MXPA00007170A - Apparatuses and processes for whole-body hyperthermia - Google Patents

Abstract

Apparatuses for use in whole-body hypothermia include a high-flow hyperthermia circuit coupled to a low-flow dialysis circuit in a manner which reduces tensioning of membranes in the dialyzer (152) of the dialysis circuit. The arrangement thereby allows proper membrane movement to assist in mixing a sorbent suspension (176) circulated on the sorbent side of the dialyzer. Additional dialysis apparatuses include advantageous disposable packs (300) including the dialyzer (152), sorbent heat exchangers (186) arranged to cooperate with heating elements on base units of the apparatuses, and adaptations for very high flow rates useful in the hyperthermic treatment of cancers.

Description

APPARATUS AND PROCESSES FOR WHOLE BODY HYPERTHERMIA Field of the Invention The present invention relates to a specialized device for whole body hyperthermia, including extra-bodily heating of the blood and dialysis.

Background of the Invention Whole body hyperthermia (BHT) as a treatment for neoplasms has been carefully studied and applied since the 1960s (3,4,27). / Prior to that period there were several reports of tumor regression that coincides with induced fever. Biochemical studies of the effects of hyperthermia indicate that temperatures above 41 ° C induce necrosis of some types of tumor (3,5). In the body, there are additional physiological effects by which hyperthermia induces tumor necrosis. In both tissues, both normal and tumorous, hyperthermia causes an initial vasodilatation of the blood vessels resulting in increased blood flow. Then, there is a decrease in blood flow due to self-regulation and REF .: 121915 vasoconstriction (6). Tumor tissue has less vascular reactivity to self-regulate blood flow, and therefore, is more prone to the effects of high temperature than normal tissue, during either local hyperthermia or WBHT (7).

/ Now, it is generally accepted that hyperthermia is a useful therapy in the treatment of cancers, and local hyperthermia for accessible tumors is used in all major cancer therapy centers in the United States. Local hyperthermia is a valuable aid for radiation and chemotherapy, because it carries a low risk, has few side effects, and usually its best effects occur in patients whose lesions do not respond to radiation or chemotherapy (3). In tumors of solid metastatic tissue, WBHT is used more than local hyperthermia, since it is difficult to apply local therapy in abdominal or pectoral injuries. Even in patients who have failed radiation or chemotherapy, there is a partial remission of tumors in about half of patients. These results are similar to those obtained with many drugs, however, with cancer drug therapy, the incidence of side effects is approximately 100%. Although there are some side effects of the WBHT, most of them are short-lived and not serious.

Kaposi's sarcoma (KS) is the most common neoplasm of patients with AIDS, it is observed mainly in male homosexuals of the population with AIDS (8). Unlike classical KS, the AIDS-related form is usually aggressive, presenting with several large cutaneous tumors and early visceral dissemination. The etiology of KS is uncertain in these patients. Viral cytomegalic infections, other sexually transmitted organisms, inhalation of volatile nitrate, oncogenes, hormones and HLA type; all have been suggested as possible cofactors. The KS is reported, in general, as the first diagnosis in -13% of hospital admissions of all patients with AIDS (9) and reports of disfiguring diseases for substantial morbidity.

Of all the tumors, KS seems to be the most sensitive to systematic hyperthermia. In a 1985 review, of the 21 patients who were treated with hyperthermia for cancer, the only patient with complete remission was one with KS (10). According to the researchers, this patient is the only one of the 21 who were treated who still survive; KS injuries have not recurred. A case reported in 1990"indicates a dramatic resolution of KS lesions during and shortly after a single WBHT treatment." 11 These lesions have not recurred one year later (12) or three years later. with HIV and Kaposi's sarcoma have been treated with WBHT Most patients have remission of Kaposi lesions and tiny evidence of HIV for four months (120 days) after treatment (29).

'Hyperthermia also helps to resolve many bacterial infections. The response of fever in mammals is specifically implied by this reason, and the beneficial effects of fever in survivors of animals after they have been reported to gram-negative blood infections (13). Hyperthermia also has beneficial effects in the resolution of many viral infections. Hornback and colleagues have studied the infection of mice by the Friend virus complex, a complex retrovirus similar to HIV that causes a uniformly fatal erythrocemia in mice, with devastating effects on T cells and natural "killer" cells similar to those of HIV . This disease can be partially controlled with WBHT at 40 ° C (once weekly, for two weeks). Mice receiving the WBHT after injection of Friend virus live twice as much as untreated controls, and more than those treated with cyclosporine alone (14,15). The function of natural "killer" cells is also increased by WBHT therapy against controls (14,15).

The HIV virus is sensitive to heat in some way. McDougal, et al. He incubated HIV at temperatures ranging from 37 ° to 60 °, and found that the death log followed a first order kinetics (16). In the natural liquid state, HIV was inactive at 40% after 30 minutes at 42 ° C; and 100% inactive at 56 ° C (17). Importantly, lymphocytes infected with HIV are eliminated very effectively at 42 ° C temperature. Since only a small portion of lymphocytes are infected with HIV, that means that the surviving cells will be free to carry out their usual immunological functions, prevented by HIV. Even if some of the lymphocytes infected with HIV survive, they have a change in the surface antigens that allow recognition by the immune system.

The beneficial effects of a unique WBHT in the treatment of HIV and Kaposi's sarcoma are no longer a theoretical possibility, but a proven reality. A study indicates that of 31 patients with HIV and Kaposi's sarcoma treated with WBHT, 70% have partial or complete regression of Kaposi's Sarcoma lesions and these patients have an increase in CD4 counts for an average of 120 days . Adenopathy and oral leukoplakia were resolved in all patients. The treatment was more effective when the CD4 pre-treatment count was about 50 / mm3. In no patient does HIV activity stimulated with WBHT speak, as determined by many antigen indicators (29).

An article by Milton B. Yatvin, Phb, indicates that "the initial effect of hyperthermia on cells is mediated by the heat-induced disorganization of membrane lipids" (28) This effect was further defined in subsequent studies (18,19). Yatvin also describes a variety of simple compounds that have flowed the effects on the bilayer lipid membranes similarly to heat, and exert antiviral effects on HIV and other viral infections. (including ethanol, anesthetics, AL721, adamantine, and common food additives called butylated hydroxytoluene or BHT) (18). In a later work, Yatvin suggests that the effects of heat on virally loaded cells were enlarged by the flow of chemical agents (27,18). These articles show that WBHT should have positive effects on HIV infection, and that these effects can be improved by adding some simple chemicals during or before WBHT.

There are many methods to induce WBHT, including paraffin wax baths, radiation heat chambers, microwave heat chambers, water layers, and extra bodily heating of the blood. These methods have been used mostly in the treatment of patients with very advanced metastatic cancer. Even in these weak patients, the heart temperature can be maintained at 42 ° C for one or two hours without unfavorable effects on cardiovascular functions, renal, or liver, although there is usually the elevation of serum transaminases, creatine phosphokinase and lactate hydrogenase (4). Three instances of mild neurological damage were noted in Parks patients in association with hypophosphatemia during treatment, but no significant problems occurred once phosphate levels were maintained (20). Larkin also reported two deaths in patients who received the WBHT from 41.5 ° to 42 ° C for 1 ^ to 2 hours; however, these patients have massive tumors in the liver, and byproducts of tumor necrosis contributed to the death of these patients (21). In the review of previous studies, Yatvin, Stowel and Steinhart found only six deaths in 275 hypertheric treatments of patients weakened with carcinoma, representing a mortality rate of only 2% (27).The extra bodily WBH is usually supplemented using a relatively simplistic circuit containing only a blood pump and a heat exchanger to heat the blood (22). The proportion of blood flow through the body system has been high, from 2 to 3 liters per minute. During this procedure, and other WBH techniques, the patient is heated to a heart temperature of 41.5 ° to 42 ° C for two hours or more. Sedation is required and regular general anesthesia and intubation is carried out (22). In the moderately sedated patient, the brain stem responds with hyperventilation, to increase heat loss. The alkalosis of the blood results, allowing the decrease of potassium, calcium, phosphate and magnesium (while these substances are transferred into the cells or bones) (23). In a patient anesthetized generally in mechanical ventilation, normal ventilation can be provided. However, the increased metabolic body ratio and centralization of blood fluid lead to acidosis with increases in potassium, calcium, phosphate and magnesium (24). Frequent blood chemistries should be measured during treatment, so that these changes in blood chemistries can be corrected by intravenous infusion of several electrolytes. Following the WBH, there is often a persistent deficiency in potassium, calcium and phosphate, until they have been replaced aggressively during treatment. Regularly, there is moderate damage to the liver, muscles and kidneys during treatment, demonstrated by changes in enzyme and toxin levels in the blood (23, 25, 26).

