WO2001039819A2

WO2001039819A2 - Method and apparatus for closed recirculation of synthetic cerebrospinal fluid

Info

Publication number: WO2001039819A2
Application number: PCT/US2000/042473
Authority: WO
Inventors: Glenn Frazer; Timothy J. Pelura; Bruce Shook
Original assignee: Neuron Therapeutics, Inc.
Priority date: 1999-12-03
Filing date: 2000-12-01
Publication date: 2001-06-07
Also published as: WO2001039819A3; CN1433328A; EP1235602A2; CA2393221A1; AU4512701A; JP2003515394A; KR20020077351A

Abstract

This generally relates to methods and apparatus for accomplishing the closed recirculation of cerebrospinal fluid (CSF), typically synthetic in nature, through the cerebral and spinal regions of the body and the replenishment and revitalization equipment. A preferred cassette variation includes a modular disposable package of equipment preferably packaged in such a way that it is readily and quickly employed in an emergency. The cassette preferably contains all or most of the components forming the fluid path which accomplishes the conditioning of the recirculated therapeutic CSF from and to the patient.

Description

METHOD AND APPARATUS FOR CLOSED RECIRCULATION

OF SYNTHETIC CEREBROSPINAL FLUID

FIELD OF THE INVENTION

This invention generally relates to methods and apparatus for accomplishing the closed recirculation of cerebrospinal fluid (CSF), typically synthetic in nature, through the cerebral and spinal regions of the body and the related replenishment and revitalization equipment. A preferred cassette variation of the inventive assembly includes a modular disposable package of equipment preferably packaged in such a way that it is readily and quickly employed in an emergency. The cassette preferably contains all or most of the components forming the fluid path which accomplishes the conditioning of the recirculated therapeutic CSF as well as its passage from and to the patient.

BACKGROUND OF THE INVENTION

Despite recent improvements in the understanding and treatment of stroke, this disease remains the third leading cause of death in the United States. It follows only heart disease and cancer. It is the largest single cause of neurologic crippling in the country, and kills nearly 160,000 Americans each year. It is also one of the leading causes of adult disability.

In addition to its tragic health consequences, stroke costs the United States about $45 billion annually in treatment and rehabilitation expenses as well as lost job productivity. Therefore, there is still a critical need for further improvement in the prevention, detection, and treatment of stroke and stroke-related injury. One difficulty with effective treatment is related to the speed with which a stroke inflicts cellular damage. For ischemic stroke, the cascade caused by the stroke-initiated infarct occurs rapidly. Without prompt medical treatment, typically within about six hours of the stroke event, brain cells in the penumbra surrounding the infarct will die. Although neural tissue in this penumbra does not exhibit notable necrosis until about 24 hours after the stroke-causing occlusion is formed, vascular tissue and smaller arterioles are susceptible to irreparable damage within 30 minutes of occlusion. Edema also begins to occur throughout the penumbra due to reduced cellular ion pump activity; this will result in swelling of the neural tissue and accelerated neural tissue damage. One method for providing timely therapy to neural tissue under such severe ischemic conditions is introducing an oxygenated fluorocarbon nutrient emulsion (OFNE) through a portion of the ventriculo-subarachnoid spaces surrounding the brain and spinal cord where the cerebrospinal fluid (CSF) exists. Emulsions such as those described in U.S. Patent No. 4,981,691, to Osterholm et al., ("Osterholm '691"), the entirety of which is herein incorporated by reference, are well-known in the art. OFNE treatment is intended to provide much-needed oxygen and nutrients to neural and vascular tissue until the occlusion is treated. It offers a powerful emergency therapy for those individuals suffering the first symptoms of ischemic stroke.

Disorders such as cerebral edema, neurosurgical sequlae, encephalitis, or neoplastic disease, as well as severe head or spinal trauma may present the need for replacing the

CSF. For instance, patients with hydrocephalus, a condition in which there is an abnormal increase in the amount of CSF within the cranial cavity, are presented with life-threatening levels of elevated intracranial pressure that must be relieved by drainage. This invention relates both to procedures for circulating cerebrospinal fluid through at least a portion of the pathway discussed below or through other various sites in or on the body where a biocompatible oxygen-containing fluid, typically a cerebrospinal fluid (CSF), would be beneficial. The invention also relates to the system of devices used to safely circulate the CSF through the body and to control the various constituents of the CSF, as well as its temperature and pressure. Central to this invention is the concept that the physical system is closed and that fluid exiting the body is recirculated into the body.

