Abstract:
A method and apparatus for preventing and treating septicemia in patient blood. The extracorporeal system includes an anti-microbial device to kill at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 90% 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 the patient&#39;s cells and 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, complement proteins C3a and C5a, and brandykinin.

Description:
BACKGROUND 
     1. Field of the Invention 
     The present invention relates, generally, to methods of and apparatus for killing bloodborne microorganisms by ultraviolet irradiation and removing target molecules from the blood by a hemoconcentrator/filter and, subsequently, removing some target molecules from the ultrafiltrate by additional filtration for endotoxins and cell mediators before returning to the blood. 
     2. Prior Art 
     Septicemia refers to a microbe-induced condition in which the patient experiences an exaggerated inflammatory response. This response can lead to varying degrees of hypotension (possibly shock), and hypoxemic and edema-related organ failure called multiple organ dysfunction syndrome (MODS). Because trauma and burns, among other causes, can lead to MODS, in the absence of infection, the more current and generic term is systemic inflammatory response syndrome (SIRS). 
     Between 1980 and 1992 the death rate due to septicemia increased 83% from 4.2 to 7.7 per 100,000 population. The greatest increases were seen in patients at least 65 years old. Bacterial infections accounted for approximately 200,000-300,000 cases of septicemia as of 1992, and was the 13th leading cause of death nationally. The mortality rate averaged 35%, with a range of 20-65%, and accounted for approximately 100,000 deaths. 
     Septicemia is usually categorized by the particular group of microorganism involved, i.e., bacterial, gram negative or gram positive, and fungal. Gram negative bacteria of concern include  Pseudomonas aeruginosa, Eschericia coli,  and  Enterobacter aerogenes.  Gram positive bacteria of interest include  Staphylococcus aureus, Streptococcus pneumoniae,  and Enterococcus spp. The usual fungus involved is the yeast, Candida spp. Septicemia and related conditions develop when certain microorganisms, the cellular products, and other target molecules stimulate cascade reaction and an exaggerated inflammatory response leading to multiple organ and system failure. Selected microbial products and other target molecules, with molecular weights, are shown in Table 1. 
     
       
         
               
             
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Selected Target Molecules of Concern in Septicemia 
               
               
                 and Potentially Removed by SPATS 
               
             
          
           
               
                   
                 Molecular Weight - 
               
               
                 Molecule 
                 KiloDaltons (kD) 
               
               
                   
               
               
                 Endotoxins (gram negative bacteria) 
                 10-40 
               
               
                 Tumor Necrosis Factor, alpha(TNF-a) 
                 17-51 
               
               
                 Interleukin 1, beta(IL 1-p) 
                 17 
               
               
                 Exotoxins (gram positive and gram negative bacteria 
               
               
                 gram+ (Diphtheria) 
                 65 
               
               
                 gram− (Cholera) 
                 82 
               
               
                 RAP, protein ( Staphylococcus aureus ) 
                 50 
               
               
                 Complement 3a and 5a 
                 9-11 
               
               
                 Bradykinin 
                 1 
               
               
                   
               
             
          
         
       
     
     These target molecules may enhance the microbe&#39;s virulence and/or stimulate the patient&#39;s defense mechanisms, but, when excessive, they may lead to multiple organ system failure. These microorganisms, their cellular products and the target molecules can stimulate various cascade reactions which may result in a life-threatening inflammatory disease state. 
     Prevention of these medical conditions is difficult at best because the early signs and symptoms may be quite vague. Treatment has generally been instituted when the condition is recognized which is, unfortunately, often very late in the course of the disease. With prophylaxis difficult and therapy often late, the results may be fatal for the patients in many cases. Treatment of the early viremic stage of H.I.V. on the other hand, is possible. The signs and symptoms are recognizable by a trained physician and reduction of the viral load has been shown to improve the prognosis of the disease. This reduction in viral load may also be effective at later stages of H.I.V. infections. We believe that the ability of SPATS to reduce bacterial load, as well, by 99% or more will also serve a significant role in the prevention of septicemia in patients undergoing coronary bypass, dialysis, and probably other conditions. SPATS can also be used to treat septicemia in patients undergoing such invasive procedures. 
     Ultraviolet blood irradiation (UBI)—originally the Knott technique—has been used in the United States since 1928 for the successful extracorporeal treatment of microbial infections. Over the years there have been scientific arguments concerning the mechanism by which UBI works and the consensus appears to be that some organisms are killed and a stimulated immune system then protects the patient by clearing the remaining organisms from the body. 
     Hemoconcentrator/filtration units are used to remove water from patients who are in acute renal failure and become overly hydrated. The devices are designed to retain all plasma proteins, including the smallest albumin, (molecular weight of 67-69 kD), while ridding the blood of excess water. Current membranes and/or hollow fiber systems have effective pore sizes which will pass molecules up to 30-50 kD. 
     The Lee et al patent describes the removal of the “toxic mediators” of SIRS by the continuous arteriovenous hemofiltration of whole blood by processing with a filter having a pore size adequate to remove substances up to 100-150 kD (although the probable size of the molecules removed is 10-40% less due to occlusion of the pores by plasma proteins). 
     