The clinically recognizable complications of hyperthermia depend to some degree on the method of administration, whether by direct contact of the skin, radiant heat, or heating of the blood, and on the temperature of the heart that is obtained and the duration of the exhibition. Skin burn with hyperthermia usually occurs only when it is created by skin contact or radiant heat. Studies in cancer patients have shown a significant incidence of fatigue, peripheral neuropathy, vomiting, diarrhea, and arrhythmias. However, these occurred mostly in severely weakened patients with Karnofsky Marks less than 50% (1, 2).

In the treatment of patients with HIV and Kaposi's sarcoma, hyperthermia is relatively safe as well. In a study of 31 patients with HIV and Kaposi's sarcoma treated with extra body WBHT with a relatively low blood flow ratio of 300 to 400 ml / min. (29), there was no significant morbidity associated with the treatment, although two patients had intravascular coagulopathy (without signs of bleeding) and several patients had skin damage by pressure point. There were two deaths of patients within 120 days of the procedure, one of intracerebral hemorrhage due to pre-existing intracerebral berry aneurysm (an unusual condition) and one of pulmonary edema and cardiac arrhythmia due to excessive aggressive fluid therapy (in a patient who I had pre-existing lung disease). The highest mortality in this study was only 7%; the mortality rate would have been zero if patients with abnormal lung conditions had been excluded from the study, and if the patient with the unusual brain condition had not been treated.

Among the known protocols for the extra corporal heating of the blood, several difficulties persist, including elevated serum transaminases and bilirubin, instances of neurological damage associated with serum hypophosphatemia, risk due to abnormal pH or abnormal levels of sodium, sodium bicarbonate or potassium, or possible death due to massive tumor necrosis. Previously tried human immunodeficiency virus treatments with hyperthermia have included only relatively minor measures to maintain the normal physiology of the blood (the addition of sodium bicarbonate from Davidner et al., For example). Therefore, there is a need for more reliable, simple, and more comprehensive treatment for extra corporal hyperthermia; and an apparatus for carrying out such treatment, in which the undesired side effects are reduced or eliminated entirely. The present invention addresses this need.

Description of the invention A preferred embodiment of the invention provides a method for carrying out whole body hyperthermia in a patient. The method includes circulating the patient's blood through a circuit of high circulation hyperthermia at a rate of at least 1500 ml / min. , the hyperthermia circuit that includes a blood access line to draw the patient's blood, a pump, a heat exchanger to heat the blood to a temperature of at least 40 ° C, and a blood return line to return the blood blood to the patient after heating it in the heat exchanger. The method also includes diverting a portion of the blood circulating in the high circulation hyperthermia circuit to the low circulation dialysis circuit, and circulating the blood in the low circulation dialysis circuit at a rate of 200 to 800 ml / min. . The low circulation dialysis circuit includes: a blood inflow line having a first end connected to the hyperthermia circuit to divert blood to the dialysis circuit from the hyperthermia circuit; a dialyzer having a blood side and an absorbent side, separated by the dialysis membranes, the membranes are formed elastically; the means for applying alternately, negative pressure and positive pressure on the absorbent side of the dialyzer; a blood inlet orifice to the blood side of the dialyzer, a second end of the blood inflow line is connected to the blood inlet; a blood outlet orifice from the blood side of the dialyzer; a line of blood effluence having a first end connected to the blood outlet orifice, and a second end connected to the hyperthermia circuit; an absorbent circuit for circulation and an absorbent suspension through the dialyzer side.

Additionally, during the operation of the high circulation hyperthermia circuit and the low circulation dialysis circuit, the dialyzer membranes expand and compress in response to alternating negative pressure and positive pressure on the absorbent side of the dialyzer, to circulate and agitate an absorbent suspension on the absorbent side wherein an effective mixture of the absorbent suspension is maintained. In more preferred forms, the method also includes heating the absorbent suspension within a heat exchanger, to decrease the transfer of heat from the blood to the absorbent suspension. In addition, the blood inflow line is preferably connected to the high circulation hyperthermia circuit at a downstream site of the blood efflux line, for example, it occurs advantageously on opposite sides of the hyperthermia circuit pump.

In another embodiment, the invention provides an apparatus for use in the treatment of a patient's entire body hyperthermia. The apparatus includes a high circulation hyperthermia circuit, equipped to circulate blood therethrough at a rate of at least 1500 ml / min. , the high circulation hyperthermia circuit includes a blood access line to draw the blood of a patient, a pump, a heat exchanger to heat the blood to a temperature of at least 40 ° C, a blood return line for return the blood to the patient after heating it inside the heat exchanger. Also included is a low circulation dialysis circuit, equipped to circulate blood through it at a rate of 200 to 800 ml / min. , the low circulation dialysis circuit is coupled to the hyperthermia circuit and is effective to divert a portion of the blood circulating therein to the hyperthermia circuit. The low circulation dialysis circuit, on the other hand, includes: a blood inflow line having a first end connected to the hyperthermia circuit, to divert blood to the dialysis circuit from the hyperthermia circuit; a dialyzer having a blood side and an absorbent side, separated by the dialysis membranes, the membranes are formed elastically; the means for applying alternately, negative pressure and positive pressure on the absorbent side of the dialyzer; a blood inlet orifice to the blood side of the dialyzer, a second end of the blood inflow line is connected to the blood inlet; . a blood outlet orifice from the blood side of the dialyzer; a line of blood effluence having a first end connected to the blood outlet orifice, and a second end connected to the hyperthermia circuit; an absorbent circuit for circulation and an absorbent suspension through the dialyzer side.

Additionally, the apparatus of the invention is configured such that during the operation of the high circulation hyperthermia circuit and the low circulation dialysis circuit, the dialyzer membranes expand and compress in response to alternating negative pressure and the positive pressure on the absorbent side of the dialyzer, to circulate and agitate an absorbent suspension on the absorbent side where the effective mixture of the absorbent suspension is maintained.

Another embodiment of the invention provides a disposable package for use with the dialysis instrument. The disposable package includes a package mounting member, and a dialysis plate that is mounted on the package mounting member having a blood side with a blood inlet orifice and a blood outlet, and an absorbent side with a Absorbent inlet port and an absorbent outlet hole. A blood inflow tube communicates with the blood inlet orifice of the dialysis plate to pass the blood of a patient to the blood side of the dialyzer. A blood effluent tube communicating with the blood outlet orifice of the dialysis plate to draw blood from the blood side of the dialyzer. The absorbent circulation tubes communicate with the absorbent side of the dialyzer through the absorbent inlet port and the absorbent outlet port, to circulate the absorbent through the absorbent side of the dialyzer. A heat exchanger through the flow communicates with the circulation tubes of the absorbent, to heat the absorbent flowing through the heat exchanger. Also, the disposable package preferably includes an accumulator reservoir that is mounted on the package mounting member and communicates with the circulation tubes of the absorbent, the accumulator reservoir is operable to alternately accumulate and expel the absorbent in response to positive pressure and negative pressure that is applied alternately to the storage tank.