The concept of stroke treatment or treatment of hypoxic/ischemic tissue disorders using an oxygenated nutrient emulsion which is delivered to the ventriculo-subarachnoid spaces is known. For instance, U.S. Patent No. 4,378,797, to Osterholm ("Osterholm

'797") and its progeny, U.S. Patent No. 4,686,085, to Osterholm ("Osterholm '085"), discuss a support system and method for treating severely ischemic brains. In those patents is a shown a procedure for passage of an oxygenated nutrient solution through at least a portion of the ventriculo-subarachnoid spaces. The nutrient emulsion described there contains an oxygenatable non-aqueous component, an aqueous nutrient component, and an emulsification component, which allow the nutrient emulsion to be physiologically acceptable in those body areas. Osterholm '797 and Osterholm '085 and all of their included information are incorporated by reference.

Specifically, Figure 1 in each of Osterholm '797 and Osterholm '085 depict a system for "circulating nutrient emulsion through a cerebrospinal pathway." A nutrient emulsion reservoir is provided for receiving and retaining that emulsion. The emulsion is introduced into the cerebrospinal pathway after a pH adjustment, filtering, temperature adjustment, oxygenation, and adjustment of the pressure and flow rate of the nutrient input stream. It is noted that the nutrient input stream is preferably delivered to a ventricle of the brain and more particularly to a lateral ventricle. This is said to be so to permit the oxygenated nutrient emulsion to come into contact with the subarachnoid spaces, miniature Virchow-Robins spaces, cerebral and cord surfaces, and the cerebral ventricles. The lateral ventricle is a preferred pathway since withdrawal of the fluid from a remote portion of the pathway, e.g., from the spinal cavity, will cause circulation of fluid within the cerebrospinal pathway. Figure 1 of the Osterholm '085 and '797 patents shows withdrawal of the fluid from the spinal subarachnoid space or alternatively from the cisterna magna at the base of the brain. Once the oxygenated nutrient emulsion is removed from the body in the procedures of Osterholm '085 and '797, that fluid is treated as a diagnostic fluid. The output monitor outlined in Osterholm '797 and Osterholm '085 is said continuously to watch various chemical and physical characteristics for such properties as flow rate, hydraulic pressure, potassium and sodium ion concentration, temperature, lactic acid concentration, gamma amino butyric acid (GAB A) and other amino acid concentrations, oxygen concentration, carbon dioxide concentration, enzymes, and ammonia concentration. These output fluid characteristics may be used both to inform the physician of certain states of the patient's neurologic tissue and to allow reconstitution, reformulation, or purification of the oxygenated nutrient emulsion to compensate for those patient's deficiencies. It should be noted, though, that the fluid leaving the patient is optionally sterilized and reconstituted to "ensure that the reconstituted fluid satisfies requirements of the nutrient emulsion reservoir." See, e.g., column 14, line 18 et seq. of Osterholm '085. These documents do not describe the closed procedure for recirculating synthetic cerebrospinal fluid through the body using a closed system, nor do they suggest the closed system described herein.

SUMMARY OF THE INVENTION

In general, this invention is a closed synthetic cerebrospinal fluid recirculation assembly made up of a fluid entry device, such as a catheter, suitable for introducing a synthetic CSF into an extravascular cerebrospinal pathway or other site in or on the human body, a fluid withdrawal device for withdrawing said cerebrospinal fluid from the body site, a fluid reservoir, and a conditioning circuit having at least an oxygenator. The conditioning circuit may also include a dialysis component or filter (preferably an ultrafilter) for removing endotoxins or metabolites and potentially for introducing drugs into the synthetic CSF. If the oxygenator design does not control carbon dioxide concentration in the synthetic CSF, the conditioning circuit may also utilize a separate carbon dioxide gas exchanger. The conditioning circuit withdraws fluid from the reservoir and reintroduces it into the reservoir. The system may include a flow controller for controlling flow of synthetic CSF back into the body.

Typically, the system will include various filtration or purification components, in addition to the to dialysis or ultrafiltration units discussed above, to remove or lessen the amount of particulates such as, e.g., blood clots, cells, bacteria, cellular debris, or biochemical/chemical compounds such as metabolic or bacterial or viral toxins, chemicals, therapeutics, or diagnostics. The system may have a diverter valve connected to a fluid collection container for collecting, e.g., a first fluid sample, which may be used for analysis and the like.

