Apparatus and method for down-regulating immune system mediators in blood

Abstract

A method and apparatus for preventing and treating septicemia in patient blood is provided. The extracorporeal system includes an antimicrobial device to inactivate at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 50-75% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms, as well as by the patient's cells. These molecules include endotoxins from Gram negative bacteria, exotoxins from Gram negative and Gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus , and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, interleukin 6, complement proteins C3a and C5a, and bradykinin.

1 . A method of treating a patient with a hematocrit of greater than 36% by removing one or more toxins from the patient's blood, comprising:
 removing at least a portion of the patient's blood having a hematocrit of greater than 36%;   diluting said at least a portion of the blood with a diluent to provide diluted blood, thereby reducing the hematocrit of said at least a portion of the blood;   concentrating the diluted blood thereby removing at least a portion of the diluent therefrom;   filtering said diluted blood to remove one or more toxins from said diluted blood, thereby producing treated blood; and   returning the treated blood to the patient.   
     
     
         2 . The method of  claim 1 , wherein said concentrating step and said filtering step occur substantially simultaneously. 
     
     
         3 . The method of  claim 1 , further comprising returning the diluent removed from the blood to a diluent source via a recycle path. 
     
     
         4 . The method of  claim 3 , wherein said recycle path comprises a recycle path filter. 
     
     
         5 . The method of  claim 4 , wherein said recycle path filter in said recycle path comprises an electrostatically charged, melt-blown material. 
     
     
         6 . The method of  claim 1 , further comprising oxygenating the blood received from the patient. 
     
     
         7 . The method of  claim 1 , further comprising heating at least a portion of the blood to about body temperature. 
     
     
         8 . The method of  claim 1 , further comprising cooling at least a portion of the blood to about body temperature. 
     
     
         9 . The method of  claim 1 , further comprising heating at least a portion of the blood to between about 34° C. to about 42° C. 
     
     
         10 . The method of  claim 1 , further comprising heating at least a portion of the blood to between about 34° C. to about 42° C. 
     
     
         11 . The method of  claim 1 , further comprising changing the temperature of at least a portion of the blood by about 1° C. to about 10° C. 
     
     
         12 . The method of  claim 1 , wherein the step of removing at least a portion of the patient's blood comprises removing at least a portion of the patient's blood having a hematocrit within the range of about 36% to about 40%. 
     
     
         13 . The method of  claim 1 , wherein the step of removing at least a portion of the patient's blood comprises removing at least a portion of the patient's blood having a hematocrit within the range of about 41% to about 50%. 
     
     
         14 . The method of  claim 1 , wherein the step of removing at least a portion of the patient's blood comprises removing at least a portion of the patient's blood having a hematocrit within the range of about 51% to about 55%. 
     
     
         15 . The method of  claim 1 , further comprising providing at least one pump for moving said blood or diluent. 
     
     
         16 . The method of  claim 1 , further comprising transporting blood and diluent through a pump with a flow rate of less than 400 ml/min. 
     
     
         17 . The method of  claim 1 , wherein the step of concentrating the diluted blood comprises providing two hemoconcentrators connected in series. 
     
     
         18 . The method of  claim 1 , wherein the step of concentrating the diluted blood comprises:
 providing a hollow cylinder; and   providing a central core formed of hollow fibers axially disposed within said hollow cylinder.   
     
     
         19 . The method of  claim 18 , wherein the step of providing a hollow cylinder comprises providing a hollow cylinder having a length of about 10 inches and a diameter of about 1.5 inches. 
     
     
         20 . The method of  claim 18 , wherein the step of providing a central core comprises providing a central core having a surface area in the range of between about 1.2 m 2  to about 2.4 m 2 . 
     
     
         21 . The method of  claim 1 , wherein returning the treated blood to the patient further comprises providing tubing for the return path. 
     
     
         22 . The method of  claim 1 , further comprising providing a reservoir connected to receive material filtered from the blood. 
     
     
         23 . The method of  claim 1 , further comprising providing an inlet monitoring means for monitoring the pressure of the blood. 
     
     
         24 . The method of  claim 1 , wherein the step of diluting the blood to provide diluted blood, thereby reducing the hematocrit of said blood further comprises reducing the hematocrit to about 5% to about 20%. 
     
