Method and apparatus for controlling concentrations in tubing system

• US 5,421,812 A
• Filed: 03/04/1992
• Issued: 06/06/1995
• Est. Priority Date: 03/04/1992
• Status: Expired due to Term

• Current Assignee: Terumo BCT, Inc. (Terumo Corporation)
• Original Assignee: COBE Laboratories Incorporated (Terumo Corporation)
• Inventors: Schwab, Michael E., Langley, Robert W.
• Primary Examiner(s): RIMELL, SAMUEL G
• Application Number:
  US07/845,677
• Time in Patent Office: 1,189 Days
• Field of Search: 604/4, 604/5, 604/6, 604/65, 604/67, 604/19, 604/27, 604/403, 604/407
• US Class Current: 604/6.07
• CPC Class Codes: A61M 1/30 Single needle dialysis ; Reciprocating systems, alternately withdrawing blood from and returning it to the patient, e.g. single-lumen-needle dialysis or single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61M 1/303 having a reservoir for treated blood to be returned
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3672 Means preventing coagulation
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: A61M 1/3696 with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
• CPC Class Codes: A61M 2205/33 Controlling, regulating or measuring
• CPC Class Codes: A61M 2205/3334 Measuring or controlling the flow rate
• CPC Class Codes: A61M 2205/50 with microprocessors or computers

Abstract

A method and apparatus for determining, controlling or establishing the level of a constituent such as anticoagulant in a body fluid such as blood in a procedure for processing the fluid. The anticoagulant flow rate from an anticoagulant reservoir, the blood flow rate, the flow rate of collected fluid and the flow rate of replacement fluid are monitored, and an anticoagulant flow balance is established whereby the flow of anticoagulant into the donor or patient will be equal to the flow rate of anticoagulant out of the anticoagulant reservoir, plus the flow rate of anticoagulant from the donor or patient, plus the flow rate of anticoagulant in the replacement fluid, minus the flow rate of anticoagulant in the collect fluid. The flow rate of anticoagulant from the donor or patient can be determined based on the anticoagulant metabolic half-life, the volume of the donor'"'"'s or patient'"'"'s blood, and the amount and time of infusion of anticoagulant into the donor or patient.

Claims

1. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining at a time after metabolism of the anticoagulant has begun the unmetabolized anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set.

2. The method of claim 1, wherein anticoagulant is infused into the tubing set at an infusion rate, the donor'"'"'s or patient'"'"'s blood flows into the tubing set at a blood flow rate, a blood constituent is withdrawn from the tubing set at a withdrawal rate, and replacement fluid flows into the tubing set at a replacement fluid flow rate, and further comprising adjusting at least one of the rate of infusion of anticoagulant into the tubing set, the rate of flow of the donor'"'"'s or patient'"'"'s blood into the tubing set, the rate of withdrawal of a blood constituent from the tubing set, and the rate of flow of replacement fluid into the tubing set, in response to the determined anticoagulant level.

3. The method of claim 2, wherein said adjustment is accomplished by programmable computing means.

4. The method of claim 3, wherein said programmable computing means includes a microprocessor in electronic communication with at least one fluid pump that controls at least one of said rates.

5. The method of claim 1, wherein the step of determining the addition of anticoagulant to the tubing set includes determining the infusion of anticoagulant from an anticoagulant reservoir into the tubing set.

6. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein anticoagulant is infused into the tubing set at an infusion rate, the donor'"'"'s or patient'"'"'s blood flows into the tubing set at a blood flow rate, a blood constituent is withdrawn from the tubing set at a withdrawal rate, and replacement fluid flows into the tubing set at a replacement fluid flow rate, and further comprising adjusting at least one of the rate of infusion of anticoagulant into the tubing set, the rate of flow of the donor'"'"'s or patient'"'"'s blood into the tubing set, the rate of withdrawal of a blood constituent from the tubing set, and the rate of flow of replacement fluid into the tubing set, in response to the determined anticoagulant level;

wherein blood with anticoagulant is returned to the donor or patient by a return line, and wherein said adjustment is such that the anticoagulant flow rate in the return line does not exceed a predetermined maximum.

7. The method of claim 6, wherein said adjustment is such that the anticoagulant concentration in the blood processor does not fall below a predetermined minimum.

8. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein anticoagulant is infused into the tubing set at an infusion rate, the donor'"'"'s or patient'"'"'s blood flows into the tubing set at a blood flow rate, a blood constituent is withdrawn from the tubing set at a withdrawal rate, and replacement fluid flows into the tubing set at a replacement fluid flow rate, and further comprising adjusting at least one of the rate of infusion of anticoagulant into the tubing set, the rate of flow of the donor'"'"'s or patient'"'"'s blood into the tubing set, the rate of withdrawal of a blood constituent from the tubing set, and the rate of flow of replacement fluid into the tubing set, in response to the determined anticoagulant level;

wherein blood with anticoagulant is returned to the donor or patient by a return line, and wherein said adjustment is such that at least one of the anticoagulant volume and anticoagulant concentration in the donor or patient does not exceed a predetermined maximum.

9. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein the step of determining the addition of anticoagulant to the tubing set includes determining the infusion of anticoagulant from an anticoagulant reservoir into the tubing set; and

wherein the step of determining the addition of anticoagulant to the tubing set includes determining the infusion of anticoagulant from a replacement fluid reservoir into the tubing set.

10. The method of claim 9, wherein the step of determining the infusion of anticoagulant from a replacement fluid reservoir includes multiplying the rate of infusion of replacement fluid into the tubing set times the concentration of anticoagulant in the replacement fluid.

11. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein the step of determining the addition of anticoagulant to the tubing set includes determining the infusion of anticoagulant from an anticoagulant reservoir into the tubing set; and

wherein the step of determining the removal of anticoagulant from the tubing set includes determining the rate of removal of anticoagulant in a collect fluid into a collect fluid reservoir.

12. The method of claim 11, wherein said step of determining the rate of removal of anticoagulant into a collect fluid reservoir includes multiplying the rate of removal of the collect fluid into the collect fluid reservoir times the concentration of anticoagulant in said collect fluid.

13. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein the step of determining the addition of anticoagulant to the tubing set includes determining the infusion of anticoagulant from an anticoagulant reservoir into the tubing set; and

wherein such step of determining the anticoagulant added to the tubing set includes determining the level of anticoagulant in the blood from the donor or patient to be processed that enters the tubing set.

14. The method of claim 13, wherein the infused anticoagulant gradually metabolizes to produce a metabolized amount and an unmetabolized amount, and wherein said step of determining the level of anticoagulant in the donor'"'"'s or patient'"'"'s blood includes determining the unmetabolized amount.

15. The method of claim 14, a known amount of the donor'"'"'s or patient'"'"'s blood is processed through the tubing set, and wherein said step of determining the amount of anticoagulant that has not metabolized added to the donor or patient from the tubing set includes the use of an equation wherein the concentration of anticoagulant in the donor'"'"'s or patient'"'"'s blood is an exponential function of at least one of amount of anticoagulant added to the donor or patient, amount of blood in the donor or patient, amount of anticoagulant removed from the donor'"'"'s or patient'"'"'s blood, volume of donor'"'"'s or patient'"'"'s blood processed, concentration of anticoagulant in the fluid added to the tubing set, volume of fluid added to the tubing set, hematocrit of the donor or patient, and half life of the anticoagulant.

16. The method of claim 15, wherein said exponential equation is of the form:

space="preserve" listing-type="equation">C.sub.DB =M.sub.t (1-e.sup.-N.sbsp.178 );

where

C_CB =concentration of anticoagulant in donor or patient'"'"'s blood ##EQU5## N_t =(V_BP /V_B)[(V_C +V_PC)/((1--H)V_BP +V_A)]+Kt

V_A =volume of anticoagulant added to tubing set

V_B =volume of blood in the donor or patient

V_C =volume of cells collected out of the tubing set

V_PC =volume of plasma collected out of the tubing set

H=donor'"'"'s or patient'"'"'s hematocrit

V_BP =volume of donor or patient'"'"'s blood processed

C_RF =concentration of anticoagulant in replacement fluid added to the tubing set

V_RF =volume of replacement fluid added to the tubing set

K=an anticoagulant metabolism constant

t=time.

17. The method of claim 16, wherein the metabolism constant K is related to the anticoagulant metabolic half-life.

18. The method of claim 17, wherein the metabolism constant is of the form:

space="preserve" listing-type="equation">K=ln2/t.sub.1/2

where

K=an anticoagulant metabolism constant

t_1/2 =metabolic half-life of the anticoagulant.

19. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein the coagulant is added to the tubing set of a known rate, and further comprising determining the volume of anticoagulant in the donor or patient by integrating over time the rate of addition of anticoagulant to the donor or patient minus the rate of removal of anticoagulant from the donor or patient.

20. The method of claim 19, wherein said tubing set includes an inlet line through which plasma moves from the donor or patient to the tubing set and a return line through which plasma moves from the tubing set to the donor or patient, and wherein said step of determining the volume of anticoagulant in the donor or patient is by an integral of an equation substantially of the form:

##EQU6## where V_AD =volume of anticoagulant in the donor'"'"'s or patient'"'"'s blood

C_RP =anticoagulant concentration in the return line plasma

Q_RP =plasma flow rate in the return line

C_DP =anticoagulant concentration in the donor'"'"'s or patient'"'"'s plasma

Q_P =plasma flow rate in the inlet line

V_P =volume of plasma in the donor'"'"'s or patient'"'"'s blood,

21. A method for establishing the anticoagulant level in a system including a tubing set in fluid communication with a donor or patient, comprising establishing the addition of anticoagulant to the tubing set;

establishing the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant to establish the anticoagulant level; and

determining the anticoagulant level in the donor or patient, based at least in part on the anticoagulant level in the tubing set;

wherein said tubing set may include a cell collect line through which collected cells flow, and wherein said steps is by an equation substantially of the form;

space="preserve" listing-type="equation">Q.sub.IN =(Q.sub.AR +A[Q.sub.PC +(1-H.sub.C)Q.sub.C ])/B

where

Q_IN =total rate of flow of donor'"'"'s or patient'"'"'s blood and anticoagulant into the tubing set