The fluid reservoir may be insulated for temperature control and may have a sonicator to maintain the CSF dispersion (where needed) and/or a stirrer. The dialyzer or ultrafilter is generally used for the removal of metabolites, toxins, and the like and potentially for introducing nutrients, drugs, or medicine into the CSF without opening the CSF circuit. The dialyzer may be of any of a variety of designs, e.g., a plurality of high surface area polymeric tubes or high surface area polymeric plates. In conjunction with the dialyzer, a heat exchanger may be used for controlling the temperature of the exchange fluids, e.g., the drug-containing or metabolite/toxin-free fluids. In keeping with the closed nature of the system, the dialyzer may also have a closed source of medicine or drugs.

One or more sensors for monitoring at least one of pH, albumin, glucose, lactate, bicarbonate ion, amino acids, alpha ketoglutaric acid, Mg ions, Ca ions, K ions, Na ions, and Cl ions concentration in said synthetic CSF may be used either with the reservoir or with a slipstream taking a sample stream from the reservoir. The sensors may be used only to monitor or to control those values.

The system usually includes a return pump for controllably returning CSF to the body.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a general, schematic outline of the components of the inventive system. Figure 2A schematically depicts the conditioning slipstream system. Figure 2B schematically depicts a preferred oxygenator for the conditioning circuit or loop.

Figure 3 is a depiction of a preferred cassette variation of the invention in a clinical cabinet.

Figure 4 is a schematic depiction of the preferred cassette variation.

DESCRIPTION OF THE INVENTION As noted above, this invention is variously: a.) a procedure for circulating an artificial or synthetic cerebrospinal fluid through a body opening, cavity, or pathway or upon the body surface and recycle of the resulting fluid through a control and a revitalization circuit, b.) a start-up variation of the recirculation procedure, c.) apparatus or a system of components for performing such processes, and d.) a cassette version of the system. The system is closed in that artificial cerebrospinal fluid is not retrieved from the recirculation circuit and reconstituted or revitalized for subsequent introduction into the circuit.

The closed synthetic cerebrospinal fluid recirculation assembly begins with a device for withdrawing or collecting fluid as it is taken from the body. This fluid withdrawal device may be one or more lumbar, cisterna magna, or intraventricular catheters (100) when the inventive system is used to recirculate the fluid through a cerebro-subarachnoid pathway, or may constitute other collection devices should the circulation system be used, e.g., with a wound treatment package. A suitable, and preferred, lumbar catheter may be found in U.S. Patent Serial No. 09/ 382,136 (Attorney Docket No. 42684-20001.00). Fluid withdrawal device (100) may also comprise a lumbar needle. It should also be made clear that this device and the related methods may be used to circulate the synthetic or artificial cerebrospinal fluid through the body in the "other" direction, i.e., from the lumbar region or lower back, and exiting from the head. The device and processes may be used both on partial and on full circuits of the cerebrospinal fluid cavity of the body, e.g., ventriculo- lumbar, ventriculo-subarachnoid, ventriculo-cisternal, cisternal-lumbar, cisternal- subarachnoid, lumbar-ventriculo, subarachnoid-ventriculo, cisternal-lumbar, etc.

Fluidly connected to fluid withdrawal device (100) is a trap or fluid collection reservoir (102). Fluid collection reservoir (102) is typically used only at the inception of a procedure in conjunction with, e.g., a three-way or diverter valve (104) to collect the first portion of a fluid exiting the body, particularly for diagnosis of maladies from that fluid or for, e.g., removal of fluid in the event that the fluid contains significant bacteria, metabolic or pathologic byproducts, or has a high solids content, as may be the case with a cerebrovascular accident. For instance, a type of hemorrhagic stroke known as a subarachnoid hemorrhage, in which an aneurysm in a large artery bursts on or near the dural matter surrounding the brain, blood may enter into the CSF pathway and present the need for capturing and/or filtering the contaminated CSF. One variation of the recirculation procedure described herein involves removing that first exit volume (usually made up of natural CSF) but recirculating the remainder of the fluid, principally containing artificial cerebrospinal fluid.