In another embodiment, the invention provides a process for preparing an absorbent suspension, which includes combining an aqueous solution having dissolved calcium ions, with an aqueous solution having dissolved phosphate ions, wherein the combination is in the presence of an agent surface pulverized adsorbent to form calcium phosphate precipitated on both, the adsorbing agent and freely within the suspension. This process is advantageously carried out by: (a) combining water, activated carbon powder and flow inducing agent; (b) adding separate solutions containing, respectively, dissolved calcium chloride and dissolved disodium phosphate, to the product of step (a); (c) stirring the product of step (b); (d) adding a cation exchange resin loaded with sodium, calcium, magnesium or potassium, to the product of step (c); (e) stirring the product of step (d); (f) adding sodium bicarbonate powder to the product of step (e); and (g) shake the product from step (f) Still another preferred embodiment of the invention provides a dialysis system having a base unit equipped with a positive pressure and negative pressure source, a heating element, the receiving means for receiving a heat exchanger in relation to the heat exchange with the heating element. Also, the system includes a disposable package for use with the base unit, which includes a package mounting member, a dialysis plate mounted to the package mounting member, the dialyzer having a blood side with a blood inlet orifice and a blood outlet, and an absorbent side with an absorbent inlet orifice and an absorbent outlet orifice, a blood inflow tube communicating with the blood inlet to the blood side of the dialyzer, a blood effluent tube communicating with the exit orifice of the dialysis plate, to draw the blood from the blood side of the dialyzer, the absorbent circulation tubes communicating with the absorbent side of the dialyzer by means of the absorbent inlet orifice and the dialyzer absorbent outlet orifice, a reservoir accumulator mounted on the package assembly member, the accumulator tank communicating with the absorbent circulation tubes, the accumulator reservoir which is operable to alternately accumulate and expel the absorbent suspension in response to the positive pressure and the negative pressure applied alternately to the storage tank, the storage tank that connects to the pressure source positive and negative pressure of the base unit, a heat exchanger by flow communicating with the absorbent circulation tubes, to heat the absorbent flowing through the heat exchanger, the heat exchanger cooperating with the receiving medium the base unit for removably positioning the heat exchanger in relation to the heat exchange with the heating element of the base unit.

It is an object of the invention to provide an apparatus that can be effectively used in whole body hyperthermia to control the patient's blood chemistry during treatments. Other objects of the invention are to provide an absorbent suspension composition that is highly effective for use in absorbent-based hemodialysis to control the calcium and phosphate levels in the patient's blood in addition to other blood chemistries, and provide the processes for preparing such compositions effectively.

Another objective of the invention is to provide the apparatuses for use in the administration of hemodialysis during whole body hyperthermia, apparatuses which include the elastic membranes that promote the mixing of the absorbent suspensions and which are not excessively stressed by the high proportions of blood flow that are used in hyperthermia circuits during treatments.

Additional objects of the invention are related to the provision of dialysis systems including convenient disposable packages and advantageous arrangements for circulating and heating the absorbent suspensions used in the systems.

The additional embodiments, features and advantages of the present invention will be apparent in the following description.

Brief description of the figures Figure 1 is a schematic diagram illustrating a preferred apparatus for conducting whole body hyperthermia.

Figure 2 is a schematic diagram of the hydraulics of a preferred hemodialysis instrument that is used in conducting whole-body hyperthermia.

Figure 3 illustrates a disposable package including disposable elements of a hemodialysis instrument of the invention.

Figure 4 provides a perspective front view of a dialysis base unit of a preferred hemodialysis system, which can be used in conjunction with the disposable package illustrated in Figure 3.

Figure 5 provides a view of the left end of the base unit illustrated in Figure 4, with an open door to show the components inside it.

Figure 6 provides an enlarged view of the upper surface of the base unit shown in Figure 4, to more clearly illustrate the components mounted thereon.

Figure 7 provides a perspective view of a hyperthermia base unit of a preferred system, which can be used in providing a high circulation hyperthermia circuit.

Description of the Preferred Modalities In order to promote an understanding of the principles of the invention, the reference will now be made to certain modalities of the invention and the specific language will be used to describe it. It will be understood, however, that the limitation of the approach of the invention is not considered by this means, such as alterations, further modifications, and applications of the principles of the invention are contemplated as would normally occur for someone with skill in the art. art for which the invention is related.

The present invention allows the application of absorbent-based hemodialysis for hyperthermia treatments in a highly efficient way. This hemodialysis technology involves the use of a specialized absorbent suspension as well as the hemodialysis solution. The dialysis procedure during hyperthermia allows many important electrolytes to be regulated and maintained at appropriate levels in the blood. In addition, many toxins, for example those incidents for the death of virally infected cells and / or Kaposi's Sarcoma cells, are removed.

Figure 1 illustrates a preferred apparatus for carrying out whole body hyperthermia according to the present invention. The patient 110 is placed for treatment, and optionally covered with a solar layer or a similar heat retaining device (and optionally a heat producing device). A blood efflux catheter 112 connects the patient to line 114 of the extracorporeal blood hyperthermia circuit. Line 114 passes through blood flow bubble detector 116 and blood flow restrictor 118. So, line 114 transports blood to a pump 120 (roller pump), and then on and through a blood side of heat exchanger 122. After draining the heat exchanger 122, the line 114 passes through the blood efflux block 124 and the blood flow bubble detector 126. A blood return catheter 128 returns blood to patient 110. Pressure sensors 130A and 130B are connected to line 114 to measure blood flow pressure within line 114 by extracting and reentering patient 110, respectively. The rinse line 133 is engaged in the rinse obstruction 132, which can be opened to facilitate the conduction of the rinsing operations. The heat exchanger 122 includes a side 134 of heat transfer fluid through which the heat transfer fluid, for example water, is passed to heat the blood passing through the blood side of the heat exchanger 122.

The line 136 of the dialysis circuit connects the blood side of a dialysis circuit to the line 114 of the hypercermia circuit at a site near the pump 120 within the hyperthermia circuit, and the effluence line 138 of the dialysis circuit connects the blood side of the dialysis circuit to line 114 of the hyperthermia circuit at a point after pump 120 within the hyperthermia circuit. Thus, blood is drained into the dialysis circuit from the hyperthermia circuit via line 138. In this way, a relatively higher flow rate (eg, about 1000 to 4000 ml / min.) Can be maintained. within the hyperthermia circuit and a relatively lower flow rate can be maintained within the dialysis circuit (typically around 200 to 600 ml / min.), while avoiding the tension of the dialysis membranes that are used, as discussed above additionally.

Referring now to Figure 2, the preferred dialysis circuit will be discussed in greater detail. The blood passes from the blood circuit of hyperthermia (Figure 1) to the dialysis circuit by means of the line 136 of inflow. Line 136 passes through blood influx obstrictor 140, bubble detector 142, blood flow rate sensor 144, blood flow obstrictor 146, and flow rate termination sensor 148. blood Then, the line 136 is directed towards the blood inlet orifice 150 of the blood side of the dialyzer plate 152. The dialyzer plate 152 has the blood outlet orifice 154 for which the line 138 of the blood outlet orifice is attached. The line 138 of the blood outlet orifice then passes through the blood filter bubble trap 156, the blood discharge obstruction 158, and the bubble detector 160, which is then connected to the tubing 114 of the hyperthermia circuit (FIG. ).

The rinse / preparation line 162 is connected to the tubing 136 at an intermediate site between the bubble detector 142 and the sensor. 114 of blood flow rate, for the introduction of preparation and rinsing solutions (for example, from solution bags hung on a pole scale, as illustrated) during the preparation and flushing operations of the system. Line 162 includes prep / rinse bubble detector 164 and prep / rinse obstruder 166.

The infusion line 168 is connected to the tubing 138 at an intermediate site between the blood outlet orifice 154 of the dialyzer and the bubble trap 156, blood filter, for the infusion of the solutions (for example, the infusion of the 100 ml Ca solution). / K) to the patient. An infusion pump 170 and a drop counter / drip chamber combination 172 are also provided for these purposes.