       
         
               
             
               
               
               
               
             
           
               
                   
               
               
                 PRIOR ART STATEMENT 
               
               
                 U.S. Patents 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 5,571,418 
                 11/1996 
                 Lee et al. 
               
               
                   
                 5,211,850 
                  5/1993 
                 Shettigar et al 
               
               
                   
                 5,211,849 
                  5/1993 
                 Kitaevich et al 
               
               
                   
                 5,151,192 
                  9/1992 
                 Matkovich et al 
               
               
                   
                 5,150,705 
                  9/1992 
                 Stinson 
               
               
                   
                   
               
             
          
         
       
     
     Other Publications 
     Barger, G. and E. K. Knott. 1950. “Blood: Ultraviolet Irradiation (Knott Technique)”, Medical Physics 11: 132-6. 
     Miley, G. P., R. C. Olney, and H. T. Lewis. 1997. “Ultraviolet Blood Irradiation: A History and Guide to Clinical Application (1933-1997)”, Silver Spring, Md.: Foundation for Blood Irradiation. 
     Schleicher, C. 1995. “Application of Ultraviolet Blood Irradiation for Treatment of HIV and Other Bloodborne Viruses.” Townsend Letter for Doctors and Patients, 147:66-72. 
     Lee, P. A., G. W. Weger, R. W. Pryor, and J. R. Matson. 1998. “Effects of Filter Pore Size on Efficacy of Continuous Arteriovenous Hemofiltration Therapy for Staphylococcus Aureus-induced Septicemia in Immature Swine”. Crit. Care Med. 26(4):730-37. 
     Sibbald, W. J. and J.-L. Vincent (Eds.) 1995. “Clinical Trials for the Treatment of Sepsis”, Springer-Verlag, Berlin, Heidelberg. 
     SUMMARY OF THE INVENTION 
     A method and apparatus for preventing and treating septicemia is described. The extracorporeal system includes an anti-microbial device to kill at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 90% of the bloodborne target molecules from patient&#39;s blood and a filter unit to remove the same target molecules from the ultra-filtrate. Target molecules are produced by microorganisms, as well as the patient&#39;s cells, and include endotoxins from gram negative bacteria, exotoxins from gram positive and gram negative bacterial and mediators such as RAP protein from  Staphylococcus aureus,  and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, complement proteins C3a and C5a and bradykinin. 
     The present invention is a method and apparatus for the continuous processing of diluted blood by a venovenous route using a double lumen cannula and a filter having a pore size of 60-95 kD. The system will remove substances, including target molecules, comparable to Lee et al. 
     The present invention also can filter the plasma filtrate for subsequent return of important smaller molecules to the patient. 
     Since hemodilution has already occurred during cardiopulmonary bypass, the filter will function in an extracorporeal circuit to remove inflammatory mediators caused by the cardiopulmonary bypass. Currently, special bonded circuits as well as pharmaceutical products are used to reduce the effects described during extracorpreal circulation. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a schematic representation of one embodiment of the system of the instant invention, i.e. direct application to a patient not undergoing extracorporeal circulation. 
     FIG. 2 is a schematic representation of another embodiment of the system of the instant invention, i.e. its application within an extracorporeal circuit already serving as cardiopulmonary support for a patient. 
     FIG. 3 is a cross-sectional view of one embodiment of an ultra-violet irradiator used in the instant invention. 
     FIG. 4 is a cross-sectional view of another embodiment of an ultra-violet irradiator used in the instant invention using a filming technique. 
     FIG. 5 is a partial cross-sectional view of one embodiment of a filter used in the instant invention to remove target molecules from untrafiltrate. 
     FIG. 6 is a partially broken away elevation view of a hemoconcentrator used in the instant invention. 
