CA2119375C

CA2119375C - Hemofiltration system and method

Info

Publication number: CA2119375C
Application number: CA002119375A
Authority: CA
Inventors: Yuli Kitaevich; Nat Hemasilpin; J. Gabriel Marchevsky; John J. Bissler; George Benzing Iii; Paul T. Mcenery
Original assignee: Cincinnati Childrens Hospital Medical Center
Current assignee: Cincinnati Childrens Hospital Medical Center
Priority date: 1991-10-11
Filing date: 1992-10-06
Publication date: 2002-08-13
Anticipated expiration: 2012-10-06
Also published as: DE69204683T3; US5344568A; JP3140781B2; ATE127352T1; JPH07500036A; US5211849B1; US5344568B1; US5211849A; DE69204683T2; EP0607301B1; DE69204683D1; WO1993006875A1; AU2862092A; EP0607301A1; EP0607301B2; CA2119375A1

Abstract

A multipurpose hemofiltration system (10) and method are disclosed for the removal of fluid and/or soluble waste from the blood of a patient. The system (10) and method are equally applicable to adult, pediatric and neonatal patients. The system (10) continuously monitors the weight of infusate in a first reservoir (50) and drained fluid (76) in a second reservoir (74) and compares those weights to corresponding predetermined computed weights. When necessary, the pumping rates of the infusate (52), drained fluid (76) and blood are adjusted in order to achieve a preselected amount of fluid removal from the patient's blood in a preselected time period. Application of this system (10) and method provide repeatable and highly precise results.

Description

HEMOFILTRATION SYSTEM AND METHOD
Field of the Invention The present invention is directed to a system and method of blood filtration, and particular-ly a continuous system and method for the regulation of the rate of filtration of fluid and/or soluble waste from the blood of a patient.
Backqround of the Invention For various reasons, including illness, injury or surgery, patients may require replacement or supplementation of their natural renal function in order to remove excess fluid or fluids containing dissolve waste products from their blood. Several procedures known for this purpose are dialysis, hemodialysis, hemofiltration, hemodiafiltration and ultrafiltration; another related procedure is plasma-pheresis. The specific procedure employed depends upon the needs of the particular patient. For exam-ple, dialysis is used to remove soluble waste and solvent from blood; hemofiltration is used to remove plasma water from blood; hemodiafiltration is used to _2_ remove both unwanted solute (soluble waste) and plasma water from blood; ultrafiltration is a species of hemofiltration; and plasmapheresis is used to remove blood plasma by means of a plasmapheresis filter.
Because the replacement of renal function may affect nutrition, erythropoiesis, calcium-phosphorus balance and solvent and solute clearance from the patient, it is imperative that there be accurate control of the procedure utilized. The accurate control of the rate of removal of intravascular fluid volume is also important to maintain proper fluid balance in the patient and prevent hypotension.
Various systems have been proposed to monitor and control renal replacement procedures. For example, U.S. Patent No. 4,132,644 discloses a dialy-sis system in which the weight of dialyzing liquid in a closed liquid container is indicated by a scale.
After the dialyzing liquid flows through the dialyzer, the spent liquid is returned to the same container and the weight is again indicated. Since the container receives the original dialyzing liquid plus ultra-filtrate, the amount of ultrafiltrate removed from the patient is equal to the increase in total weight in the container. This system is not driven by a weight measuring device and does not offer precise control of the amount of liquids used in the procedure.
1 _._ _... . . __.~._. _._ 1.

