Prescribing During Continuous Renal Replacement Therapy

Continuous renal replacement therapy removes drugs in proportion to the effluent rate, the membrane, the mode (haemofiltration, haemodialysis or haemodiafiltration), the drug's sieving coefficient and its volume of distribution. A delivered effluent dose of 20 to 30 mL/kg/h gives a drug clearance roughly equal to a GFR of 25 to 50 mL/min for dialysable drugs.

Underdosing risk. Critically ill patients have an enlarged volume of distribution and variable clearance. Give full loading doses and avoid reducing antimicrobials in the first 48 hours.

Sieving. Protein binding limits removal. Highly bound drugs such as ceftriaxone are removed little, while unbound small molecules are removed freely.

Citrate. Regional citrate anticoagulation needs ionised calcium monitoring and can accumulate in liver failure.

Antimicrobials. Prefer agents with predictable dosing and level availability. Beta-lactams may be given by extended infusion.

Avoid. Enoxaparin, metformin, NSAIDs, nephrotoxins and, where possible, aminoglycosides.

Special groups.

• Children: dose by mg/kg with the effluent rate scaled to weight.

• Liver failure: citrate accumulates, so consider heparin or no anticoagulation.

• Pregnancy: needs specialist support.

• East Africa: continuous therapy is available only in a few centres, so many patients receive prolonged intermittent or acute peritoneal dialysis instead and need dosing by those methods.

• Meropenem: 1 g intravenously every 8 to 12 hours, using every 8 hours in the first 48 hours or for a higher minimum inhibitory concentration.

• Piperacillin with tazobactam: 4.5 g intravenously loading dose, then 4.5 g every 8 hours.

• Vancomycin: loading 25 mg/kg (maximum 3 g), then 10 to 15 mg/kg every 24 hours directed by a level aiming for 15 to 20 mg/L before the dose.

• Amikacin: 25 mg/kg once, then redose by level.

• Fluconazole: 400 to 800 mg once daily after a loading dose.

• Ceftriaxone: 2 g once daily, no change.

Monitoring. Check electrolytes at least every 6 to 12 hours. Hypophosphataemia, hypokalaemia and hypomagnesaemia are frequent and need replacement. Monitor ionised calcium and the total to ionised calcium ratio (over 2.5 signals citrate accumulation).

Dose changes. Review doses daily. When therapy stops, change doses to the band for the patient's own function.

Stop rules. Reduce or stop drugs whose levels are rising despite therapy, and stop citrate if the calcium ratio rises over 2.5.

Referral and escalation. Involve the intensivist, nephrologist and pharmacist for narrow index drugs, for unexplained loss of effect, and when levels are unavailable.

Common errors. Reducing antimicrobials too early, not replacing phosphate, and carrying CRRT doses over after therapy ends.