Correspondence
Continuous Hemofiltration
N Engl J Med 1997; 337:712-714September 4, 1997
- Article
To the Editor:
The review article by Forni and Hilton on continuous hemofiltration for the treatment of acute renal failure (May 1 issue)1 suggests that this therapy should be used more widely. That may prove to be the case. However, as the article notes, there is little support for this approach in published reports. None of the references cited demonstrated in a randomized, controlled trial that this therapy reduces morbidity or mortality. Moreover, a preliminary report of a multicenter randomized trial comparing continuous therapy with intermittent dialysis found that continuous therapy had no benefit.2
There are important considerations of cost. The personnel requirements for administering continuous therapy are formidable, and considerable training is needed for nurses in the intensive care unit. Charges to insurers for continuous therapy are substantially higher than those for intermittent dialysis. Another issue is safety. Since the therapy is continuous, serious deviations from the normal volume and composition of fluid in the body can occur unless there is extremely vigilant monitoring.
We acknowledge that this therapy may be useful in limited numbers of patients who do not tolerate intermittent therapy. We do, however, question the wisdom of promoting this approach broadly before adequate trials are conducted. This therapy is costly, has largely not been compared with existing treatments, and may carry an increased risk to patients if it is used widely.
2 ReferencesThomas H. Hostetter, M.D.
Connie L. Manske, M.D.
Mark S. Paller, M.D.
University of Minnesota, Minneapolis, MN 554551
Forni LG ,Hilton PJ . Continuous hemofiltration in the treatment of acute renal failure. N Engl J Med 1997;336:1303-1309
Full Text | Web of Science | Medline2
Mehta R ,McDonald B ,Gabbai F , et al. Continuous versus intermittent dialysis for acute renal failure (ARF) in the ICU: results from a randomized multicenter trial. J Am Soc Nephrol 1996;7:1457-1457 abstract.
To the Editor:
Forni and Hilton state that in cases of intolerance to heparin, prostacyclin can be substituted or anticoagulation can be withheld. For the past two years, we have used a simple method of citrate anticoagulation in continuous venovenous hemofiltration circuits, without systemic anticoagulation.1
In brief, we infuse an isotonic sodium citrate–based replacement-fluid filter. The solution is calcium-free and contains citrate (40 meq per liter) as a base instead of lactate or bicarbonate. The blood-flow rate is set at 180 ml per minute, and the ultrafiltration rate at 33 ml per minute. Calcium is replaced through a separate infusion. Volume control is achieved solely by varying the rate of infusion of the replacement fluid. The citrate prevents clotting by chelating calcium in the extracorporeal blood. When the blood returns to the systemic circulation, the citrate is rapidly metabolized into bicarbonate, and hence there is minimal systemic chelation of calcium and no detectable systemic anticoagulation.
We have now used this system in more than 30 patients, with an average filter life similar to that with systemic heparin anticoagulation. Metabolic control is equivalent to that with lactate-based solutions, and bleeding has not been a problem.1 The main contraindications to the citrate replacement fluid are severe liver dysfunction and lactic acidosis. In these conditions, the citrate may not be adequately metabolized into bicarbonate and may accumulate, causing hypocalcemia and worsening acidosis.
Regional anticoagulation with citrate for continuous arteriovenous hemodiafiltration has been described 2,3 but has not been widely used because of logistic difficulties. We believe that our technique represents a simple solution to the problem facing patients who require continuous hemofiltration but cannot tolerate systemic anticoagulation.
3 ReferencesChi-yuan Hsu, M.D.
Massachusetts General Hospital, Boston, MA 02114Runolfur Palsson, M.D.
Reykjavik City Hospital, Reykjavik, IcelandJohn L. Niles, M.D.
Massachusetts General Hospital, Boston, MA 021141
Palsson R ,Bazari H ,Fang LST ,Rubin NT ,Niles JL . Regional citrate anticoagulation in continuous venovenous hemofiltration (CVVH) in critically ill patients with high risk of bleeding. J Am Soc Nephrol 1996;7:1416-1417 abstract.2
Mehta RL ,McDonald BR ,Aguilar MM ,Ward DM . Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int 1990;38:976-981
CrossRef | Web of Science | Medline3
Ward DM ,Mehta RL . Extracorporeal management of acute renal failure patients at high risk of bleeding. Kidney Int 1993;43:Suppl 41:S237-S244
Web of Science
To the Editor:
. . . One potential benefit of continuous venovenous hemofiltration that Forni and Hilton do not mention may be the continuous clearing of circulating large-molecular-weight substances with vasoactive, proteolytic, and immunosuppressive properties.1-3 This may antagonize the often exaggerated systemic inflammatory response in complicated acute renal failure, and it may translate into an improvement in clinical course and outcome.1-4 This one factor may help explain the decrease in mortality coincident with the introduction of continuous hemofiltration that Forni and Hilton have observed; a similar effect on mortality has not been seen with the introduction of other techniques of continuous hemofiltration.1,4 In addition, a positive correlation between the ultrafiltration volume (that is, a convective purification rate) and the time to the recovery of diuresis and outcome has been observed in patients with acute renal failure.1,4 Therefore, we believe that continuous venovenous hemofiltration is preferable, not only because it provides adequate renal replacement, but also because it potentially assists the recovery of the kidneys from disease or injury and ultimately improves the outcome.
