Daily Hemodialysis Improves Survival
Daily Hemodialysis Improves Survival
Abstract & Commentary
Synopsis: Critically ill patients often develop renal failure as part of their clinical course. Performing hemodialysis every day instead of every other day resulted in improved hemodynamic stability, better control of uremia, and reduction of mortality from 46% to 28% in this prospective, randomized trial.
Source: Schiffl H, et al. N Engl J Med. 2002;346: 305-310.
Despite universal availability and improvements in renal replacement therapy, the mortality in ICU patients who develop acute renal failure remains high. Some small studies have suggested that more frequent dialysis not based on the classic indications (ie, blood urea nitrogen [BUN] > 100 mEq/dL, creatinine > 3 mg/dL, acidosis, volume overload, etc.) results in improved outcome with a lower rate of complications. Other studies with continuous renal replacement therapy suggest that patients with higher ultrafiltration volumes fare better.
Schiffl and colleagues undertook a prospective, randomized study of the treatment of acute renal failure with daily or every other day hemodialysis. Using standard diagnostic criteria, the evaluated adult patients with the diagnosis of acute renal failure (usually acute tubular necrosis due to hypotension or a nephrotoxin). Exclusion criteria included obstructive uropathy, interstitial nephritis, renal transplant, pre-existing chronic renal failure, and rapidly progressive glomerulonephritis. Using a standard approach, the patient’s required dialysis dose (calculated ultrafiltration volume) was prescribed for each session. The actual delivered dialysis "dose" was measured for each episode. Patients were sequentially entered to receive daily and every other day dialysis. Using routine ICU monitoring, the stability during dialysis was assessed. Patients were followed for survival at 14 days following the last dialysis episode.
Of the 172 patients requiring acute hemodialysis during a 5-year period, 11 declined to participate and 1 had received dialysis for a radiographic dye load; leaving 160 for the study. Fourteen of these were removed from the study for a variety of reasons. A total of 74 received daily dialysis and 72 patients received every other day dialysis. There were no demographic or entry characteristic differences between the groups. The prescribed dialysis dose was greater than that delivered in both groups, but the dose during each episode was identical. BUN and creatinine were lower in the daily group (60 ± 20 vs 104 ± 18 mg/dL). Hemodynamic stability was also greater in the daily dialysis group. The most important outcome differences were in mortality (46 vs 28%; P = .01) and days to resolution of acute renal failure (16 ± 6 vs 9 ± 2; P = .001).
Comment by Charles G. Durbin, Jr., MD
This is an interesting and important study in that it strongly suggests that in critically ill patients with acute renal failure, a higher frequency of dialysis can produce a much better outcome. There are several possible mechanisms to explain this improvement. There were fewer acute dialysis-related complications with daily dialysis than with the alternating day schedule. This was despite receiving the same dose of dialysis during each episode. This improved hemodynamic stability may have resulted in less use of vasopressors and less administration of fluid boluses. These treatments themselves may produce a worsened outcome; by avoiding them, improved survival resulted.
The improved electrolyte and acid-base stability from daily dialysis may have had an ameliorating effect on organ function leading to reduced mortality. Cerebral function may be improved by having less fluctuation in serum osmolality. Likewise, cardiac function may have been improved by this same mechanism. The actual causes of mortality were not reported in this study so it is difficult to identify a specific organ function, which may be particularly important. Another possibility for the positive effects seen in this study with daily hemodialysis is that the more frequent dialysis resulted in more complete removal of toxic factors, which perpetuate critical illness and cause organ failure. Some studies of the septic syndrome have demonstrated that continuous hemofiltration even in the absence of acute renal failure improves stability and may improve mortality.
A concern with this paper is the method of randomization. Using an alternating entry pattern, clinicians would not be blind to the fact that the next patient would go to a particular group. Since all eligible patients were entered, however, this probably did not significantly affect randomization.
The costs of implementing daily dialysis, while a concern, are somewhat offset by the reduction in time to resolution of acute renal failure. However, there was an increase of about 50% in the number of dialysis sessions in the daily treatment group. While a larger, multicenter trial would be helpful, the huge reduction in mortality seen in this study suggests that daily dialysis should be strongly considered today in patients who meet the criteria used in this study.
Dr. Durbin is Professor of Anesthesiology, Medical Director of Respiratory Care, University of Virginia.
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