2 ~ ~ 9 3 7 5 p~/US92/08495 U.S. Patent No. 4,204,957 discloses an artificial kidney system which utilizes weight mea-surement to control the supply of substituate fluid to a patient. In this system, the patient's blood is pumped through a filter and the filtrate from the blood is discharged to a measuring vessel associated with a weighing device. A second measuring vessel containing substituate fluid is associated with a second weighing device and is connected to the puri-fied blood line. By means of a pump, the substituate fluid and the purified blood are pumped back to the patient. The first and second weighing devices are coupled to one another by a measuring system in such a way that a fixed proportion of substituate is supplied to the purified blood stream from the second measuring vessel depending on the weight of the filtrate re-ceived in the first measuring vessel. This system does not utilize circulating dialysate fluid in the blood filtration.
U.S. Patent No. 4,767,399 discloses a system for performing continuous arteriovenous hemofiltration (CAVH). The disclosed system relies upon utilizing a volumetric pump to withdraw a desired amount of fluid from the patient's blood and return a selected amount of fluid volume to the patient.
U.S. Patent No. 4,923,598 discloses an apparatus for hemodialysis and hemofiltration which WO 93/06875 21 19 3 l 5 PCT/US92/08495 comprises an extracorporeal blood circuit including a dialyzer and/or filter arrangement. The system deter-mines fluid withdrawal per unit time and total amount of fluid withdrawn by utilizing flow sensors in conjunction with an evaluating unit located upstream and downstream of the dialyzer or filter arrangement in the blood circuit.
U.S. Patent No. 4,728,433 discloses a system for regulating ultrafiltration by differential weigh-ing. The system includes a differential weighing to receptacle having an inlet chamber and an outlet chamber which allows a fixed amount of fresh dialy-sate, by weight, to flow through the hemodialyzer.
This system operates in a sequence of weighing cycles during which the amount of ultrafiltrate removed from the blood may be calculated. Additionally, the ultrafiltration rate for each weighing cycle may be calculated. This system provides a mechanism for determining and regulating the amount of ultrafiltrate removed from the blood while delivering dialysate to the patient in alternating fill and drain cycles of the inlet and outlet chambers of the differential weighing receptacle.
The need exists for a multipurpose renal function replacement/supplementation system which is accurate, reliable, capable of continuous, long-term I _ __.. ......_.

_5_ 2119315 operation, and which can be used effectively on adult, pediatric and neonatal patients.
U.S. Patent 4,769,132 discloses a hemodialysis system which includes first and second weighing means. The system also includes a pump for pumping blood from the patient through a hemodialysis filter, and pumps for pumping the clean and contaminated dialysing fluid, respectively, to and from the filter. An additional pump is provided for transferring clean dialysing fluid from the supply thereof to a reservoir. A
controller monitors signals generated by the second weighing means indicative of the weight of fluid in the reservoir and controls the additional pump. The system is arranged so that the amount of fluid withdrawn from the patient directly correlates to the amount of fluid transferred by the additianal pump and so the controller can set the water balance of the patient at any desired value.
Generally speaking, the present invention may be considered as providing continuous hemofiltration system for removal of fluid from the blood of a patient, comprising:
hemofiltration means; means for pumping blood from a patient through the hemofiltration means and back to the patient; a first reservoir for maintaining a supply of infusate; first pumping means for pumping the infusate from the first reservoir to the hemofiltration means;
a second reservoir for receiving drained fluid from the hemofiltration means;
second pumping means for pumping the drained fluid from the hemofiltration means to the second reservoir;
weighing means for monitoring the weight of the infusate and the drained fluid and generating weight data signals correlated thereto; and control means operably connected to the blood pumping means and to each of the first and second pumping means and the weighing means, the control means comprising a computer programmed to operate the first and second pumping means only when the blood pumping means is operating; the blood pumping means - 5a -and the first and second pumping means being responsive to signals generated by the control means; the control means receiving the weight data signals generated by the weighing means, determining from the weight data signals the weight of infusate and drained fluid in the first and second reservoirs, respectively, at regular intervals, comparing those weights to corresponding predetermined computed weights, and generating control signals to adjust and thereby automatically adjusting as necessary on an ongoing basis during hemofiltration the rates of pumping at least two of the following: the infusate, drained fluid, and blood, while the pumps are pumping during hemofiltration, so as to remove a preselected amount of fluid from the blood over a preselected time period.
The present invention is directed to a multipurpose system and corresponding method for removal of fluid and/or soluble waste from the blood of a patient:
ultrafiltration only, hemodiafiltration, hemodiafiltration and ultrafiltration and plasmapheresis with or without fluid replacement. The system and method of the present invention can provide reliable, long-term operation (5-10 days) with a great degree of accuracy (on the order of t2 grams regardless of the total volume of fluid passing through the system). The system and method of the invention are advantageous because of the multipurpose nature thereof, the repeatability and accuracy of the processes, and the simultaneous, continuous flow of fluids in an extra-corporeal blood circuit, while being equally applicable to adult, paediatric and neonatal patients.
As used herein the term "hemofiltration" is be broadly construed to include hemodialysis, hemofiltration, hemodiafiltration, ultrafiltration and plasmaphersis processes.
As used herein, the term "infusate" is defined to include dialysate fluid or any other fluids which may be supplied to the patient as a part of the hemofiltration procedures.

