Method and apparatus for controlling concentrations in vivos and in tubing systems

• US 5,817,042 A
• Filed: 03/27/1996
• Issued: 10/06/1998
• Est. Priority Date: 03/04/1992
• Status: Expired due to Term

• Current Assignee: Terumo BCT, Inc. (Terumo Corporation)
• Original Assignee: Cobe Cardiovascular Incorporated (LivaNova Plc)
• Inventors: Langley, Robert W., Dumont, Larry Joe, Waeg, Geert Van
• Primary Examiner(s): Brown, Michael A.
• Application Number:
  US08/622,642
• Time in Patent Office: 923 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 1/36 Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
• 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 2205/3334 Measuring or controlling the flow rate

Abstract

A method and apparatus for maximizing the total amount of blood processed during an apheresis procedure by optimizing the concentration of anticoagulant in a donor/patient and the associated extracorporeal tubing set is provided. A simplified model of anticoagulant accumulation in a donor/patient'"'"'s body is used to calculate an optimal anticoagulant infusion rate profile to the donor/patient during a blood processing procedure. A maximum acceptable anticoagulant concentration in the donor/patient acts as an upper limit on the rate at which anticoagulant may be infused to the donor/patient using the optimized infusion rate profile. A minimum acceptable anticoagulant level acts as a lower limit in optimally controlling the anticoagulant concentration in the extracorporeal tubing set. Both the maximum acceptable anticoagulant level in the donor/patient and the minimum acceptable anticoagulant level in the extracorporeal tubing set may be customized for a specific donor/patient thereby allowing the optimized infusion rate profile and the extracorporeal tubing set anticoagulant concentration to be customized for the specific patient.

Claims

1. A method for controlling the level of anticoagulant to be infused into a donor comprising:

receiving blood from a donor;

adding anticoagulant to the received blood;

returning at least a portion of the received blood to the donor;

infusing the anticoagulant in the returned blood to the donor at an infusion rate; and

varying the infusion rate of the anticoagulant as a function of time;

said varying step further comprising;

predicting a rate at which the anticoagulant accumulates in the donor over time to arrive at a predicted accumulation rate;

determining an optimal infusion rate profile using the predicted accumulation rate that varies the infusion rate with time; and

infusing the anticoagulant to the donor at the optimal infusion rate profile.

2. The method of claim 1, further comprising:

processing the received blood prior to infusing the anticoagulant in the received blood to the donor at the optimal infusion rate profile.

3. The method of claim 2, wherein determining the optimal infusion rate profile further comprises:

predicting a maximum donor anticoagulant level; and

determining the optimal infusion rate profile so that the anticoagulant achieves a level in the donor that approaches but remains below the predicted maximum donor anticoagulant level.

4. The method of claim 3, wherein determining the optimal infusion rate profile further comprises maximizing an amount of blood processed during a predetermined procedure time.

5. The method of claim 4, wherein the optimal infusion rate maximizes the amount of blood processed during the procedure time by allowing the anticoagulant to accumulate rapidly in the donor at a start of a procedure time while always maintaining the level of the anticoagulant in the donor below the predicted maximum donor anticoagulant level, thereby allowing blood to flow more rapidly from the donor into the extracorporeal blood processor at the start of the procedure.

6. The method of claim 5, further comprising determining a donor specific maximum donor anticoagulant level.

7. The method of claim 5, further comprising:

predicting a minimum anticoagulant level that may be present in the extracorporeal processor; and

varying a rate of addition of the anticoagulant to the received blood such that the anticoagulant always remains above the predicted minimum constituent level.

8. The method of claim 7, further comprising determining a donor specific minimum anticoagulant level that may be present in the extracorporeal processor.

9. The method of claim 7, wherein the step of varying the anticoagulant addition rate further comprises accounting for an amount of anticoagulant recirculated from the donor to the extracorporeal processor in varying the rate of addition of the anticoagulant to received blood.

10. The method of claim 7, wherein the predicted maximum donor anticoagulant level varies with time.

11. The method of claim 7, wherein the optimal infusion rate profile may be changed at least once during a procedure.

12. The method of claim 3, wherein determining the optimal infusion rate profile further comprises minimizing a blood processing procedure time.

