CA1144841A - Method and apparatus for effecting hyperthermic treatment - Google Patents
Method and apparatus for effecting hyperthermic treatmentInfo
- Publication number
- CA1144841A CA1144841A CA000399707A CA399707A CA1144841A CA 1144841 A CA1144841 A CA 1144841A CA 000399707 A CA000399707 A CA 000399707A CA 399707 A CA399707 A CA 399707A CA 1144841 A CA1144841 A CA 1144841A
- Authority
- CA
- Canada
- Prior art keywords
- liquid
- flow
- patient
- blood
- heat exchanger
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Landscapes
- External Artificial Organs (AREA)
Abstract
ABSTRACT
Apparatus for providing a constant flow of temperature controlled liquid into and out of a heat exchanger in heat exchange relation to a flow of blood through said heat exchanger which forms a part of a systemic extracorporeal flow circuit of a human patient for systemically treating the patient hyperthermically to retard the growth of cancer cells in the patient. The apparatus comprises first and second reservoirs for respectively containing first and second bodies of liquid; first and second pumps for pumping liquid from said first and second reservoirs, respectively; means for directing a predetermined constant flow of liquid from said pumps into said heat exchanger;
means for directing the liquid from said heat exchanger to said reservoirs; means for maintaining the liquid in said first reservoir at a substantially constant elevated temperature of approximately 45°C; means for maintaining the liquid in said second reservoir at a substantially constant reduced temperature of approximately 30°C; and means for varying the amount of liquid from said first pump directed into said liquid flow directing means from 0 to 100% while proportionately varying the liquid from said second pump directed into said liquid flow directing means from 100% to 0 and while maintaining the constant flow as aforesaid.
Apparatus for providing a constant flow of temperature controlled liquid into and out of a heat exchanger in heat exchange relation to a flow of blood through said heat exchanger which forms a part of a systemic extracorporeal flow circuit of a human patient for systemically treating the patient hyperthermically to retard the growth of cancer cells in the patient. The apparatus comprises first and second reservoirs for respectively containing first and second bodies of liquid; first and second pumps for pumping liquid from said first and second reservoirs, respectively; means for directing a predetermined constant flow of liquid from said pumps into said heat exchanger;
means for directing the liquid from said heat exchanger to said reservoirs; means for maintaining the liquid in said first reservoir at a substantially constant elevated temperature of approximately 45°C; means for maintaining the liquid in said second reservoir at a substantially constant reduced temperature of approximately 30°C; and means for varying the amount of liquid from said first pump directed into said liquid flow directing means from 0 to 100% while proportionately varying the liquid from said second pump directed into said liquid flow directing means from 100% to 0 and while maintaining the constant flow as aforesaid.
Description
~ 8 This invention relates to hyperthermia, and - more particularly to improved method and apparatus for effecting hyperthermic treatment specifically for the purpose of re~arding the grow~h of growing cancer cells.
5 There is mountinq evidence that the application o heat within the range of 41.5C to 43.0C can be used effectively to retard the growt~ of cancer cells.
Recent interest in this subject has intensified to the extent that an International Symposium on Cancer Therapy by Hyperthermia and Radiation was held in ~'.
8'~
Washington, D.C. in April of 1975 under the joint sponsorship of The National Cancer Institute of the ~.S. Public Health Service and The American College of Radiology, in cooperation with the University of Maryland School of Medicine.
The Proceedings of this symposium are transcribed in a three hundred and four page volume containing many articles dealing with varied aspects of hyperthermia and cancer. These articles and the cited references thereof represent a comprehensive listing of available literature publications.
Other articles of interest since 1975, the date of the symposium are as follows:
Hofer, K.G., Choppin, D.A. and Hofer, M.G.: Effect of Hyperthermia on the Radiosensitivity of Normal and Malignant Cells in Mice. Cancer, 38:279, 1976.
Larkin, J.M., Edwards, W.S. and Smith, D.E.: Total Body Hyperthermia and Preliminary Results in Human Neoplasmus. Surg.
~orum, 27:121, 1976.
Wheldon, T.E.: Exploiting Heat Sensitivity of Leukemic Cells. Lancet, 1:1363, 1976.
Hyperthermia in the Treatment of the Cancer Patient.
Cancer, 37:2075-2983, 1976.
Much of the above literature includes reports to the effect that hyperthermia utilized in a range of f~
temperatures between 41.5C and 43~C causes specific anti-cancer effects when used either as a primary or ad~uvant agent against a wide spect~um of malignant diseaseO
The literature indicates that hyperther~ia has been shown to induce C~totoxicity in sarcorna and melanoma cells in tissue culture (Stehlin et al.) and strongly enhance anti-tumor effects of irradiation in vivo of L-1210 and Erlich ascites cells (~ofer et al.). The additlon of hyperthermia to regional perfusion chemotherapy of melanoma resulted in an increased incidence of tumor control and patient survival without increased adverse'effects (Stehlin et al.). Employed as'a s~stemic a~ent, hyperthermia induced objective regression in 13 of 18 (70~6) patients with disseminated disease resistant to other therapy, six of whom were survivin~ 11 to 22 months post treatment (Larkin et al.).
Experimental work undertaken in contemplation of the present invention indicates the effectiveness of hyper-thermia against systemic disease may be even greater than indicated by Larkin et al. Although the levels of hyper-thermia employed by Larkin et al. (approximately 42.0C)were adequate, the period of application was only five hours.
Moreover, the procedures undertaken to effect the hyper-thermic treat,ment would indicate that a stable temperature level of 42C was not maintained systemically for five hours. Larkin et al. employed insulaLing sheets and liquid ~ L~
heating blankets surrounding the patients for heat appli-cation. Due to the relatively poor conductivity of the ski and the further adverse effect to conductivity of profuse sweating, elevated systemic temperatures cannot be rapidly 5 induced. Moreover, this adverse conductivity condition can be expected to maintain the existence of large tem-perature differentials throughout the system. For example~
blanket control temperaturPs of 120F (48.89C) were utilized, a lethal systemic level.
Based upon the analysis of the type of problems enunciated above which are evident rom the systemic pro-cedures and devices heretofore proposed and utilized, a set of desirable criteria for method and devices for effecting ; hyper.hermic treatment can be listed as follows:
1. Systemic temperatures of 41.5 to 43.0C
induced.
5 There is mountinq evidence that the application o heat within the range of 41.5C to 43.0C can be used effectively to retard the growt~ of cancer cells.
Recent interest in this subject has intensified to the extent that an International Symposium on Cancer Therapy by Hyperthermia and Radiation was held in ~'.
8'~
Washington, D.C. in April of 1975 under the joint sponsorship of The National Cancer Institute of the ~.S. Public Health Service and The American College of Radiology, in cooperation with the University of Maryland School of Medicine.
The Proceedings of this symposium are transcribed in a three hundred and four page volume containing many articles dealing with varied aspects of hyperthermia and cancer. These articles and the cited references thereof represent a comprehensive listing of available literature publications.
Other articles of interest since 1975, the date of the symposium are as follows:
Hofer, K.G., Choppin, D.A. and Hofer, M.G.: Effect of Hyperthermia on the Radiosensitivity of Normal and Malignant Cells in Mice. Cancer, 38:279, 1976.
Larkin, J.M., Edwards, W.S. and Smith, D.E.: Total Body Hyperthermia and Preliminary Results in Human Neoplasmus. Surg.
~orum, 27:121, 1976.
Wheldon, T.E.: Exploiting Heat Sensitivity of Leukemic Cells. Lancet, 1:1363, 1976.
Hyperthermia in the Treatment of the Cancer Patient.
Cancer, 37:2075-2983, 1976.
Much of the above literature includes reports to the effect that hyperthermia utilized in a range of f~
temperatures between 41.5C and 43~C causes specific anti-cancer effects when used either as a primary or ad~uvant agent against a wide spect~um of malignant diseaseO
The literature indicates that hyperther~ia has been shown to induce C~totoxicity in sarcorna and melanoma cells in tissue culture (Stehlin et al.) and strongly enhance anti-tumor effects of irradiation in vivo of L-1210 and Erlich ascites cells (~ofer et al.). The additlon of hyperthermia to regional perfusion chemotherapy of melanoma resulted in an increased incidence of tumor control and patient survival without increased adverse'effects (Stehlin et al.). Employed as'a s~stemic a~ent, hyperthermia induced objective regression in 13 of 18 (70~6) patients with disseminated disease resistant to other therapy, six of whom were survivin~ 11 to 22 months post treatment (Larkin et al.).
Experimental work undertaken in contemplation of the present invention indicates the effectiveness of hyper-thermia against systemic disease may be even greater than indicated by Larkin et al. Although the levels of hyper-thermia employed by Larkin et al. (approximately 42.0C)were adequate, the period of application was only five hours.
Moreover, the procedures undertaken to effect the hyper-thermic treat,ment would indicate that a stable temperature level of 42C was not maintained systemically for five hours. Larkin et al. employed insulaLing sheets and liquid ~ L~
heating blankets surrounding the patients for heat appli-cation. Due to the relatively poor conductivity of the ski and the further adverse effect to conductivity of profuse sweating, elevated systemic temperatures cannot be rapidly 5 induced. Moreover, this adverse conductivity condition can be expected to maintain the existence of large tem-perature differentials throughout the system. For example~
blanket control temperaturPs of 120F (48.89C) were utilized, a lethal systemic level.
Based upon the analysis of the type of problems enunciated above which are evident rom the systemic pro-cedures and devices heretofore proposed and utilized, a set of desirable criteria for method and devices for effecting ; hyper.hermic treatment can be listed as follows:
1. Systemic temperatures of 41.5 to 43.0C
induced.
2. Selected temperatures obtained within one hour.
3. Hyperthermia maintained for 24 to 48 hours.
4. Fine temperature control and potential auto-regulation of temperature possible.
5. A rapid cooling as well as a heating effect readily achieved.
6. General anesthesia unnecessary or required for only a brief period.
7. Patients undergoin~ hyperthermic treatment maintained in ~ settin~ conduct:ive ~o conventional care.
8. Hyperthermia possible in diverse settings such as radiation therapy or isolation areas.
~. Repetitious induction of courses of hyperthermia over a several day period possible.
10. Hyperthermia induced with reasonable safety in neutropenic or thrombocytopenic patients.
It is an object of the present invention to provide a method and apparatus for effecting hyperthermic treatment whi~h will meet the above-listed desirable criteria. In accordance with the procedural principles of the present invention, this objective is obtained by establishing a sterile extracorporeal flow path for blood having an inlet, an outlet and a temperature control zone therebetween, establishing communication of the inlet of the extxacorporeal flow path with the patient's bloodstream so that blood can be withdrawn and supplied to the extracorporeal flow path without adversely affecting the blood depleted areas from which the blood is withdrawn, establishing co~lunication of the outlet of ~he extracorporeal flow path with the patient's blo~dstream so that blood flowing from the extracorporeal flow path is returned to the bloodstream in such a way as to be distributed systemically, pumping blood withdrawn from the patl~nt's bloodstream along the extracorporeal flow path through the temperature control zon~ at a con~rolled rate and returning the same to the patient's bloodstream to be distribute~ systemically, as a~oresaid, con~rolling the temperature of the blood flowing along ~he extracorporeal flow path through ~he temperature control zone for an initial period during which the temperature level of the blood within the zone is raised without subjecting the s~ne to localized temperatures in e~cess of approximately 45 C so that -the systemic distribution of the returned blood gradually in-creases the core temperature of the patient's body to a generally stable temperature condition at a level of ap-proximately 41.5C, but not higher than approximately 42.5C, and maintaining control of the temperature o~ the blood flowing along the extracorporeal flow path through the temperature con~rol zone at the generally stable ~emperatur~
condition for a second time period sufficient to retard the growth of cancer cells.