On the absorbent side of the dialysis system of Figure 2, an absorbent bag 174 is provided which includes an absorbent suspension 176. The absorbent inflow line 178 has an opening that resides in the absorbent suspension 176 to remove the suspension 176 from the bag 174. The absorbent inflow line 178 engages in the absorber inflow obstruent 180, and then passes to the orifice 182 of absorbent inlet of the absorbent side of the dialyzer 152.

The absorber inflow line 178 is also connected to the absorbent filling line 178A, which provides a line for the flow connection to the saline bags (for example, by holding them on a pole scale) or something similar, for fill the absorbent bag with saline before starting the treatment. The filling line 178A can then be switched off.

The absorbent return line 184 has an opening that resides in the absorbent bag 174, to return the absorbent suspension 176 to the absorbent bag 174. Located on the absorbent return line 184 is the absorbent heat exchanger 186, to heat the absorbent suspension to prevent the absorbent system from acting as a heat sink that extracts substantial heat from the blood in the hypothermia circuit. The absorbent heater 186 has a temperature sensor 188 associated therewith for monitoring the temperature of the absorbent.

Also, located on the absorber return line 184 is the blood leak detection module 190, which extracts a filtrate from the absorbent suspension and examines the filtrate for the presence of blood (hemoglobin). The module 190 is connected via line 192 to a pressure / aspiration source that allows the module to obtain the filtrate. Located within line 192 is filtering obstruder 194, which automatically opens and closes periodically to allow filtering to be processed in blood spill detection module 190.

The absorbent return line 184 is also coupled to the external absorber obstructor 196, which is also opened and closed at controlled intervals to facilitate the circulation cycle of the absorbent through the dialyzer 152. The absorbent return line 184 is connected to the dialyzer 152 by an absorbent exit orifice 198 on the absorbent side of the dialyzer 152.

The temperature sensors 200 and 202 are connected to the absorbent bag 174, and serve to monitor the temperature of the absorbent suspension 176 within the absorbent bag 174. In addition, the absorbent bag 174 is hung on the absorbent balance 204, which is used to monitor the weight of the absorbent suspension.

The circulation of the absorbent suspension 176 within the blood absorber system on the blood side of the dialyzer 152 is driven by the action of the accumulator reservoir 206. The accumulator reservoir 206 has an internal diaphragm 208 that is directed up and down within the reservoir 206 in response to the alternating negative pressure (vacuum) and the positive pressure that is applied to the reservoir 206 by means of the pressure line 210 / Vacuum cleaner. The pressure / vacuum line 210 includes the disposable biohazard filter 212 and the disposable coupling 214, such that these disposable elements can be removed and discarded after the treatments. The pressure / vacuum line 210 also includes an internal biohazard filter 216.

The pressure / vacuum line 210 is connected to the vacuum pump 218 with the associated silencer 220 by means of the vacuum line 222. The line 222 vacuum includes the air flow valve 224, which opens and closes automatically at controlled intervals to participate in the supply of alternating pressure and suction to the accumulator tank 206. Also, associated with vacuum pump 218 and vacuum line 222, are vacuum regulator 226 and vacuum transducer 228, as illustrated.

The pressure / vacuum line 210 is connected to the pressure pump 230 with the associated muffler 232 by means of the pressure line 234. The pressure line 234 has inside it the air effluence valve 236, which opens and closes automatically at controlled intervals (alternately to the air flow valve 224) to participate in the alternating supply of pressure and suction to the air. tank 206 accumulator. Also, associated with pressure pump 230 and pressure line 234, are pressure regulator 238 and pressure transducer 240, and vent 242, as illustrated.

Sensors 244, 246 and 248 of fluid level are also provided which are placed to monitor the level of the absorbent suspension in the storage tank.

As discussed above, the preferred hemodialysis system used in the invention contains the absorbent suspension 176 within the dialysis side. The flow of the suspension is countercurrent generally with respect to the blood fluid and is in one aspect in both, bidirectional between the accumulator 206 and the dialyzer 152, and circulating between the dialyzer 152 and the absorbent bag 174.

To supplement this, during the first part of the blood flow, the obstrictor 180 in line 178 of absorber inflow opens automatically, and the obstructor 196 closes automatically, allowing the absorbent suspension 176 to flow from the absorbent bag 174 through the dialyzer 152, filling the accumulator reservoir 206. The obstructor 180 then closes and remains closed during the blood flow residue and all of the effluence, when the pressure that is applied by the accumulator reservoir 206 returns some suspension of the dialyzer 152 and passes something through the return line 184 of absorbent (with the obstructor 196 automatically open at this time), to return to the absorbent bag 174. This, together with the expansion and contraction of the dialyzer membranes, keeps the absorbent suspension well mixed on the surface of the dialyzer membrane.

In the preferred system, the blood system preparer for the dialysis system is 5% dextrose in water (D5W). This solution flows to line 136 of blood flow through line 162, driven by the expansion and contraction of diaphragms of dialysis plate 152 in response to alternating positive and negative pressure which is applied by means of reservoir 206 accumulator . During rinsing or preparation operations, the rinsing / preparation obstruder 166 opens automatically and the blood-flow obstruder 140 automatically closes, and the obstructions 146 and 158 alternately open and close to cause unidirectional flow of the fluid through the dialyzer 152 driven by the expansion and contraction of the dialysis membranes of the dialyzer 152 in response to the alternating negative and positive pressure that is applied to the absorbent side by the accumulator reservoir 206. The preparatory or rinsing fluid is thus pulled into the system before the blood, and circulated through the dialyzer 152. The preparation operations can be automated, and serve to remove air from the lines and from the dialyzer 152 on both, the side blood and the dialyzer side. Rinsing operations can also be automated, and scheduled to occur both, periodically during treatment (eg, to periodically return fluids (eg, saline)) to the patient, and / or until the end of treatment.

During the blood inflow cycles, the rinsing / preparation obstruder 166 automatically closes and the blood inflow obstruder 140 opens automatically. Thus, the blood is drawn into the system from the hyperthermia circuit via line 136 of blood flow and circulated from the hyperthermia circuit through the dialyzer 152 by means of the action of the dialysis membranes and the alternating opening and closing the obstruders 146 and 158, similarly to the preparation / rinsing fluids described above.

In the dialysis circuit, the proportion of blood flow is around 200-800 ml / minute will be typical, with the flow rates in the range of about 200-600 ml / minute that are preferred.

In the hyperthermia circuit, the blood flow ratios are higher than about 4000 ml / min. are preferred, typically in the range of about 1500 ml / min. up to about 2000 ml / min. These high circulation ratios can be carried out by altering the hull of the roller pump 120 (Figure 1) to provide higher revolutions per minute. Such extremely high flow rates are important for the use of the apparatus in the treatment of certain cancer patients, for example patients having tumors of solid metastatic tissue such as metastatic cancer tumors of non-small cells of the lung, and allowing it for the rapid warming of patients. This allows the optimization of the treatment time before the overregulation of the calorific shock proteins in the patients.

Other characteristics in the device and its use, also assist in carrying out these high flow rates while avoiding excessive pressure in the lines of inflow and blood flow. For these purposes, the blood access is "from vein to vein", with the catheter 112 of blood inflow (figure 1) which is located in the superior vena cava by means of the internal jugular and the catheter 128 of blood effluence is located in the femoral vein. The venous catheters used are preferably wire-supported, thin-walled catheters varying in size from 10-18 French, located percutaneously. As in the preferred high circulation device, the blood return circuit of the heat exchanger 134 the blood return catheter 128 can optionally be de-provisioned from blood filters such as the bubble filter 126 which causes a substantial decrease in pressure in the preferred proportions of blood flow that are employed. The heat exchanger 134 can also be equipped with a conical shaped lid (a feature of commercially available heat exchangers such as the Electromedics D1079E heat exchanger), to collect any present bubble serve as well as the last bubble trap before returning the patient. The conical shaped lid, on the other hand, can be equipped with a Luer connection or a similar device for a sterile removal of any air trapped (for example, by the syringe).