An example of such a fluid collection apparatus is found in U.S. Patent No. 5,772,607, to Magram. This device includes a rigid, transparent sheath and an inflatable pouch to receive the CSF. The sheath also contains a balloon. Subatmospheric containers are also suitable for collecting this initial volume of effluent. It is highly desirable that the container (102) be automatically self-isolating via valve (104) upon filling. The container need normally be no greater in size than about 500 milliliters. This container (102) typically is believed to generally contain the highest concentration of potential toxins present in the initial effluent.

Once the trap (102) is filled, valve (104) is switched, and the fluid is passed through optional filter (106). Filter (106) may be either a macro filter for removing osseous particles or the like or a microfilter to remove particles down to and including blood detritus or bacteria. The filter should be of the type which does not upset the micellar dispersion or emulsion of synthetic CSF, should such be present.

The filtered effluent is then directed to reservoir (108). This reservoir (108) is central in this overall system. The overall system itself is minimized inside so it has a nominal dead volume. Nevertheless, reservoir (108) contains the largest volume in the recirculation system. Reservoir (108) may be insulated to maintain temperature or in the event it is a polymeric bag, be adapted to allow ease of temperature maintenance.

Reservoir (108) may be attached to sonificator (110) or may include a stirring device (112) as desired to promote mixing and to preserve the micellar dispersion or emulsion of the synthetic CSF. The use of a reservoir (108) is highly desirable because it contains a critical mass of the system fluid. The complex mixture of the fluid is not highly perturbed when the fluid leaving the patient for recycle is significantly different in composition (or other physical or chemical or biological parameters) than that introduced to the patient. For instance, if the fluid from the patient has been significantly deoxygenated, then mixing that fluid with the larger volume in the reservoir (which is appropriately oxygenated) will cause only modest perturbation to the otherwise controlled composition in the reservoir. Further, the amount of compositional adjustment needed to correct the perturbation is easily achieved.

An auxiliary drug port (130) may be included for quick introduction of materials into the reservoir (108).

It is desirable, but not required, that each of the chemical or biological monitors noted below analyze the circulated fluid either by direct contact with the fluid in the reservoir (108) or via the optional slipstream (114). It is preferred that most of the materials added be added to the reservoir (108) rather than to the slipstream (114) to minimize the interaction between various of the monitoring and analysis devices and to utilize the mixing devices related to the reservoir (108). When slipstream (114) is used, a small pump (116) may be desirable to carry the fluid past the analyzer detectors. Utilizing a separate slipstream is often desirable in that it allows the healthcare institution to change the type of monitors utilized for a particular procedure. The analyzers found in analyzer circuit (118) typically will be for monitoring at least one of pO₂, pCO₂, pH, albumin, glucose ion, lactate ion, bicarbonate ion, amino acids, alpha ketoglutaric acid, and the like. Ionic balance and concentration, i.e., of Mg, Ca, K, Na, and Cl ions, may also be controlled via monitors placed in the slipstream or in the reservoir. Another slipstream (300), or conditioning circuit, may be used for adjusting or balancing pO , pCO , and for the addition of medicines or drugs. This slipstream (300) is shown in Figure 2. Circulation pump (302) pulls a controllable volume from the reservoir (108) and passes the stream to an oxygenator (304). Oxygenators are well known devices and often, when used on blood, are used in conjunction with heat exchangers to control the temperature of the fluid, and hence the blood's absorptivity. In general, blood oxygenators may be used on artificial cerebral spinal fluid. Suitable oxygenator designs are well known and typically are comprised of hollow fiber bundles having a significant surface area. The fibers are essentially small pieces of tubing having a desired gas, e.g., oxygen or mixtures of oxygen and carbon dioxide, on one tubing surface and the fluid on the other surface. There are a variety of polymers which are suitable for these fiber bundles, including certain polyethylenes, polypropylenes, and silicones. U.S. Patent Nos. 5,823,987, to Elgas et al.; 5,855,201, to Fukui et al.; and RE 36,125 to Haworth et al. show typical small gas exchange apparatus suitable for this service. Elgas et al. further shows a heat exchanger suitable for use in this device. The heat exchanger used variously to warm or to cool the fluid is shown at (306) in Figure 2. It need not be physically integral with the oxygenator but to the extent it is used to vary the temperature of the recirculated fluid and thereby partially control the O or CO₂ partial pressure of the fluid, it should be at least on the fluid upstream of the oxygenator

(304).