It is recognized that extracorporeal heating of blood for anti-cancer purposes has been undertaken in regional perfusion practices. Procedures of this type are discussed by Cavaliere et al. and Stehlin and are to be distinguished from the systemic hyperthermia induced by the present pro-ceduresl as indicated above. In these regional perfusion practices, the main femoral artery and vein are temporarily occluded by vascular clamps or tourniquets and a closed extracorporeal sys~em is established, solely within the femoral extremity. In this extracorporeal circuit, heat is applied as an adjunct to the other treatments, such as chemotherapy, Which arc utilized in ~he regional circulating S system. This system necessitates the utilization of oxy-genating equipment of a type similar to that used in open heart surgery. As is evident rom the kno~m time limi-tations imposed upon open heart surgery by virtue of the utili~ation of oxygenating equipment, the time frame within which such combined oxygenating and heating treatments can be continued even on a regional basis without imposing at least a percentile permanent damage to the blocked emoral areas of the patient is quite limited.
Pettigrew, in referring to these regional per-usion practices as background to his preferred co~bined hot wax bath and heated respiratory gases procedure fo~ inducing total body hyperthermia, appears to consider the regional perfusion procedures to be applicable to induce both reg-ional hyperthermia as well as total body hyperthermia, perhaps by analogy to the open heart ex~racorporeal shunt-ing. (Induction of Controlled Hyperthermia in Treatmen~ of Cancer, Henderson, M.~. and Pettigrew, R.T. ~ancet, 1:1275, 1971 and Cancer Therapy by Whole Body Heating, Pettigrew, R.T. Proceedings, p. 282). The Pattigrew Lancet article ~ 25 characterized the re~ional perfusion -~ork of Cavaliere et ; al. ("Selective Heat Sensiti~rity of Cancer Cells", Cancer, 1967, 20-1351) as having "achieved ~ery sa~isfactory tem-peratures in the malignancies using an arteriovenous shunt and a heat exchanger, but since thi~ requires surgery it cannot be repeated indefinitely and can only be applied easily to p~ripheral malignancy."
It is of significance, however, to note that the recognized practitioners of regional perfusion, namely Cavaliere e~ al. and Stehlin et alO, have both indicated that the regional perfusion practices utilizing a shunt and an extxacorporeal heat exchanger are limited to regional extremity applications and both have utilized other pro-cedures for inducing total body hyperthermia.
On page 135 of the cancer article Cavaliere et al.
state:
"I'his method of high temperature treatment obviously has limitations and at present is indicated in patients with primary or recurrent malignant tumors of the limbs for whom the only alternative therapy would be amputation, which often does not prevent metastases.
... It is evident that future progress in this field will come from total-body high-temperature treatment. We are now in the process of developing tecn-niques towards this end, which are considerably different from those now being used."
The last paragraph of the Stehlin article in the Proceedings publication, page 271, sets forth the following:
_ 9 _ - \~
8~
"As a result of our experience with regional perfusion with heat, we are currently, and have for the past five years been investigating the possi-bility that systemic hyperthermia induced with bacterial toxins will enhance the antitumor effects of various chemotherapy agents on melanomas and sarcomas."
A pre~erred minimum flow rate in accordance with the principles of the present invention, is approximaterly 1 liter per minute. Such flow rate can be achieved by following the procedu.res of the present invention without affecting the femoral areas from which the blood is withdrawn. Thus, with the present procedure, there is no systemic femoral isolation as by a clamp or tourniquet occludin~ the main femoral artery and vein, but rather, a preferred procedure is to effect communication of the extracorporeal flow path between the femoral artery and the femoral vein through a side wall of each, so that systemic circulation in the femoral areas can ; continue. The pumping procedure undertaken to effect flow of the withdrawn blood through the temperature control zone of the extracorporeal flow path achieves an adequate controlled flow rate while permitting adequate systemic circulatory flow through the femoral areas sufficient to prevent the type of adverse effects over extended periods of time which will occur in the a~oresaid regional perfusion techniques.
:.
: - 10 -The present invention also contemplates an improved implantable device for facilitating the con-nection of the extracorporeal flow ~ircuit with the blood system of the patient. Devices for establishing an extra-corporeal blood flow path for the purposes of kidney di-alysis as distinguished from systemic hyperthermic treat-ments are well-known. These devices, known as shunts, are made commercially available by several manufacturers.
Typically, these shunt devices are implanted in the patient and include tubes which extend extracorporeally. These : exteriorized tubes have caused considerable difficulty.
A good discussion o the difficulties encountered in the practices relating to such exteriorized shunt de~
vices is contained in U.S. patent No. 3,998,222. In the opening paragraphs of the specification, one type of shunt device is descxibed as a U-shaped loop, one end of which is connected to a vein and the other end of which is con-. nected to an artery. The loop itself is implanted sub~
cutaneously but outlet conduits extending from the sides of the loo~ pro~rude through open holes in th~ skin tooutlet terminals on the outside of the body. Removable plugs fit in the outlet tubes and block the flow through these tubes during norntal conditions~ When the patient is subjected to dialysis, the plugs are removed and the out-~ 25 let ter.~.inals are connected to inlet fittin~s for a ,' dialysis machine. ~See 3,826,25~).
. . .
' ,, L~f e~
One of the problems e~un~iated in the openingparagraphs of the specification att~ibutable to this type of exteriorized shunt is the risk o~ infection in the location where the outlets protrude through the opening holes in the skin. While there is considerable reference to problems relating to blood clotting in shunt devices of the prior art, there is proposed in the patent a shunt arrangement which would at least have ~he effect of al-leviating the infection problem, in that the shunt device of the invention is arranged to be implanted in a com-pletely interiorized or totally subcutaneous condition:
In order to effect communication of the totally interiorized shunt device with the extracorporeal flow path, the im--planted device is provided with mechanically movable valve s members. These valve members are normally retained in a position within housings provided by the shunt device which maintain the valve members out of communicating re-lation with the ~lood flow through the shunt device. The valve members are provided with cooperating surfaces such as square apertures or threads which are operable to initially establish a fluid-tight communication with a hollow needle. The hollow needle is thus capable of being inserted through the skin into fluid contact with the valve member and then after such fluid coupling has been effected, the hollow needle is capable of effectinq the ; - 12 -' .
movement of the valve member into flow communicating re-lation with the bloodstream.
While the patent describes the utilization of a Fogarty catheter for effecting the cleaning and declotting of the device, no provision is made for preventing the clotting of the blood within the central flow passages of th~ valve members when they are disposed in their normal closed positions. Moreover, while provision is made for circulating blood between the periphery of the valve members and the housing retaining the same when the valve members are in their opened position, no such provision is made for the valve members when they are in closed position and, indeed, the peripheral passages provided for continued flow when the valve members are open are themselves closed when the valve lS member is closed, thus presenting, along with the interior passages of the valve members, spaces where blood would be trapped and become clotted.
While it is recognized to be desirable to overcome the disadvantages of the commercially available exteriorized 2~ shunt device, the arrangement disclosed in the aforesaid ; patent would appear to present clotting problems equal to, if not worse ~han the clotting problems noted in the prior art, When it is considered that it is quite usual for cancer patients to be hypercongulable, the clotting problems o~ the prior art assum~ greater proportions .
when contemplating the utilization ~f such shunts for hyperthermic treatment of a patient for anti-cancer pur-poses. Moreover, effective hypert~.ermic treatments in accordance with the principles of ~he present invention require flow rates considerably in excess o that normally provided for kidney dialysis.
Accordingly, it is a further object of the present invention to provide a shunt device of the totally sub-cutaneous type which ls particularly suitable for use in hyperthermic treatment of a patient for an~i-cancer pur-poses in accordance with the present invention, which device overcomes, or at least substantially alleviates, the clotting problems of the prior art heretofore noted.
This objective is obtained by providing a totally subcutaneoLs implant for use with the apparatus providing the extracorporeal blood flow path, including both a blood withdrawing and a blood xeturning percutaneous cannula, each of which is cooperable with a trocar for e~fecting the percutaneous disposition thereof, which cannulas co-operate with the implant to achieve the extrac rporealblood flow. The implant comprises a body of elastomeric ~aterial adapted to be implanted totally subcutaneously in a femoral extremity, the body having an arterial pas-sage therein, a spaced venous passa~e, and a bypass conduit extendil~ from one end o the arterial passage to one end of the venous passage. An arterial tube and a venous tube of vascular prosthesis material are provided, each having one end connected in communicating relation with the other end o~ ~he respective arterial or venous passage and an opposite end ad~ted to be connecte~ with a respective main ~emoral artery or vein side wall in communicating relation respecti~ely with the respective interior of the ~emoral artery or vein.
The elastomeric body is provided with means extend-~ ing from two spaced positions exterior of said elastomeric body inwardly thereof to two positions in communicating relation respectively with the arterial and venous pas-sages operable to move in response to the insertion of a cannula-trocar assembly from (1) a closed condition ex-cluding fluid containing space within the body between therespective two positions so that blood flowing ~rom the arterial tube through the arterial passage will pass there-~rom through the bypass conduit into the venous passage and out of said venous tube into (2) an open condition 2~ excluding fluid receiving space within the body from the exterior periphery of the.portions of the respective cannula extending between the two respective positions each of which also extends percutaneously and in com-municating relation with the respective arterial or venous passage so that blood flowing ~rom the arterial -~g~
tube through the arterial passage will flow throu~h the bypass conduit as aforesaid and, in addition, will also flow into the blood withdrawing cannula (with its trocar removed), through the extracorporeal flow path, through the blood returning cannula (with its trocar removed), back into the venous passage.
The invention further contemplates apparatus for providing a constant flow of temperature controlled liquid into and out of heat exchanger means in heat exchange relation to a flow of blood through said heat exchanger means which forms a part of a systemic extracorporeal flow circuit of a human patient for systemically treating the patient hyperthermically to retard the growth of cancer cells in the patient, said apparatus comprising, first reservoir means for containing a first body of liquid, second reservoir means for containing a second body of liquid, first pump means for pumping liquid from said first reservoir means, second pump means for pumping liquid from said second reservoir meansl means for directing a predetermined constant flow of liquid from said pump means into said heat exchanger means, means for d.irecting the liquid from said heat exchanger means to said reservoir mean.C~
means for maintaining the liquid in said Eirst reservoir means at a substantially constant elevated temperature of approximately 45C, means for maintaining the liquid in said second reservoir means at a substantially constant reduced temperature oE
approximately 30C, and means for varying the amount of liquid from said Eirst pump means directed into said liquid flow directing means from 0 to 100% while proportionately varying the liquid from said second pump means direc~ed into said liquid flow directing means from 100% to 0 and while maintaining the constant flow as aforesaid.