For the treatment of whole body hyperthermia of solid metastatic tissue tumors such as non-small cell lung metastatic cancer tumors (for example, metathesis to the contralateral lung), treatment is carried out for about two hours at the heart of the lung. patient at a temperature of 42.5 °. For such treatments, the temperature of the water in the heat exchanger 134 is preferably set at a maximum at a temperature of about 52 ° C, several degrees higher than what is typically used for HIV infection therapies.

Referring now to FIGS. 3-6, a disposable package and a base unit are illustrated which can be used together to provide the characteristics of the dialysis circuit shown in FIG. 2. In particular, FIG. 3 is shown in FIG. Disposable package 300, which contains several elements of the dialysis system that can be discarded - after treatment. The package 300 includes the package assembly member 302, in which several components of the package 300 are fixed. The package assembly member 302, in a preferred form, includes structures such as depressions, openings, and the like, to hold the various elements at convenient locations. The pack 300 generally includes the dialyzer 152, the blood inlet and outlet lines 136 and 138 connected to the blood inlet orifice 150 and the blood outlet orifice 154 of the dialyzer 152 respectively, to the bubble / blood filter trap 156, the absorbent inflow and return lines 178 and 184 connected to the absorbent inlet orifice 182 and the absorbent outlet orifice 198 of the dialyzer 152, respectively, and to the heat exchanger 186 to heat the absorbent suspension 176. The filter generator 190A (a component of the blood spill detection module 190) is located on the absorber return line 184, and is connected to the filter tube 192 which, however, is connected to the pressure / vacuum line 210. to provide the means to form the filter sample for examination. The package 300 also includes the sterile solution inlet line 162 (for preparation / rinsing operations), and the infusion line 168 with the drip chamber 172A. The package 300 additionally includes the reservoir 206 accumulator connected to and operated by means of the pressure / vacuum line 210.

Shown in Figures 4-6 are several components of a dialysis base unit 400 for use with the disposable pack 300. Referring to Figure 4, a full perspective view of the base unit 400 is shown. The base unit 400 includes a service door 402, a pneumatic extractor 404 (containing the pressure / vacuum components as described above), an absorbent chamber door 406, the components of the blood spill detection module 190 (discussed below), a 172B meter of drops for the line 168 of infusion, a removable IV pole with a pole balance 408, a pressure / suction port 410 that connects to the pressure / suction feed system described in figure 2. The base unit 400 also includes a panel 412 of control and an upper surface that is usually denoted in 414, which contains a number of system components, as described below in conjunction with figure 6.

Referring now also to Figure 5, a left side view of the base unit 400 illustrated in Figure 4 is shown, with the hinge door 406 of the absorbent chamber open to reveal the components therein. In particular, the heater plate 416 having a surface correspondingly shaped to a surface of the heat exchanger 186 (for example, both, generally flat), is shown to optimize the exchange of heat therebetween. The heater plate 416 includes the slot 418 near the bottom thereof to receive the bottom edge of the heat exchanger 186 to or from the heater plate 416, and the connection 422 for receiving the connectors 424 (in dotted line) of the sensors 200. and 202 of temperature on the absorbent bag 174. In addition, the hooks 424 are provided to hold the absorbent bag 174 (shown in dashed line).

Also, FIG. 5 illustrates that the pneumatic extractor 404 projects outwardly relative to the service door 402, creating a shelf on which the slot 428 is provided to receive the bottom edge of the disposable package 300 when mounted on the front. of the 400 base unit. Also, the absorbent stripping tube 178A and the absorbent return tube 184A forming a portion of the absorbent line 178 and the absorbent line 184 of the dialysis system, respectively, are shown in dotted line (see Figure 2).

Refer now to Figure 6, an enlarged view of the upper surface 414 of the base unit 400 is shown. Mounted on the surface 414 are the blood flow obstructors 140 and 146, the bubble detectors 142 and 160, the blood efflux cuff 158, and the blood flow rate sensors 144 and 148. Also mounted on the surface 414 are the preparation / rinsing detector 168, the preparation / rinsing obstruder 166, the absorber inflow obstruder 180, and the absorbent effluent obstruder 196. In addition, the surface 4124 also has mounted on it the 190B hemoglobin indicator which together with the generator filter 190A provides the blood leakage detector module 190 (see figure 2). Also on the surface 414 the filter obstruder 194 is mounted.

For the placement of the dialysis system shown in Figures 3-6, the saline bags can be hung on the pole balance 408 of the base unit 400. The absorbent bag 174 can then be hung on the hooks 426, and the bottom edge of the disposable package, which is assembled as shown in Figure 3, can be placed within the groove 428 on the front of the base unit 400. The upper part of the package 300, which is configured with the openings to avoid covering the components, generally rests on the front half of the upper surface 414. The heat exchanger 186 can be mounted and secured to the heater plate 416, and the pressure / aspirator tube 210 is connected to the pressure / aspirator port 410. The absorbent filling tubing 178A can be connected to the absorbent effluent line 178, used to drain the saline bags into the absorbent bag 174 (and the agitated bag), after the absorption effluent line 178 which occurs on the absorbent bag 174, it can be connected to the corresponding segment of the absorbent effluent line 178 which is connected to the adsorber input hole 182 of the dialyzer 152. The inflow line 136 can be coupled to the blood inflow obstruster 140, in the bubble detector 142, in the blood flow rate start sensor 144, in the blood flow obstrictor 146, and in the blood flow rate sensor 148. The blood efflux line 138 can be coupled to the blood efflux block 158 and the bubble detector 160. The absorber inflow line may be coupled to the absorber inflow obstruent 180, and the blood effluent line may be coupled to the blood efflux cuff 196. The prep / rinse line 162 can be coupled to the prep / rinse bubble detector 164 and the prep / rinse obstruder 166. The filter generator 190A can then be installed within the hemoglobin indicator cassette 190B of the blood leak detection module 190, and the line 193 coupled within the filter obstrictor 194. The infusion line 168 can be installed inside the infusion pump 170.

An infusion bag that is connected to the infusion line 168 via the drip chamber 172A can be filled with a calcium / potassium infusion solution. The bag can be held with a hook and the drip chamber 172A can be prepared. The drip chamber 172A is installed in the drop counter 172B. The rinse and rinse solutions can be connected to the preparation / rinse line 162. During a preparation cycle, rinsing solutions can be manually released to allow the unique feed of system preparation solution. Thereafter, the manual clamps can be removed to allow the flow of rinsing solutions into the system during the rinsing cycles. Referring now to Figures 1 and 7, there is shown in Figure 7 a hyperthermia base unit 500 that can be used in the high circulation hyperthermia circuit supply shown in Figure 1. Hyperthermia base unit 500 includes generally, a trolley provided with wheels that has mounted on it the components of the circuit of high circulation or that cooperate with such circuit. Base pump 500 is included in pump 500, flow and flushing effluents 118, 124 and 132, and bubble detectors 116 and 126. Also, a clamp 502 is included to hold the heat exchanger 122, the water line connectors 504 for the water inlet port and the water outlet port of the heat exchanger 122, and the blood temperature monitor 506. to measure the blood temperature in the circuit. The hyperthermia base 500 also includes the input connections 508 for the multiple monitors of the patient temperature that are employed, and the input connection 510 for the patient's cardiac output bioimpedance monitor that is employed. A flexible disk reader 510 is also located on the front of the unit 500, to provide the ability to store the data relating to the treatments on the disk. A blood pump speed control knob 514 allows users to control the speed of pump 120. Pressure transducer ports 516 are provided to cooperate with monitors 130A and 130B. In addition, a user interface 518, for example a touch screen computer, is provided in the base unit 500 to allow users to interact with a computer system.

As will be appreciated, the dialysis base unit 400 and the hyperthermia base unit 500 can be used together to conveniently provide a whole-body hyperthermia system as illustrated in FIGS. 1 and 2, by connecting the inflow tubes 136 and 138 and blood effluence of the dialysis circuit (located in the dialysis base 400) to appropriate the connections of the high circulation hyperthermia circuit (located in the hyperthermia base unit 500). In addition, a communication bridge can be established between the computers on the two base units using a conventional cable.