If a separate carbon dioxide exchanger is used, the so-oxygenated fluid is passed to carbon dioxide gas exchanger (308). The structure of the carbon dioxide exchanger (308) may be the same as that of the oxygenator (304). The partial pressure of carbon dioxide is interrelated to the addition of bicarbonate ion as a buffer and both are used to control pH of the fluid. Control or monitoring of pH is, of course, necessary in any physiologic fluid. However, some additional pH control may be desirable when adding various nutrients, medicines, or drugs to or when removing substances from the fluid in following stage

(310).

Dialysis unit (310) may be used variously to introduce desired various nutrients, drugs, or medicines to the CSF or to remove materials such as metabolites or toxins or even diagnostic and therapeutic media from contaminated CSF. The dialyzer or dialysis component (310) works in the following fashion. The dialyzer (310) may be either one using flat plates or hollow fibers or other high surface structures. When used to introduce materials into the CSF, the CSF is introduced to one surface of a plate or fiber and fluid containing the desired nutrients, drugs, or medicines is situated on the other side of the polymeric surface. By varying the temperature and concentration of the drug in the fluid on the opposite side of the polymeric membrane, the amount of material infused into the CSF is controllable.

Similarly, when the dialyzer or dialysis component (310) is used to remove materials from contaminated CSF, the CSF is also placed on one surface of a dialysis plate or fiber and a non-contaminated fluid of some type is situated on the other side of the polymeric surface. By varying the temperature and concentration of the respective fluids, undesirable material is transported though the dialysis membrane and into the fluid on the opposite side of the polymeric membrane thus controlling the amount of undesired material in the CSF. As shown in Figure 2, dialysis unit (310) may include a line (312) containing a concentration-controlled or temperature-controlled drug-containing solution. That solution is introduced into the dialysis device (310). The drug may be introduced using line (314). Ideally, it would be mixed in some fashion in a mixing chamber (314). Heat exchanger (316) partially controls the rate and concentration of material removal from or drug perfusion into the circulating CSF by varying the temperature of the heat exchange fluid introduced into line (318). It should be understood that the loop containing the fluid passing through the dialysis unit (310) and the heat exchanger (316) is closed. The temperature of line (312) may be controlled in conjunction with the pH of CSF entering dialysis unit (310) at (320) in order to adequately dissolve and maintain the drug in solution.

The so-constructed fluid at line (322) may then be returned to the reservoir (108) as shown in Figure 1. It should be apparent that the sequence of steps in the slipstream (300) need not necessarily be in the order shown in Figure 2.

Returning to Figure 1, makeup fluid, e.g., saline solution, CSF, artificial cerebrospinal fluid, or the like, may be introduced from source (400) through a control valve (402) into reservoir (108). It is contemplated that since there are but only two places into which the fluid may go, into the body itself and into the trap (102), little makeup fluid will be necessary. Control valve (402) desirably is controlled by a level monitor found in reservoir (108).

Another auxiliary drug port (132) is shown in the line passing to the patient. Reservoir (108) should contain generally a steady state composition. The fluid may then be introduced to the patient using (if necessary) pump (410). Pump (410) is shown to be a roller pump. This design is a volumetric pump and is often used for pumping blood since it is quite gentle with the fluid and can be used with surgical tubing. The flow of fluid from the pump to the patient may also be controlled using a control valve (not shown). The flow to the patient may be maintained to hold a specific pressure based on a pressure monitor (414) found in the body. It is highly desirable to use a cooler (412) to slightly cool the fluid either for therapeutic purposes or for the purpose of lowering the partial pressure of the blood gases and to lower the potential for any bubbles.

A suitable spinal column fluid pressure measurement device is found in U.S. Patent No. 5,935,083, to Williams. Other devices are known and readily available.

We consider the most viable variation of this inventive asasembly be as a one-use cassette which is packaged in such a way that the cassette may be may be readily and quickly employed in an emergency situation. Of course it is not our intent that the device is only for use in the treatment of cerebral edema associated with stroke, it is a device which is also suitable for treatment of a variety of other maladies where an oxygenated artificial fluid such as the noted OFNE is desirable, e.g., such as in the peritoneum.