5 2 ~ 19 3 7 5 PCT/US92/0$495 p In a preferred embodiment, the system of the present invention includes a hemofilter, a blood pump for pumping blood from a patient through the hemo-filter and back to the patient, and suitable tubing for carrying the pumped blood to and from the patent.
The system further includes a first reservoir for maintaining a supply of infusate, a first weighing means for continuously monitoring the weight of the infusate and generating signals correlated to the monitored weight, and a first pump for pumping the infusate from the first reservoir to the hemofilter or appropriate blood tubing access port. A second reservoir receives drained fluid (e. g., spent infusate or ultrafiltrate, including the fluids and solutes removed from the blood) from the hemofilter, and a second weighing means monitors the weight of the drained fluid and generates signals correlated to the monitored weight. A second pump pumps the drained fluid from the hemofilter to the second reservoir.
The system also includes a controller operably con-nected to the blood pump, the infusate pump, the drain pump and the first and second weighing means.
The controller periodically interrogates, at predetermined intervals, the signals that are continu ously generated by the first and second weighing means and is designed to determine therefrom the weight of infusate and drained fluid in the first and second reservoirs at the predetermined intervals. The rate of fluid withdrawal from the blood is also determined.
The controller compares the infusate and drained fluid weights to corresponding predetermined computed weights in the memory of the controller, and, when necessary, the controller generates signals which adjust the pumping rates of the infusate and drained fluid pumps in order to achieve a preselected amount of fluid removal from the patient's blood. addition-ally, the controller is programmed to operate the infusate and drained fluid pumps only when the blood pump is operating. Furthermore, the blood pump is operably connected to and is responsive to signals generated by the controller to vary the flow rate of the blood through the hemofilter as required to achieve the desired level of fluid removal °rom the blood.
In a preferred embodiment or the method blood from a patient is pumped through a hemofilter and a supply of infusate, ~.~hich is maintained in a first reservoir, is pumped from the first reservoir through the hemofilter, countercurrent to the blood. The weight of infusate in the First reservoir is continuously monitored and signals correlated to that weight are generated: Draw ed fluid (e.g., spent infusate! is pumped from the hemozilter and is received in a second reservoir. The ~~~~T

2119375 - ;

weight of the drained fluid in the second reservoir is continuously monitored and signals correlated thereto are generated. The signals correlated to the weight of infusate and drained fluid are interrogated at regular intervals (for example every minute) by a system controller and are compared to corresponding predetermined computed weights in the memory of the controller. The controller determines the amount and rate of fluid withdrawal from the patient's blood. If those values differ prom preselected, pre-programmed desired values, the controller generates signals which independently adjust the pumping rates of the infusate and drained fluid pumps so as to achieve the desired amount of fluid removal.
The advantages of the system and corresponding method are achieved at least in part due to the continuous monitoring and periodic interro-gation of the fluid weights and the adjustment o=
fluid pumping rates, including the blood pumping rate, so as to achieve ideal or nearly ideal fluid removal and replacement if necessary from a patient's blood.
Further features and advantages of the system and method will become appar-ent with reference to the Figure and the detailed description which follows.
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WO 93/06875 2 1 1 9 3 7 5 'VS92/08495 _g_ Brief Description of the Drawing The Figure is a diagrammatic representation of one embodiment of the system of the present inven-tion; an alternative embodiment is shown in phantom.
Detailed Descriptian of the Invention The Figure shows a diagrammatic representa-tion of a preferred embodiment of the system of the present invention. The portion of the Figure shown in phantom represents an alternative embodiment of the present invention which will be described hereinbelow.
Hemofiltration system 10 is operated and controlled by a suitable controller designated generally as 12.
Controller 12 may be a programmable computer such as a COMPAQ 386/S having a display 13 and is operably connected to various components of hemofiltration system 10, as will be described in greater detail hereinafter.