As shown in Figure 1, for whole body hyperthermia, the blood side of the dialysis apparatus is coupled to the hyperthermia circuit in which the relatively high blood flow rates are maintained with a roller pump. Such high proportions of blood flow can cause the results of increased tension in the restricted movement of the membranes, thus reducing the mixture of the absorbent otherwise provided by the expansion and contraction of the yielding membranes. The coupling of the dialysis circuit as shown in Figure 2, with a blood inflow line 136 that is generally connected downstream of the blood effluent line 138 and is preferably located on the opposite sides of the roller pump 120 within the system, the deadly increased tension of the membrane is minimized or avoided. The prevention of the concentrations or solutions located of the components within the absorbent suspension is carried out in this way, improving the effectiveness of the treatment.

Membranes that are used for absorbent-based dialysis preferably allow the passage of soluble chemicals under about 5,000 molecular weight. The first function of hemodialysis with absorbent suspensions is to correct abnormalities in blood cationic electrolytes that include potassium, sodium, calcium, magnesium and hydrogen ions (blood pH). This is carried out by loading the cation exchanger in the absorbent with sufficient amounts of cations to be in equilibrium with the desired (normal) blood levels. If the blood concentration of a particular cation is lower than the equilibrium level, the cation will be released from the cation exchanger. If the blood concentration is above normal, the cation will be absorbed by the cation exchanger.

There are many dialyzer membranes that are known for use in dialyzing body fluids such as blood, and these membranes can be used with the absorbent suspension as if the absorbent suspension were a simple dialysis solution. An appropriate membrane of this type of cellulosic membrane is composed of regenerated cuproammonium cellulose (Cuprophan).

In a preferred dialysis circuit, the dialyzer can be a 1.6 m2 parallel plate-screen dialyzer COBE having the dialysis membranes composed of regenerated cuproammonium cellulose (Cuprophan) and having a functional molecular weight cut-off of about 3000 daltons, that is, only molecules of around 3000 daltons or less will pass through the membrane.

The absorbent suspension used in the invention generally works as follows. When blood is opposed to the absorbent suspension, separated only by the dialysis membrane, diffusion causes many chemicals to pass from the blood to the absorbent suspension on the other side of the membrane. Depending on the agglutination characteristics of the absorbers, some chemicals remain at a low concentration in the absorbent suspensions (and therefore are effectively removed from the blood) and others reach concentrations similar to those in the blood (and therefore are not removed). of the blood) . The inclusion of certain chemicals in the composition of the absorbent suspension can partially saturate the binding sites of the absorbent, and cause the return of those chemicals to the blood during the treatment. Thus, the absorber suspension can be tailored to remove very specific compounds from the blood, without removing others.

The absorbent suspensions which are used in the invention generally include surface activated adsorbent agents, physiological electrolytes and macromolecular flow inducing agents. In general, these components are present in effective amounts to carry out the desired removal of the substances from the electrolyte balance in the patient's blood while maintaining the stability and fluidity of the absorbent suspension. The activated surface adsorbent agent is usually activated carbon , prefey with an average particle diameter not exceeding about 100 microns. Even more prefey, the average particle diameter does not exceed 50 microns. Macromolecular flow-inducing agents such as glycol derivatives help maintain the flow properties and stability of particle suspensions.

Electrolytes in the absorbent suspension typically include one or more of the electrolytes selected from sodium, chlorine, bicarbonate, potassium, calcium, magnesium or any other electrolyte to be regulated in the patient.

Absorber suspensions may also include ion exchange substances to agglomerate ions, such as ammonium, which may appear in the patient's blood. Many suitable ion exchangers include polymeric ion exchangers, for example polystyrene sulfonate, and the minerals are known in the art and can be used in the present invention. When included, the ion exchanger is prefey a cation exchange resin, which is charged in the desired manner with one or more cations representing the electrolytes that occur in the blood. For example, to cite, sodium polystyrene sulfonate has been a preferred cation exchange resin. For use in conjunction with whole-body hyperthermia, cation exchangers are massively charged preferentially with Ca, K and Mg ions at the start of hyperthermia in an amount to be in substantial equilibrium with the normal blood concentration of these cations.

The surface adsorbing agent, electrolytes, flow-inducing agents and any other additives will usually comprise about 5% to 30% of the weight of the formulation of the absorbent suspension as an integer, with the surplus being water. Typically, the solid absorbent will comprise about 2% to 25% of the weight of the suspension formulation, and the electrolytes will comprise about 1% to 5% of the weight of the suspension formulation. Within these parameters, more preferred absorbent suspension formulations comprise about 2% to 20% of the weight of the activated surface adsorbent agent, above about 10% of the ion exchanger weight and above about 1% of the weight of the ion exchanger. weight of active surface or flow agent such as a polyol and / or polyvinylpyrrolidone (PVP).

According to one aspect of the invention, the absorbent suspension also includes solid or precipitated calcium phosphate, which is used to assist in the control of calcium and phosphate levels in the patient's blood. Control the phosphate concentration of. Plasma is somehow more complicated than controlling the other blood components. In the body, the calcium and phosphate concentrations are determined by their mathematical product. When the concentration of calcium in the blood plasma increases, calcium phosphate precipitates in the bones and the plasma phosphate level falls. Conversely, when the plasma calcium concentration decreases, calcium phosphate is solubilized and plasma phosphate levels increase. In the present invention, the calcium phosphate precipitated in the absorbent suspension mimics the calcium phosphate system of the body, carrying out the control of calcium and phosphate levels. Thus, when the blood phosphate level decreases, the calcium phosphate in the absorbent suspension dissolves and the phosphate is released into the blood. Conversely, if the level of blood phosphate decreases, the phosphate can be removed from the blood by the precipitation of calcium phosphate in the absorbent suspension. The calcium loaded cation exchanger moderates the calcium concentration during these changes in phosphate concentration. Accordingly, the absorbent suspension can be optimized to release more or less phosphate to a patient during the treatment by adding, respectively, more or less calcium in the precipitation step of the calcium phosphate in the preparation of the absorbent pension. Because changes in the concentration of calcium and phosphates in the blood are not likely to be quantified in the same way during hyperthermia, the 10% calcium chloride solution can also be stored appropriately for separate infusion into the returning blood. to the patient, as needed.

Preferred absorbent suspensions including precipitated calcium phosphate are carefully prepared to ensure that the calcium phosphate precipitate has the maximum surface area to liberate or adsorb calcium phosphate; forming the precipitate on the surface of the coal or other surface adsorbing agent that accomplishes this goal. A preferred process for preparing the absorbent suspension includes adding sterile water for irrigation to a container (e.g., an absorbent bag as described above) which contains activated carbon powder and flow-inducing agents. The electrolyte suspensions of calcium chloride and sodium chloride, and a solution of disodium phosphate, are then added to the container. The mixture is then stirred, for example by stirring the absorbent bag, and the cation exchange resin (recharged with sodium, calcium, magnesium, and potassium) is added. The contents are stirred again, and the sodium bicarbonate powder is then added, followed by further stirring. This process effectively prepares an absorbent suspension containing precipitated calcium phosphate, and which is essentially free of limestone.

In such an absorbent system, the surface adsorbing agent provides the surface area in which substantial amounts of calcium phosphate can be supported, and thus, in most absorbent suspensions calcium phosphate will be supported by the adsorbing agent of surface as well as in the mix generally.

In the present invention, the cation exchanger of the preferred absorbent suspension also has some buffering effect, to assist in maintaining normal blood pH.