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
     Referring now to FIG. 1, there is shown a schematic representation of the system of the instant invention, including several alternative configurations. The septicemia prevention and treatment system (SPATS) comprises a plurality of components, typically, connected by standard medical extracorporeal tubing and connectors. As such, the system may be attached to a patient via cannulation or it may be incorporated into extracorporeal circuitry already serving a patient such as in hemodialysis or cardiopulmonary bypass (see, for example, FIG. 2) or hemodialysis. As represented herein, the SPATS component circuitry most resembles that of modern hemodialysis in terms of vascular access, bypass mode (venovenous or arteriovenous), blood flow rate, the use of a hemoconcentrator (a device constructed in the fashion of a dialyzer), and duration of application. Therefore, some or all of the components described herein could be incorporated into a hemodialysis system, as well. 
     As noted, FIG. 1 shows one embodiment of the system of the instant invention, including several alternative configurations. As in hemodialysis, blood from the patient  100  enters the SPATS tubing  151  via a suitable connector such as a venous cannula  101  of sufficient diameter to permit drainage flow of whole blood up to about 300 ml/min. Double lumen cannulae that satisfy this requirement are available and, thus, permit return flow as well, for example, via. tubing  107 , as described hereinafter. This latter technique is not required, but has the advantage of reducing vascular access to a single site such as, but not limited to, a brachial vein. 
     The patient&#39;s venous blood proceeds via polyvinyl chloride (PVC) or other suitable tubing to a pump  102 , which can be a positive displacement or centrifugal pump, for example, which regulates flow at about 200-300 ml/min. through the system. 
     As shown in FIG. 1, blood from pump  102  passes through a polycarbonate “Y” connector  103 B where the blood mixes with a suitable isotonic diluent, such as plasmalyte solution. A variety of such solutions, referred to as “crystalloids”, are available. The diluent is supplied from diluent source  113  which, typically, comprises a large capacity reservoir for storing an admixture of reclaimed (or converted) ultrafiltrate. 
     The diluent is delivered by pump  114  which can be a roller pump or the like at a flow rate which results in a hematocrit of about 10-20%. 
     The diluted venous blood then passes through tubing to the bactericidal ultraviolet (UV) irradiation device  104  (shown schematically in FIGS.  3  and  4 ). Controlled in-vitro experiments have demonstrated that UV irradiation is substantially more effective as a bactericidal agent when whole blood (35-45% hematocrit) is diluted to a hematocrit of about 10-20% (see Table II). Furthermore, when diluted blood is presented to the hemoconcentrator  106 , target molecules are more effectively removed by sieving, as described infra. 
     
       
         
               
               
               
               
               
             
               
               
             
           
               
                   
                   
               
               
                   
                 Period of Treatment (minutes) 
                 60 
                 90 
                 120 
               
               
                   
                   
               
             
             
               
                   
                 HEMATOCRIT % 
                   
                   
                   
               
               
                   
                  0 
                 99.75 
                 99.97 
                 99.99 
               
               
                   
                 20 
                 97.26 
                 99.44 
                 99.98 
               
               
                   
                 38 
                 — 
                 82 
                 86.2 
               
               
                   
                 Whole Blood 
                 — 
                 49.4 
                 66.9 
               
             
          
           
               
                   
                 Percent Reduction 
               
               
                   
                   
               
             
          
         
       