The invention may best be understood with reference to the accompanyiny drawinys, wherein an illustrative embodimen-t is shown.
In the drawings:
Figure 1 is a perspective view illustrating the method and apparatus embodying the principles of the present invention;
- 16a -Figure 2 is an enlarged vertical sectional view taken along the line 2-2 o~ Figure ~;
Figure 3 is a plan view o~ the implant part of the apparatus;
Figure 4 is a longitudinal section taken along the line 4-4 of Figure 3;
Figure 5 is an end view of the implant shown in Figure 3;
Figure ~ is an enlarged, fragmentary sectional view illustrating the entry of the blood withdrawing can-nula with its cooperating trocar assembled therein into cooperating relation with the implant and specifically the arterial passage thereof;
Figure 7 is an enlarged fragmentary sectional lS view taken along the line 7-7 of Figure l;
Figure 8 is a top plan view of the blood with~
drawing cannula with its cooperating trocar assembled therein;
~ igure 9 is a side view of the cannula shown in ~igure 8;
Figure 10 is an end view of the cannula shown in Figure 8; and Figure 11 is a perspective view of the trocar shown in Figure 8.
Referring now more particularly ~o the drawings, there is shQwn therein a preferred apparatus 10 embodying the princi?les of the present invention ~or practic.ng the method of the present invention. ~ile it is possible to utilize other apparatus in practicing the present method, since the apparatus 10 is preferred the principles of the present invention can best be understood by first consider-ing the preferred apparatus 10 and then considering the method procedures involved in utilizing the preferred ap-paratus.
In its broadest aspects, the apparatus 10 includes ; sterile tubing, generally indicated at 12, wh.ich defines an extracorporeal blood flow path. A pump mechanism prefer-ably in the form o~ a peristaltic roller pump, generally indicated at 14, is provided ~or pumping blood along the extracorporeal flow path at a controlled rate from the inlet tubing end to the outlet tubing end. In addition, there is provided a temperature control zone preferably in the form of a heat exchanger assembly 16 through which the blood flowing along the extracorporeal flow path has its temperatuxe controlled, preferably both by heating and cooling, through a control device, generally indicated at 18, for the liquid circuit of the heat exchanger assembly 16. Finally, the apparatus 10 includes means, generally indicated at 20, for communicating the inlet end of the :
t~L~
tubing 12 defining the extracorporeal flow path with the bloodstream of a patient and the outlet end of the tubing 12 defining the extracorporeal flow path with the bloodstream of the patient, so that the returning blood is systemically distributed ~ithout adversely affecting the blood depleted areas frorn which the blood is withdrawn.
The tubing 12 may be formed of any suitable plastic material, as, for example, vinyl polymer (e.g. Tygon~), polytetraflouroethylene (e.g. Teflon~), or other plastic 10 materials having known uses in medical applications (e.g.
Silastic~). An exemplary tubing size is 1/4" i.d., with a convenient length being from 3 - 5'. The pump assembly 14, as previously indicated, preferably embodies a peristaltic roller type pump driven by a variable speed electric motor. A
peristaltic pump is preferred because it can utilize the replacement sterile tubing 12 for blood contact and does not provide pump part which must be maintained in a sterile condition. An exemplary pump is manufactured by Sarns, having a 1-2 liter per minute capacity.
A preferred embodiment of the heat exchanger assembly 16 is available comrnercially under the tradename Travenol Mini-Prime, 5M0 337, which has a 57 cc capacity and rated flow of 1-3 liters per minute.
~ 'ith reference to ~igure 2, the ccntrol device 18 is made up of indivldually known components. As shown, there is pYovided a cooled liquid reservoir 22 and a heated liquid reservoir 24 each containing a body of liquid. ~hile any liquid may be utilized a preferred embodiment is water.
Each reservoir is provided with a stirring or agitating means 26 for purposes of mixing the liquid contained therein so as to render the temperature thereof more uniform throughout. The cool liquid reservoir ~2 is provided ~ith a cooling unit, schematically indicated at 28, while the ; heated liquid reservoir 24 is provided with a heating unit 30. A liquid circulatin~ system is provided in cooperating ; relation between the cooled liquid reservoir 22 and heated liquid reservoir 24 anA the liquid side of the heat ex-changer 16. Such circulating system include~ the utili7ation of two pump assemblies, schematically indicated in the drawings at 32 and 34.
; As shown in Figure 2, the pump assembly 3~ i5 associate~ with the cooling liquid reservoir 22 and includes an inlet or suction pipe 36 extending from the reservoir 22 to one side of the pump 32 and an outlet pipe 38 extending therefrom. Similarly, an inlet pipe 40 ex-tends from the heated liquid reservoir 2~ to one side of the pump 34 which side has an outlet pipe 42 extending therefrom. Outlet pipes 38 and 42 are interconnected by a :
;
;' t ~ ~ r~
T-connector 44 which has a pipe 46 extending therefrom to the liquid inlet side of the heat exchanger 16. ~ pipe 48 extends from the outlet of the liquid side of the heat exchanger 16 which by means of a Y-connection S0 communi-cates with two branch conduits 52 ~nd 54 extending respec-tively to the opposite sides of the pumps 32 and 34. The circuit is completed by pipes 56 and 58 connected respec~
tively to the outlet of the opposite sides of pumps 32 and 34 and the cooled liquid reservoir 22 and heated liquid reservoir 24 respectively. As shown, an overflow pipe 59 is connected between the reservoirs.
The cooling unit 28 is of conventional nature and is adapted to maintain the liquid in the reservoir 22 at a substantially constant temperature as, for example, 30C.
Likewise, the heating unit 30 is of conventional construc-tion and is adapted to maintain the liquid within the heated liquid reservoir 24 at a substantially constant temperature as, for example, 45C. Pump 32, when operated, serves to metex from the reservoir 22 through pipe 35 an amount of 2~ liquid which is equal to the amount of liquid returned through pipe 56. In a simi.lar manner, pump 34 when operated serves to meter an amount of flow from the reservoir 24 which is always equal to the amount returned through return pipe 58. A control, schematically indicated at 60/ for varying the rate of movement of the pumps 32 and .
34, e.g. electrical controls for th~ variable speed elec-trical motors dxiving the same whic~ form a part of the pump assemblies schematically illusorated is operable so that the total output of the two p~ps is adjusted to and maintained at a substantially constant rate, as for example, approximately lO liters per minute. The control 60 is also operable to effect a proportional variation in the rate which each of the two pumps assume of this total out-put from 0-lO to lO~0.
l~ Control of the pump assemblies 32 and 34 is undertaken in accordance with the readout of three tem-perature recording devices 62, 64 and 66 placed respectively to sense the core tempera~ure of the patient's body te.g. a rectal probe or isophageal probe), the temperature of ~he lS blood leaving the heat exchanger 16 being returned to the patient and the temperature of the liquid entering the heat exchanger. A pressure sensing device 68 is also provided in the liquid inlet line 46. I~ will be understood that the temperature sensing devices and pressure sensing devices are of any conventional design, preferably of the ype providing a remote readout, as sche~atically indicated by corres-ponding primed numerals~
For illustrative purposes it is sufficient t.o note that control 60 can be manually operated to determine the propor~ion of the total liquid flow through the heat exchangex which is provided by the ~ooled liquid at 30C and the heated liquid at 45C. Control 60 thus serves to directly vary t~e liquid temperature sensed by device 66 between the low limit of 30C and upper limit of 45~C, which in turn will vary the temperature of the blood sensed by device 64 which in turn will affect the patient's systemic blood temperature and hence the temperature sensed by device 62. It will be understood that while the operation of control 60 is set forth for illustrative puxposes as bein~
manual, the control 60 may be rendered automatic and ~ro-grammable if desired.
Referring now more particularly to Fi~ures 3-11, the communicating means 20 preferably comprises a totally subcutaneous implant device, generally indicated at 70, which serves as the means communicating with the patient's bloodstream and a pair of percutaneous cannula~trocar assem-blies, generally indicated at 72 and 74, which serve as the means for operatively communicating the implant de-vice 70 with tubing 12 defining the extracorporeal flowpath. As best shown in Figures 3-7, the implant device includes a body 76 of elastomeric material such as Silastic~, molded so as to provide an arterial passage 78, a spaced venous pas~age 80 and a by-pass conduit 82 connect~d between the inner end of the passage 78 and , the inner ~nd of the passage 80. ~s best shown in Figure 3, the passage, 78 and 80, together with the ~y-pass conduit 82, are of generally ~-shaped configuration.
Each of the passages 78 and 80 has a peripheral S cross-sectional configuration which is elongated in one direction; namely, the direction ln which they are spaced apart, with sharp points defining opposite ends in the direction of elongation. The preferred configuration shown is further characterized by a pair of convexly curved lines extending between the sharp points~ the distance between the central portions of the convex lines being approximately one-half the dis~ance between the two end points. Wnlile the by-pass conduit may be of other cross-sectional configura-tion, as shown, it too is of similar cross-sectional con-figuration. This preferred cross-sectional configuration for the passages 78 and 80 is provlded for the purpose of cooperatively receiving the correspondingly shaped exterior peripheries of the cannulas of the assemblies 72 and 74, which assemblies are so shaped for the purpose of co-operating with a pair of slits 84 and 86 formed in thebody 76 in operative association with the passages 78 and 80 respectively.
As shown, each slit 84 and 86 extends from a position exterior of the body 76 to a position of com-munication with the inner end of the associated passage 78 or 80. The width of each slit is generally equal to the distance between the end points of the associated passage and is oriented in its closed conditionr as best shown in Figure 4, in longitudinal alignment with a plane passing between the end points of the associated passage.
In the closed condition sho~l, the two planar interior surfaces of the body 76 which d~fine the respective slit 84 or 86 are resiliently urged into engagement by the elastomeric characteristics of the body material. The engagement of the surfaces serves to exclude any spaces which could contain fluid such as blood between the two positions of extent of the slit, as aforesaid.
The resiliency of the elastomeric material of the body 76 also permits each slit a4 and 86 to be moved by its respective cannula-trocar assembly 72 and 74 into an open condition where the planar body surfaces defining the slit are spxead arcuately so that the profile thereo~ coincides with the peripheral configuration o~ the associated passage 78 or 80.
To aid the entry and insertion of each cannula-trocar assembly through its associated slit, there is molded in embedded relation within the body 76 a pair of metallic guide structures 88 and 90. Each guide structure is pre-ferably made of a medically accepta~le interior use metal, such as stainless steel (e.g. Vitallium Metal manufactured by Howmedica). The guide structures include similar ;
inwardly tapering annular parts 92 and 94 respecti~ely fixed to the exterior end face of the body 76 and similar parallel spring finger parts 96 and 98 respectively em-bedded in the exterior of the body on opposite sides of associated slit. The tapered part~ 92 and 94 provi~e the guide assist function previously no~ed while the spring finger parts 96 and 98 provide a spring assist function for the slits of the elastomeric body serving to resiliently urge the slit defining surfaces toward one another in addition to the spring function provided by the elasto-meric characteristics of the material of the body 76.