An exemplary absorbent suspension contains: 140 grams of activated carbon powder; 22.1 grams of NaHP04 * 7H20 and 3.0 grams of CaCl * 2H20 (added together with the carbon suspension); 200 grams of cation exchange resin Amberlite IRP-69 loaded with blood equilibrium levels of Na, Ca, Mg and K ions; 13.0 grams of NaCl; 15.1 grams of NaHCO3; and 1.5 grams of each of glycol derivative and PVP to improve the stability and flow properties of the absorbent suspension. This is just an example and is not considered to be limited.

During hyperthermia, other toxins may be involved, due to decreased liver or kidney function. The surface adsorbing agent (e.g., carbon) and the cation exchangers in the absorbent suspension will remove many of these toxins, including: creatinine; aromatic amino acids; gammaamino butyric acid; phenols, mercaptans; ammonium ions; nitric oxides; and various vasodilating hormones. Naturally, the absorbent suspension is not considered to remove proteins, intercellular messengers or cells, although to the extent that bound albumin toxins can be dissociated from albumin, they can also be transferred through the membranes and bound by the absorbents. in the suspension.

In addition, during hyperthermia, additional calcium chloride can be infused to the patient (e.g., via a blood return line of the apparatus) as is necessary to maintain the normal blood calcium concentration. Also, plasma phosphate levels can be analyzed during hyperthermia and disodium phosphate added to the suspension-absorber as many times the patient's plasma phosphate levels fall downstream from normal. This addition can be made by using a solution of disodium phosphate and sodium bicarbonate, for example.

More preferably, the absorbent suspension is maintained at moderate temperatures such that the blood tubing, dialyzer and absorbent suspension containers touch the blood only at moderately elevated temperatures. Temperatures of 42 ° C are appropriate for these purposes, although higher temperatures, for example above 48 ° C or more, can also be used. The heat exchanger and the tubing that returns the blood to the patient will touch the blood at temperatures of around 47 ° to 48 ° C in the preferred processes. The same components are used in open heart surgery to warm patients and safe contact with blood at these temperatures has been thoroughly documented. Prior to the treatment of hyperthermia according to the invention, patients are screened to highlight heart disease; highlight lung disease (including Kaposi's pulmonary sarcoma if one or more lesions are larger than a certain size); pregnancy; a Karnofsky brand of less than 60%; a hematocrit of less than 30 ml .; hemoglobin less than 10%; active opportunistic infection; bleeding disorders; or diabetes Mellitus. Any of the above conditions of careful consideration of the risks against the benefits in the practice of the present technique as much as the patient can tolerate. Prehyperthermia evaluation requires a routine physical examination and history, routine laboratory studies, chest X-rays, urinalysis, electrocardiogram and pulmonary function studies, special studies include the P-24 antigen level test; the reverse transcriptase assay; cultures of human immunodeficiency virus; the quantitative analysis of lymphocytes and the profile of the thyroid.

Hyperthermia protocols can be conducted by using conscious sedation, analgesics, or anesthetics (and intubation). The use of sedative amounts - as distinguished from the amounts of thiopenal sodium anesthetic - can be used as well. A commercially available exemplary analgesic is Sublimaze (fetranyl citrate, or N- (l-phenethyl-4-piperidyl) propionanilide citrate), a synthetic narcotic analgesic. An exemplary conscious sedation induction drug is Propofol, which is a sedative (or hypnotic agent) widely used in out-of-patient applications. The chemical formula for Propofol is 2,6-diisopropylphenol; The trade name is Diprivan inion. These drugs are only exemplary, and the invention is not considered as a limitation for these illustrative medicaments. (However, Versed (midazolam hydrochloride, or 8-chloro-6- (2-fluorophenyl) -l-methyl-4H-imidasol [-1,5-a] [1,4] benzodiazepine hydrochloride), a short-acting benzodiazepine central nervous system depressant, should not be used, and other benzodiazepine derivatives are contraindicated in the same way Midazolam hydrochloride and benzodiazepine derivatives are generally biologically incompatible with hyperthermia: while the Versed demonstrates typical pharmacological activity (including reversibility) during the present procedure, the combination of hyperthermia with the body biochemical incident of hyperthermia causes disastrous central nervous system trauma (and possible death) 6 hours after the procedure is completed) . With the patient sedated but still responsive, the activity of the central nervous system can be monitored easily during hyperthermia treatment. When absorbent-based hemodialysis is used, the absorbent clears about 50% of the blood flow sedative.

Therefore, administration of approximately twice the dose of sedative will give the same sedative effect as when dialysis is not used.

The modification of the absorbent suspension can also be used to control other blood chemistries. For example, the absorbent suspension may be loaded with a sedative such as thiopental sodium to be in equilibrium at a level that causes sedation. The blood level of the patient will then be rapidly reached at this level during the hyperthermia treatments of the invention. Additional sedation can be carried out to administer a thiopental sodium inion to the blood; then the pre-charged absorbent suspension would not remove significant amounts of the drug during the treatment. Other agents to increase the hyperthermia treatment could be loaded into the absorbent suspension and sent during the treatment, to maintain a reasonable constant blood concentration of the agents.

Because of the natural drastic reduction of the patient's carbohydrates and fat stores, these substances must be administered during and / or after treatment to ensure that these precursors are adequately available to marginally compete for metabolic symptoms. Hemodialysis maintains phosphate and calcium levels during treatment-levels that would otherwise fall as a result of hyperthermia-especially when the acid / bicarbonate water is used as the dialysate solution. Maintaining arterial oxygen tensions as high as possible during hyperthermia by using 100% oxygen for ventilation must meet the need to maintain more than normal the blood and tissue oxygen tensions that are needed by the consumption of oxygen from increased hyperthermia.

While the invention has been described in detail in the above passages, the same is considered illustrative and not restrictive in character, it being understood - that only the preferred modalities have been shown and described and that all the changes and modifications that come within the spirit of the invention are desired to be protected.

References The following references, and all other publications cited herein, are incorporated herein by reference as if each had been incorporated individually as a reference and set forth fully hereinbelow. 1. Bull JMD. An update of the anticancer effects of a combination of chemotherapy and hyperthermia. Cancer Res 1984; 44: 487. 2. Robins Hl, Dennis WH. Role of whole body hyperthermia in the treatment of neoplastic desease: its current status and future prospects. Cancer Res 1984; 44: 487. 3. Hornback NB. Historical aspects of hyperthermia in cancer therapy. Radiologic Clinics of North America 1989; 27: 481-488. 4. Cavaliere R, Ciocatto EC Giovanella BC, et al. Selective heat sensitivity of cancer cells: Biochemical and clinical studies. Cancer 1967; 20: 1351.

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Yatvin MB, Cramp WA. Role of cellular membranes in hyperthermia: some observations and theories reviewed.

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Radio Clin N Amer 1989; 27: 603-610. 27. Yatvin MB, Stowell MHB, Steinhart CR. Sheding Light on the Use of Heat to Treat HIV Infections. Oncology 1993; 50: 380-389. 28. Yatvin MB. An Approach to AIDS Therapy Using Hyperthermia and Membrane Modification. Medical Hypotheses 1998; 27: 163-165. 29. Alonso K, Pontiggia P, Sabato A, Calvi G, Curto FC, Bartolomei E, Nardi C, Cereda P. Systemic Hyperthermia in the Treatment of HIV Related Disseminated Malignancy, Presented at the 10th Annual Meeting, American Soc. Clin. Hyperthermic Oncology, Oct. 1993, Memphis, TN.