Q_PC =rate of flow of collected plasma

H_C =hematocrit in cell collection line

Q_C =cell collect flow rate

A=[C_DB (R-1)+1]/[R(1-H)+H]-C_RF F

B=C_DB (1-1/R)+(1-C_RF)/R ##EQU7## C_DB =concentration of anticoagulant in donor'"'"'s or patient'"'"'s blood H=hematocrit of donor'"'"'s or patient'"'"'s blood

C_RF =anticoagulant concentration in replacement fluid added to tubing set

Q_AR =specified anticoagulant flow rate in the return line

F=ratio of fluid volume added to, to fluid volume removed from, tubing set.

22. A method for processing a body fluid using a tubing set having an inlet on the upstream end in fluid communication with the body, an outlet on the downstream end in fluid communication with the body, a constituent inlet in fluid communication with the tubing set for adding a constituent to the body fluid, and a fraction outlet for removing a fluid fraction from the body fluid downstream from the constituent inlet and upstream from the outlet end, comprising determining the flow rate of constituent between the constituent inlet and the fraction outlet;

determining the flow rate of constituent out of the fraction outlet;

determining the flow rate of constituent between the fraction outlet and the tubing set outlet by subtracting the flow rate of constituent out of the fraction outlet from the flow rate of constituent between the constituent inlet and the fraction outlet, and adjusting the flow rate of constituent into and out of the tubing set to maintain a desired constituent flow rate between the fraction outlet and the tubing set outlet.

23. The method of claim 22, wherein said desired constituent flow rate is based upon the constituent level in the donor or patient.

24. The method of claim 23, wherein said constituent level in the body is determined with reference to at least one of the amount of such body fluid in the body, the amount of body fluid processed, and the amount of constituent flowing into the body.

25. The method of claim 24, wherein said constituent decays in the body over time and said constituent level in the body is determined with reference to the time the constituent has been in the donor or patient.

26. A system for controlling the level of anticoagulant infused into a donor or patient in a blood processing procedure, comprising:

a blood tubing set having an inlet for establishing fluid communication with the donor'"'"'s or patient'"'"'s blood and an outlet for establishing fluid communication with the donor'"'"'s or patient'"'"'s blood, an anticoagulant source in communication with the tubing set, a blood fractionalizer in communication with the tubing set, a blood flow rate monitor to monitor the blood flow rate through the inlet of the tubing set, an anticoagulant flow rate monitor to monitor the anticoagulant flow rate through the anticoagulant source, at least one fraction flow rate monitor to monitor a blood fraction flow rate from the blood fractionalizer, and a processor for using at least one of said monitors to determine at least one of the anticoagulant flow rate through the tubing set outlet, the anticoagulant concentration in the tubing set outlet, and the total flow of anticoagulant through the tubing set outlet over a predetermined period of time.

27. The system of claim 26, wherein said processor determines the flow rate of anticoagulant through the tubing set outlet by subtracting the flow rate of anticoagulant out of the blood fractionalizer from the flow rate of anticoagulant between the anticoagulant source and the blood fractionalizer.

28. The system of claim 27, wherein said processor further determines the flow rate of anticoagulant through the tubing set outlet by considering the flow rate of anticoagulant through the tubing set inlet.

29. The system of claim 27, further comprising a replacement fluid source in communication with the tubing set, and wherein the processor further determines the flow rate of anticoagulant through the tubing set outlet by considering the flow rate of anticoagulant through the replacement fluid source in communication with the tubing set.

30. The system of claim 26, wherein said processor includes a microprocessor.

31. The system of claim 26, further comprising a flow rate controller to control the flow rate of at least one of the flow through the tubing set inlet, the flow through the anticoagulant source, and the flow out of the tubing set outlet, to produce a desired level of at least one of the flow rate of the anticoagulant out of the tubing set outlet, the concentration of anticoagulant flowing out of the tubing set outlet, the total flow of anticoagulant through the tubing set outlet, and the concentration of anticoagulant in the donor or patient.

32. A method for controlling the anticoagulant level in a system including a tubing set used for processing blood from a donor or patient using a blood processor, comprising determining the addition of anticoagulant to the tubing set;

determining the removal of anticoagulant from the tubing set;

subtracting the removal of anticoagulant from the addition of anticoagulant, determining the level of the unmetabolized anticoagulant in the donor or patient at a time after metabolism of said anticoagulant has begun; and

controlling the anticoagulant level in the donor or patient, based at least in part on the determined anticoagulant level in the tubing set.