This chapter is related to the aims of Section H3(i) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the principles of dialysis and renal replacement fluid". Extending this definition some of the way towards the professional competencies of the Fellowship Exam candidates, one could probably justify positioning this chapter in the middle between Part I and Part II revision material. On one hand, prescribing dialysis is very much the prerogative of senior medical staff; on the other hand being able to explain how the prescription is determined seems like something we should all know from an early age. Ergo, the chapter will have heavy emphasis on definitions and basic foundational science, but with the option to digress into the evidence upon which current dialysis dosing is based.
In brief:
Theoretically:
- Definition of "dose" in CRRT is volume of blood "purified."
- Measure of "dose" in CRRT: clearance rate of a representative marker solute.
Practically:
- Dialysis dose is equivalent to the effluent rate in ml/kg/hour.
- Effluent rate is the ultrafiltration rate for haemofiltration (CVVH), or the sum of ultrafiltration rate and dialysis rate for CVVHDF
Relevance to CRRT:
- Prescribed dose is the effluent rate
- No benefit in outcomes with doses in excess of 25ml/kg/hr
- Practically, higher doses may be necessary to compensate for circuit downtime
Traditionally, urea has been the marker solute since the clearance of all accumulated "renal toxins" correlates to some extent with urea clearance. However, it is not used to prescribe a dialysis dose.
Most studies prescribe weight-based effluent rates as their dose of dialysis. In practical terms, the "volume of blood purified" dose of dialysis is essentially the effluent flow rate (i.e. the combination of dialysate and ultrafiltrate flow rates). Thus, when one signs the patient up for "two litre exchanges" one is prescribing an effluent rate of 2000ml/hr, and a replacement rate of 2000ml/hr (that is the "exchange volume"). The "exchange" here being a term which recalls a time when CVVHF was the dominant modality, when in effect one would remove 2000ml of ultrafiltrate from the patient, "exchanging" it for 2000ml of clean replacement fluid. With CVVHDF, of the 2000 ml exchange volume, not all will be ultrafiltrate because some dialysate is also being discarded.
This works out to be a dialysis dose of 2000ml/hr, or 28.6ml/kg/hr for a 70kg lump of human tissue. This prescribed "dose of effluent" is usually about 20% less than the actual dose of dialysis measured by marker solute, largely because the filter efficiency tends to diminish over the course of a CRRT session.
There is some disagreement as to what the ideal dialysis dose should be. Thus far, nobody has demonstrated any improvement in outcomes with doses higher than 25ml/kg/hr. Practically speaking, one may wish to prescribe a higher dose to compensate for anticipated filter downtime.
The RENAL group of investigators concluded that "increasing the intensity of continuous renal-replacement therapy from 25 to 40 ml of effluent flow per kilogram per hour does not reduce mortality or the rate of dependence on dialysis among critically ill patients".
Yes, in theoretical terms the dose of dialysis is the volume of blood purified per unit time, and colloquially the "intensity" of dialysis is the scale of that dose (i.e. a higher dose is said to be more "intense"). In practical terms, the dose of dialysis is essentially the effluent flow rate (i.e. the combination of dialysate and ultrafiltrate flow rates).
Thus, when one signs the patient up for "two litre exchanges" one is prescribing an effluent rate of 2000ml/hr, and a replacement rate of 2000ml/hr (that is the "exchange"). This works out to be a dialysis dose of 28.6ml/kg/hr for a 70kg lump of human tissue.
This has been asked about in Question 12 from the first paper of 2010.
Specifically, " Briefly outline the relationship between dose of dialysis and outcome"
This question makes reference to the following "relevant studies":
Since then, there have been a few more:
In summary:
Higher intensity renal replacement therapy does not reduce mortality rates or improve renal recovery among patients with AKI.
There is no evidence to recommend a dose in excess of 25ml/kg/hr.
It seems beyond a certain dose, renal replacement therapy removes as many useful molecules as it does toxins, and the benefit from escalating the dose deteriorates.
In detail:
So, though small trials occasionally found a mortality benefit, large well-designed studies were unable to detect one. At this stage, the issue could be said to have been put to rest. Subsequent investigators have made attempts to find subtle non-survival benefits, or to investigate higher dialysis doses in patients with sepsis. More negative trials ensued.
For a definitive treatment of all of this, you ought to pay homage to the gigantic and all-encompassing "Critical Care Nephrology" by Ronco Bellomo and Kellum (2009).
The Gambro and Fresenius websites have also been an excellent source of information.
Bellomo, Rinaldo, and Claudio Ronco. "Nomenclature for continuous renal replacement therapies." Critical Care Nephrology. Springer Netherlands, 1998. 1169-1176.
Locatelli, Francesco, et al. "Dialysis dose and frequency." Nephrology Dialysis Transplantation 20.2 (2005): 285-296.
Claure-Del Granado, Rolando, et al. "Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis." Clinical Journal of the American Society of Nephrology 6.3 (2011): 467-475.
Clark, William R., et al. "Dose determinants in continuous renal replacement therapy." Artificial organs 27.9 (2003): 815-820.
O'Reilly, Philip, and Ashita Tolwani. "Renal Replacement Therapy III: IHD, CRRT, SLED." Critical care clinics 21.2 (2005): 367-378.
Ronco, Claudio, et al. "Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial." The Lancet 356.9223 (2000): 26-30.
Saudan, P., et al. "Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure." Kidney international 70.7 (2006): 1312-1317.
Bouman, Catherine SC, et al. "Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial." Critical care medicine 30.10 (2002): 2205-2211.
Tolwani, Ashita J., et al. "Standard versus high-dose CVVHDF for ICU-related acute renal failure." Journal of the American Society of Nephrology 19.6 (2008): 1233-1238.
VA/NIH Acute Renal Failure Trial Network. "Intensity of renal support in critically ill patients with acute kidney injury." The New England journal of medicine359.1 (2008): 7.
Bellomo, R., et al. "Intensity of continuous renal-replacement therapy in critically ill patients." The New England journal of medicine 361.17 (2009): 1627-1638.
Jun, Min, et al. "Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis." Clinical Journal of the American Society of Nephrology 5.6 (2010): 956-963.
Zhang, Ping, et al. "Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial." Nephrology Dialysis Transplantation 27.3 (2012): 967-973.
Vesconi, Sergio, et al. "Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury." Crit Care 13.2 (2009): R57.
Van Wert, Ryan, et al. "High-dose renal replacement therapy for acute kidney injury: systematic review and meta-analysis." Critical care medicine 38.5 (2010): 1360-1369.
Joannes-Boyau, Olivier, et al. "High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial." Intensive care medicine 39.9 (2013): 1535-1546.
Clark, Edward, et al. "High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis." Critical Care 18.1 (2014): R7.
Clark, Edward G., and Sean M. Bagshaw. "Unnecessary Renal Replacement Therapy for Acute Kidney Injury is Harmful for Renal Recovery." Seminars in dialysis. Vol. 28. No. 1. 2015.
Zhang, Ping, et al. "Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial." Nephrology Dialysis Transplantation 27.3 (2012): 967-973.