In operation, blood is pumped from a patient (not shown), which may be an adult, pediatric or neonatal patient, through a suitable catheter (not shown) and input tubing 14 by means of a blood pump 16. Blood pump 16, which is preferably of the roller type, is operably connected to controller 12 by line 18. One suitable blood pump is the RS-7800 Minipump manufactured by Renal Systems, Minneapolis, MN. Input tubing 14 through which the patient's blood is pumped preferably includes a pressure transducer 20 upstream WO 93/06875 2 ~ 19 3 7 ~ PCT/US92/08495 -l0-of pump 16. Pressure transducer 20 is operably connected to controller 12 via line 21. Means are included downstream of blood pump 16 for accessing input tubing 14 to enable the injection or infusion of desired fluids, including medications and anti-clotting compounds such as heparin, into the patient's blood. The injection or infusion of such fluids to the blood may be accomplished in any suitable manner;
the Figure shows diagrammatically a syringe and tube arrangement 22, but it will be appreciated that other means could be employed for the same purpose.
The patient's blood is pumped through hemofilter 24 by blood pump 16. Filters of the type suitable for use in the system of the present inven-tion are readily available; one example of a suitable hemofilter is the Diafilter manufactured by AMICON, Danvers, MA. Where the present system is used to perform plasmapheresis, a suitable plasmapheresis filter such as the Plasmaflo manufactured by Parker Hannifin, Irvine, CA can be employed.
Input tubing 14 includes a second pressure transducer 26 slightly upstream of hemofilter 24.
Pressure transducer 26 is operably connected to controller 12 via line 28. The patient's blood exits hemofilter 24, passes through output tubing 30 and is returned to the patient via any suitable means such as a venous catheter arrangement (not shown). Output .__ I _. i WO 93/06875 . ~ ~ 19 3 7 5 PCT/US92/08495 tubing 30 preferably includes a suitable blood flow detector 31 which verifies that there is blood flow in the system and an air bubble/foam control device such as air bubble clamp 32 to prevent the passage of air bubbles to the patient. Blood flow detector 31 and air bubble clamp 32 may be operably connected (not shown) to controller 12 or directly to the pumps to interlock all pumps upon detection of any air bubbles in the blood or upon the cessation of blood flow. A
suitable foam-bubble detector is the RS-3220A man-ufactured by Renal Systems. Output tubing 30 also preferably includes a pressure transducer 34 immedi-ately downstream of hemofilter 24. Pressure trans-ducer 34 is operably connected to controller 12 via line 36.
A first reservoir 50 maintains a supply of suitable dialysate or other fluid, referred to herein generally as infusate 52. The infusate-containing reservoir 50 is supported by a weighing device such as electronic scale 54 which is operably connected to controller 12 via line 56. Infusate 52 is pumped from reservoir 50 via tubing 58 by means of infusate pump 60, which is preferably of the roller variety. A
suitable pump for this purpose is a 3%," Roller Pump manufactured by PEMCO, Cleveland, OH. Infusate pump 60 is operably connected to controller 12 via line 62 and pumps infusate 52 through hemofilter 24 WO 93/06875 2 ~ ~ 9 3 T~ ~ PCT/US92/08495 countercurrent to the blood pumped therethrough. In accordance with known principles, infusate 52 may extract certain components (fluids and/or soluble waste) from the blood passing through hemofilter 24.
The fluid drained from hemofilter 24 includes spent infusate and the components removed from the blood, which are referred to herein as drained fluid 76. In an alternative embodiment wherein system 10 is used as a fluid or plasma replacement system, e.g., to perform l0 plasmapheresis, the infusate (which may be blood plasma) from reservoir 5o is pumped via tubing 59 (shown in phantom) to blood output tubing 30, thereby replacing the fluid volume removed from the blood. In this embodiment, tie drained fluid 76 from hemofilter or plasmapheresis filter 24 does not include any spent infusate since the infusate is pumped directly to blood output tubing 30 and supplied to the patient.
The drained fluid 76 is pumped from hemo-filter 24 through outlet tubing 64 by means of drain pump 66, which is preferably a roller-type pump, and may be the same as infusate pump 60. Drain pump 66 is operably connected to controller 12 via line 68.
Output tubing 64 preferably includes a pressure transducer 70 downstream of hemofilter 24, but up-stream of drain pump 66. Pressure transducer 70 is operably connected to controller 12 via line 72.
output tubing 64 also preferably includes a blood leak ~ i WO 93/06875 ~ ~ ~ ~' ~ ~ . p~'l~JS92/08495 detector 67 which detects the presence of blood in the drained fluid 76, as may occur if hemofilter 24 ruptures. A suitable blood leak detector is sold by LOBE, Lakewood, CO as model 500247000. Blood leak detector 67 may be operably connected (not shown) to controller 12 or directly to the pumps to interlock all pumps upon the detection of blood in the drained fluid. Drained fluid 76 pumped from hemofilter 24 is pumped into a second reservoir 74 which collects the drained fluid. Second reservoir 74 is supported by a weighing device such as electronic scale 78, which is operably connected to controller 12 via line 80.
Scales 54 and 78, which may be model 140 CP
sold by SETRA of Acton, MA continuously generate signals correlated to the weight of infusate and drained fluid contained in reservoirs 50 and 74, respectively. Those signals are continuously fed to controller 12, to which the scales are linked through an RS-232 interface. Likewise, pressure transducers 20, 26, 34 and 70 all continuously measure the pres-sure at their respective locations in hemofiltration system 10 and generate signals correlated thereto which are fed to controller 12. A suitable type of pressure transducer is model number 042-904-10 sold by COBS of Lakewood, CO.
Controller 12 is preferably a programmable computer that is capable of sending and receiving 21 1'9315 signals from auxiliary equipment including pressure transducers 20, 26, 34 and 70, first and second scales 54 and 78, respectively, and blood pump 16, infusate pump 60, and drain pump 66. In operation, controller 12 interrogates, at regular intervals, the signals generated by first and second scales 54 and 78. From the signals, controller 12 determines the weight of infusate and drained fluid in the first and second reservoirs 50 and 74 at that point in time, and compares those weights to corresponding predetermined computed weights which have been programmed into and are stored by controller 12. By monitoring the weight of infusate in reservoir 50 and the weight of drained fluid in reservoir 74 at regular intervals, the rate of change of those weights and the rate of hemo-filtration can be calculated by the computer portion of controller 12. When the weights deviate from the predetermined computed weights and/or the rate of hemofiltration deviates from a preselected, pre-programmed desired rate, controller 12 generates signals which control or adjust the rates at which blood pump 16, infusate pump 60 and drain pump 66 are operated, as necessary, to adjust the hemofiltration rate to the desired rate, or to stop the pumps when preselected limits have been reached. This is accom-plished in a continuous manner; i.e., continuous signal generation, periodic interrogation of those _ __ __ 1 WO 93/06875 ~ ~ , ~ ~ 3 7 ~ PCT/US92/08495 signals and computation of the required weight and/or rate information, comparison to predetermined computed values and adjustment of the pumping rate of the pumps, as necessary, to achieve the desired amount and/or rate of hemofiltration.
Controller 12 is programmed so that infusate pump 60 and drain pump 66 are operated only when blood pump 16 is being operated. In the case when ultrafil-tration is being performed, the pumping rate of drain Pump 66 must equal the pumping rate of infusate pump 60 plus the desired ultrafiltration rate.
Controller 12 continuously receives signals from pressure transducers 20, 26, 34 and 70 and is programmed to generate alarm signals when high and low pressure limits are exceeded at any of the monitored locations. Furthermore, an alarm signal is generated when the pressure differential across hemofilter 24 exceeds a predetermined upper limit, as monitored specifically by pressure transducers 26, 34 and 70.
Additionally, controller 12 may stop the pumps when preselected pressure limits (high or low) are exceeded, as for example may occur if the system tubing becomes occluded or ruptures or if pump occlu-sion occurs. Finally, controller 12 may signal when the infusate level in reservoir 50 reaches a prede-termined lower limit and when the drained fluid level in reservoir 76 reaches a predetermined upper limit.