     
     The above data represents testing performed with varying flow rates and various anticoagulants and prototype UV delivery systems in four (4) liters of animal blood treated with UVC at room temperature. The four (4) liter volume represents a mammal, including human, of approximately 123 pounds. 
     The diluted blood leaves the UV device  104  and passes through tubing  105  and connector  155  to a hemoconcentrator  106  which has approximately 1.2 to 2.4 m 2  exchange surface with pore size of about 60-95 kD. The hemoconcentrator  106  (described relative to FIG. 6) is preferably oriented vertically in the SPATS so that blood flows from bottom to top. This arrangement aids in priming and debubbling the SPATS with crystalloid diluent before blood enters the circuit. In actual practice, positioning the hemoconcentrator  106  a few centimeters below the patient but as far above the floor of the treatment area as practicable provides the potential for maximal ultrafiltration flow by gravity drainage. 
     The blood leaves the hemoconcentrator  106  at port  157  at a hematocrit approximating its entry into the SPATS and returns to the patient via tubing  107  and double lumen cannula  101 . 
     The pressure across the hemoconcentrator  106  is monitored at sample ports and decreases about 70-100 mmHg from inlet  155  port to outlet  157  port at a combined blood and diluent flow of 400-500 ml/min and blood hematocrit of about 20%. At a constant flow rate, a decrease in hematocrit results in a lesser pressure drop and lower inlet pressure, while an increase in hematocrit results in a greater pressure drop and higher inlet pressure. Thus, changes in inlet pressure signal changes in hematocrit and on-line monitoring of pressure can aid a technician in regulating hematocrit. Additionally, hematocrit can be monitored by an in-line optical device or the like, if so desired. 
     The material filtered from the blood is collected in a filtrate collection reservoir  109  via tubing  108  connected to the outlet port  158 . The reservoir  109  is designed to be disposable in a preferred embodiment. 
     Among other factors, the ultrafiltrate rate is dependent on membrane area, relative amount of diluent flow, i.e., hematocrit, and transmembrane pressure (TMP). In this system, the volume of ultrafiltrate realized is maximized if the collection reservoir  109  is placed a substantial distance below the hemoconcentrator  106  in the operating arena. Typically, this distance is about two feet. This configuration increases the TMP because the increased negative (siphon) pressure results in increased untrafiltration rate. Ultrafiltrate collected from the hemoconcentrator  106  can be discarded (in an approved manner) or conserved within the SPATS. 
     In an alternative system configuration, pump  110  (such as a roller pump or the like) propels the ultrafiltrate from reservoir  109  through a secondary circuit (shown in dashed lines). The secondary circuit or path operates independently of the primary circuit and includes filter  111  which is, typically, constructed of several layers of positively-charged meltblown fabric. The filter  111  is designed for the removal of endotoxins containing protein and negatively charged lipopolysaccheride (LPS). That is, the filter fabric captures 94% of endotoxin LPS which is liberated from the cell wall of disrupted gram negative bacteria. In a preferred embodiment, the fabric is produced in a five-layer configuration. 
     Other target molecules mainly pass through filter  111  and are removed by a hollow fiber membrane module  112  with a porosity of about 10 kD, for example. Endotoxin, from the cell wall of Gram negative bacteria and containing protein and negatively-charged lipopolysaccharide (LPS), is 99% captured in filter  111 . Thus, the majority of the smaller molecules pass through filter  111  and module  112  to the large-capacity diluent reservoir  113  where they mix with crystalloid. Pump  114  propels the admixture of crystalloid and filtrate from the secondary circuit back to the primary circuit via Y-connector  103 . Thus, smaller molecules can be conserved by passage thereof completely through the secondary circuit, while plasma proteins and other large molecules are conserved by retention thereof in the primary circuit at the hemoconcentrator. 
     Pump flow is initially based on the hematocrit of the patient  100  and can be subsequently regulated with knowledge of hemoconcentrator inlet pressure as determined by inlet port  155 . That is, port  155  may include a stopcock for monitoring the inlet pressure and/or for sampling of the fluid. Connection of the components in the secondary circuit is by tubing. Components  111  and  112  may be physically incorporated into diluent reservoir  113 , thereby eliminating some connecting tubing and, thereby simplifying supplying the circuit. 
     An on-line optical sensor for the purpose of monitoring hematocrit during hemodialysis has been reported by Jabara and Murta (1995). In this arrangement, electrical feedback control from such a sensor to pump  114  would eliminate the need for manual control at this point of the system. 
