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Continuous arteriovenous hemofiltration and multiple organ failure
Journal of Critical Care SEPTEMBER 1988
VOL III. NO 3 EDITORIAL
Continuous Arteriovenous Hemofiltration Multiple Organ Failure ONTINUOUS arteriovenous hemofiltration (CAVH) was used as an adjunct to C conventional hemodialysis therapy in anuric, intensive care patients in 1980.’ In the same year, CAVH was used to maintain fluid balance in patients requiring large amounts of parenteral fluid, such as vasoactive drugs, antibiotics, and total parental nutrition.2 Since that time, others have reported their experience with CAVH in the intensive care setting.3-8 In this issue of the Journal, Barzilay et al describe the use of CAVH with sequential plasmafilter-dialysis in five patients with polymicrobial sepsis, respiratory distress syndrome, and renal failure.’ All the patients who received this therapy survived. By contrast, survival in the two “control” groups of patients was 0 and 50%. There are several major deficiencies in the design of the present study. First, the purported improved survival rate in the experimental group has no statistical power when the small size of the groups with large confidence intervals are considered. Second, enrollment of patients into the study was neither prospective nor randomized. The “historical control” groups, of which there were two, received either “conventional” therapy or continuous arteriovenous hemodialysis alone. Third, multiple interventions, including aprotinin to inhibit proteases, allopurinol and vitamin C as scavengers of oxygen radicals, hemofiltration to remove excess fluid, hemodialysis to remove nitrogenous wastes, and plasmapheresis to remove possible mediators of multiple organ failure, were used simultaneously in the experimental group. This design leaves the reader Journal
of Critical
Care, Vol 3, No 3 (September),
1988:
pp 16 1- 162
and
struggling to determine which intervention contributed to the 100% survival rate noted in the experimental group. Fourth, plasmapheresis was used to remove putative mediators and toxic substances that might be associated with multiple organ failure. Unfortunately, the plasma and hemodialysate were not analyzed for the presence of mediators such as prostaglandins, thromboxanes, endotoxin, or complement. Finally, no mention of the complications associated with these various interventions is given. CAVH has become a routine technique for control of fluid and electrolyte imbalance and removal of nitrogenous waste products in critically ill patients. There are several advantages of CAVH over hemodialysis in critically ill patients. CAVH rarely results in hemodynamic instability in this group of patients who already may be hemodynamically unstable. Low blood flow rates (20 mL/min to 50 mL/min) can result in high ultrafiltration rates (300 mL/hr to 500 mL/hr) and removal of excess fluids. In addition to ultrafiltration, CAVH can remove significant amounts of nitrogenous waste products. In patients who produce 510 g/d of urea nitrogen, the BUN can be maintained at t90 mg/dL with an exchange of 10 L to 12 L in 24 hours. In catabolic patients, CAVH can be used to remove excess fluid and allow use of hyperalimentation to promote anabolism and reduce urea nitrogen production. The decrease in platelets, leukocytes, complement components, or PO2 and the disequilibrium syndrome do not occur with CAVH.” As with many new modalities of therapy, 161
162
HOWARD
prospective, randomized, controlled trials to determine the efficacy of CAVH are lacking. Since 1980, several anecdotal reports documenting the use of CAVH in the intensive care setting with or without multiple organ failure have appeared.‘-’ Indeed, none of these reports contained a control group and all have been of the descriptive variety. The use of CAVH for removal of excess fluid with maintenance of hemodynamic stability and compensation of uremia with and without hyperalimentation has been well documented. Additionally, a relatively low complication rate and simplicity of design are evident.
AND
ANDERSON
The present study by Barzilay et al is yet another descriptive study without an appropriate control group. The results are interesting. However, in view of the unproven benefit and potential costs and risks of such a multiinterventional approach to therapy, this study primarily serves to strongly reinforce the need for well-designed, controlled clinical trials. Randy L. Howard and Robert J. Anderson Veterans Administration Medical Center University of Colorado Health Sciences Center Denver
REFERENCES 1. Kramer P, Kaufhold G, Grone HJ, et al: Management of anuric intensive-care patients with arteriovenous hemofiltration. Int J Artif Organs 3:225-300, 1980 2. Paganini EP, Nakamoto S: Continuous slow ultrafiltration in oliguric acute renal failure. Trans Am Sot Artif Intern Organs 26:201-204,198O 3. Olbricht C, Mueller C, Schurek HJ, et al: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am Sot Artif Intern Organs 28:33-37,1982 4. Kramer P, Bohler J, Kehr A, et al: Intensive care potential of continuous arteriovenous hemotiltration. Trans Am Sot Artif Intern Organs 28:28-32, 1982 5. Lauer A, Saccaggi A, Ronco C, et al: Continuous arteriovenous hemofiltration in the critically ill patient. Ann Intern Med 99:455-460, 1983 6. Kaplan AA, Longnecker RE, Folkert VW: Continuous
arteriovenous hemofiltration. Ann Intern Med 100:358-367, 1984 7. Ossenkoppele GT, Van Der Meulen J, Bronsveld W, et al: Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock. Crit Care Med 13:102-104,1985 8. Weiss L, Danielson BG, Fellstrom B, et al: Continuous arteriovenous hemofiltration (CAVH) for treatment of acute renal failure (ARF) in critically ill patients. Kidney Int 33:757, 1988 (abstr) 9. Barzilay E, Weksler N, Kessler D, et al: Sequential plasmafilter-dialysis with slow continuous hemofiltration: Additional treatment for sepsis-induced AOSF patients. J Crit Care 3:163-166, 1988 10. Maguire WC, Anderson RJ: Continuous arteriovenous hemofiltration in the intensive care unit. J Crit Care 1:54-56, 1986
VOL III. NO 3 EDITORIAL
Continuous Arteriovenous Hemofiltration Multiple Organ Failure ONTINUOUS arteriovenous hemofiltration (CAVH) was used as an adjunct to C conventional hemodialysis therapy in anuric, intensive care patients in 1980.’ In the same year, CAVH was used to maintain fluid balance in patients requiring large amounts of parenteral fluid, such as vasoactive drugs, antibiotics, and total parental nutrition.2 Since that time, others have reported their experience with CAVH in the intensive care setting.3-8 In this issue of the Journal, Barzilay et al describe the use of CAVH with sequential plasmafilter-dialysis in five patients with polymicrobial sepsis, respiratory distress syndrome, and renal failure.’ All the patients who received this therapy survived. By contrast, survival in the two “control” groups of patients was 0 and 50%. There are several major deficiencies in the design of the present study. First, the purported improved survival rate in the experimental group has no statistical power when the small size of the groups with large confidence intervals are considered. Second, enrollment of patients into the study was neither prospective nor randomized. The “historical control” groups, of which there were two, received either “conventional” therapy or continuous arteriovenous hemodialysis alone. Third, multiple interventions, including aprotinin to inhibit proteases, allopurinol and vitamin C as scavengers of oxygen radicals, hemofiltration to remove excess fluid, hemodialysis to remove nitrogenous wastes, and plasmapheresis to remove possible mediators of multiple organ failure, were used simultaneously in the experimental group. This design leaves the reader Journal
of Critical
Care, Vol 3, No 3 (September),
1988:
pp 16 1- 162
and
struggling to determine which intervention contributed to the 100% survival rate noted in the experimental group. Fourth, plasmapheresis was used to remove putative mediators and toxic substances that might be associated with multiple organ failure. Unfortunately, the plasma and hemodialysate were not analyzed for the presence of mediators such as prostaglandins, thromboxanes, endotoxin, or complement. Finally, no mention of the complications associated with these various interventions is given. CAVH has become a routine technique for control of fluid and electrolyte imbalance and removal of nitrogenous waste products in critically ill patients. There are several advantages of CAVH over hemodialysis in critically ill patients. CAVH rarely results in hemodynamic instability in this group of patients who already may be hemodynamically unstable. Low blood flow rates (20 mL/min to 50 mL/min) can result in high ultrafiltration rates (300 mL/hr to 500 mL/hr) and removal of excess fluids. In addition to ultrafiltration, CAVH can remove significant amounts of nitrogenous waste products. In patients who produce 510 g/d of urea nitrogen, the BUN can be maintained at t90 mg/dL with an exchange of 10 L to 12 L in 24 hours. In catabolic patients, CAVH can be used to remove excess fluid and allow use of hyperalimentation to promote anabolism and reduce urea nitrogen production. The decrease in platelets, leukocytes, complement components, or PO2 and the disequilibrium syndrome do not occur with CAVH.” As with many new modalities of therapy, 161
162
HOWARD
prospective, randomized, controlled trials to determine the efficacy of CAVH are lacking. Since 1980, several anecdotal reports documenting the use of CAVH in the intensive care setting with or without multiple organ failure have appeared.‘-’ Indeed, none of these reports contained a control group and all have been of the descriptive variety. The use of CAVH for removal of excess fluid with maintenance of hemodynamic stability and compensation of uremia with and without hyperalimentation has been well documented. Additionally, a relatively low complication rate and simplicity of design are evident.
AND
ANDERSON
The present study by Barzilay et al is yet another descriptive study without an appropriate control group. The results are interesting. However, in view of the unproven benefit and potential costs and risks of such a multiinterventional approach to therapy, this study primarily serves to strongly reinforce the need for well-designed, controlled clinical trials. Randy L. Howard and Robert J. Anderson Veterans Administration Medical Center University of Colorado Health Sciences Center Denver
REFERENCES 1. Kramer P, Kaufhold G, Grone HJ, et al: Management of anuric intensive-care patients with arteriovenous hemofiltration. Int J Artif Organs 3:225-300, 1980 2. Paganini EP, Nakamoto S: Continuous slow ultrafiltration in oliguric acute renal failure. Trans Am Sot Artif Intern Organs 26:201-204,198O 3. Olbricht C, Mueller C, Schurek HJ, et al: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am Sot Artif Intern Organs 28:33-37,1982 4. Kramer P, Bohler J, Kehr A, et al: Intensive care potential of continuous arteriovenous hemotiltration. Trans Am Sot Artif Intern Organs 28:28-32, 1982 5. Lauer A, Saccaggi A, Ronco C, et al: Continuous arteriovenous hemofiltration in the critically ill patient. Ann Intern Med 99:455-460, 1983 6. Kaplan AA, Longnecker RE, Folkert VW: Continuous
arteriovenous hemofiltration. Ann Intern Med 100:358-367, 1984 7. Ossenkoppele GT, Van Der Meulen J, Bronsveld W, et al: Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock. Crit Care Med 13:102-104,1985 8. Weiss L, Danielson BG, Fellstrom B, et al: Continuous arteriovenous hemofiltration (CAVH) for treatment of acute renal failure (ARF) in critically ill patients. Kidney Int 33:757, 1988 (abstr) 9. Barzilay E, Weksler N, Kessler D, et al: Sequential plasmafilter-dialysis with slow continuous hemofiltration: Additional treatment for sepsis-induced AOSF patients. J Crit Care 3:163-166, 1988 10. Maguire WC, Anderson RJ: Continuous arteriovenous hemofiltration in the intensive care unit. J Crit Care 1:54-56, 1986