7.2 Nutrition Support

Nutrition Support

Appropriate nutrition support is a fundamental component of critical care and chronic disease management. The clinical pharmacist is frequently responsible for designing, calculating, and monitoring Parenteral Nutrition (PN) regimens, ensuring both metabolic efficacy and physical stability while circumventing potentially fatal complications.

Enteral Nutrition (EN) vs. Parenteral Nutrition (PN)

The golden rule of clinical nutrition is: "If the gut works, use it." Enteral nutrition maintains gut mucosal integrity, prevents bacterial translocation from the gut lumen to the systemic circulation, is more cost-effective, and carries a significantly lower risk of severe infectious complications (like central line-associated bloodstream infections) compared to PN.

Enteral Access and Formulations

• Access Routes: Nasogastric/Orogastric Tubes (NGT/OGT) are temporary (usually < 4 weeks). Percutaneous Endoscopic Gastrostomy (PEG) / Jejunostomy (PEJ) are for long-term feeding. Post-pyloric feeding (PEJ) is preferred for patients with severe gastroparesis, high risk of aspiration, or acute pancreatitis.
• Formulations:
  • Polymeric formulas: Contain intact proteins, carbohydrates, and fats. Requires a fully functioning digestive system.
  • Elemental formulas: Contain pre-digested macronutrients (free amino acids, simple sugars, medium-chain triglycerides). Utilized for patients with malabsorption, short bowel syndrome, or pancreatic insufficiency.
• Osmolality Considerations: Hyperosmolar EN formulas can draw water into the gut lumen, causing severe osmotic diarrhea. Additionally, concurrent administration of liquid medications formulated with sorbitol frequently masquerades as EN-induced diarrhea.

Parenteral Nutrition Macronutrient Calculations

When the GI tract is inaccessible or non-functional (e.g., bowel obstruction, severe short bowel syndrome, high-output enterocutaneous fistula), PN is indicated. Pharmacists must accurately calculate the macronutrient composition to meet energy goals without causing metabolic derangements like hyperglycemia or hepatic steatosis.

Caloric Densities

• Dextrose (Carbohydrates): Provides 3.4 kcal/gram. (Note: This is lower than oral carbohydrates, which provide 4 kcal/g, because parenteral dextrose is a monohydrate).
• Amino Acids (Protein): Provides 4 kcal/gram.
• Lipid Injectable Emulsions (IVFE):
  • 10% emulsion provides 1.1 kcal/mL.
  • 20% emulsion provides 2 kcal/mL.
  • 30% emulsion provides 3 kcal/mL.
  • Alternatively, lipids can be calculated as providing 10 kcal/gram of fat.
  • Clinical Pearl: Propofol, a common ICU sedative, is formulated in a 10% lipid emulsion (providing 1.1 kcal/mL). The calories from a propofol infusion must be subtracted from the daily PN lipid calculations to prevent hypertriglyceridemia and overfeeding.

Dosing Guidelines

• Fluid Requirements: Generally estimated as 1500 mL for the first 20 kg, plus 20 mL for each kg > 20 kg; or roughly 30-35 mL/kg/day for a normal adult.
• Protein Requirements:
  • Maintenance: 0.8 to 1.0 g/kg/day.
  • Moderate stress/malnutrition: 1.2 to 1.5 g/kg/day.
  • Severe stress, trauma, or burns: 1.5 to 2.5 g/kg/day.
  • Renal failure (not on dialysis): May restrict to 0.6 to 0.8 g/kg/day to limit BUN accumulation, though guidelines are evolving toward standard protein provision if dialysis is initiated.
• Dextrose Infusion Rate (DIR): Should not exceed 4-5 mg/kg/min in adults to prevent severe hyperglycemia, fatty liver (hepatic steatosis), and excess CO2 production which can complicate ventilator weaning.

