Phosphate Replacement

Phosphate replacement corrects hypophosphataemia (serum phosphate under 0.8 mmol/L; severe under 0.3 mmol/L). Causes include refeeding, alcohol use disorder, diabetic ketoacidosis treatment, respiratory alkalosis, hyperparathyroidism, vitamin D deficiency, renal tubular losses and some drugs.

Mechanism. Phosphate is needed for ATP, 2,3-diphosphoglycerate (oxygen release from haemoglobin), cell membranes and bone. Low levels cause muscle weakness, respiratory failure, haemolysis, heart failure and seizures.

Pharmacokinetics. Oral phosphate is absorbed in the small intestine and often causes diarrhoea. Intravenous phosphate distributes into cells over hours, and serum levels can fall again after infusion ends. Elimination is renal.

Rules for intravenous use.

• Moderate (0.3 to 0.6 mmol/L): oral if possible, or 10 to 20 mmol intravenously over 6 to 12 hours.
• Severe (under 0.3 mmol/L) or symptomatic: 20 to 30 mmol over 6 hours, repeated and adjusted to the levels.
• Do not exceed 10 mmol/hour peripherally.
• Dilute in at least 250 mL.

Refeeding. Check phosphate, potassium and magnesium before feeding and daily for the first week. Give thiamine 100 mg three times daily before and with feeds. Start feeding at 10 kcal/kg/day or less in high-risk patients, and increase gradually.

• First-line. Oral phosphate for mild to moderate deficiency or for chronic tubular loss.
• Alternative. Dietary phosphate (dairy, meat); vitamin D and calcium in rickets and osteomalacia.
• Specialist. X-linked hypophosphataemia (oral phosphate with calcitriol, or burosumab), tumour-induced osteomalacia, parenteral nutrition adjustment.
• Emergency. Severe hypophosphataemia with respiratory failure, haemolysis, rhabdomyolysis or seizure.

Selection. Treat the cause. Use intravenous phosphate for severe or symptomatic cases only and recheck often.

Contraindications. Hyperphosphataemia, hypocalcaemia that is not corrected, severe kidney failure, tissue necrosis or hypercalcaemia (calcium phosphate deposition).

Serious adverse effects.

• Hypocalcaemia and tetany, hyperkalaemia (potassium phosphate) or hypernatraemia (sodium phosphate).
• Hyperphosphataemia, calcium phosphate deposits, kidney injury.
• Diarrhoea, nausea, abdominal cramps with oral use.
• Hypotension if infused fast.

Major interactions. Calcium and magnesium salts (precipitate in lines and bind in the gut); potassium-sparing drugs and ACE inhibitors with potassium phosphate; antacids containing aluminium or calcium reduce absorption.

Common prescribing errors.

• Giving phosphate with calcium in the same line.
• Using potassium phosphate in hyperkalaemia or kidney failure.
• Over-replacing in kidney impairment.
• Failing to treat low calcium first or at the same time.
• Missing refeeding risk.

Special groups.

• Pregnancy: no routine need; replace with the usual adult doses.
• Breastfeeding: compatible.
• Children: weight-based; X-linked hypophosphataemia is a specialist condition.
• Older adults: monitor kidney function and calcium.
• Kidney: avoid, or use small doses with close monitoring.
• Liver: no adjustment.
• East Africa: premixed or glycerophosphate products may not be stocked; oral phosphate supplements may be limited; malnutrition, alcohol use, and refeeding of severely undernourished children and adults are exposures that raise risk.

Monitoring. Phosphate, calcium, magnesium, potassium and creatinine every 6 to 12 hours during intravenous replacement; ECG for severe cases.

Referral and escalation. Respiratory failure, haemolysis, rhabdomyolysis, seizure, or phosphate that does not rise.

Comparison with alternative classes. Phosphate replacement is the only way to correct a significant deficit quickly. Diet and vitamin D work in chronic states but are too slow for acute deficiency.