What electrolyte has not been adequately replaced in the nutritional program of a 19-year-old anorexic woman with a body mass index (BMI) of 16.3, who developed muscle weakness, hypotension, tachycardia, and bilateral crackles on auscultation of her chest shortly after starting parenteral nutrition?

Refeeding Syndrome with Phosphate Depletion

This patient has developed refeeding syndrome due to inadequate phosphate replacement (Answer D), a life-threatening complication that occurs when nutrition is reintroduced too aggressively in severely malnourished patients without proper electrolyte supplementation. 1

Clinical Presentation Confirms Refeeding Syndrome

This 19-year-old woman with anorexia nervosa (BMI 16.3) presents with the classic triad of refeeding syndrome occurring within hours of initiating parenteral nutrition:

• Muscle weakness - directly caused by severe hypophosphatemia affecting cellular energy metabolism 1
• Hypotension (BP 95/60) - cardiovascular dysfunction from electrolyte derangements and potential cardiac arrhythmias 1
• Bilateral crackles - acute fluid retention and potential heart failure from sudden insulin surge causing sodium and water retention 1
• Tachycardia (pulse 95) - compensatory response to cardiovascular compromise 1

Why Phosphate is the Answer

Hypophosphatemia is the most frequent and clinically significant electrolyte disturbance in refeeding syndrome. 1 When nutrition is reintroduced after starvation:

• Sudden glucose/calorie influx triggers massive insulin release 1
• Insulin drives phosphate (along with potassium and magnesium) from extracellular space into cells for anabolic metabolism 1
• Serum phosphate plummets to dangerously low levels despite normal baseline values 1
• Severe hypophosphatemia (<0.32 mmol/L) causes respiratory failure, cardiac dysfunction, muscle weakness, and death 2, 1

The patient's presentation of muscle weakness, hypotension, and respiratory compromise (bilateral crackles suggesting impending respiratory failure) are pathognomonic for severe hypophosphatemia in the refeeding context. 2, 1, 3

High-Risk Patient Profile

This patient meets multiple high-risk criteria for refeeding syndrome:

• BMI <16.3 kg/m² (guideline threshold is <16) 1
• Anorexia nervosa - one of the highest risk conditions 1, 4
• Severely malnourished - described as "dangerously ill" 1
• Parenteral nutrition initiated - can occur with any route but PN carries particular risk 1

Why Not the Other Electrolytes

While potassium, magnesium, and calcium deficiencies also occur in refeeding syndrome, phosphate depletion produces the most dramatic and life-threatening acute clinical manifestations described in this case:

• Potassium (B): Causes primarily cardiac arrhythmias but less commonly the acute respiratory/muscle weakness triad 1
• Magnesium (C): Often accompanies hypophosphatemia but doesn't typically cause bilateral crackles or this acute presentation 1
• Calcium (A): Less commonly depleted acutely in refeeding; not the primary culprit 2, 1
• Sodium (E): Actually retained (not depleted) in refeeding syndrome, causing the fluid overload and crackles 1

Critical Evidence from Guidelines

The ESPGHAN/ESPEN guidelines explicitly warn that extreme hypophosphatemia can result in muscle weakness, respiratory failure, cardiac dysfunction, and death in malnourished patients on parenteral nutrition. 2 This precisely matches the clinical scenario presented.

Multiple guidelines emphasize that phosphate 0.3-0.6 mmol/kg/day must be provided prophylactically when initiating nutrition in high-risk patients. 1 The "on-call dietician over the weekend" likely prepared standard PN without adequate phosphate supplementation for this high-risk patient.

Supporting Research Evidence

Case reports confirm that severe hypophosphatemia develops within 3 days of initiating nutrition in malnourished patients, causing life-threatening neurological and cardiovascular symptoms, even with standard phosphate supplementation. 3 Hypophosphatemia has been documented in anorexia nervosa patients receiving oral refeeding alone, with levels dropping to 0.9 mg/dL. 5

Proper Prevention Protocol (What Should Have Been Done)

For patients with BMI <16 and anorexia nervosa, the following protocol is mandatory: 1

• Start at 5-10 kcal/kg/day (not aggressive full nutrition) 1
• Thiamine 200-300 mg IV before any feeding 1
• Aggressive electrolyte supplementation from day 1: 1
  • Phosphate: 0.3-0.6 mmol/kg/day IV
  • Potassium: 2-4 mmol/kg/day
  • Magnesium: 0.2 mmol/kg/day IV or 0.4 mmol/kg/day orally
• Daily electrolyte monitoring for first 72 hours 1
• Gradual increase over 4-7 days 1

Common Pitfall in This Case

The critical error was initiating parenteral nutrition without a comprehensive refeeding syndrome prevention protocol in a patient with obvious high-risk features. 1 Weekend coverage and lack of specialized nutrition support likely contributed to this preventable complication. 1

Answer: D. Phosphate