Nevertheless, Figure 3 shows a desirable variation of the inventive device. In particular, the system is shown as a cassette (500) which is placed into a cabinet (502). Cabinet (502) would normally be clinical equipment to be used again and again as necessary. Cassette (500) desirably is used one time per patient. It is of such a configuration that cassette (500) is dropped into cabinet (502) and the pertinent lines connected to catheters in the patient and, after equilibrium is established in the system, the artificial cerebrospinal fluid is passed into and out of the patient.

Specifically, Figure 3 shows a typical IV bag (504) having artificial cerebrospinal fluid therein. The artificial cerebrospinal fluid is pumped to the patient through a line

(506). The lines ((506) and (512) discussed below) are typically of a polymeric, biocompatible tubing used for transport of fluids in surgical situations. In this exemplified setup, the input line (506) is connected to a catheter (508) which is introduced through the skull and into the ventricles. As has been described above, the artificial cerebrospinal fluid flows through the subarachnoid space to the lower back where it is withdrawn using catheter (510) and recirculated via line (512) back to the cassette assembly (500) found in cabinet (502). Again, this is only a preferred variation of the invention. The inventive concept described herein is not so limited.

Figure 4 shows in somewhat greater detail, the components of the cassette variation portrayed in the Figure 3.

Figure 4 shows a source of artificial cerebrospinal fluid (504), typically in an IV bag, which is in a fluid communication with the fluid reservoir (530). The fluid which exits from reservoir (530) passes through line (532) and encounters pump (534). Pump (534) may be of any typically used design. For instance, since line (534) preferably is of a polymeric soft surgical tubing, pump (534) may be a roller pump such as may be used in many other fluid delivery devices used in the human body. The artificial cerebrospinal fluid then passes to oxygenator/heat exchanger surface (536). As described above, oxygenator (536) typically involves some manner of heat transfer to control the solubility and equilibrium of CO₂ and of O₂ in the cerebrospinal fluid. A cooperating heat source (538) is also shown but is not incorporated into the modular cassette assembly shown in Figure 4. Referring back to Figure 3, heat source (538) would be integral with, at least a resident in, the cabinet (502) shown in that drawing. Returning to Figure 4, a stream of mixed oxygen and carbon dioxide is introduced into oxygenator (536) as is needed for proper gas balance in the cerebrospinal fluid circulating in the loop. As the fluid exits from the oxygenator (536), it then passes to dialyzer (540). Dialysis unit (540) may be used in a variety of ways. It may be used to remove materials from the circulating cerebrospinal fluid by a choice of temperatures and exchange fluids. It may be used to introduce drugs or medicines into the circulating cerebrospinal fluid. Additionally, it is contemplated that the dialysis unit (540) will have some filtration function. This filtration capacity will be for removal of smaller materials, e.g. microorganisms, blood cells, etc. It is not likely that the dialyzer-filter unit (540) will be used to remove gross artifacts such as clots or the like. That function is desirably reserved for filter (106) as shown in Figure 1. Once the composition-adjusted artificial cerebrospinal fluid leaves dialysis unit

(540), it is split into two streams; one line (542) returns to reservoir (530) and the other stream via (544) is pumped via pump (546) into heat exchanger plates (548). Heat exchanger (548) is typically a cooler. The cerebrospinal fluid as it leaves the oxygenator is at equilibrium with the gases found in the fluid. Consequently, just as a matter of safety, the fluid is chilled slightly in heat exchanger (548) to maintain the various gases in solution. Of course, it is within the scope of this invention that the fluid be chilled to a still lower temperature for specific therapeutic purposes. Pressure manometer and relief valve (550) is also shown.

After artificial cerebrospinal fluid leaves cooler (548), it passes by a line (506) into a catheter (508). The distal end of catheter (508) is shown to be in the vicinity of the ventricles. The flow direction is preferably as shown in Figure 4 but, depending on the infirmity treated, the flow may be reversed from that shown in Figure 4 or may be over a shorter path not involving the spine. For instance, in certain clinical situations, it may be desirably simply to circulate oxygenated artificial cerebrospinal fluid through the upper portions of the cerebrospinal fluid cavity and not down into the subarachnoid space in the spine. This would prevent whatever modest amounts of, e.g. blood, that may be present from passing down into that region. Drainage may alternatively be accomplished by removal from or introduction into the cisterna magna or the subarachnoid space surrounding the brain. Also shown in this variation is a pressure monitor (550). As needed, in aseptic air break (552) is also shown.

This invention has been described and specific examples of the invention have been portrayed. Use of those specific examples is not intended to limit the invention in any way.