WO 93/06875 21 19 3 7 5 . ~ ~ ~ P~/US92/08495 Hemofiltration system 10 may also include suitable blood warmer and infusate warmer devices (not shown) to adjust and/or maintain the blood and infusate temperatures at desired levels. Such devices may also generate alarm signals when the fluid temperatures are outside of preselected limits.
Display 13 offers updated display of measured and computed parameters such as pressures, pressure differentials, temperatures, flow rates and amounts of infusate, drain and ultrafiltration, and alarm conditions. Controller 12 generates both visual and audible alarms and all the pumps are interlocked to prevent operation thereof under alarm conditions.
Users have the option of disabling or unabling the alarms (the audible part of the alarm and its inter-lock with the pumps) to perform a procedure under close supervision. A printer (not shown) is operably connected (not shown) to controller 12 to generate a hard copy of procedural data currently displayed or stored at regular intervals, at the completion of a procedure or at any desired time.
Hemofiltration system 10 can be operated in one of two modes: 1) a manual mode wherein the pumping rates of blood pump 16, infusate pump 60 and drain pump 66 are provided by controller 12 when fixed voltages are applied; and 2) an automatic mode wherein the pumps are controlled by controller 12 when the 21 19~7~r desired hemofiltration amount or rate has been pro-grammed into the controller. The automatic mode allows the system to be paused and later continued without losing previously measured and computed data.
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Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE PROPERTY OR
PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Continuous hemofiltration system for removal of fluid from the blood of a patient, comprising:
hemofiltration means; means for pumping blood from a patient through said hemofiltration means and back to the patient;
a first reservoir for maintaining a supply of infusate;
first pumping means for pumping the infusate from said first reservoir to said hemofiltration means;
a second reservoir for receiving drained fluid from said hemofiltration means;
second pumping means for pumping the drained fluid from said hemofiltration means to said second reservoir;
weighing means for monitoring the weight of the infusate and the drained fluid and generating weight data signals correlated thereto; and control means operably connected to said blood pumping means and to each of said first and second pumping means and said weighing means, said control means comprising a computer programmed to operate said first and second pumping means only when said blood pumping means is operating;
said blood pumping means and said first and second pumping means being responsive to signals generated by said control means;
said control means receiving said weight data signals generated by said weighing means, determining from said weight data signals the weight of infusate and drained fluid in said first and second reservoirs, respectively, at regular intervals, comparing those weights to corresponding predetermined computed weights, and generating control signals to adjust and thereby automatically adjusting as necessary on an ongoing basis during hemofiltration the rates of pumping at least two of the following: the infusate, drained fluid, and blood, while the pumps are pumping during hemofiltration, so as to remove a preselected amount of fluid from the blood over a preselected time period.