The implant device 70 also includes a pair of tubes 100 and 102 made of vascular prosthesis material.
A preferred vascular prosthesis material is woven Dacron~
marketed commercially by Meadox Medicals although any othex acceptable vascular prosthesis material may be utilized. As bes~ shown in Figure 1, the tube 100 has one end thereof fixed in communicating relation with the outer end portion of the arterial passage 78, as by being molded in embedded relation. The opposite end of the tube 100 is adapted to be connected, as by suture, to a surgical open1ng ~ormed in the side wall of a femoral artery so that the interior of the tube 100 is in com-municating relation with the interior of the femoral artery. In a like manner, one end of the tube 102 is 8'~
embedded in communicating relation with the outer end por-tion of the venous passage 80 and its opposite end is adapted to be sutured to a surgical side wall opening in the associated femoral vein so that its interior is in com-municating relation with the interior of the femoral vein.
The implant device 70 also includes a layer offabric 104 which is fixed to the inner side wall of the elastomeric body as by Silastic~ glue or the like. The fabric 104 includes marginal portions extending laterally outwardly from the operative inner side wall of the body 76 to which it is fixed. The fabric layer 104 and particularly the marginal portions thereof provide for initial fixa~ion by suture of the body 76 during implant and for subsequent semi-pe~nanent fixation by tissue ingrowth. A preferred fabric material is Dacron~ double velour which is marketed commercially by Meadox Medica 16 .
For identification purposes directly from the implant device itself, radiopaque identification (not shown) is provided on the operative outer side wall of the elastomeric body 76. Such identification insul~s that the proper cooperating cannula-trocar assemblies 72 and 74 will always be used since such assemblies can be ascer-tained from the implant itself after total implantation has been effected through X-ray identification.
Re~erring now more particularly to Figures 8-11 ~L ~ L~
of the drawings, the details of con~tr~ction of the carnula-trocar assemblies 72 and 74 are sho~n therein. It will be understood that since the assemblies 72 and 74 are left and right hand mirror images of one another, a description of one of the assemblies will suffice to give an understanding of both. The assembly 74 is shown in assembled condition in ~igure 8 and includes a percutaneous cannula, generally indicated at 106 and a c~operating trocar, generally indi-cated at 108.
The cannula 106 includes a tubular body which includes a straight section llO defining the subcutaneous end portion of the cannula and an angular section 112 which, together with an adjacent part of the strai~ht section llO, defines the extracorporeal end portion of the cannula. The cannula 106 is pre~erably molded of radiopaque plastic material having sufficient rigidity to prevent interior collapse when in operative position within the implant device 70. Thermoset plastics are preferred al-though thermoplastic materials with sufficient functional rigidity and heat stability for sterilization can be used.
An exemplary material is ethyle~e-propylene-terpolymer (e.g.
where the third monomer is norbornadiene) impregnated with a radiopa~ue material such as barium sulfate.
As shown, the entire straight section llO of the cannula 106 has its exterior periphery formed with a cross-sectional configuration which conforms with and engages ; - 2~ -~ithin the interior periphery of the body 76 defining the artery passage 78 or venous passage 80. Such configura~
tion, however, is re~uired only in the extent of the sub cutaneous end portion which is disposed within the passage and ~ssociated slit of the implant body during operation.
The cannula 106 includes an interior passage 114 which extends through the angular section 112 into the straight section 110 and out of the extremity thereof.
In order to maximize the interior passage cross-sectional area for an optimum exterior cross-sectional size, the cross-sectional configuration of the interior passage ,114 at least in the straight section 110, conforms to the exteriox cross-sectional configuration.
In this regard it will be noted that the trocar 108 consists essentially of a molded body of plastic ma-terial, sirnilar to the plastic material of the cannula 106, which provides a b7ade part 116 and a handle part 118. The blade part 116 is of a longitudinal extent generally equal to the longitudinal extent of the straight 2~ section 110 of the cannula 106. T~le main extent of the blade part 116 has an exterior peripheral cross-sectional configuration conforming with the interior cross-sectional configuration o~ the portion of the interior passage 114 extending through the straight cannula sec-tion 110. The blade par~ 116 includes a sharpened tip _ ~9 _ portion 120 whic~ tapers gradually in cross-sectional con-figuration outwardly from the aforesaid configuration to a point.
It will be noted that the extracorporeal end of the straight section 110 of the cannula 106 is closed as by a diaphragm or plug of elastomeric material 1~2 which pref~
erably is preslit (although may be imperforate) to permit .the passage of the trocar 10~, pointed end 120 ~irst, therethrough.
The exterior periphery of the outer end of the angular section 112 is provided with gripping flanges,l24 operable to effect a fluid-tight connection with the in-terior of the tubing 12. When the trocar 10~ is withdrawn, the elastomeric plug slit, which has expanded to receive the ~5 trocar) contracts to close the end of the straight section of the cannula and insure that all of the blood will flow outwardly through the angular section 112 and into the tubing 12.
Formed on the exterior periphery o~ the straight 2~ section 110 of the cannula is an annular shoulder 126 which ~orms a stop surface acing in a direction toward the open extremity of the s~raight cannula section operable to engage the guide part 92 or 94 of the implant device when the cannula is in its ully inserted operative position, as 2S shown in Figure 7. The straigh~ cannula section 110 is ~ 30 -,,f~f,~
formed with an opening 128 which extends inwardly from one exterior end point into communication with the interior passage 114 at a position to register with the by-pass conduit 82 of the implant body 76 when the cannula is fully S inserted, as aforesaid. Formed on the exterior periphery of the extracorporeal portion of the straight cannula sec~ion 110 is a stabilizing shield 130 which ~acilitates main-tenance of the cannula on the patient when in operative position.
A preferred procedure is to soat all of the blood contacting sur~aces of the cannulas 106 ti.e. interior passages 114) tubing 12 and elastomeric body 76 (passages 78 and 80, conduit 82 and slits 84 and 86) with an anti-coagulant coating. A suitable coating material for this purpose is marke~ed commercially under the tradename TDMAC~.
The manner in which the device 70 is suryically implanted is in accordance with usual implant procedures well known to those skilled in the art. For present pur-poses suf~ice it to say that the elastomeric body 76 isimplanted in an arterior ~emorai region spaced downwardly from the position o~ bending at the hip approximately the distance o~ the width of a normal-si2ed palm ~ap-proximately 4") as is clearly shown in Figure 1. The large area faces of the body 76 are preferably disposed parallel with the skin with the face having the ~abric 104 fixed tllereto innermost. The a~texial and venous tubes 100 and 102 extend upwardly and the free ends are tapered and sutured to surgical openings in the side walls o~ the ~emoral artery and vein respectively so as to extend there~rom at an angle of approximately 45.
This procedure is accomplished in accordance with usual practices relating to the use of vascular prosthesis material.
The marginal edge portions of the fabric 104 are sutured to t~le adjacent tissue to provide initlal body 76 fixation, as aforesaid. A11 of the exterior surfaces o~ the implant device 76 are contacted with tissue includ-ing tapered guide parts 92 and 94 (with fat).
~s previously indicated, it is possible to use known shunt devices ~e.g. U.S. patent No. 3,713,441) in lieu of the device 70 so long as they provide the neces-sary capacity which is ordinarily not the case without modification.
The advantages of the use of the implant device 21 70 is that it is speeifically intended for long-term surgical implantation in the thigh of cancex patients, whereby its anastomosis to the femoral artery and vein~
creates a high-flow (1-2 litexs per minute) arterio-venous conduit which may be repeatedly entered by per-cutaneous insertion of the cannula assemblies 72 and7~.
~ 32 -As compared with other prosthetic partially exteriorized A-V Shunt devices as ~sed for renal hemo-dialysis the implant device 70 red~ces the ris~ of in~
fection, reduces ~he risk of thrombosis t reduces the ris~ of disruption and improves the esthetics of normal usage. The renal dialysis experience indicates that partially exteriorized lower extremity shunts frequently develop infection along the tract of the shunt tubing.
The incidence and severity of this type of infection would be increased in cancer patients by the immunosup-pressive effects of malignancy, and the chemotherapy and radiotherapy they frequently receive. The implantable device 70 greatly diminishes the risk of infection and requires no increase in th~ amount of surgery needed for insertion. Cancer patients have a state of hypercoagul-ability or lncreased tendency to form blood clots in their normal and any artificial circulations. Ordinary A-V
shunts last only 2-5 months in hypocoagulable dialysis patients, and likely will clot much sooner in those with the "Stic~y blood" of disseminated malignancy The im-plantable device 70 has a shorter fluid path, much of which will be covered by a patient's own intravascular tissues, and hence will be less likely to thrombose.
Partially exteriorized shunts have press connections which Il.dy b~ inadvertently loosened or disconnected.
.
Such events have caused deaths in dialysis patients but, in general, those shunts are small and a patient can control a bleeding shunt before exsanguination occurs. However, disruption of the large shunt necessaxy for hyperthermia would result in massive bleeding, which could render a patient unconscious even before the shu~ could be reached through normal clothing. This cannot happen with the de-vice 70 as the connections are permanent, as well as totally protected.
Unlike commercially known shunts, there is no external tubin~ associated with the device 70. A nor~al bath or shower could be taken by the implanted patient, whereas those with partially exteriorized shunts cannot submerge them and must resort to less hygienic methods, a probable factor in theix increased incidence of in-fections. Furthermore, the device 70 does not interfere with clothing or require any sort of dressing, leaving a patient's appearance unimpaired, an important asset to the depressed cancer patient.
~3 The manner in which each cannula assembly 72 or 74 is inserted into cooperating relation to the im-planted device 70 should be apparent rom the above. I~
is of significance to note ~he advantages of the utili-zation of a main implant body 76 which provides increased palpation facility during cannulation. Moreover, cannu-; lation is effected in a straight line relationship resulting in a straight line percutaneous communication with the extracorpor~al flow path. The preferred cross-sectional configuration of the cannula enables simple but effective alignment to be accomplished duxing insertion.
Such cross-sectional configuration a:Lso provides optimal cooperation with the slits 84 and 86 of the elastomeric body 76 both in expanding the slits during insertion and in contracting the peripheral portion of the cannula extending therethrough to insure a good fluid-tight con-nection. The extension of this cannular cross-sectional configuration with the elastomeri.c body passages 78 and 80 also insures non-distortion of these passages and a full flow area of 4 mm or larger.
The flow capacity provided is of extreme im-portance since it is a critical determining factor in the time required to bring the patient's blood up to the desired treatment temperature and to the sensitivity of the temperature control available. The approximate 1 liter minute capacity provided is based upon the aver-2 age size of an average adult patient and, of course, should be varied to suit the particular size of the patient being treated. The term approximately 1 liter per minute is therefore intended to comprehend within its meaning such variation to suit the patient size.