Trace Elements and Electrolytes in PN

PN formulations require daily supplementation of trace elements. Standard adult multi-trace element products include zinc, copper, manganese, chromium, and selenium.

• Biliary Obstruction/Cholestasis: Copper and manganese undergo biliary excretion. In severe hepatic dysfunction or cholestasis, these elements must be restricted or omitted to prevent hepatotoxicity and neurotoxicity (manganese can accumulate in the basal ganglia causing Parkinsonian symptoms).
• Severe Renal Impairment: Chromium and selenium are primarily eliminated renally; their dosing should be minimized or withheld in severe AKI without renal replacement therapy.

Calcium-Phosphate Solubility in PN

One of the most dangerous, potentially fatal complications in compounding PN is the precipitation of calcium and phosphate, which forms a dense, insoluble matrix that can cause a massive pulmonary embolus.

Physical Chemistry & Mitigation Strategies

1. Choice of Calcium Salt: Calcium gluconate is highly preferred over calcium chloride. Calcium gluconate is significantly less dissociable (less reactive), leaving less free unbound calcium cations available to electrostatically bind with phosphate anions.
2. Order of Addition: When compounding, add phosphate first to the amino acid/dextrose mixture, followed by other components, and add calcium last. This maximizes the total volume they are dispersed in before they ever interact, drastically reducing their molar concentrations.
3. Concentration Limits: A standard safety rule is that the sum of calcium and phosphate should not exceed 45 mEq/L (though modern automated compounders use complex multi-variable solubility nomograms).
4. Temperature and pH Dynamics: Lower temperatures and lower pH (more acidic environments) increase solubility. As a refrigerated PN bag warms to room temperature, the risk of calcium-phosphate precipitation increases exponentially. Higher amino acid concentrations generally lower the pH, acting as a protective buffer.

Refeeding Syndrome

Refeeding syndrome is a potentially fatal metabolic disturbance that occurs when nutrition is reintroduced rapidly to severely malnourished patients (e.g., anorexia nervosa, prolonged starvation, chronic alcoholism, or oncologic cachexia).

Pathophysiology

During starvation, the body shifts from carbohydrate to fat and protein metabolism. Intracellular stores of electrolytes are severely depleted, though serum blood levels may remain misleadingly normal due to homeostatic shifts. Upon the sudden reintroduction of carbohydrates, there is a massive surge in endogenous insulin secretion. Insulin forcibly drives glucose, potassium, magnesium, and critically, phosphate, rapidly from the serum into the intracellular space for ATP synthesis, stripping the bloodstream of these vital electrolytes.

Clinical Presentation

• Severe Hypophosphatemia: The hallmark of refeeding. Manifests as profound muscle weakness, respiratory failure (inability to wean from ventilator due to diaphragmatic weakness), rhabdomyolysis, and hemolysis.
• Hypokalemia: Causes lethal cardiac arrhythmias and EKG changes.
• Hypomagnesemia: Results in neuromuscular excitability, tetany, and arrhythmias (e.g., Torsades de Pointes).
• Volume Overload: Insulin causes massive renal sodium and water retention, potentially precipitating congestive heart failure and pulmonary edema.

Prevention and Management

• Identify High-Risk Patients: BMI < 16, unintentional weight loss > 15% in 3-6 months, little to no nutritional intake for > 10 days, or pathologically low baseline electrolytes.
• Thiamine Supplementation: Administer Thiamine 100 mg IV/PO daily prior to or alongside the initiation of feeding to prevent Wernicke's encephalopathy, as thiamine is an obligate cofactor for carbohydrate metabolism.
• Start Low and Go Slow: Initiate feeding at a very conservative rate of approximately 10 to 15 kcal/kg/day (or ~50% of the patient's eventual goal) and advance cautiously over 4 to 7 days.
• Vigilant Monitoring: Check K, Mg, and Phos daily for the first week. Aggressively replete all electrolyte deficits prior to starting nutrition, and continuously during the advancement of caloric intake.