However, we disagree with Forni and Hilton that predilution continuous hemofiltration is a less efficient treatment than postdilution continuous hemofiltration. In our experience, high rates of ultrafiltration can be achieved more easily with predilution. Predilution reduces the viscosity of blood as it enters the filter and increases flow and hydrostatic pressure across the membrane. It also increases the availability of urea for convective transfer by favoring its movement from the erythrocyte, while the sieving properties of the membrane are better preserved. Although a proportion of the filtrate generated is actually replacement fluid, the net effect is better clearance.
4 ReferencesEric F.H. van Bommel, M.D., Ph.D.
Drechtsteden Hospital, NL-3317 NM Dordrecht, the NetherlandsAlbert F. Grootendorst, M.D., Ph.D.
St. Clara Hospital, NL-3078 HT Rotterdam, the Netherlands1
van Bommel EF . Should continuous renal replacement therapy be used for `non-renal' indications in critically ill patients with shock? Resuscitation 1997;33:257-270
CrossRef | Web of Science | Medline2
van Bommel EF ,Hesse CJ ,Jutte NH ,Zietse R ,Bruining HA ,Weimar W . Impact of continuous hemofiltration on cytokines and cytokines inhibitors in oliguric patients suffering from systemic inflammatory response syndrome. Ren Fail 1997;19:443-454
CrossRef | Web of Science | Medline3
Grootendorst AF ,van Bommel EFH ,van der Hoven B ,van Leen-goed LAMG ,Osta ALM . High-volume hemofiltration improves hemodynamics of endotoxin-induced shock in the pig. J Crit Care 1992;7:67-75
CrossRef | Web of Science4
Storck M ,Hartl WH ,Zimmerer E ,Inthorn D . Comparison of pump-driven and spontaneous continuous hemofiltration in postoperative acute renal failure. Lancet 1991;337:452-455
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Hostetter and colleagues question our advocacy of continuous hemofiltration to treat acute renal failure in the absence of satisfactory randomized, controlled trials. We acknowledge this lack of firm evidence but would point to our own experience and that of others. We observed a decrease in mortality due to acute renal failure in the intensive care unit, from 80 percent to 35 percent, after the introduction of hemofiltration.1 We accept that hemofiltration was probably not the sole cause of the improved survival, but an improvement of this magnitude makes it unlikely that the therapy increases the risk and at least makes the contrary view plausible.
We do not agree that the report of Mehta et al.2 can be taken as evidence against the superiority of hemofiltration. Their study excluded patients with mean arterial pressures of less than 70 mm Hg, who are those expected to benefit most, and there were acknowledged difficulties with the randomization. We also disagree that the personnel requirements for administering continuous therapy are formidable. With appropriate in-service training, the staff members in our intensive care unit initiate and monitor hemofiltration while continuing to care for the patient. Intermittent hemodialysis in the intensive care unit requires many hours a week from the dialysis nurse. Overall, we see a savings in staff costs associated with the use of hemofiltration rather than dialysis. We agree that in continuous hemofiltration there is the potential for serious deviations from normal body-fluid volumes unless there is adequate monitoring. However, this is much less of an issue with modern, fully automated hemofiltration systems that reliably convert physicians' decisions on fluid balance into practice.
We agree with Dr. Hsu and colleagues that citrate can be used as an anticoagulant in continuous hemofiltration systems. Caution is needed, however, particularly if the replacement fluid is lactate-based, because both compounds contain a substantial amount of the later constituents of intermediary metabolism, and in this respect the effects of the two are additive.
Drs. van Bommel and Grootendorst suggest that continuous hemofiltration has a beneficial effect because it removes inflammatory mediators from the circulation. For this to be an important advantage, the mediator removed should have a half-life long enough that the clearance of, typically, 25 to 40 ml of plasma per minute represents a substantial reduction. This question can also be linked to the contentious issue of the “biocompatibility” of hemofilters as compared with dialyzers. Drs. van Bommel and Grootendorst disagree with our assertion that predilution hemofiltration is less efficient than postdilution hemofiltration. We referred to value for money (improvement in chemical balance per liter of replacement fluid consumed), rather than technical performance. In the former respect, postdilution is unarguably superior.
Dr. Marc Silverstein has brought to our attention that he and his colleagues wrote a report published in 1974 3 that antedates the description of hemofiltration by Kramer et al.4 We stand corrected and are pleased to acknowledge the contribution made by that article.
4 ReferencesL.G. Forni, M.B., Ph.D.
P.J. Hilton, M.D.
St. Thomas' Hospital, London SE1 7EH, United Kingdom1
Barton IK ,Hilton PJ ,Taub NA , et al. Acute renal failure treated by haemofiltration: factors affecting outcome. Q J Med 1993;86:81-90[Erratum, Q J Med 1993;86:283.]
Web of Science | Medline2
Mehta R ,McDonald B ,Gabbai F , et al. Continuous versus intermittent dialysis for acute renal failure (ARF) in the ICU: results from a randomized multicenter trial. J Am Soc Nephrol 1996;7:1457-1457 abstract.3
Silverstein ME ,Ford CA ,Lysaght MJ ,Henderson LW . Treatment ofsevere fluid overload by ultrafiltration. N Engl J Med 1974;291:747-751
Full Text | Web of Science | Medline4
Kramer P ,Wigger W ,Rieger J ,Matthaei D ,Scheler F . Arteriovenous haemofiltration: a new and simple method for treatment of over-hydrated patients resistant to diuretics. Klin Wochenschr 1977;55:1121-1122
CrossRef | Medline
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