It will be understood that once the inlet and outlet ends of the tubing 12 are connected over the flanges 124 of the ~annula of the assemblies 72 and 74 and the associated trocars 108 of the assemblies are withdrat~n, pump 14 can be started t~ commence the flow of blood along the extracorporeal flow path at the approximate 1 li~er per minu~e as aforesaid and through the temperature control zone thereof. Initially, control 60 is set to pass 100% 45C water through the heat exchanger 16. During this initial treatment phase withdrawn blood temperatures measured at 62' will show a gradual increase ~rom the initial normal reading of approximately 37C. The cap acity and effectiveness of the heat exchanger 16 is such that readings of the returning blood taken at 64 closely approximate the 45C maximum water temperature utilized.
As the heated blood is returned to the femoral vein through the blood receiving percutaneous cannula 106, venous passage 80 and tube 102, it is distributed systemically which in turn, has the effect of increasing the total systemic tem~erature. As the patient's core body tem-perature increases tohard the 41.5C level control 60 must be operated to lower the liquid reading at 66 to a value below 45C as, for example, 42.SCo The liquid temperature level stabilized at 42.5C, the patient core body tempera-ture readings at 62, and returning blood readings will stabilize at a desired level of approximately 41.SC and ~0.0C
respectively. This critical phase wherein the patient's .
t9~
systemic temperature is increased and stabilized should, as aforesaid, normally be completed within one hour, al-thou~h here again, variation because of patient si~e will occur.
Once temperature stabilization is achieved as aforPsaid, treatment is continued for a time period ef-fective for the particular cancer which the patient has.
A preferred minimum time for all types including simple carcinomas is six hours although treatment ~imes of 20 hours and longer will be required for more complex cancer situations.
Preferably, a third phase of the pxesent method involves utilizing the continued blood flow through the temperature co~trol zone of the extracorporeal flow path to reduce the blood temperature to normal and, hence, the patient' 5 systemic temperature to normal. This phase is initiated by turning control 60 to pass predominately 30C
water through the heat exchanger 16. This has the ef~ect of substantially lowering the readings of the returning blood taken at 6~. Again, this cooler blood is distributed systemically, causing the systemic temperature to lower until a normal of 37bC is reached. The decreasing tem~
perature phase normally will require a time period ap-proximately ~he same as the initial increasing temperat~re phase although usually somewhat less.
.
~4~
Preferably, the patient is maintained during treatment il a skin contacting environment approximating that of an intensive care room. While it is within the contemplation of the invention to provide a skin insulat-ing environment and even comparable elevated temperaturesto inhaled ~ases, the intensive care like environment is preferred because the temperature level o~ the skin and respiratory system does no~ vary significantly from ~he induced hyperthermia systemic level and access to th~
patient is much more readily obtained. Moreover, the ap-plication of radiation or chemotherapy treatmen~s can be carried on simultaneously if desired.
It thus will be seen that the objects of this invention have been fully and effectiv21y accomplished.
lS It ~ill be realized, however, that the foregoing preferred specific embodiment has been shown and described or the purpose of illustrating the functional and structural principles of this invention and is subject to ch~nge without departure from such principles. Therefore, this invention includes all modif~cations encompassed within the spirit and scope of the following claims.
~. Repetitious induction of courses of hyperthermia over a several day period possible.
10. Hyperthermia induced with reasonable safety in neutropenic or thrombocytopenic patients.
It is an object of the present invention to provide a method and apparatus for effecting hyperthermic treatment whi~h will meet the above-listed desirable criteria. In accordance with the procedural principles of the present invention, this objective is obtained by establishing a sterile extracorporeal flow path for blood having an inlet, an outlet and a temperature control zone therebetween, establishing communication of the inlet of the extxacorporeal flow path with the patient's bloodstream so that blood can be withdrawn and supplied to the extracorporeal flow path without adversely affecting the blood depleted areas from which the blood is withdrawn, establishing co~lunication of the outlet of ~he extracorporeal flow path with the patient's blo~dstream so that blood flowing from the extracorporeal flow path is returned to the bloodstream in such a way as to be distributed systemically, pumping blood withdrawn from the patl~nt's bloodstream along the extracorporeal flow path through the temperature control zon~ at a con~rolled rate and returning the same to the patient's bloodstream to be distribute~ systemically, as a~oresaid, con~rolling the temperature of the blood flowing along ~he extracorporeal flow path through ~he temperature control zone for an initial period during which the temperature level of the blood within the zone is raised without subjecting the s~ne to localized temperatures in e~cess of approximately 45 C so that -the systemic distribution of the returned blood gradually in-creases the core temperature of the patient's body to a generally stable temperature condition at a level of ap-proximately 41.5C, but not higher than approximately 42.5C, and maintaining control of the temperature o~ the blood flowing along the extracorporeal flow path through the temperature con~rol zone at the generally stable ~emperatur~
condition for a second time period sufficient to retard the growth of cancer cells.
It is recognized that extracorporeal heating of blood for anti-cancer purposes has been undertaken in regional perfusion practices. Procedures of this type are discussed by Cavaliere et al. and Stehlin and are to be distinguished from the systemic hyperthermia induced by the present pro-ceduresl as indicated above. In these regional perfusion practices, the main femoral artery and vein are temporarily occluded by vascular clamps or tourniquets and a closed extracorporeal sys~em is established, solely within the femoral extremity. In this extracorporeal circuit, heat is applied as an adjunct to the other treatments, such as chemotherapy, Which arc utilized in ~he regional circulating S system. This system necessitates the utilization of oxy-genating equipment of a type similar to that used in open heart surgery. As is evident rom the kno~m time limi-tations imposed upon open heart surgery by virtue of the utili~ation of oxygenating equipment, the time frame within which such combined oxygenating and heating treatments can be continued even on a regional basis without imposing at least a percentile permanent damage to the blocked emoral areas of the patient is quite limited.
Pettigrew, in referring to these regional per-usion practices as background to his preferred co~bined hot wax bath and heated respiratory gases procedure fo~ inducing total body hyperthermia, appears to consider the regional perfusion procedures to be applicable to induce both reg-ional hyperthermia as well as total body hyperthermia, perhaps by analogy to the open heart ex~racorporeal shunt-ing. (Induction of Controlled Hyperthermia in Treatmen~ of Cancer, Henderson, M.~. and Pettigrew, R.T. ~ancet, 1:1275, 1971 and Cancer Therapy by Whole Body Heating, Pettigrew, R.T. Proceedings, p. 282). The Pattigrew Lancet article ~ 25 characterized the re~ional perfusion -~ork of Cavaliere et ; al. ("Selective Heat Sensiti~rity of Cancer Cells", Cancer, 1967, 20-1351) as having "achieved ~ery sa~isfactory tem-peratures in the malignancies using an arteriovenous shunt and a heat exchanger, but since thi~ requires surgery it cannot be repeated indefinitely and can only be applied easily to p~ripheral malignancy."
It is of significance, however, to note that the recognized practitioners of regional perfusion, namely Cavaliere e~ al. and Stehlin et alO, have both indicated that the regional perfusion practices utilizing a shunt and an extxacorporeal heat exchanger are limited to regional extremity applications and both have utilized other pro-cedures for inducing total body hyperthermia.
On page 135 of the cancer article Cavaliere et al.
state:
"I'his method of high temperature treatment obviously has limitations and at present is indicated in patients with primary or recurrent malignant tumors of the limbs for whom the only alternative therapy would be amputation, which often does not prevent metastases.
... It is evident that future progress in this field will come from total-body high-temperature treatment. We are now in the process of developing tecn-niques towards this end, which are considerably different from those now being used."
The last paragraph of the Stehlin article in the Proceedings publication, page 271, sets forth the following:
_ 9 _ - \~
8~
"As a result of our experience with regional perfusion with heat, we are currently, and have for the past five years been investigating the possi-bility that systemic hyperthermia induced with bacterial toxins will enhance the antitumor effects of various chemotherapy agents on melanomas and sarcomas."
A pre~erred minimum flow rate in accordance with the principles of the present invention, is approximaterly 1 liter per minute. Such flow rate can be achieved by following the procedu.res of the present invention without affecting the femoral areas from which the blood is withdrawn. Thus, with the present procedure, there is no systemic femoral isolation as by a clamp or tourniquet occludin~ the main femoral artery and vein, but rather, a preferred procedure is to effect communication of the extracorporeal flow path between the femoral artery and the femoral vein through a side wall of each, so that systemic circulation in the femoral areas can ; continue. The pumping procedure undertaken to effect flow of the withdrawn blood through the temperature control zone of the extracorporeal flow path achieves an adequate controlled flow rate while permitting adequate systemic circulatory flow through the femoral areas sufficient to prevent the type of adverse effects over extended periods of time which will occur in the a~oresaid regional perfusion techniques.
:.
: - 10 -The present invention also contemplates an improved implantable device for facilitating the con-nection of the extracorporeal flow ~ircuit with the blood system of the patient. Devices for establishing an extra-corporeal blood flow path for the purposes of kidney di-alysis as distinguished from systemic hyperthermic treat-ments are well-known. These devices, known as shunts, are made commercially available by several manufacturers.
Typically, these shunt devices are implanted in the patient and include tubes which extend extracorporeally. These : exteriorized tubes have caused considerable difficulty.
A good discussion o the difficulties encountered in the practices relating to such exteriorized shunt de~
vices is contained in U.S. patent No. 3,998,222. In the opening paragraphs of the specification, one type of shunt device is descxibed as a U-shaped loop, one end of which is connected to a vein and the other end of which is con-. nected to an artery. The loop itself is implanted sub~
cutaneously but outlet conduits extending from the sides of the loo~ pro~rude through open holes in th~ skin tooutlet terminals on the outside of the body. Removable plugs fit in the outlet tubes and block the flow through these tubes during norntal conditions~ When the patient is subjected to dialysis, the plugs are removed and the out-~ 25 let ter.~.inals are connected to inlet fittin~s for a ,' dialysis machine. ~See 3,826,25~).
. . .
' ,, L~f e~
One of the problems e~un~iated in the openingparagraphs of the specification att~ibutable to this type of exteriorized shunt is the risk o~ infection in the location where the outlets protrude through the opening holes in the skin. While there is considerable reference to problems relating to blood clotting in shunt devices of the prior art, there is proposed in the patent a shunt arrangement which would at least have ~he effect of al-leviating the infection problem, in that the shunt device of the invention is arranged to be implanted in a com-pletely interiorized or totally subcutaneous condition:
In order to effect communication of the totally interiorized shunt device with the extracorporeal flow path, the im--planted device is provided with mechanically movable valve s members. These valve members are normally retained in a position within housings provided by the shunt device which maintain the valve members out of communicating re-lation with the ~lood flow through the shunt device. The valve members are provided with cooperating surfaces such as square apertures or threads which are operable to initially establish a fluid-tight communication with a hollow needle. The hollow needle is thus capable of being inserted through the skin into fluid contact with the valve member and then after such fluid coupling has been effected, the hollow needle is capable of effectinq the ; - 12 -' .
movement of the valve member into flow communicating re-lation with the bloodstream.