     
         25 . The method of  claim 1 , wherein the step of concentrating the diluted blood comprises providing a concentrator having a transmembrane pressure greater than 76 mmHg. 
     
     
         26 . The method of  claim 1 , wherein the step of removing at least a portion of the patient's blood comprises removing at least a portion of the blood from a patient having an inflammatory disease. 
     
     
         27 . The method of  claim 26 , wherein the step of removing at least a portion of the patient's blood comprises removing at least a portion of the blood from a patient having an inflammatory disease, wherein said inflammatory disease is selected from the group consisting of: sepsis, acute renal failure, ischemic stroke, Sudeck's syndrome, chronic fatigue syndrome, heat stroke, Hodgkin's Disease, lupus, myocardial infarction, AIDS, viremia, HCV, HBV, tuberculosis, muscular dystrophy or multiple sclerosis, Acute Respiratory Distress Syndrome, and heart disease. 
     
     
         28 . The method of  claim 1 , further comprising administering one or more vitamins to the blood. 
     
     
         29 . The method of  claim 28 , further comprising exposing a portion of the patient's blood to one or more vitamins in a dose sufficient to reduce at least one free radical in said portion of the patient's blood. 
     
     
         30 . The method of  claim 28 , further comprising administering one or more vitamins selected from the group consisting of one or more of the following: Zn, Cu, manganese, selenium, vitamin A, C, E, B complex, K, P, lycopene, superoxide dismutase, co-enzyme Q10, catechins, polyphenols, flavanols, depsides, quinic acids, carotenoids, thearubigens, theaflavin, theaflavic acids and ethyl pyruvate. 
     
     
         31 . The method of  claim 30 , wherein said depside is chlorogenic acid, coumaroylquinic acid or theogallin. 
     
     
         32 . The method of  claim 1 , further comprising administering a cocktail consisting of vitamin A, vitamin C, vitamin E and zinc to a portion of the patient's blood. 
     
     
         33 . The method of  claim 1 , further comprising administering insulin therapy to a patient's blood, comprising exposing a portion of the patient's blood to insulin in a dose sufficient to facilitate cellular glucose entry. 
     
     
         34 . The method of  claim 1 , further comprising administering nitroglycerin to a patient's blood, comprising exposing a portion of the patient's nitroglycerin in a dose sufficient to facilitate microcirculation. 
     
     
         35 . A method for removing toxins from the blood of a patient comprising:
 removing blood having a hematocrit greater than about 36% from the patient;   diluting the blood with a diluent, thereby reducing the hematocrit of said blood and producing diluted blood;   filtering the diluted blood with a first filter to receive the blood and extract cell mediators and diluent therefrom to produce filtered blood;   re-filtering the filtered blood with a second filter to produce treated blood; and   returning the treated blood to the patient.   
     
     
         36 . The method of  claim 35 , further comprising returning the diluent to a diluent source after re-filtering. 
     
     
         37 . The method of  claim 35 , wherein the step of filtering the diluted blood comprises filtering the diluted blood using a filter with a porosity of about 70 kilodaltons to about 90 kilodaltons. 
     
     
         38 . The method of  claim 35 , wherein the step of filtering the diluted blood comprises filtering the diluted blood using a filter material comprising polysulfone fibers. 
     
     
         39 . The method of  claim 35 , wherein the step of re-filtering the filtered blood comprises filtering the filtered blood using a filter with a porosity of about 10 kilodaltons to about 30 kilodaltons. 
     
     
         40 . The method of  claim 35 , wherein the step of re-filtering the filtered blood comprises filtering the filtered blood using two filters connected in parallel, each filter having a porosity of about 10 kilodaltons. 
     
     
         41 . A blood treatment system comprising:
 a removal device to remove a portion of the patient's blood, wherein said portion of the blood has a hematocrit greater than about 36%;   a diluent source for supplying a diluent to reduce the hematocrit of the blood, thereby producing diluted blood;   a concentrator device to receive said diluted blood in order to filter said diluted blood and to remove the diluent therefrom, thereby producing filtered blood; and   a return path connected for returning said filtered blood from said concentrator device to a blood source.