Hemostatic system and components for extracorporeal circuit

Abstract

A method and system for use in the course of extracorporeal blood flow, e.g., cardiopulmonary bypass, dialysis, and angioplasty procedures, in order to reduce or minimize inflammation, excessive bleeding, and other undesirable side effects. The system can include one or more automated blood parameter sensor modules and one or more blood parameter regulating modules. The system is particularly well suited to monitor and / or regulate blood parameters that include blood analytes (e.g., biomolecules, drugs or metabolites) as well as blood functions (e.g., clotting time, fibrinolytic activity, immune response). The system is particularly well suited for use in the management of clotting (e.g., heparin / protamine) and bleeding (e.g., aprotinin).

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation application of U.S. patent application Ser. No. 10 / 806,795, filed Mar. 23, 2004, which is a continuation of U.S. patent application Ser. No. 09 / 662,044, filed Sep. 15, 2000, now U.S. Pat. No. 6,733,471, which is a continuation of and claims priority to International Application No. PCT / US99 / 05679 (published as International Publication No. WO 99 / 47190), filed Mar. 15, 1999 and designating the United States, which in turn claims the benefit of Provisional Application No. 60 / 078,054, filed Mar. 16, 1998, the entire disclosure of each of which is incorporated herein by reference.TECHNICAL FIELD [0002] The present invention relates to surgical and other procedures, such as cardiopulmonary bypass procedures, that involve the use of extracorporeal blood flow. In a related aspect the invention relates to sensors and filters for determining and affecting the presence or level of blood components such as hepari...

AI Technical Summary

Benefits of technology

[0027] In one aspect the present invention relates to a system and related method for use in the course of medical procedures that involve extracorporeal blood flow, e.g., cardiopulmonary bypass, dialysis, and angioplasty procedures. The system can be used to reduce or minimize inflammation, excessive bleeding, and other undesirable side effects, and particularly those side effects that are amenable to being monitored and / or regulated in the course of the surgery or treatment. The system is particularly well adapted to address the adverse reactions related to the use of heparin and protamine in the course of coagulation management methodologies, as well as the practical difficulties in using drugs such as aprotinin. In another aspect, and in certain preferred embodiments, sensor modules and regulating modules of this invention are considered novel in their own right, and moreover, can be used for their intended purpose and without the need for an entire system as described herein.

[0032] One or more corresponding regulating modules, in turn, can be included in the system and adapted to affect the blood parameter(s) being monitored, e.g., by affecting the concentration and / or activity of one or more blood modules. In so doing, the filter permits the operator, or the system itself, to detectably and promptly alter the concentration, form and / or presence of the blood analyte.

[0034] The use of a sensor, as described herein, can eliminate the need for the perfusionist or anesthesiologist to take time for “hands on” measurements. In turn, the system itself can be used to provide substantially “real-time” determinations of both blood parameter analyte (e.g., heparin) concentration and function (e.g., ACT times), therefore providing required patient data in a time frame not presently available in practice. A real-time heparin / clot management system, in turn, can improve patient outcome, for instance, by allowing tighter control of heparin and protamine dosing. The modules are adapted to be used separately or in any suitable combination, and can be independently incorporated either within or external to the blood flow path of a CPB circuit, as by appropriate access / sampling ports and shunting paths.

[0037] A second preferred regulating (e.g., filter) module of this invention is used for the extracorporeal removal of heparin from the blood stream. In a preferred embodiment, for instance, the removal of heparin is accomplished by anionic exchange of heparin with an immobilized positively charged species on the surface of a membrane contained within the filter. For instance, the use of a suitable polyalkyleneimmine (e.g., polyethyleneimine) as, or on, the surface of a suitable support (e.g., membrane or microfiber) provides an interactive surface that supports removal of heparin from circulation.

[0041] The system, including modules and related method, of this invention provide new opportunities to the practitioner in the course of procedures involving extracorporeal blood flow, including the ability to periodically or continually monitor and / or regulate various blood parameters in order to better control such unwanted side effects as inflammation and excessive bleeding.

Problems solved by technology

Protamine, however, has its own drawbacks, in the form of potential allergenic and inflammatory responses.

Extracorporeal circulation, such as that used during cardiopulmonary bypass, continues to be associated with various drawbacks, however, including both inflammation and excessive bleeding.

Inflammation, in turn, can cause both cell damage and diminished organ function, leading to increased morbidity and a longer recovery time with an increase in both length of hospital stay and costs.

The inflammation reaction induced by extracorporeal circulation also has the potential of increasing patient risk of inducing the “whole body inflammatory response” and ensuing organ failure.

As mentioned above, the use of heparin and protamine may be associated with a number of adverse effects.

Close monitoring of the heparin concentration and clotting time is required due to risk of clotting, if the heparin levels drop excessively low.

Similarly, excessively high levels of heparin can require correspondingly high dosages of protamine.

Still, the use of protamine is broadly problematic and severe reactions to protamine complex are idiosyncratic.

Moreover, protamine is difficult to titrate.

However, there is evidence that fixed-ratio dosing schemes tend to result in excessive protamine administration.

While the ACT is used as a functional test for the adequacy of heparin reversal, it does not provide an index of how much protamine is required to reverse heparin.

Typically, however, heparin concentration is not accurately recorded during CPB, due largely to the lack of suitable methods and instrumentation.

Such an approach has several drawbacks, however, including the lack of a direct measurement of heparin concentration, the need for manual blood draws, and heparin concentrations that are provided in gross increments.

Another complication of surgical procedures that involve CPB is excessive bleeding.

Aprotinin was studied for use mainly in heart surgery because the circulation of the blood outside the body in this surgery increases the likelihood of excessive bleeding during and after surgery.

Postoperative bleeding is a cause of morbidity and mortality in this patient population.

While the ACT is used as a functional test for the adequacy of heparin reversal, it does not provide an index of how much protamine is required to reverse heparin.

It has been suggested that prolonged CPB may require higher infusion rates which significantly increase cost.

Since there is currently no way to provide a real time monitor for either aprotinin, per se, or its metabolic effectiveness, aprotinin tends to be provided in large doses and at multiple times during the CPB surgery, this in spite of its high cost.

In spite of these and other advances, both inflammation and excessive bleeding continue to be common problems that plague the use of CPB.

Images