While the patent describes the utilization of a Fogarty catheter for effecting the cleaning and declotting of the device, no provision is made for preventing the clotting of the blood within the central flow passages of th~ valve members when they are disposed in their normal closed positions. Moreover, while provision is made for circulating blood between the periphery of the valve members and the housing retaining the same when the valve members are in their opened position, no such provision is made for the valve members when they are in closed position and, indeed, the peripheral passages provided for continued flow when the valve members are open are themselves closed when the valve lS member is closed, thus presenting, along with the interior passages of the valve members, spaces where blood would be trapped and become clotted.
While it is recognized to be desirable to overcome the disadvantages of the commercially available exteriorized 2~ shunt device, the arrangement disclosed in the aforesaid ; patent would appear to present clotting problems equal to, if not worse ~han the clotting problems noted in the prior art, When it is considered that it is quite usual for cancer patients to be hypercongulable, the clotting problems o~ the prior art assum~ greater proportions .
when contemplating the utilization ~f such shunts for hyperthermic treatment of a patient for anti-cancer pur-poses. Moreover, effective hypert~.ermic treatments in accordance with the principles of ~he present invention require flow rates considerably in excess o that normally provided for kidney dialysis.
Accordingly, it is a further object of the present invention to provide a shunt device of the totally sub-cutaneous type which ls particularly suitable for use in hyperthermic treatment of a patient for an~i-cancer pur-poses in accordance with the present invention, which device overcomes, or at least substantially alleviates, the clotting problems of the prior art heretofore noted.
This objective is obtained by providing a totally subcutaneoLs implant for use with the apparatus providing the extracorporeal blood flow path, including both a blood withdrawing and a blood xeturning percutaneous cannula, each of which is cooperable with a trocar for e~fecting the percutaneous disposition thereof, which cannulas co-operate with the implant to achieve the extrac rporealblood flow. The implant comprises a body of elastomeric ~aterial adapted to be implanted totally subcutaneously in a femoral extremity, the body having an arterial pas-sage therein, a spaced venous passa~e, and a bypass conduit extendil~ from one end o the arterial passage to one end of the venous passage. An arterial tube and a venous tube of vascular prosthesis material are provided, each having one end connected in communicating relation with the other end o~ ~he respective arterial or venous passage and an opposite end ad~ted to be connecte~ with a respective main ~emoral artery or vein side wall in communicating relation respecti~ely with the respective interior of the ~emoral artery or vein.
The elastomeric body is provided with means extend-~ ing from two spaced positions exterior of said elastomeric body inwardly thereof to two positions in communicating relation respectively with the arterial and venous pas-sages operable to move in response to the insertion of a cannula-trocar assembly from (1) a closed condition ex-cluding fluid containing space within the body between therespective two positions so that blood flowing ~rom the arterial tube through the arterial passage will pass there-~rom through the bypass conduit into the venous passage and out of said venous tube into (2) an open condition 2~ excluding fluid receiving space within the body from the exterior periphery of the.portions of the respective cannula extending between the two respective positions each of which also extends percutaneously and in com-municating relation with the respective arterial or venous passage so that blood flowing ~rom the arterial -~g~
tube through the arterial passage will flow throu~h the bypass conduit as aforesaid and, in addition, will also flow into the blood withdrawing cannula (with its trocar removed), through the extracorporeal flow path, through the blood returning cannula (with its trocar removed), back into the venous passage.
The invention further contemplates apparatus for providing a constant flow of temperature controlled liquid into and out of heat exchanger means in heat exchange relation to a flow of blood through said heat exchanger means which forms a part of a systemic extracorporeal flow circuit of a human patient for systemically treating the patient hyperthermically to retard the growth of cancer cells in the patient, said apparatus comprising, first reservoir means for containing a first body of liquid, second reservoir means for containing a second body of liquid, first pump means for pumping liquid from said first reservoir means, second pump means for pumping liquid from said second reservoir meansl means for directing a predetermined constant flow of liquid from said pump means into said heat exchanger means, means for d.irecting the liquid from said heat exchanger means to said reservoir mean.C~
means for maintaining the liquid in said Eirst reservoir means at a substantially constant elevated temperature of approximately 45C, means for maintaining the liquid in said second reservoir means at a substantially constant reduced temperature oE
approximately 30C, and means for varying the amount of liquid from said Eirst pump means directed into said liquid flow directing means from 0 to 100% while proportionately varying the liquid from said second pump means direc~ed into said liquid flow directing means from 100% to 0 and while maintaining the constant flow as aforesaid.
The invention may best be understood with reference to the accompanyiny drawinys, wherein an illustrative embodimen-t is shown.
In the drawings:
Figure 1 is a perspective view illustrating the method and apparatus embodying the principles of the present invention;
- 16a -Figure 2 is an enlarged vertical sectional view taken along the line 2-2 o~ Figure ~;
Figure 3 is a plan view o~ the implant part of the apparatus;
Figure 4 is a longitudinal section taken along the line 4-4 of Figure 3;
Figure 5 is an end view of the implant shown in Figure 3;
Figure ~ is an enlarged, fragmentary sectional view illustrating the entry of the blood withdrawing can-nula with its cooperating trocar assembled therein into cooperating relation with the implant and specifically the arterial passage thereof;
Figure 7 is an enlarged fragmentary sectional lS view taken along the line 7-7 of Figure l;
Figure 8 is a top plan view of the blood with~
drawing cannula with its cooperating trocar assembled therein;
~ igure 9 is a side view of the cannula shown in ~igure 8;
Figure 10 is an end view of the cannula shown in Figure 8; and Figure 11 is a perspective view of the trocar shown in Figure 8.
Referring now more particularly ~o the drawings, there is shQwn therein a preferred apparatus 10 embodying the princi?les of the present invention ~or practic.ng the method of the present invention. ~ile it is possible to utilize other apparatus in practicing the present method, since the apparatus 10 is preferred the principles of the present invention can best be understood by first consider-ing the preferred apparatus 10 and then considering the method procedures involved in utilizing the preferred ap-paratus.
In its broadest aspects, the apparatus 10 includes ; sterile tubing, generally indicated at 12, wh.ich defines an extracorporeal blood flow path. A pump mechanism prefer-ably in the form o~ a peristaltic roller pump, generally indicated at 14, is provided ~or pumping blood along the extracorporeal flow path at a controlled rate from the inlet tubing end to the outlet tubing end. In addition, there is provided a temperature control zone preferably in the form of a heat exchanger assembly 16 through which the blood flowing along the extracorporeal flow path has its temperatuxe controlled, preferably both by heating and cooling, through a control device, generally indicated at 18, for the liquid circuit of the heat exchanger assembly 16. Finally, the apparatus 10 includes means, generally indicated at 20, for communicating the inlet end of the :
t~L~
tubing 12 defining the extracorporeal flow path with the bloodstream of a patient and the outlet end of the tubing 12 defining the extracorporeal flow path with the bloodstream of the patient, so that the returning blood is systemically distributed ~ithout adversely affecting the blood depleted areas frorn which the blood is withdrawn.
The tubing 12 may be formed of any suitable plastic material, as, for example, vinyl polymer (e.g. Tygon~), polytetraflouroethylene (e.g. Teflon~), or other plastic 10 materials having known uses in medical applications (e.g.
Silastic~). An exemplary tubing size is 1/4" i.d., with a convenient length being from 3 - 5'. The pump assembly 14, as previously indicated, preferably embodies a peristaltic roller type pump driven by a variable speed electric motor. A
peristaltic pump is preferred because it can utilize the replacement sterile tubing 12 for blood contact and does not provide pump part which must be maintained in a sterile condition. An exemplary pump is manufactured by Sarns, having a 1-2 liter per minute capacity.
A preferred embodiment of the heat exchanger assembly 16 is available comrnercially under the tradename Travenol Mini-Prime, 5M0 337, which has a 57 cc capacity and rated flow of 1-3 liters per minute.
~ 'ith reference to ~igure 2, the ccntrol device 18 is made up of indivldually known components. As shown, there is pYovided a cooled liquid reservoir 22 and a heated liquid reservoir 24 each containing a body of liquid. ~hile any liquid may be utilized a preferred embodiment is water.
Each reservoir is provided with a stirring or agitating means 26 for purposes of mixing the liquid contained therein so as to render the temperature thereof more uniform throughout. The cool liquid reservoir ~2 is provided ~ith a cooling unit, schematically indicated at 28, while the ; heated liquid reservoir 24 is provided with a heating unit 30. A liquid circulatin~ system is provided in cooperating ; relation between the cooled liquid reservoir 22 and heated liquid reservoir 24 anA the liquid side of the heat ex-changer 16. Such circulating system include~ the utili7ation of two pump assemblies, schematically indicated in the drawings at 32 and 34.
; As shown in Figure 2, the pump assembly 3~ i5 associate~ with the cooling liquid reservoir 22 and includes an inlet or suction pipe 36 extending from the reservoir 22 to one side of the pump 32 and an outlet pipe 38 extending therefrom. Similarly, an inlet pipe 40 ex-tends from the heated liquid reservoir 2~ to one side of the pump 34 which side has an outlet pipe 42 extending therefrom. Outlet pipes 38 and 42 are interconnected by a :
;
;' t ~ ~ r~
T-connector 44 which has a pipe 46 extending therefrom to the liquid inlet side of the heat exchanger 16. ~ pipe 48 extends from the outlet of the liquid side of the heat exchanger 16 which by means of a Y-connection S0 communi-cates with two branch conduits 52 ~nd 54 extending respec-tively to the opposite sides of the pumps 32 and 34. The circuit is completed by pipes 56 and 58 connected respec~
tively to the outlet of the opposite sides of pumps 32 and 34 and the cooled liquid reservoir 22 and heated liquid reservoir 24 respectively. As shown, an overflow pipe 59 is connected between the reservoirs.
The cooling unit 28 is of conventional nature and is adapted to maintain the liquid in the reservoir 22 at a substantially constant temperature as, for example, 30C.
Likewise, the heating unit 30 is of conventional construc-tion and is adapted to maintain the liquid within the heated liquid reservoir 24 at a substantially constant temperature as, for example, 45C. Pump 32, when operated, serves to metex from the reservoir 22 through pipe 35 an amount of 2~ liquid which is equal to the amount of liquid returned through pipe 56. In a simi.lar manner, pump 34 when operated serves to meter an amount of flow from the reservoir 24 which is always equal to the amount returned through return pipe 58. A control, schematically indicated at 60/ for varying the rate of movement of the pumps 32 and .
34, e.g. electrical controls for th~ variable speed elec-trical motors dxiving the same whic~ form a part of the pump assemblies schematically illusorated is operable so that the total output of the two p~ps is adjusted to and maintained at a substantially constant rate, as for example, approximately lO liters per minute. The control 60 is also operable to effect a proportional variation in the rate which each of the two pumps assume of this total out-put from 0-lO to lO~0.
l~ Control of the pump assemblies 32 and 34 is undertaken in accordance with the readout of three tem-perature recording devices 62, 64 and 66 placed respectively to sense the core tempera~ure of the patient's body te.g. a rectal probe or isophageal probe), the temperature of ~he lS blood leaving the heat exchanger 16 being returned to the patient and the temperature of the liquid entering the heat exchanger. A pressure sensing device 68 is also provided in the liquid inlet line 46. I~ will be understood that the temperature sensing devices and pressure sensing devices are of any conventional design, preferably of the ype providing a remote readout, as sche~atically indicated by corres-ponding primed numerals~
For illustrative purposes it is sufficient t.o note that control 60 can be manually operated to determine the propor~ion of the total liquid flow through the heat exchangex which is provided by the ~ooled liquid at 30C and the heated liquid at 45C. Control 60 thus serves to directly vary t~e liquid temperature sensed by device 66 between the low limit of 30C and upper limit of 45~C, which in turn will vary the temperature of the blood sensed by device 64 which in turn will affect the patient's systemic blood temperature and hence the temperature sensed by device 62. It will be understood that while the operation of control 60 is set forth for illustrative puxposes as bein~
manual, the control 60 may be rendered automatic and ~ro-grammable if desired.