     In one embodiment, a single pump  102 , positioned as shown, regulates patient blood and diluent flows. Either a pump with the capability of dual raceway control or a traditional single raceway pump coupled with thumb screw control of diluent flow can be used. In the latter case, the pump flow would be regulated at 400-500 ml/min, accounting for the combined flows from the patient  100  and the diluent reservoir  113 . 
     In the first embodiment, the secondary circuit, shown in dashed outline, is eliminated and the ultrafiltrate from the hemoconcentrator  106  is collected in reservoir  109  and discarded. The diluent source  113  remains, however. This version is likely to be deployed in the case where supplementing important small molecules is more cost effective than conserving them. 
     The rate of pump  110  can be regulated via feedback from a negative pressure controller  109 A established on the reservoir  109 . This eliminates the need for human operation of pump  110 . 
     In FIG. 2, the SPATS is shown in a cardiopulmonary bypass (i.e. open heart blood oxygenator) circuit. In this embodiment, the blood of the patient has already been diluted to a hematocrit of 20-25%. Thus, blood from the patient  200  drains via connecting tubing  201  to a venous reservoir  216  from which pump  217  supplies the blood to a membrane oxygenator  218  where it is arterialized (i.e. oxygenated). The oxygenated blood is passed through an arterial filter  219  from which most of the arterialized blood is returned to the patient via tubing  207 . 
     However, arterialized blood which is to be processed by the SPATS is shunted via purge line  220  from the arterial filter  219  to the cardiotomy reservoir  215  via a one-way valve  202 . The shunt flow range is 300-400 ml/min under the usual total CPB total flow of 4-6 liters per minute. 
     Ultrafiltrate may be pumped and regulated with a negative pressure feedback controller through the target molecule removal system including UV source  204  and hemoconcentrator  206  into the same cardiotomy reservoir  215  via connecting tubing  203  and another inlet. Blood and/or ultrafiltrate collecting in the reservoir  215  is conveyed to the venous reservoir  216  at inlet  205  completing the cardiopulmonary bypass circuit (CPB). 
     As an alternative, 20-25% hematocrit blood could be diluted to 10-15% hematocrit using diluent available to CPB bypass in the fashion described previously. The ultrafiltrate is collected in reservoir  209  connecting tubing  208  from which it is pumped through filters  211  and  212  by pump  210  for removal of target molecules. This operation makes the bactericidal effects of UV device  204  and the sieving of target molecules through the hemoconcentrator  206  even more effective. This approach has the benefit of potentially shortening the duration of treatment. In either case, blood passes through the primary SPATS circuit, consisting of UV irradiator  204  and hemoconcentrator  206 . 
     Ultrafiltration occurs in the hemoconcentrator  206  at the pressure drop previously indicated much as it does in the glomerular units of the natural kidney. However, the natural kidney prevents the passage of the small and plentiful plasma protein albumin (67-69 kD molecular weight) and permits occasional passage of free plasma hemoglobin (64 kD molecular weight), thereby demonstrating a sharp cutoff at a molecular weight of about 65 kD. The hemoconcentrator  206 , with 60-95 kD porosity, is relatively effective at prohibiting passage of plasma proteins (&lt;5% of plasma albumin, &lt;2% of plasma globulin sieved) while permitting sufficient passage of electrolytes, BUN, and glucose to insure normal plasma osmolality. Larger molecules such as cholesterol and creatinine are incompletely sieved (25-95% of plasma concentrations). Permeability of target molecules TNF, IL-1B and LPS are about 100% (appearing in the ultrafiltrate in concentrations equivalent to plasma) in this system; IL-2, although about the same molecular weight as IL-1B (i.e. 17 kD), is almost entirely retained in the blood (primary circuit), thereby reminding that factors other than simple molecular weight are important. Thus TNFa, IL-1β, and LPS have a high percentage potential for removal by this system. 
     Referring now to FIG. 3, there is shown a cross-sectional view of one embodiment of a UV irradiator  300  used in the instant invention. The irradiator  300  includes an outer cylinder  312  which is, typically, molded or otherwise formed of polycarbonate or similar material. The cylinder  312  is, typically, open at end  312 A and substantially closed at end  312 B with a small inlet  301  therethrough. In one embodiment, the cylinder  312  (including the inlet  301 ) is approximately 18 to 20 inches long and about 1 inch inside diameter. The inlet  301  is about {fraction (3/16)} inch inside diameter and about ½ inch long or any suitable length for secure connection to the tubing described supra. 
