1. Management of Respiratory Failure and Muscle Weakness

Severe hypophosphatemia depletes intracellular ATP and reduces 2,3-diphosphoglycerate (2,3-DPG) in red blood cells, leading to diaphragmatic dysfunction and impaired tissue oxygen unloading. Early ventilatory support combined with phosphate repletion is essential.

Pathophysiology

• Phosphate is a critical cofactor in glycolysis and oxidative phosphorylation for ATP production.
• Reduced ATP impairs muscle contraction, while decreased 2,3-DPG shifts the oxyhemoglobin dissociation curve to the left, hindering oxygen release to tissues.
• Diaphragmatic fatigue manifests as reduced maximal inspiratory pressure and prolonged muscle relaxation time.

Indications for Mechanical Ventilation

• Hypercapnia (PaCO₂ > 50 mm Hg) that is unresponsive to noninvasive positive pressure ventilation.
• Tachypnea (respiratory rate > 30 breaths/min) with evidence of low tidal volume (< 5 mL/kg ideal body weight).
• Visible signs of increased work of breathing, such as accessory muscle use, paradoxical breathing, or associated hemodynamic instability.

Ventilator Strategies and Weaning

• Initiate with assist-control ventilation: set tidal volume to 6–8 mL/kg of ideal body weight and use moderate PEEP to optimize oxygenation.
• As serum phosphate levels normalize and muscle strength improves, transition to pressure support ventilation to re-engage the diaphragm.
• Perform daily spontaneous breathing trials once serum phosphate is consistently ≥ 0.8 mmol/L.

Phosphate Repletion Protocol

• IV Infusion (Severe/Symptomatic): For serum phosphate < 0.5 mmol/L, administer 0.08–0.16 mmol/kg over 6–12 hours.
• Oral/Enteral (Mild/Moderate): If the patient is tolerating enteral intake, provide 250–500 mg every 6 hours.
• Monitoring: Check serum phosphate, calcium, and potassium every 4–6 hours during IV repletion.

2. Prevention of ICU-Related Complications

Refeeding Syndrome

Aggressive nutritional support in chronically malnourished patients triggers a rapid, insulin-mediated intracellular shift of electrolytes. This can precipitate severe hypophosphatemia, hypokalemia, and hypomagnesemia, leading to cardiac arrhythmias, respiratory failure, and neurologic sequelae.

• High-Risk Patients: Chronic alcoholism, anorexia nervosa, BMI < 16 kg/m², recent weight loss > 15%, or fasting for > 7 days.
• Nutrition Strategy: Start with a conservative dose of 10–20 kcal/kg/day and advance by only 10–20% daily as tolerated.
• Prophylactic Supplementation: Administer phosphate (0.3–0.6 mmol/kg/day), magnesium (8–15 mmol/day), and potassium (20–40 mEq/day) with the initial nutrition.
• Thiamine: Provide 100 mg IV daily for the first 3 days before starting nutrition to prevent Wernicke’s encephalopathy.
• Monitoring: Check electrolytes every 12 hours for the first 72 hours of refeeding.

Stress Ulcer Prophylaxis (SUP)

Prophylaxis is recommended for high-risk ICU patients (e.g., those with coagulopathy or on mechanical ventilation > 48 hours) to reduce the risk of clinically significant gastrointestinal bleeding. This benefit must be balanced against the potential risks of therapy, such as nosocomial infections.

• Non-pharmacologic: Elevate the head of the bed to 30–45 degrees; initiate enteral feeding as early as feasible.
• De-escalation: Discontinue SUP once major risk factors resolve (e.g., after extubation).

Venous Thromboembolism (VTE) Prophylaxis

Critically ill patients are at high risk for VTE due to immobility and systemic inflammation. A combination of pharmacologic and mechanical prophylaxis is often warranted.

• Unfractionated Heparin (UFH): 5,000 units subcutaneously every 8–12 hours.
• Low-Molecular-Weight Heparin (LMWH): Enoxaparin 40 mg subcutaneously daily. Dose-adjust to 30 mg daily for CrCl < 30 mL/min. Consider anti-Xa monitoring in select populations (target 0.2–0.4 IU/mL).
• Monitoring: Check platelet counts every 2–3 days to screen for heparin-induced thrombocytopenia (HIT).
• Mechanical Prophylaxis: Use intermittent pneumatic compression (IPC) devices, especially when anticoagulants are contraindicated.

3. Management of Iatrogenic Complications

Hypocalcemia from Phosphate Repletion

Rapid intravenous phosphate infusion can lead to the precipitation of calcium phosphate in the serum, causing acute hypocalcemia. This can manifest as neuromuscular irritability (tetany, paresthesias) and cardiac arrhythmias (QT prolongation).

• Monitoring: Check serum calcium every 4–6 hours during IV phosphate therapy and monitor the ECG for QT interval prolongation.
• Symptomatic Treatment: Administer calcium gluconate 1–2 grams IV over 10 minutes.
• Asymptomatic Treatment: Provide oral calcium carbonate 500–1,000 mg.
• Prevention: Slow the phosphate infusion rate to minimize the risk of recurrence.

Hyperkalemia from Phosphate Preparations

Many intravenous phosphate formulations are potassium-based (potassium phosphate). Their administration can significantly elevate serum potassium levels, particularly in patients with renal dysfunction.

• Monitoring: Check serum potassium before each dose and again 2 hours after the infusion is complete.
• Emergency Management (K+ > 6.5 mmol/L or ECG changes): Administer calcium gluconate 10 mL of 10% solution IV for membrane stabilization, followed by insulin 10 units IV with 25 grams of dextrose. Consider sodium bicarbonate if metabolic acidosis is present.
• Refractory Cases: Dialysis may be required for severe or refractory hyperkalemia.

Trace Element Toxicity

Excessive supplementation of trace elements like copper or selenium, often included in parenteral nutrition formulations, can lead to organ toxicity. Copper toxicity can cause liver damage, while selenium toxicity can lead to neurologic symptoms and hair loss.

• Monitoring: Recheck trace element levels 48–72 hours after initiating high-dose or long-term therapy.
• Management: If levels are elevated, reduce the supplementation dose by 50% or hold it temporarily. For severe toxicity, consider chelation therapy (e.g., penicillamine for copper toxicity).
• Assessment: Monitor for clinical signs of toxicity, such as new-onset liver dysfunction or unexplained neurologic changes.

4. Multidisciplinary Goals of Care Conversations

The use of invasive supportive care, such as prolonged mechanical ventilation or continuous renal replacement therapy (CRRT), carries significant morbidity and may not align with all patients’ values. Early and recurrent discussions involving the patient, family, and clinical team are crucial to ensure that care plans are consistent with patient-centered goals.

• Ethical Principles: Ground discussions in the core principles of autonomy (respecting patient wishes), beneficence (acting in the patient’s best interest), nonmaleficence (avoiding harm), and justice (fair allocation of resources).
• Communication Strategies: Schedule structured family meetings with clear agendas. Use decision aids to explain complex treatments. Involve palliative care specialists early to facilitate communication and symptom management.
• Documentation: Clearly document advance directives, designated healthcare surrogates, and the consensus care plan in the medical record to ensure all team members are aligned.
• Interdisciplinary Rounds: Use daily rounds as an opportunity to review the patient’s clinical trajectory and collaboratively adjust goals of care as the situation evolves.