. US Patent No. 5,277,820. 31. US Patent No. 5, 476,444.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (1)

1. Claims A method for carrying out the hyperthermia of the entire body of a patient, characterized in that it comprises: circulating the blood of said patient through a high circulation hyperthermia circuit at a rate of at least 1500 ml / min. , said hyperthermia circuit includes a blood access line to draw the patient's blood, a pump, a heat exchanger to heat said blood to a temperature of at least 40 ° C, and a blood return line to return said blood to said patient after heating it in said heat exchanger; diverting a portion of said circulating blood within said high circulation hyperthermia circuit to a low circulation dialysis circuit, and circulating said blood in said low circulation dialysis circuit at a rate of 200 to 800 ml / min., said low circulation dialysis circuit includes: a blood inflow line having a first end that is connected to said hyperthermia circuit, for diverting blood to said dialysis circuit from said hyperthermia circuit; a dialyzer that has a blood side and an absorbent side separated by the membranes of 5 dialysis, said membranes are formed elastically; the means for applying alternating negative pressure and positive pressure on said absorbent side of said dialyzer; 10 a blood inlet orifice for said blood side of said dialyzer, a second end of said blood inflow line is connected to said blood inlet orifice; a blood outlet hole from that side 15 blood of said dialyzer; a line of blood effluence having a first end connected to said blood outlet orifice and a second end connected to said hyperthermia circuit; 20 an absorbent circuit for circulating an absorbent suspension through said absorbent side of said dialyzer; and wherein during the operation of said high circulation hyperthermia circuit and said low circulation dialysis circuit, said dialyzer membranes expand and compress in response to said alternating negative pressure and positive pressure on said absorbent side of said dialyzer, for circular and agitating an absorbent suspension on said absorbent side wherein the effective mixture of said absorbent suspension is maintained. The method of claim 1, characterized in that it also includes: heating said absorbent suspension within a heat exchanger to decrease the transfer of heat from the blood to the absorbent suspension. The method of claim 2, characterized in that it includes circulating the blood within said circuit of high circulation hyperthermia at a rate of 1500 ml / min. up to 4000 ml / min. The method of claim 1, characterized in that said blood inflow line is connected to said high circulation hyperthermia circuit in a site downstream of said line of blood effluence. The method of claim 4, characterized in that said blood inflow line and said line of blood effluence are connected to said hyperthermia circuit on opposite sides of said pump. The method of claim 4, characterized in that said absorbent suspension includes precipitated calcium phosphate, water, and a surface adsorbing agent in the form of particles. The method of claim 6, characterized in that said surface adsorbing agent is carbon. The method of claim 7, characterized in that said expansion and contraction of said membranes causes blood circulation in said low circulation dialysis circuit. An apparatus for use in the treatment of a patient's entire body hyperthermia, characterized in that it comprises: a high circulation hyperthermia circuit equipped to circulate blood therethrough at a rate of at least 1500 ml / min. said high circulation hyperthermia circuit includes a blood access line to draw a patient's blood, a pump, a heat exchanger to heat the blood to a temperature of at least 40 ° C, and a line of blood return to return the blood to the patient after heating it inside the heat exchanger; a low circulation dialysis circuit equipped to circulate the blood therethrough at a rate of 200 to 800 ml / min., said low circulation dialysis circuit is coupled to the hyperthermia circuit and is effective to bypass said hyperthermia circuit a portion of the blood circulating therein, said low circulation dialysis circuit includes: a blood inflow line having a first end connected to the hyperthermia circuit, to divert blood to said dialysis circuit from said hyperthermia circuit; a dialyzer having a blood side and an absorbent side that are separated by the dialysis membranes, said membranes are elastically formed; the means for applying the alternating negative pressure and positive pressure on said absorbent side of said dialyzer; a blood inlet orifice to said blood side of said dialyzer, a second end of said blood inlet line which is connected to said blood inlet orifice; a blood outlet orifice of said blood side of said dialyzer; a line of blood effluence having a first end connected to said blood outlet orifice, and a second end connected to said hyperthermia circuit; an absorber circuit for circulating an absorbent suspension through said absorbent side of said dialyzer; and wherein said apparatus is configured such that during the operation of the high circulation hyperthermia circuit and the low circulation dialysis circuit, said dialyzer membranes expand and compress in response to said alternating negative pressure and positive pressure on said absorbent side. of said dialyzer, for circulating and agitating an absorbent suspension within said absorbent side by means of which the effective mixture of said absorbent suspension is maintained. . The apparatus of claim 9, characterized in that it also includes: a heat exchanger within the dialysis circuit, for heating the absorbent suspension. . The apparatus of claim 10, characterized in that the blood inflow line is connected to the high-circulation hyperthermia circuit at a site downstream of the blood effluent line. . The apparatus of claim 11, characterized in that the blood inflow line and the blood efflux line are connected to the hyperthermia circuit on opposite sides of the pump. . The apparatus of claim 11, characterized in that the absorbent suspension includes precipitated calcium phosphate, water, and a surface adsorbing agent in the form of particles. . The apparatus of claim 13, characterized in that said surface adsorbing agent is carbon. . The apparatus of claim 14, characterized in that said expansion and contraction of said membranes causes the circulation of said blood within said low circulation dialysis circuit. . A disposable package for use with a dialysis instrument, characterized in that it comprises: a package mounting member; and a variety of components attached to the package mounting member, including: a dialysis plate having a blood side with a blood inlet orifice and a blood outlet orifice, and an absorbent side with an absorbent inlet orifice and an absorbent outlet; a blood inflow tube communicating with the blood entry orifice of the dialysis plate to pass blood from a patient to the blood side of the dialyzer; a blood effluent tube communicating with the blood outlet orifice of the dialysis plate, to draw blood from the blood side of the dialyzer; the absorbent circulation tubes communicating with the absorbent side of the dialyzer by means of the absorbent inlet orifice and the outlet of the absorbent, to circulate the absorbent through the absorbent side of the dialyzer; a heat exchanger by flow communicating with said absorbent circulation tubes, to heat the absorbent flowing through the heat exchanger. . The disposable package of claim 16, characterized in that it also comprises, attached to said package assembly member: an accumulator reservoir communicating with said absorbent circulation tubes, said accumulator reservoir is operated to, in turn, accumulate and expel "the absorbent in response to the positive pressure and the negative pressure that is applied alternately to the storage tank. . A process for preparing an absorbent suspension, characterized in that it comprises: combining an aqueous solution having dissolved calcium ions with an aqueous solution having dissolved phosphate ions, wherein said combination is in the presence of an activated surface adsorption agent for to form precipitated calcium phosphate in both, in the adsorption agent and in the suspension freely. . The process of claim 18, characterized in that it comprises: (a) combining water, activated carbon powder and a flow inducing agent; (b) adding the separate solutions containing, respectively, dissolved calcium chloride and dissolved disodium phosphate, to the product of step (a); (c) stirring the product of step (b); (d) add a cation exchange resin loaded with sodium, calcium, magnesium and potassium to the product of step (c); and (e) stirring the product of step (d); (f) adding sodium bicarbonate powder to the product of step (e); and (g) stirring the product of step (f). . A dialysis system, characterized in that it comprises: a base unit equipped with: a source of positive pressure and negative pressure; a heating element; and the receiving means for receiving a heat exchanger in heat exchange relationship with the heating element; and a disposable package for use with said base unit, which includes: a package assembly member; a dialysis plate mounted on said package mounting member, said dialyzer having a blood side with a blood inlet orifice and a blood outlet orifice, and an absorbent side with an absorbent inlet orifice and an outlet orifice absorbent; a blood inflow tube communicating with the blood entry orifice of the dialysis plate, to pass the blood of a patient to the blood side of the dialyzer; 5 a blood effluent tube communicating with the blood outlet orifice of the dialysis plate, to draw blood from the blood side of the dialyzer; the absorbent circulation tubes that 10 communicate with the absorbent side of the dialyzer by means of the absorbent inlet orifice and the outlet of the absorbent, to circulate the absorbent through the absorbent side of the dialyzer; 15 an accumulator reservoir mounted on said package assembly member, said accumulator reservoir communicating with said absorbent circulation tubes, said accumulator reservoir is alternately operated to accumulate and expel the accumulator. The absorbent suspension in response to the positive pressure and negative pressure applied alternately to the accumulator reservoir which is connected to said source of positive pressure and negative pressure of said base unit; a heat exchanger by flow communicating with said absorbent circulation tubes, 5 to heat the absorbent flowing through the heat exchanger; said heat exchanger coperating with said receiving means of said base unit to removably place the heat exchanger in relation to 10 heat exchange with the heating element of said base unit.