Renal Replacement Therapy Prescription

OVERVIEW

Prescription of renal replacement therapy (RRT) is typically standardised according to local protocols, with approaches varying between different ICUs due to tradition, logistics, feasibility, and other practical factors.

• no evidence for the benefit of different modalities over one another (e.g. hemodialysis versus haemofiltration)
• hemofiltration more efficiently removes middle molecules than dialysis, in addition to small molecules, but this is of uncertain clinical significance
• continuous venovenous haemodialofiltration (CVVHDF) with predilution and/or post-dilution fluid replacement is commonly used in ICUs worldwide, but not universally.

RRT prescription is altered depending on:

• aims of treatment
• patient factors (e.g. fluid balance, haemodynamics, metabolic derangement)
• filter life and occurrence of technical problems
• equipment and resources available

Aims of Treatment include:

• fluid management
• acidosis correction
• hyperkalaemia correction
• uraemia
• toxin removal

Monitoring of RRT (See & Bellomo, 2021)

• check electrolytes q6-8h
• check calcium (ionised and total) and bicarbonate q4-6h if citrate anticoagulation

PRESCRIPTION ELEMENTS

Mode

• continuous veno-venohaemofiltration (CVVH)
• continuous veno-venohaemodialysis (CVVHD)
• continuous veno-venohaemodialofiltration (CVVHDF)

Blood flow rate (Q_B)

• e.g. 150mL/min
• 50-200mL/min is the typical range for CVVHDF
• often RRT is commenced at 20-30 mL/h blood flow then incrementally stepped up (e.g. 50mL/h at a time) to ensure patient tolerance (about 150 mL of blood is transferred into the RRT circuit from the patient on commencement)
• lower blood flow rates (e.g. 120 mL/min) are typically targeted if citrate anticoagulation is used, otherwise higher doses of citrate are required which carries higher risk of citrate toxicity (see & Bellomo, 2021)

Dialysate flow rate (Q_D)

• Volume of dialysis fluid running into (and out of) the circuit per unit of time
• e.g. 16mL/kg/min (1000mL/h)
• should not be more than 1/2 of blood flow rate (See & Bellomo, 2021)

Ultrafiltrate flow rate (Q_UF)

• Total volume of fluid removed in the filter by positive transmembrane pressure (TMP) per unit of time
• Filtration fraction should be <0.25
  • FF = plasma water removal / plasma flow = Q_UF / Q_B x (1 – Hct)
• ~1:1 ratio of dialysis flow rate to ultrafiltration flow rate is common for CVVHDF

Replacement fluid (Q_R) (mL/h)

• Sterile fluid administered upstream and/or downstream of the filter to replace the ultrafiltrate
• Composition
  • most bags are now bicarbonate-based (lactate-free) or phosphate-based (less hypophosphataemia, but more acidosis and hypocalcaemia) (See & Bellomo, 2021)
  • K+ supplementation if needed (up to 20 mmol/5L bag i.e. 4 mmol/L)
  • calcium free bags are used if citrate anticoagulation is used
• Dilution technique refers to where in the RRT circuit the replacement fluid is administered
  • pre-filter (Q_R^PRE)
    • decreases dialysis efficacy
    • decreases filter clotting
    • may promote extracellular shift of red blood cell urea
  • post-filter (Q_R^POST)
    • lower filter life
  • 70:30 is a commonly used ratio

Fluid removal (mL/h)

• results from ultrafiltration (convection), not dialysis (diffusion)
• adjusted based on patient’s overall fluid status and haemodynamics, and to compensate for other therapeutic fluids administered (nutrition, drugs, etc)
  • can usually tolerate up to 300-400 mL/h
  • the speed of fluid removal and should be <2 mL/kg/h, unless life-threatening fluid overload is present, as excessive rate may be harmful (Bellomo et al, 2009).
• Net ultrafiltration (NUF or Q_UF^NET) rate
  • Net volume of fluid removed from the patient by the machine per unit of time
  • Q_UF^NET = Q_UF – Q_R

Effluent flow rate (Q_E) = dialysate (Q_D) + ultrafiltrate (Q_F) = “dose” of RRT

• Waste fluid per unit of time coming from the outflow port of the dialysate/ultrafiltrate compartment of the filter
  • (Q_E) = Q_F + Q_D = Q_UF^NET + Q_R + Q_D
• minimum of 20-25 mL/kg/h
  • approximates urea clearance (Kt/V) = 1 achieved by intermittent haemodialysis
  • no evidence of mortality benefit with increased dose of 40 mL/kg/h (but increases rate of solute clearance and fluid removal) (see Renal replacement therapy: Dose)
• effluent rate is used as the dose for practical reasons, though it tends to over-estimate the “true dose” (renal clearance of urea) by 20-25% due to decreased filter efficacy over time (Claure-Del Granado et al, 2011)
• higher doses are used for severe metabolic derangement, e.g. 50 mL/kg/h of effluent flow rate for hyperammonaemia to target levels < 100 µmol/L (See & Bellomo, 2021)
• higher doses are sometimes used to compensate for circuit “down time” (e.g. if filter clots)

Anticoagulation Strategy

• none
• regional citrate (most common)
• heparin
• LMWH
• regional heparinsation (protamine post filter)
• prostacycline
• heparinoids (danaparoid)
• serine protease inhibitors
• direct thrombin inhibitors (bivalirudin, hirudin)
• fondaparinux
• NSAIDS
• anti-platelet agents
• warfarin

What do if filters fails (filters typically have a maximum life-span of 72 hours)

• re-start
• give patient time off RRT (e.g. if acceptable solute clearance, pH, potassium, volume state, and urine output)

EXAMPLE

RRT prescription for a critically ill 80 kg male with acute kidney injury (AKI)

• CVVHDF with regional citrate anticoagulation
• blood flow rate (QB) = 120 mL/min
• dialysis flow rate (Q_D) = 1,000 mL/h
• Replacement fluid flow rate (Q_R) = 800 mL/h
• ultrafiltration flow rate (Q_F) = 1,000 mL/h
• net fluid removal = Q_UF^NET = Q_UF – Q_R = 1,000 – 800 = 200 mL/h
• effluent flow rate (Q_E) = Q_F + Q_D = Q_UF^NET + Q_R + Q_D = 2,000 mL/h = 25 mL/kg/h

References and Links

LITFL CCC

• Renal replacement therapy: Dose
• RRT Indications
• RRT principles in fluid management
• RRT Types
• RRT terminology and nomenclature
• RRT troubleshooting

FOAM and websites

• Portsmouth ICU – Renal Replacement Therapy in Critical Care Guideline (pdf)

Journal articles and textbooks

• Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361:1627–38. [article]
• Claure-Del Granado R, Macedo E, Chertow GM, et al. Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis [published correction appears in Clin J Am Soc Nephrol. 2011 Jul;6(7):1802]. Clin J Am Soc Nephrol. 2011;6(3):467-475. doi:10.2215/CJN.02500310 [article]
• Kellum JA, Bellomo R, Ronco C. Continuous Renal Replacement Therapy. Second Edition. Oxford University Press, 2016. [google books]
• Ronco C, Bellomo R, Kellum JA, Ricci Z. Critical Care Nephrology. Third edition, Elsevier Health Sciences, 2019 [google books]
• See, E.J., Bellomo, R. How I prescribe continuous renal replacement therapy. Crit Care 25, 1 (2021). https://doi.org/10.1186/s13054-020-03448-7 [article]