Additionally, to the extent that there are variations in the invention which are within the spirit of the disclosure and yet are equivalent to the inventions found in the claims, it is our intent that those claims cover those variations as well.

Claims

WE CLAIM AS OUR INVENTION:

1. A closed synthetic cerebrospinal fluid recirculation assembly comprising: a fluid entry device suitable for introducing a synthetic cerebrospinal fluid into an extravascular cerebrospinal pathway, a fluid withdrawal device suitable for withdrawing said cerebrospinal fluid from an extravascular cerebrospinal pathway, a synthetic cerebrospinal fluid reservoir, a conditioning circuit comprising an oxygenator and a heat exchanger, where said conditioning circuit withdraws fluid from said synthetic cerebrospinal fluid reservoir and reintroduces said fluid into said synthetic cerebrospinal fluid reservoir, and a flow controller for controlling flow of synthetic cerebrospinal fluid through said fluid entry device into said extravascular cerebrospinal pathway.

2. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 further comprising a dialyzer.

3. The closed synthetic cerebrospinal fluid recirculation assembly of claim 2 wherein said dialyzer is configured for removing materials from said synthetic cerebrospinal fluid.

4. The closed synthetic cerebrospinal fluid recirculation assembly of claim 2 wherein said dialyzer is configured for adding materials to said synthetic cerebrospinal fluid.

5. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 further comprising a diverter valve fluidly connected to said fluid withdrawal device further switchedly connected to a fluid collection container in a first position and to said synthetic cerebrospinal fluid reservoir in a second position.

6. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said synthetic cerebrospinal fluid reservoir is insulated.

7. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said synthetic cerebrospinal fluid reservoir further comprises a sonicator.

8. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said synthetic cerebrospinal fluid reservoir further comprises a stirrer.

9. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said conditioning circuit further comprises a carbon dioxide gas exchanger.

10. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said conditioning circuit dialyzer comprises a plurality of high surface area polymeric tubes.

11. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 wherein said conditioning circuit dialyzer comprises a plurality of high surface area polymeric plates.

12. The closed synthetic cerebrospinal fluid recirculation assembly of claim 2 wherein said conditioning circuit dialyzer further comprises a heat exchanger for controlling an exchange temperature of the dialyzer.

13. The closed synthetic cerebrospinal fluid recirculation assembly of claim 4 wherein said conditioning circuit dialyzer further comprises a closed source of medicine or drugs.

14. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 further comprising a source of synthetic cerebrospinal fluid controllably, fluidly connected to said reservoir.

15. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 further comprising one or more sensors for monitoring at least one of pO₂, pCO , pH, albumin, glucose, lactate, bicarbonate ion, amino acids, alpha ketoglutaric acid, Mg ions, Ca ions, K ions, Na ions, and Cl ions concentration in said synthetic cerebrospinal fluid.

16. The closed synthetic cerebrospinal fluid recirculation assembly of claim 15 wherein said one or more sensors monitor synthetic cerebrospinal fluid in said reservoir.

17. The closed synthetic cerebrospinal fluid recirculation assembly of claim 15 wherein said one or more sensors monitor synthetic cerebrospinal fluid in an analyzer circuit which withdraws synthetic cerebrospinal fluid from said reservoir and returns it to said reservoir.

18. The closed synthetic cerebrospinal fluid recirculation assembly of claim 15 further comprising devices operating in response to said one or more sensors and adjusting at least one of said pO , pCO , pH, albumin, glucose, lactate, bicarbonate ion, amino acids, alpha ketoglutaric acid, Mg ions, Ca ions, K ions, Na ions, and Cl ions concentration in said synthetic cerebrospinal fluid.

19. The closed synthetic cerebrospinal fluid recirculation assembly of claim 1 further comprising a return pump controllably, fluidly connected to said reservoir for returning synthetic cerebrospinal fluid to said extravascular cerebrospinal pathway.

20. The closed synthetic cerebrospinal fluid recirculation assembly of claim 19 further comprising at least one sensor for monitoring a patient's intracranial pressure.

21. The closed synthetic cerebrospinal fluid recirculation assembly of claim 20 wherein said at least one sensor for monitoring a patient's intracranial pressure controls said return pump.

