved state, then carbohydrate reintroduction leads to an insulin surge. This surge causes intracellular shifts of phosphate, potassium, and magnesium, and increases thiamine consumption, resulting in severe electrolyte deficiencies, fluid retention, and potential organ failure. Starvation State Catabolism, depleted stores Carbohydrate Refeeding Abrupt metabolic switch Massive Insulin Surge Drives anabolism Intracellular Shift ↓ Serum PO₄, K⁺, Mg²⁺ (Cardiac, Neuromuscular) ↑ Thiamine Use Thiamine Deficiency (Wernicke’s, Beriberi) ↑ Sodium Reabsorption Fluid Retention (Edema, Heart Failure)
Figure 1: The Pathophysiologic Cascade of Refeeding Syndrome. Reintroduction of carbohydrates triggers an insulin surge, which drives phosphate, potassium, and magnesium into cells for ATP production. This, combined with increased thiamine consumption and sodium retention, leads to the hallmark electrolyte derangements and fluid shifts of RFS.

Key Mechanisms

  • Insulin-Mediated Electrolyte Shifts: The surge in insulin activates the Na+/K+ ATPase pump, driving potassium into cells. It also promotes cellular uptake of phosphate and magnesium, which are essential for glycolysis and ATP synthesis. The resulting hypophosphatemia is particularly dangerous as it impairs 2,3-diphosphoglycerate (2,3-DPG) production, leading to reduced oxygen delivery to tissues.
  • Thiamine-Dependent Metabolism: Thiamine is a critical cofactor for enzymes in carbohydrate metabolism (e.g., pyruvate dehydrogenase). Refeeding rapidly consumes already-depleted thiamine stores, which can precipitate acute thiamine deficiency, leading to lactic acidosis, Wernicke encephalopathy, or high-output cardiac failure (wet beriberi).
  • Fluid and Sodium Retention: Insulin directly promotes sodium reabsorption in the renal tubules. This effect, often in the context of pre-existing hypoalbuminemia, leads to rapid expansion of the extracellular fluid volume, causing peripheral and pulmonary edema and potentially precipitating acute heart failure.
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl: Thiamine First, Feed Second +

Always administer thiamine before initiating carbohydrate-containing nutrition in any at-risk patient. A standard prophylactic dose is 100–300 mg IV daily for the first 3 days of refeeding. Monitor electrolytes (phosphate, potassium, magnesium) every 12 hours for the first 72 hours to detect and manage shifts early.

3. Impact of Pre-Existing Chronic Diseases

Chronic organ dysfunction significantly alters baseline metabolic and electrolyte handling, magnifying the risk and complicating the management of RFS.

Renal Failure

Patients with renal failure present a unique challenge. Baseline hyperphosphatemia can mask severe intracellular phosphate depletion. When refeeding begins, phosphate can shift rapidly into cells, and subsequent dialysis can further exacerbate hypophosphatemia. Uremia-induced insulin resistance also contributes to glycemic instability.

Hepatic Failure

In liver disease, impaired gluconeogenesis increases the risk of hypoglycemia during starvation and lactic acidosis upon refeeding. Furthermore, hypoalbuminemia lowers plasma oncotic pressure, predisposing patients to severe edema and ascites when insulin-driven sodium retention occurs.

Obesity

The “malnourished-obese” patient is a growing concern. Despite a high BMI, these individuals, particularly after bariatric surgery or a prolonged ICU stay, can have significant micronutrient and electrolyte deficiencies, making them highly susceptible to RFS.

Malabsorptive Syndromes

Conditions like inflammatory bowel disease (IBD), short gut syndrome, and chronic pancreatitis lead to chronic losses of electrolytes and essential cofactors. These patients require particularly cautious refeeding protocols and aggressive micronutrient repletion.

4. Social Determinants of Health as Precipitating Factors

Malnutrition is not solely a clinical issue; it is deeply intertwined with social and economic factors that increase a patient’s vulnerability to RFS.

Food Insecurity and Socioeconomic Status

Patients with limited financial resources are more likely to experience periods of prolonged undernutrition or rely on nutritionally poor diets. This “hidden” malnutrition may not be apparent until the stress of acute illness and subsequent refeeding unmasks severe deficiencies.

Health Literacy and Access to Care

Limited health literacy can make it difficult for patients to understand and adhere to complex nutrition plans. Lack of access to prescribed supplements, specialized formulas, or follow-up care can derail preventive strategies and increase the risk of complications.

Cultural, Behavioral, and Psychological Factors

Underlying conditions such as eating disorders, depression, cognitive impairment, or substance use disorders can significantly impede consistent nutritional intake. Cultural or religious practices, such as prolonged fasting, can also precipitate a state of starvation that increases RFS risk upon re-nourishment.

Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl: Integrate Social Screening +

Incorporate screening for social determinants of health (SDOH) into admission assessments and electronic health record alerts for malnutrition risk. Early referral to social work, nutrition services, and case management is a critical preventive measure to address the root causes of undernutrition and ensure a safe refeeding process.

References

  1. da Silva JSV, Seres DS, Sabino K, et al. ASPEN consensus recommendations for refeeding syndrome. Nutr Clin Pract. 2020;35(2):178–195.
  2. National Collaborating Centre for Acute Care. Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. NICE Clin Guideline 32. 2006.
  3. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding syndrome. Nutr Clin Pract. 2005;20(6):625–633.
  4. Dunn RL, Stettler N, Mascarenhas MR. Refeeding syndrome in hospitalized pediatric patients. Nutr Clin Pract. 2003;18(4):327–332.
  5. Windpessl M, Mayrbaeurl B, Baldinger C, et al. Refeeding syndrome in oncology: report of four cases. World J Oncol. 2017;8(1):25–29.
  6. Heuft L, Voigt J, Selig L, et al. Refeeding syndrome: diagnostic challenges and potential of clinical decision support systems. Dtsch Arztebl Int. 2023;120(7):107–114.