2. The hemofiltration system of claim 1 wherein said hemofiltration means includes a hemofilter, input tubing through which blood is pumped to said hemofilter, output tubing through which blood is pumped from said hemofilter, feed tubing connecting said first pumping means to said hemofilter, and drain tubing connecting said second pumping means to said hemofilter.

3. The hemofiltration system of claim 2 further comprising:
first pressure monitoring means for monitoring the pressure in said input tubing to said hemofilter;
second pressure monitoring means for monitoring the pressure in said output tubing;
third pressure monitoring means for monitoring the pressure in said drain tubing; and fourth pressure monitoring means for monitoring the pressure in said input tubing to said blood pump.

4. The hemofiltration system of claim 1 further comprising means for adding an anti-clotting medication to the blood prior to pumping the blood through said hemofiltration means.

5. Continuous hemofiltration system for removal of fluid from the blood of a patient, comprising:
hemofiltration means;

means for pumping blood from a patient through said hemofiltration means and back to the patient;
a first reservoir for maintaining a supply of infusate;
first pumping means for pumping the infusate from said first reservoir to the patient;
a second reservoir for receiving drained fluid from said hemofiltration means;
second pumping means for pumping the drained fluid from said hemofiltration means to said second reservoir;
weighing means for monitoring the weight of the infusate and the drained fluid and generating weight data signals correlated thereto; and control means operably connected to said blood pumping means and to each of said first and second pumping means and said weighing means, said control means comprising a computer programmed to operate said first and second pumping means only when said blood pumping means is operating;
said blood pumping means and said first and second pumping means being responsive to signals generated by said control means;
said control means receiving said weight data signals generated by said weighing means, determining from said weight data signals the weight of infusate and drained fluid in said first and second reservoirs, respectively, at regular intervals, comparing those weights to corresponding predetermined computed weighs, and generating control signals to adjust and thereby automatically adjusting as necessary on an ongoing basis during hemofiltration the rates of pumping at least two of the following: the infusate, drained fluid, and blood, while the pumps are pumping during hemofiltration, so as to remove a preselected amount of fluid from the blood over a preselected time period.