     The irradiator  300  includes a conventional ultra-violet light source  306  with a radiation wavelength of 254 nm although other suitable sources can be utilized. The UV source  306  is connected to a suitable power source via connector  311 . The UV source  306  is enclosed within a quartz tube  305  which is doped with cesium or any other suitable material which blocks ozone producing wavelengths. 
     The UV assembly, including quartz tube  305 , is mounted within hollow, open-ended quartz tube  304  which is transparent to UV light. As will be seen, the tube  304  protects the UV light source  306  and the protective tube  305  therefore. The tube  304  is a part of the disposable portion of the irradiator  300 . 
     Top cap  302 , fabricated of polycarbonate is sealed tightly to the upper end of quartz tube  304  and establishes a chamber  303  between the top cap  302  and the inner surface of the upper end of cylinder  312 . An annular bushing  313  surrounds quartz tube  305  and securely positions the UV assembly (source  106  and tube  305 ) within tube  304 . Seal  315 , formed of silicone for example, tightly seals the bushing  313  in the doped quartz tube  304  adjacent the open bottom thereof and positions the lower end of UV source  306  therein. 
     Bottom end cap  309 , fabricated of polycarbonate, is attached to the outer surface of cylinder  312 , for example, by ultrasonic welding, adhesive or the like. An outlet  310 , typically of about ¼ inch diameter and of suitable length to provide a secure connection to tubing as described supra, extends outwardly from tube  312  and bottom cap  309 . 
     In a preferred embodiment, the outer surface of cylinder  304  and the inner surface of cylinder  312  are spaced apart by an annular passageway  308  of about 0.006-0.015 inches in order to establish a narrow space for blood flow therethrough. Likewise, at least one of these surfaces is coated with a thin layer  307  of hydrophilic material such as parylene and then plasma treated in order to produce a surface contact angle of less than 5° whereby the fluid passing through the passageway  308  will flow readily as a sheet or film. 
     In operation, heparinized blood in the extracorporeal circuit shown in FIGS. 1 or  2  enters the inlet  301  and then into chamber  303  at the upper end of tube  312 . The chamber  303  is kept as small as possible with a typical volume of less than 20 cc. The blood flows around top cap  302  which has, preferably, a rounded upper surface, and into the annular passageway  308 . The blood flows downward in this passageway. The flow is maximized by the hydrophilic coating  307  with a contact angle of 0°-5° which keeps the surface tension to a minimum, thus reducing the possibility of stagnant areas that can cause fibrin to deposit and, eventually, cause clots to form. A heparin-bonded surface is also an option to preventing thrombus formation or possibly combining bonded heparin and hydrophilic treatment. The blood continues down the annular passageway  308  and pools at the bottom of the bottom cap  309 . The blood is then routed out of the irradiator  300  through outlet  310 . 
     Inasmuch as the UV assembly is sealed from the blood flow by bushing  313  and seal  315  as noted, the UV assembly—including UV source  306 —is reusable while the other components including tube  304  are disposable. 
     Referring now to FIG. 4, there is shown a cross-sectional view of another embodiment of a an irradiator, viz. UV irradiator  400 , used in the instant invention. Once again, as in FIG. 3, a UV lamp  406 , approximately 18″ long, radiates at about 254 nm radially through a doped quartz jacket  405  to prevent ozone producing UV wavelengths. The UV rays emanate through a ½″ to 1″ diameter quartz jacket or tube  405  which is transparent to UVC (i.e. type C UV radiators) and which is closed at the top end with a cap  402 , preferably formed of polycarbonate, and then sealed and adhered to the bottom of tube  405  with silicone adhesive  415 . The silicone adhesive prevents and cracking of quartz tube  405  with changes of temperature during operation. An electrical cord  411  connects to an external power source. 
     In this embodiment, the outer tube  404  is a cylinder which is closed by a top cap  417  bonded with an adhesive or ultrasonically welded to a diverter  418  formed therewith. 
     In addition, an approximately 0.01 inch thick cone-shaped wiper  419 , made of polyester or polycarbonate, is formed in cylinder  404 . The wiper distends slightly under pressure from blood flow allowing a thin, uniform film  420  of blood to flow past the wiper onto the inner surface of the cylinder  404 . 
     In operation, blood enters inlet  401  which is integral with top cap  417  and flows around diverter  418 . The diverter  418  also disperses the blood evenly through a small chamber  403  formed by diverter  418  and top cap  417 , which is, typically, less than 20 cc. The blood in chamber  403  flows onto cone shaped wiper  419  which is flexible and will distend slightly under pressure from an external pump (not shown). The wiper  419 , thus, causes a film  420  of blood to emanate circumferencially, and downwardly, along the inside wall of cylinder  404  and, finally, into a small pool of blood in bottom cap  409 . The blood then exits through outlet port  410  under pressure from an external pump in the system as described supra. 