Referring now more particularly to Fi~ures 3-11, the communicating means 20 preferably comprises a totally subcutaneous implant device, generally indicated at 70, which serves as the means communicating with the patient's bloodstream and a pair of percutaneous cannula~trocar assem-blies, generally indicated at 72 and 74, which serve as the means for operatively communicating the implant de-vice 70 with tubing 12 defining the extracorporeal flowpath. As best shown in Figures 3-7, the implant device includes a body 76 of elastomeric material such as Silastic~, molded so as to provide an arterial passage 78, a spaced venous pas~age 80 and a by-pass conduit 82 connect~d between the inner end of the passage 78 and , the inner ~nd of the passage 80. ~s best shown in Figure 3, the passage, 78 and 80, together with the ~y-pass conduit 82, are of generally ~-shaped configuration.
Each of the passages 78 and 80 has a peripheral S cross-sectional configuration which is elongated in one direction; namely, the direction ln which they are spaced apart, with sharp points defining opposite ends in the direction of elongation. The preferred configuration shown is further characterized by a pair of convexly curved lines extending between the sharp points~ the distance between the central portions of the convex lines being approximately one-half the dis~ance between the two end points. Wnlile the by-pass conduit may be of other cross-sectional configura-tion, as shown, it too is of similar cross-sectional con-figuration. This preferred cross-sectional configuration for the passages 78 and 80 is provlded for the purpose of cooperatively receiving the correspondingly shaped exterior peripheries of the cannulas of the assemblies 72 and 74, which assemblies are so shaped for the purpose of co-operating with a pair of slits 84 and 86 formed in thebody 76 in operative association with the passages 78 and 80 respectively.
As shown, each slit 84 and 86 extends from a position exterior of the body 76 to a position of com-munication with the inner end of the associated passage 78 or 80. The width of each slit is generally equal to the distance between the end points of the associated passage and is oriented in its closed conditionr as best shown in Figure 4, in longitudinal alignment with a plane passing between the end points of the associated passage.
In the closed condition sho~l, the two planar interior surfaces of the body 76 which d~fine the respective slit 84 or 86 are resiliently urged into engagement by the elastomeric characteristics of the body material. The engagement of the surfaces serves to exclude any spaces which could contain fluid such as blood between the two positions of extent of the slit, as aforesaid.
The resiliency of the elastomeric material of the body 76 also permits each slit a4 and 86 to be moved by its respective cannula-trocar assembly 72 and 74 into an open condition where the planar body surfaces defining the slit are spxead arcuately so that the profile thereo~ coincides with the peripheral configuration o~ the associated passage 78 or 80.
To aid the entry and insertion of each cannula-trocar assembly through its associated slit, there is molded in embedded relation within the body 76 a pair of metallic guide structures 88 and 90. Each guide structure is pre-ferably made of a medically accepta~le interior use metal, such as stainless steel (e.g. Vitallium Metal manufactured by Howmedica). The guide structures include similar ;
inwardly tapering annular parts 92 and 94 respecti~ely fixed to the exterior end face of the body 76 and similar parallel spring finger parts 96 and 98 respectively em-bedded in the exterior of the body on opposite sides of associated slit. The tapered part~ 92 and 94 provi~e the guide assist function previously no~ed while the spring finger parts 96 and 98 provide a spring assist function for the slits of the elastomeric body serving to resiliently urge the slit defining surfaces toward one another in addition to the spring function provided by the elasto-meric characteristics of the material of the body 76.
The implant device 70 also includes a pair of tubes 100 and 102 made of vascular prosthesis material.
A preferred vascular prosthesis material is woven Dacron~
marketed commercially by Meadox Medicals although any othex acceptable vascular prosthesis material may be utilized. As bes~ shown in Figure 1, the tube 100 has one end thereof fixed in communicating relation with the outer end portion of the arterial passage 78, as by being molded in embedded relation. The opposite end of the tube 100 is adapted to be connected, as by suture, to a surgical open1ng ~ormed in the side wall of a femoral artery so that the interior of the tube 100 is in com-municating relation with the interior of the femoral artery. In a like manner, one end of the tube 102 is 8'~
embedded in communicating relation with the outer end por-tion of the venous passage 80 and its opposite end is adapted to be sutured to a surgical side wall opening in the associated femoral vein so that its interior is in com-municating relation with the interior of the femoral vein.
The implant device 70 also includes a layer offabric 104 which is fixed to the inner side wall of the elastomeric body as by Silastic~ glue or the like. The fabric 104 includes marginal portions extending laterally outwardly from the operative inner side wall of the body 76 to which it is fixed. The fabric layer 104 and particularly the marginal portions thereof provide for initial fixa~ion by suture of the body 76 during implant and for subsequent semi-pe~nanent fixation by tissue ingrowth. A preferred fabric material is Dacron~ double velour which is marketed commercially by Meadox Medica 16 .
For identification purposes directly from the implant device itself, radiopaque identification (not shown) is provided on the operative outer side wall of the elastomeric body 76. Such identification insul~s that the proper cooperating cannula-trocar assemblies 72 and 74 will always be used since such assemblies can be ascer-tained from the implant itself after total implantation has been effected through X-ray identification.
Re~erring now more particularly to Figures 8-11 ~L ~ L~
of the drawings, the details of con~tr~ction of the carnula-trocar assemblies 72 and 74 are sho~n therein. It will be understood that since the assemblies 72 and 74 are left and right hand mirror images of one another, a description of one of the assemblies will suffice to give an understanding of both. The assembly 74 is shown in assembled condition in ~igure 8 and includes a percutaneous cannula, generally indicated at 106 and a c~operating trocar, generally indi-cated at 108.
The cannula 106 includes a tubular body which includes a straight section llO defining the subcutaneous end portion of the cannula and an angular section 112 which, together with an adjacent part of the strai~ht section llO, defines the extracorporeal end portion of the cannula. The cannula 106 is pre~erably molded of radiopaque plastic material having sufficient rigidity to prevent interior collapse when in operative position within the implant device 70. Thermoset plastics are preferred al-though thermoplastic materials with sufficient functional rigidity and heat stability for sterilization can be used.
An exemplary material is ethyle~e-propylene-terpolymer (e.g.
where the third monomer is norbornadiene) impregnated with a radiopa~ue material such as barium sulfate.
As shown, the entire straight section llO of the cannula 106 has its exterior periphery formed with a cross-sectional configuration which conforms with and engages ; - 2~ -~ithin the interior periphery of the body 76 defining the artery passage 78 or venous passage 80. Such configura~
tion, however, is re~uired only in the extent of the sub cutaneous end portion which is disposed within the passage and ~ssociated slit of the implant body during operation.
The cannula 106 includes an interior passage 114 which extends through the angular section 112 into the straight section 110 and out of the extremity thereof.
In order to maximize the interior passage cross-sectional area for an optimum exterior cross-sectional size, the cross-sectional configuration of the interior passage ,114 at least in the straight section 110, conforms to the exteriox cross-sectional configuration.
In this regard it will be noted that the trocar 108 consists essentially of a molded body of plastic ma-terial, sirnilar to the plastic material of the cannula 106, which provides a b7ade part 116 and a handle part 118. The blade part 116 is of a longitudinal extent generally equal to the longitudinal extent of the straight 2~ section 110 of the cannula 106. T~le main extent of the blade part 116 has an exterior peripheral cross-sectional configuration conforming with the interior cross-sectional configuration o~ the portion of the interior passage 114 extending through the straight cannula sec-tion 110. The blade par~ 116 includes a sharpened tip _ ~9 _ portion 120 whic~ tapers gradually in cross-sectional con-figuration outwardly from the aforesaid configuration to a point.
It will be noted that the extracorporeal end of the straight section 110 of the cannula 106 is closed as by a diaphragm or plug of elastomeric material 1~2 which pref~
erably is preslit (although may be imperforate) to permit .the passage of the trocar 10~, pointed end 120 ~irst, therethrough.
The exterior periphery of the outer end of the angular section 112 is provided with gripping flanges,l24 operable to effect a fluid-tight connection with the in-terior of the tubing 12. When the trocar 10~ is withdrawn, the elastomeric plug slit, which has expanded to receive the ~5 trocar) contracts to close the end of the straight section of the cannula and insure that all of the blood will flow outwardly through the angular section 112 and into the tubing 12.
Formed on the exterior periphery o~ the straight 2~ section 110 of the cannula is an annular shoulder 126 which ~orms a stop surface acing in a direction toward the open extremity of the s~raight cannula section operable to engage the guide part 92 or 94 of the implant device when the cannula is in its ully inserted operative position, as 2S shown in Figure 7. The straigh~ cannula section 110 is ~ 30 -,,f~f,~
formed with an opening 128 which extends inwardly from one exterior end point into communication with the interior passage 114 at a position to register with the by-pass conduit 82 of the implant body 76 when the cannula is fully S inserted, as aforesaid. Formed on the exterior periphery of the extracorporeal portion of the straight cannula sec~ion 110 is a stabilizing shield 130 which ~acilitates main-tenance of the cannula on the patient when in operative position.
A preferred procedure is to soat all of the blood contacting sur~aces of the cannulas 106 ti.e. interior passages 114) tubing 12 and elastomeric body 76 (passages 78 and 80, conduit 82 and slits 84 and 86) with an anti-coagulant coating. A suitable coating material for this purpose is marke~ed commercially under the tradename TDMAC~.
The manner in which the device 70 is suryically implanted is in accordance with usual implant procedures well known to those skilled in the art. For present pur-poses suf~ice it to say that the elastomeric body 76 isimplanted in an arterior ~emorai region spaced downwardly from the position o~ bending at the hip approximately the distance o~ the width of a normal-si2ed palm ~ap-proximately 4") as is clearly shown in Figure 1. The large area faces of the body 76 are preferably disposed parallel with the skin with the face having the ~abric 104 fixed tllereto innermost. The a~texial and venous tubes 100 and 102 extend upwardly and the free ends are tapered and sutured to surgical openings in the side walls o~ the ~emoral artery and vein respectively so as to extend there~rom at an angle of approximately 45.
This procedure is accomplished in accordance with usual practices relating to the use of vascular prosthesis material.
The marginal edge portions of the fabric 104 are sutured to t~le adjacent tissue to provide initlal body 76 fixation, as aforesaid. A11 of the exterior surfaces o~ the implant device 76 are contacted with tissue includ-ing tapered guide parts 92 and 94 (with fat).
