Methods for reducing levels of pro-inflammatory or anti-inflammatory stimulators or mediators in the blood
View Patent ↗Devices, systems, and methods reduce levels of pro-inflammatory or anti-inflammatory stimulators or mediators in blood by selective adsorption. The devices, systems, and methods are useful in situations where abnormal levels of or unregulated or excessive interaction among pro-inflammatory or anti-inflammatory stimulators or mediators occur, or during events that do induce or have the potential for inducing abnormal production of pro-inflammatory or anti-inflammatory stimulators or mediators. The devices, systems, and methods serve to prevent, control, reduce, or alleviate the severity of the inflammatory response and disease states that are associated with abnormal levels of or unregulated or excessive interaction among pro-inflammatory or anti-inflammatory stimulators or mediators.
1. A method comprising
selecting for use an adsorption medium comprising a group of polymeric particles each comprising a hydrophobic core and a biocompatible hydrophilic coating, the adsorption medium selected to have a Biocompatibility Index of not greater than 14 derived by a protocol consisting essentially of
(i) selecting blood indicators which quantify, physiologic changes based upon contact between the adsorption medium and blood, the blood indicators consisting essentially of (1) white blood cell count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter; (2) red blood cell count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter; (3) platelet count diminution as a result of contact with the adsorption medium ascertained by Coulter Counter; (4) leukocytes activation as a result of contact with the adsorption medium ascertained by measuring polymorphonuclear leukocyte elastase concentration (PMN Elastase Concentration); (5) complement activation as a result of contact with the adsorption medium ascertained by measuring anaphylatoxin C3a-desArg concentrations; (6) occurrence of hemolysis as a result of contact with the adsorption medium ascertained by determining concentrations of Lactate dehydrogenase (LDH); and reduction of clot formation as a result of contact with the adsorption medium ascertained by measuring concentrations of thrombin-antithrombin-complex (TAT),
(ii) for each indicator, ascertaining a maximum difference between the indicator values over 25 ml of flow of heperinized blood heperinized to a final concentration of 1.0 IU heparin/ml blood passed through a biocompatible housing without the adsorption medium, comprising a baseline value, and heparinized blood passed through the housing containing the adsorption medium, and for each indicator, expressing the maximum change as a percentage change, relative to the baseline value,
(iii) scoring the percentage change for each indicator as a dimensionless numeric quantity 1, 2, or 3, depending upon the magnitude of the percentage change, in accordance with a Biocompatibility Index Score Table consisting essentially of
Numeric Scores □
1
2
3
(Signifying
(Signifying an
(Signifying a
Most Desired
Acceptable
Least Desired
Degree of
Degree of
Degree of
Biocompati-
Biocompati-
Biocompati-
Blood Indicator
bility)
bility)
bility)
Loss of White
Maximum
Maximum
Maximum
Blood Cells
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 ml)
Medium (25 ml)
(25 ml)
≦15%
>15%
>20%
≦20%
Loss of Red
Maximum
Maximum
Maximum
Blood Cells
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 m1)
Medium (25 ml)
(25 ml)
≦15%
>15%
>20%
≦20%
Loss of Platelets
Maximum
Maximum
Maximum
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 ml)
Medium (25 ml)
(25 ml)
≦15%
>15%
>20%
≦20%
PMN Elastase
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 ml)
Medium (25 ml)
(25 ml)
≦15%
>15%
>20%
≦20%
LDH
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between
Baseline and
Baseline and
Baseline and
Medium (25 ml)
(25 ml)
Medium (25 ml)
≦15%
>15%
>20%
≦20%
C3a-desArg
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 ml)
(25 ml)
(25 ml)
≦20%
>20%
>25%
≦25%
TAT
Maximum
Maximum
Maximum
Concentration
Difference
Difference
Difference
Between
Between
Between Baseline
Baseline and
Baseline and
and Medium
Medium (25 ml)
Medium (25 ml)
(25 ml)
≦15%
>15%
>20%
≦20%
(iv) after scoring each indicator with a numeric quantity of 1, 2, or 3, adding the numeric quantities scored for all the indicators to obtain a total, the total comprising the Biocompatibility Index,
placing the adsorption medium in a housing, and
conveying blood into the housing and through the adsorption medium.
2. A method according to claim 1
further including returning the blood to an individual following conveyance through the adsorption medium.
3. A method according to claim 1
wherein the conveyance includes conveyance of the blood through an extracorpreal blood processing path that includes the adsorption medium.
4. A method according to claim 1
wherein the conveyance includes subjecting the blood to hemodialysis either before or after conveyance through the adsorption medium.
5. A method according to claim 1
wherein the conveyance includes subjecting the blood to hemofiltration either before or after conveyance through the adsorption medium.
6. A method according to claim 1
wherein the conveyance includes subjecting the blood to oxygenation either before or after conveyance through the adsorption medium.
7. A method according to claim 1
further including identifying an individual in an acute condition, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
8. A method according to claim 1
further including identifying an individual experiencing a condition on a continuum from sepsis to septic shock, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
9. A method according to claim 1
further including identifying an individual experiencing a chronic disease state, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
10. A method according to claim 1
further including identifying an individual exposed to a biological or chemical agent, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
11. A method according to claim 1
further including identifying an individual for which surgery is contemplated, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
12. A method according to claim 1
further including identifying an individual having undergone surgery, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
13. A method according to claim 1
further including identifying an individual having undergone trauma, and
wherein conveying includes conveying blood from the individual into the housing an through the adsorption medium for a therapeutic affect.
14. A method according to claim 1
further including administration of an antibiotic, antimicrobial agent, antifungal agent, antiviral agent, or other therapeutic agent.
15. A method according to claim 1
wherein the hydrophobic core comprises hydrophobic, cross-linked porous divinylbenzene material, and
wherein the hydrophilic coating comprises biocompatible hydrophilic polyvinylpyrrolidone material.