     As previously noted, the blood film is sufficiently diluted with saline (10 to 20% hematocrit) and thin enough (approximately 0.006 to 0.020 thick) to allow the UVC light radiation (i.e. UV light radiation of range C) from source  406  to penetrate easily. The hydrophilic coating  407  or treatment reduces the contact angle of the base plastic of the cylinder to 0° to 5° allowing the blood to film uniformly and inhibit dribbling downward. 
     The significance of a filmer approach, as shown in FIG. 4, is that the outermost portion of the blood film  420  is moving faster than the boundary layer thereby exposing more blood to the UV light although it may be more difficult to control the blood flow. 
     Referring now to FIG. 5, there is shown a partially broken away, partially cross-sectional view of a filter  500 . The unit  500  includes a top cap  501  and a bottom cap  503  with an inlet  507  and an outlet  508 , respectively. The top and bottom caps are, typically, cone shaped with generally circular configurations. The caps include mating edges  501 A and  503 A, respectively. The edges can be reversed from those shown in FIG. 5 or take any alternative shape, so long as a secure seal between the caps can be achieved. 
     Mounted within the unit  500 , typically, secured by the mating edges  501 A and  503 A, is a filter  502 . In this embodiment, the filter is fabricated of an electrostatically charged, melt blown, layer of polypropylene with a minimum basis weight of 140 grams/square meter. In a preferred embodiment, the filter comprises seven (7) layers each of which is 20 grams/square meter although this number of layers is not intended to be limitative. The filter area should be sufficiently large to handle the filtrate flow rate. Ideally, a filter with a minimum area of 27 square inches is selected. 
     In operation, filtrate flows into top cap  501  through inlet  507  and onto and through the charged, meltblown polypropylene filter  502 . The endotoxins are removed from the blood by electrostatic attraction in filter  502 . Since the blood proteins such as albumin, have been retained by a hemoconcentrator (e.g. hemoconcentrator  206 ) they do not foul the filter media and fight for sites on the media fibers. 
     Referring now to FIG. 6, there is shown a partially broken away elevation view of a hemoconcentrator  600  which corresponds to the hemoconcentrator  106  or  206  described supra. The hemoconcentrator is constructed of a hollow cylinder  601  formed of polycarbonate or similar material. The cylinder is, in one embodiment, approximately 10″ long and 1.5″ in diameter. An inlet  602  and an outlet  603  of suitable configuration to be attached to conventional medical tubing are provided in caps  604  and  605  at opposite ends of the cylinder. The caps are, typically, threadedly attached to the cylinder. In addition, at least one effluent or drainage port  606  is provided adjacent one end of the cylinder. The interior of the cylinder is filled with filter material  610  comprising polysulphone hollow fibers, has between 1.2 and 2.4 m 2  area with a nominal pore size of 60,000 to 95,000 Daltons capable of removing blood proteins and cell mediators whose molecular weight is less than 55,000 Daltons. Because the blood is diluted to 10% to 20% hematocrit, the gel layer formed by the blood, is not thick enough to substantially reduce the effective pore size of the hollow fibers. It is estimated that the pore size is reduced 5% to 20% by the gel layer formed by the layer. 
     A hollow fiber or filter surface area of about 1.2 to 2.4 m 2  is desirable to provide sufficient area to reconstitute the diluted blood in volumes equivalent to those added to the circuit. This is significant because blood returning to a septic patient must not be substantially diluted because that patient will, typically, have secondary pulmonary dysfunction. 
     Thus, there is shown and described a unique design and concept of a septicemia prevention and treatment system. The device described in this patent is capable of preventing and/or treating SIRS by any etiology although the emphasis is on septicemia or microbial sepsis. The particular configuration shown and described herein relates to a Septicemia Prevention and Treatment System. While this description is directed to a particular embodiment, it is understood that those skilled in the art may conceive modifications and/or variations to the specific embodiments shown and described herein. Any such modifications or variations which fall within the purview of this description are intended to be included therein as well. It is understood that the description herein is intended to be illustrative only and is not intended to be limitative. Rather, the scope of the invention described herein is limited only by the claims appended hereto.