13. The method of claim 1, wherein the anticoagulant is citrate.

14. The method of claim 13, wherein the optimum infusion rate profile is determined by an equation of substantially the following form:

space="preserve" listing-type="equation">I/I.sub.CRIT =1+(γ

-1)exp(-γ

α

t)

where;

I_CRIT =(C_CRIT -C_O) (1000 α

a/C_AC)

C_AC =Citrate concentration in anticoagulant, in μ

mol/ml

C_CRIT =MADEC, in μ

mol/ml

C₀ =C at t=0, in μ

mol/ml

α

=decay constant for a single compartment model, =0.0348 min^-1

t=time, in minutes

γ

=parameter that determines the rate at which C approaches C_CRIT

a=constant empirically determined by correlating the single compartment model to measured citrate concentrations in human subjects.

15. The method of claim 13, wherein the predicted minimum anticoagulant level is determined by an equation substantially of the following form:

space="preserve" listing-type="equation">R=(C.sub.AC -C)/(C.sub.TS -C)

Where

C_TS =target extracorporeal citrate concentration in the tubing set 81 in μ

mol/ml.

C_AC =citrate concentration in anticoagulant, in μ

mol/ml

C=C₀ +(C_CRIT -C₀) 1-exp -y_N α

((t+τ

_N)!!, t≧

τ

_N

C_CRIT =MADEC, in μ

mol/ml

C₀ =C at t=0, in μ

mol/ml

α

=decay constant for a single compartment model, =0.0348 min^-1

t=time, in minutes

y=parameter that determines the rate at which C approaches C_CRIT

τ

_N =time shift.

16. The method of claim 13, wherein the step of changing the optimal infusion rate profile at least once during a procedure further comprises:

calculating a new value for the optimum infusion rate;

calculating a new value for the parameter that determines the rate at which the anticoagulant accumulates in the donor;

calculating a new time shift that matches the new donor anticoagulant accumulation rate with the new optimum infusion rate value; and

infusing the anticoagulant to the donor at the new optimum infusion rate profile.

17. A method for regulating the level of an anticoagulant in a donor and an extracorporeal tubing set comprising:

receiving blood from the donor into an inlet line of the extracorporeal tubing set of a blood processor;

adding anticoagulant to the received blood at an anticoagulant flow rate to achieve an inlet anticoagulant level;

processing the blood in the extracorporeal blood processor;

delivering at least a fraction of the processed blood to an outlet line of the extracorporeal tubing set;

determining an outlet anticoagulant level in the outlet line;

returning at least a fraction of the processed blood, having the predetermined anticoagulant level, to the donor through the outlet line at an infusion rate;

predicting a minimum extracorporeal anticoagulant level that may be present in the extracorporeal tubing set; and

varying the anticoagulant flow gradually with time so that the anticoagulant in the extracorporeal tubing set remains above the predicted minimum extracorporeal anticoagulant level.

18. The method of claim 17, further comprising:

predicting a maximum donor anticoagulant level;

varying the infusion rate as a function of time such that the maximum donor anticoagulant level is never exceeded.

19. The method of claim 18, further comprising:

circulating blood through the inlet line at an inlet flow rate;

estimating a donor anticoagulant accumulation rate;

using the estimated donor anticoagulant accumulation rate to determine an optimal anticoagulant infusion rate that maximizes the inlet flow rate while simultaneously maintaining the anticoagulant level in the donor below the predicted maximum donor anticoagulant level.

20. The method of claim 17, further comprising:

predicting an amount of unmetabolized anticoagulant recirculated from the donor to the inlet line; and

varying the anticoagulant flow rate to account for the recirculated unmetabolized anticoagulant while maintaining the anticoagulant level above the predicted minimum extracorporeal anticoagulant level.

21. The method of claim 20, further comprising

determining a donor specific maximum anticoagulant level;

and

adjusting the optimal anticoagulant infusion profile to maintain the anticoagulant level in the donor below the donor specific maximum anticoagulant level.

22. The method of claim 20, further comprising:

determining a donor specific minimum extracorporeal anticoagulant level; and

adjusting the anticoagulant flow rate to maintain an anticoagulant level in the extracorporeal tubing set above the donor specific minimum extracorporeal anticoagulant level.