~s previously indicated, it is possible to use known shunt devices ~e.g. U.S. patent No. 3,713,441) in lieu of the device 70 so long as they provide the neces-sary capacity which is ordinarily not the case without modification.
The advantages of the use of the implant device 21 70 is that it is speeifically intended for long-term surgical implantation in the thigh of cancex patients, whereby its anastomosis to the femoral artery and vein~
creates a high-flow (1-2 litexs per minute) arterio-venous conduit which may be repeatedly entered by per-cutaneous insertion of the cannula assemblies 72 and7~.
~ 32 -As compared with other prosthetic partially exteriorized A-V Shunt devices as ~sed for renal hemo-dialysis the implant device 70 red~ces the ris~ of in~
fection, reduces ~he risk of thrombosis t reduces the ris~ of disruption and improves the esthetics of normal usage. The renal dialysis experience indicates that partially exteriorized lower extremity shunts frequently develop infection along the tract of the shunt tubing.
The incidence and severity of this type of infection would be increased in cancer patients by the immunosup-pressive effects of malignancy, and the chemotherapy and radiotherapy they frequently receive. The implantable device 70 greatly diminishes the risk of infection and requires no increase in th~ amount of surgery needed for insertion. Cancer patients have a state of hypercoagul-ability or lncreased tendency to form blood clots in their normal and any artificial circulations. Ordinary A-V
shunts last only 2-5 months in hypocoagulable dialysis patients, and likely will clot much sooner in those with the "Stic~y blood" of disseminated malignancy The im-plantable device 70 has a shorter fluid path, much of which will be covered by a patient's own intravascular tissues, and hence will be less likely to thrombose.
Partially exteriorized shunts have press connections which Il.dy b~ inadvertently loosened or disconnected.
.
Such events have caused deaths in dialysis patients but, in general, those shunts are small and a patient can control a bleeding shunt before exsanguination occurs. However, disruption of the large shunt necessaxy for hyperthermia would result in massive bleeding, which could render a patient unconscious even before the shu~ could be reached through normal clothing. This cannot happen with the de-vice 70 as the connections are permanent, as well as totally protected.
Unlike commercially known shunts, there is no external tubin~ associated with the device 70. A nor~al bath or shower could be taken by the implanted patient, whereas those with partially exteriorized shunts cannot submerge them and must resort to less hygienic methods, a probable factor in theix increased incidence of in-fections. Furthermore, the device 70 does not interfere with clothing or require any sort of dressing, leaving a patient's appearance unimpaired, an important asset to the depressed cancer patient.
~3 The manner in which each cannula assembly 72 or 74 is inserted into cooperating relation to the im-planted device 70 should be apparent rom the above. I~
is of significance to note ~he advantages of the utili-zation of a main implant body 76 which provides increased palpation facility during cannulation. Moreover, cannu-; lation is effected in a straight line relationship resulting in a straight line percutaneous communication with the extracorpor~al flow path. The preferred cross-sectional configuration of the cannula enables simple but effective alignment to be accomplished duxing insertion.
Such cross-sectional configuration a:Lso provides optimal cooperation with the slits 84 and 86 of the elastomeric body 76 both in expanding the slits during insertion and in contracting the peripheral portion of the cannula extending therethrough to insure a good fluid-tight con-nection. The extension of this cannular cross-sectional configuration with the elastomeri.c body passages 78 and 80 also insures non-distortion of these passages and a full flow area of 4 mm or larger.
The flow capacity provided is of extreme im-portance since it is a critical determining factor in the time required to bring the patient's blood up to the desired treatment temperature and to the sensitivity of the temperature control available. The approximate 1 liter minute capacity provided is based upon the aver-2 age size of an average adult patient and, of course, should be varied to suit the particular size of the patient being treated. The term approximately 1 liter per minute is therefore intended to comprehend within its meaning such variation to suit the patient size.
It will be understood that once the inlet and outlet ends of the tubing 12 are connected over the flanges 124 of the ~annula of the assemblies 72 and 74 and the associated trocars 108 of the assemblies are withdrat~n, pump 14 can be started t~ commence the flow of blood along the extracorporeal flow path at the approximate 1 li~er per minu~e as aforesaid and through the temperature control zone thereof. Initially, control 60 is set to pass 100% 45C water through the heat exchanger 16. During this initial treatment phase withdrawn blood temperatures measured at 62' will show a gradual increase ~rom the initial normal reading of approximately 37C. The cap acity and effectiveness of the heat exchanger 16 is such that readings of the returning blood taken at 64 closely approximate the 45C maximum water temperature utilized.
As the heated blood is returned to the femoral vein through the blood receiving percutaneous cannula 106, venous passage 80 and tube 102, it is distributed systemically which in turn, has the effect of increasing the total systemic tem~erature. As the patient's core body tem-perature increases tohard the 41.5C level control 60 must be operated to lower the liquid reading at 66 to a value below 45C as, for example, 42.SCo The liquid temperature level stabilized at 42.5C, the patient core body tempera-ture readings at 62, and returning blood readings will stabilize at a desired level of approximately 41.SC and ~0.0C
respectively. This critical phase wherein the patient's .
t9~
systemic temperature is increased and stabilized should, as aforesaid, normally be completed within one hour, al-thou~h here again, variation because of patient si~e will occur.
Once temperature stabilization is achieved as aforPsaid, treatment is continued for a time period ef-fective for the particular cancer which the patient has.
A preferred minimum time for all types including simple carcinomas is six hours although treatment ~imes of 20 hours and longer will be required for more complex cancer situations.
Preferably, a third phase of the pxesent method involves utilizing the continued blood flow through the temperature co~trol zone of the extracorporeal flow path to reduce the blood temperature to normal and, hence, the patient' 5 systemic temperature to normal. This phase is initiated by turning control 60 to pass predominately 30C
water through the heat exchanger 16. This has the ef~ect of substantially lowering the readings of the returning blood taken at 6~. Again, this cooler blood is distributed systemically, causing the systemic temperature to lower until a normal of 37bC is reached. The decreasing tem~
perature phase normally will require a time period ap-proximately ~he same as the initial increasing temperat~re phase although usually somewhat less.
.
~4~
Preferably, the patient is maintained during treatment il a skin contacting environment approximating that of an intensive care room. While it is within the contemplation of the invention to provide a skin insulat-ing environment and even comparable elevated temperaturesto inhaled ~ases, the intensive care like environment is preferred because the temperature level o~ the skin and respiratory system does no~ vary significantly from ~he induced hyperthermia systemic level and access to th~
patient is much more readily obtained. Moreover, the ap-plication of radiation or chemotherapy treatmen~s can be carried on simultaneously if desired.
It thus will be seen that the objects of this invention have been fully and effectiv21y accomplished.
lS It ~ill be realized, however, that the foregoing preferred specific embodiment has been shown and described or the purpose of illustrating the functional and structural principles of this invention and is subject to ch~nge without departure from such principles. Therefore, this invention includes all modif~cations encompassed within the spirit and scope of the following claims.
Claims
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Apparatus for providing a constant flow of temperature controlled liquid into and out of heat exchanger means in heat exchange relation to a flow of blood through said heat exchanger means which forms a part of a systemic extracorporeal flow circuit of a human patient for systemically treating the patient hyperthermically to retard the growth of cancer cells in the patient, said apparatus comprising, first reservoir means for containing a first body of liquid, second reservoir means for containing a second body of liquid, first pump means for pumping liquid from said first reservoir means, second pump means for pumping liquid from said second reservoir means, means for directing a predetermined constant flow of liquid from said pump means into said heat exchanger means, means for directing the liquid from said heat exchanger means to said reservoir means, means for maintaining the liquid in said first reservoir means at a substantially constant elevated temperature of approximately 45°C, means for maintaining the liquid in said second reservoir means at a substantially constant reduced temperature of approximately 30°C, and means for varying the amount of liquid from said first pump means directed into said liquid flow directing means from 0 to 100% while proportionately varying the liquid from said second pump means directed into said liquid flow directing means from 100% to 0 and while maintaining the constant flow as aforesaid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000399707A CA1144841A (en) | 1977-05-31 | 1982-03-29 | Method and apparatus for effecting hyperthermic treatment |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US802,033 | 1977-05-31 | ||
| US05/802,033 US4181132A (en) | 1977-05-31 | 1977-05-31 | Method and apparatus for effecting hyperthermic treatment |
| CA303,444A CA1127033A (en) | 1977-05-31 | 1978-05-16 | Method and apparatus for effecting hyperthermic treatment |
| AU53195/79A AU518660B2 (en) | 1977-05-31 | 1979-11-26 | An elongate percutaneous cannula |
| CA000399707A CA1144841A (en) | 1977-05-31 | 1982-03-29 | Method and apparatus for effecting hyperthermic treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1144841A true CA1144841A (en) | 1983-04-19 |
Family
ID=27423445
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000399707A Expired CA1144841A (en) | 1977-05-31 | 1982-03-29 | Method and apparatus for effecting hyperthermic treatment |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1144841A (en) |
-
1982
- 1982-03-29 CA CA000399707A patent/CA1144841A/en not_active Expired
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4181132A (en) | Method and apparatus for effecting hyperthermic treatment | |
| US4479798A (en) | Subcutaneous implant useful in effecting hyperthermic treatment | |
| US4476867A (en) | Apparatus for effecting hyperthermic treatment | |
| US4298006A (en) | Systemic hyperthermia with improved temperature sensing apparatus and method | |
| US3140716A (en) | Heat exchanger for blood | |
| JP4456764B2 (en) | Heat exchange indwelling catheter cooling system | |
| Seneviratne | Physiological and pathological responses in the blood‐vessels of the liver | |
| US3826257A (en) | Prosthetic shunt | |
| US7189253B2 (en) | Cerebral temperature control | |
| US7135008B2 (en) | Method and apparatus for ultrafiltration utilizing a peripheral access dual lumen venous cannula | |
| US20060079916A1 (en) | Body fluid cartridge exchange platform device | |
| CN102781378A (en) | Extracorporeal blood treatment apparatus, system and method for selectively cooling the brain relative to the body during hyperthermia or inducing brain hypothermia | |
| AU2003248190A1 (en) | Circulatory support system and method of use for isolated segmental perfusion | |
| Work | Hemodialysis catheters and ports | |
| CA1144841A (en) | Method and apparatus for effecting hyperthermic treatment | |
| Hadaway | Comparison of vascular access devices | |
| CA1144836A (en) | Method and apparatus for effecting hyperthermic treatment | |
| CA1144837A (en) | Method and apparatus for effecting hyperthermic treatment | |
| Fish et al. | Preparation of chronic thoracic duct lymph fistulas in man and laboratory animals | |
| IE47074B1 (en) | Apparatus for effecting hyperthermic treatment | |
| KR820000226B1 (en) | Apparatus for effecting hyperthermic treatment | |
| Lee et al. | The pediatric burned patient | |
| CN220142014U (en) | Multifunctional arteriovenous fistula postoperative rehabilitation exercise support | |
| Twardowski et al. | PD catheters: evolution towards optimal design | |
| CN217409126U (en) | Heating blanket for operation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |