CURRENT CONCEPTS Review Article Current Concepts normalization of the plasma as possible. Thus, the sodium concentration of the dialysis fluid is physio- logic, but the potassium concentration is lower than that of normal plasma in order to establish a gradi- CONTINUOUS HEMOFILTRATION IN ent from plasma to the fluid that promotes the re- THE TREATMENT OF ACUTE RENAL moval of potassium ions from the patient’s blood. The concentrations of substances that are to be re- FAILURE moved completely (such as urea, creatinine, and phosphate) are zero in the dialysis fluid. The remov- L.G. FORNI, M.B., PH.D., AND P.J. HILTON, M.D. al of salt and water is achieved by the creation of a transmembrane pressure gradient (with lower pres- sure in the dialysis-fluid compartment). According CUTE renal failure that requires renal- to the laws of diffusion, the larger the molecule, the replacement therapy is a relatively common slower will be its rate of transfer across the mem- condition, with an annual incidence of at brane. A small molecule, such as urea (60 daltons), A 1 least 30 cases per 1 million population. Historically, is cleared efficiently, and a larger molecule, such as the replacement of renal function in acute renal fail- creatinine (113 daltons), less well. Phosphate ions ure has involved techniques also employed in the have such low rates of clearance that hyperphos- treatment of end-stage chronic renal failure — inter- phatemia is always a problem for patients on inter- mittent hemodialysis and peritoneal dialysis.2,3 Hemo- mittent dialysis. Dialysis has no similarity to the nor- filtration was first described in 1977 as a means of mal physiologic processes of the kidney, but it is removing extracellular fluid from patients with ede- effective, and many patients have lived for decades ma refractory to diuretic agents.4 Continuous hemo- entirely dependent on intermittent hemodialysis.5 filtration, combined with the administration of an Hemofiltration (Fig. 1, lower panel) works in a appropriate fluid, is now recognized as a form of re- different manner.6,7 In the simplest form of the pro- nal-replacement therapy in acute renal failure. The cedure, blood under pressure passes down one side technique is widely used in intensive care units for of a highly permeable membrane allowing both wa- the treatment of acute renal failure, although inter- ter and substances up to a molecular weight of about mittent hemodialysis continues to be used for pa- 20,000 to pass across the membrane by convective tients with acute renal failure but without multior- flow, as in glomerular filtration. During hemofiltra- gan failure. tion, in contrast to hemodialysis, urea, creatinine, and phosphate are cleared at similar rates, and pro- BASIC PRINCIPLES found hypophosphatemia may develop unless the Hemofiltration has many superficial similarities to patient’s phosphate intake is supplemented. Larger hemodialysis. In both techniques, access to the cir- molecules such as heparin, insulin, myoglobin, and culation is required and blood passes through an ex- vancomycin, which are cleared from the blood in tracorporeal circuit that includes either a dialyzer or only negligible quantities in a dialyzer, are cleared a hemofilter. However, the mechanisms by which the efficiently by the hemofilter. composition of the blood is modified differ marked- In the kidney, the glomerular filtrate is selectively ly (Fig. 1). During dialysis (Fig. 1, upper panel), blood reabsorbed by the renal tubules, a process too com- flows along one side of a semipermeable membrane plex to be artificially reproduced with current tech- as a solution of crystalloids is pumped along the oth- nology. Instead, during hemofiltration, the filtrate is er side of the membrane against the direction of the discarded and the patient receives infusions (usually blood flow. Small molecules diffuse across the mem- through the distal part of the hemofiltration circuit) brane from regions of greater concentration to re- of a solution in which the major crystalloid compo- gions of lesser concentration, and the composition nents of the plasma are at physiologic levels (the typ- of the dialysis fluid is designed to produce as near ical composition of hemofiltration replacement fluid is shown in Table 1). If there is no need for the re- moval of fluid from the patient, the rate at which the replacement fluid is administered is matched exactly with the rate of production of hemofiltrate. Usually, From St. Thomas’ Hospital, London SE1 7EH, United Kingdom, where reprint requests should be addressed to Dr. Hilton. however, there is a need to remove fluid, because of ©1997, Massachusetts Medical Society. either fluid overload or the clinical need to adminis- Volume 336 Number 18 ؒ 1303 The New England Journal of Medicine Hemodialysis Urea Phosphate K+ Creatinine Urea Phosphate K+ Creatinine K+ Creatinine Phosphate Urea To From patient K+ Creatinine Phosphate Urea patient Dialysis fluid Dialysate Hemofiltration Replacement fluid + + Na HH2OK HH2O Phosphate H2O Creatinine H2O Na+ K+ Phosphate Creatinine K+ Phosphate Na+ Urea To From patient patient + + K HH2O Phosphate H2O Na HH2O Urea H2O Hemofiltrate Figure 1. Hemodialysis and Hemofiltration. The arrows that cross the membrane indicate the predominant direction of movement of each solute through the membrane; the relative size of the arrows indicates the net amounts of the solute transferred. Other arrows indicate the direction of flow. ter fluids to a patient with oliguria. A net loss of ex- the principal constituents of the filtrate. Hemofiltra- tracellular fluid is achieved by replacing less fluid tion therefore inevitably leads to an increase in the through infusion than is removed by hemofiltration. concentration of both red cells and plasma protein It is important to recognize that certain physical in the blood of the extracorporeal circuit8; there is constraints affect hemofiltration as they do glomer- thus a tendency to produce viscous blood of high ular filtration. In both processes, the plasma compo- hematocrit and high colloid oncotic pressure at the nent of the blood flowing through the circuit repre- distal end of the hemofilter. It is therefore generally sents the sole source of the salt and water that are unwise to induce a filtration rate that is more than May 1, 1997 ؒ 1304 CURRENT CONCEPTS care unit, a number of variants were developed (Ta- TABLE 1. TYPICAL COMPOSITION ble 2). These are outlined below. OF HEMOFILTRATION REPLACEMENT FLUID.* CONTINUOUS ARTERIOVENOUS COMPONENT VALUE HEMOFILTRATION mmol/ Continuous arteriovenous hemofiltration is the liter original and simplest form of the technique.4,9 The Sodium 140 femoral artery and vein are cannulated, and blood Potassium 0 passes through the hemofilter under the influence of Calcium 1.6 arterial pressure alone (Fig. 2). Because the pressure Magnesium 0.75 in the system exceeds the atmospheric pressure, Chloride 101 there is no possibility of air being drawn into the cir- Lactate 45 cuit and no precautions need to be taken to prevent Glucose 11 this from occurring. However, the simplicity of the *The values shown are for Gambro Hemofiltrasol system is offset by several disadvantages. First, a dis- 22. Potassium chloride is added to the solution im- connection or leak in the circuit can result in rapid mediately before use in concentrations of up to loss of blood. Second, the efficiency of hemofiltra- 4 mmol per liter, depending on the serum potassium concentration. To convert the value for calcium to tion depends on the arterial pressure, which is fre- milligrams per deciliter, divide by 0.25; to convert quently low or unstable in patients with acute renal the value for magnesium to milliequivalents per liter, failure. The effectiveness of the system is therefore divide by 0.5; and to convert the value for glucose to milligrams per deciliter, divide by 0.05551. determined mainly by factors outside the direct con- trol of the physician. Low blood flow is associated with frequent clotting of the extracorporeal circuit, and the prolonged arterial cannulation typically used carries a risk of complications at the puncture site. 30 percent of the blood-flow rate. Keeping the ratio Continuous arteriovenous hemofiltration often re- between the two rates under 25 percent minimizes sults in clearance rates as low as 10 to 15 ml per the unwanted effect. An alternative approach, known minute even in normotensive patients; clearance rates as predilution, circumvents the problem by adminis- may drop to below 10 ml per minute if a patient has tering the replacement fluid proximal to the hemo- marked hypotension. filter. This rarely used procedure reduces the ef- ficiency and increases the cost of hemofiltration CONTINUOUS ARTERIOVENOUS because a proportion of the generated filtrate is ac- HEMODIALYSIS WITH FILTRATION tually replacement fluid. The recognition of the inadequacy of continuous As hemofiltration became an increasingly popular arteriovenous hemofiltration when used alone led to form of renal-replacement therapy in the intensive the addition of a dialysis circuit to the hemofilter.10,11 TABLE 2. TYPES OF RENAL-REPLACEMENT THERAPY FOR ACUTE RENAL FAILURE. EXTRA- ANTI- CELLULAR-FLUID USE IN COAGULANT RISK OF RISK OF VOLUME HYPO- TYPE COMPLEXITY EFFICIENCY COST THERAPY HEMORRHAGE INFECTION CONTROL TENSION Peritoneal dialysis Low Moderate Moderate No Low High Moderate Yes Intermittent hemodialysis Moderate High Low Yes Moderate Low Intermittent No Continuous arteriovenous Moderate Low and Moderate