Drug dosing in continuous renal replacement therapy (CRRT)

The dosing spine is a sequence, not a dose reduction. On day one a loading dose is required to compensate the increased volume of distribution, "regardless of impaired organ function"; an additional loading dose may be required when CRRT is initiated because clearance variation breaks the steady state. From day two, dosing must be adjusted to CRRT settings and residual renal function.^[16] Published regimens that hold their own in CRRT cohorts include meropenem 1 g every 6 h over 30 min, 1 g every 8 h over 3 h, or 2–4 g every 24 h by continuous infusion (non-trauma), and the unadjusted beta-lactam regimens piperacillin/tazobactam 4 g q6h and ceftazidime/cefepime 2 g q8h.^[18][10] Then verify with TDM: one-size-fits-all dosing is exactly the error the CRRT literature warns against.^[16]

Two targets define success. Vancomycin targets an AUC/MIC ratio of 400–600 (assuming a broth microdilution MIC of 1 mg/L), with AUC-guided dosing "the most accurate and optimal way" to manage therapy — trough monitoring was associated with more nephrotoxicity than the 2009 consensus surrogate.^[17] Beta-lactams target free drug above the MIC for a defined fraction of the dosing interval — DALI scored patients against 50% and 100% fT>MIC, and a CRRT cohort defined adequate exposure as trough concentrations between four and eight times the MIC of Pseudomonas aeruginosa.^[4][10] Miss low and the infection smoulders; miss high and neurological worsening tracks the trough-to-MIC ratio.^[11]

Meet the patient

A 62-year-old, 80 kg man with hospital-acquired pneumonia, septic shock and KDIGO stage 3 AKI is started on CVVHDF at 25 mL/kg/h with regional citrate. The registrar reaches for empirical meropenem and vancomycin — and instinctively halves the doses, "because he is in renal failure."^[5]

That instinct is the central error this topic exists to correct. The circuit is now doing his renal work while sepsis has already changed his pharmacokinetics: increased volume of distribution, hypoalbuminaemia, and altered renal and non-renal clearances.^[5] Under-dose and the pneumonia smoulders: in DALI, the 16% of infected patients who never reached even 50% fT>MIC were 32% less likely to have a positive clinical outcome (OR 0.68, P = .009).^[4]

The question that decides his course is not "how do I dose-reduce for renal failure?" but "how do I dose for a circuit that clears like a kidney, plus a septic volume of distribution?" IHD accumulation tables applied to CRRT have produced significant underdosing.^[7][5]

References23ShowHide

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