22. A method for recirculating artificial cerebrospinal fluid comprising the steps of: a) introducing an artificial cerebrospinal fluid into a cerebrospinal fluid cavity in a human body that contains cerebrospinal fluid, at a first location, b) withdrawing a first amount of cerebrospinal fluid from said cerebrospinal fluid cavity at a second location, c) withdrawing a second amount of cerebrospinal fluid which second amount of cerebrospinal fluid contains at least a portion of said artificial cerebrospinal fluid at said second location, and d) reintroducing said second amount of cerebrospinal fluid into said cerebrospinal fluid cavity.

23. The method of claim 22 wherein said second amount of cerebrospinal fluid is reintroduced at said first location.

24. The method of claim 22 wherein said first amount of fluid comprises natural cerebrospinal fluid.

25. The method of claim 22 wherein said first amount of fluid is discarded.

26. The method of claim 23 wherein said first amount of fluid is discarded.

27. The method of claim 22 wherein said second amount of fluid comprises fluorocarbon.

28. The method of claim 22 wherein the first location is a ventricle region.

29. The method of claim 22 wherein the first location is in the subarachnoid space.

30. The method of claim 22 wherein the first location is in the spine.

31. The method of claim 30 wherein the first location is in the lumbar region of the spine.

32. The method of claim 22 wherein the first location is in the cisterna magna.

33. The method of claim 22 wherein the second location is a ventricle region.

34. The method of claim 22 wherein the second location is in the subarachnoid space.

35. The method of claim 22 wherein the second location is in the spine.

36. The method of claim 35 wherein the second location is in the lumbar region of the spine.

37. The method of claim 22 wherein the second location is in the cisterna magna.

38. A method for recirculating artificial cerebrospinal fluid in a human body comprising the steps of: a) introducing an artificial cerebrospinal fluid into a cerebrospinal fluid cavity in a human body at a first location, b) withdrawing at least a portion of said artificial cerebrospinal fluid from said cerebrospinal fluid cavity at a second location, c) measuring physical, chemical, or biological parameters of the artificial cerebrospinal fluid and adjusting at least one of those parameters in a conditioning loop, and d) reintroducing the artificial cerebrospinal fluid into said cerebrospinal fluid cavity.

39. The method of claim 38 wherein the adjusted artificial cerebrospinal fluid is reintroduced at said first location.

40. The method of claim 38 wherein the artificial cerebrospinal fluid comprises fluorocarbon.

41. The method of claim 38 wherein the first location is selected from the group consisting of a ventricle region, the subarachnoid space, the spine, and the cisterna magna.

42. The method of claim 41 wherein the first location is in the lumbar region of the spine.

43. The method of claim 38 wherein the second location is selected from the group consisting of a ventricle region, the subarachnoid space, the spine, and the cisterna magna.

44. The method of claim 43 wherein the second location is in the lumbar region of the spine.

45. The method of claim 38 wherein the artificial cerebrospinal fluid comprises a fluorocarbon micellar dispersion, which dispersion is not substantially coalesced during steps a.) through d.).

46. A kit for use in an artificial cerebrospinal fluid recirculation system comprising in fluid connection: a source of artificial cerebrospinal fluid , a heat exchanger for warming said artificial cerebrospinal fluid, an oxygenation surface, and a heat exchanger for cooling said artificial cerebrospinal fluid.

47. The kit of claim 46 additionally comprising a recirculation reservoir.

48. The kit of claim 46 additionally comprising a dialysis surface.

49. The kit of claim 46 additionally comprising a filter for removing filterable material from said artificial cerebrospinal fluid.

50. The kit of claim 46 wherein said heat exchanger for warming said artificial cerebrospinal fluid, said an oxygenation surface, and said recirculation reservoir are fluidly connected with flexible tubing.

51. The kit of claim 46 further containing an outlet line for delivering said artificial cerebrospinal fluid to a human or animal body and wherein said heat exchanger for cooling said artificial cerebrospinal fluid is fluidly connected with flexible tubing with said outlet line.

52. The kit of claim 46 wherein said source of artificial cerebrospinal fluid is open to said recirculation reservoir.

53. The kit of claim 46 further comprising a fluid entry device suitable for introducing a synthetic cerebrospinal fluid into an extravascular cerebrospinal pathway.

54. The kit of claim 46 further comprising a fluid withdrawal device suitable for withdrawing a synthetic cerebrospinal fluid from an extravascular cerebrospinal pathway.