A number of clinical situations exist in medicine in which automated control of the temperature, pressure and chemistry of liquid within a body cavity are likely to be therapeutically useful. These include:                1. Traumatic or ischemic brain and spinal cord injuries, in which temperatures below normal and control of pressure may improve outcome.        2. Hemorrhage in the regions of the brain and spinal cord, in which removal of blood may improve outcome.        3. Infection in the regions of the brain and spinal cord, in which addition of antibiotics or antivirals to the CSF spaces may be beneficial. Hypothermia, hyperthermia, or oscillation between hypothermia and hyperthermia, pressure control, and removal of infectious organisms (pus) and inflammatory mediators from the cerebrospinal fluid (CSF) may also be beneficial.        4. Brain edema related to liver failure, in which hypothermia has been shown to be beneficial.        5. Malignancy in the regions of the brain and spinal cord, in which hyperthermia has been shown to increase the efficacy of chemotherapy and radiation in the treatment of glioblastoma multiforme, the most common, and usually fatal, form of brain cancer.        6. Infection in the region of other body cavities, including peritonitis, pleuritis, and mediastinitis, in which the continuous delivery of antibiotic, antiviral, or related therapies under controlled temperature and pressure could be useful. Such therapies have been delivered into the peritoneum and other cavities, but without feedback control of temperature or pressure.        7. Malignancy in the region of body cavities, including the peritoneum, pelvis, mediastinum, and pleural space, in which hyperthermia and/or the local delivery of chemotherapeutic agents have shown greater effectiveness than conventional therapies in some studies.        8. Ischemia of the intestine or colon, in which hypothermia might protect the tissues from ischemic damage. Such protection may apply in other organs subject to ischemia, such as the heart.        9. Surgery involving any of the above regions, in which local hypothermia can decrease the metabolic demands of tissues, resulting in decreased susceptibility to injury and decreased bleeding due to lower blood flow, and post-operative adverse events in such regions.Hypothermia in Brain and Spinal Cord Injuries        
The protective effects of hypothermia applied during injuries has been extensively documented, and is currently in use intraoperatively in certain forms of brain surgery and cardiac surgery.
Hypothermia has been shown to be effective when applied contemporaneously with the injury in both brain trauma and brain ischemia in animals in a large number of studies. Disappointing early results with delayed hypothermia, and the resultant widespread notion of a narrow ‘therapeutic window’ dampened enthusiasm in this area for many years. Recent reports suggest that much longer hypothermic times than were previously contemplated can compensate for delays in treatment and produce outcomes comparable to contemporaneous hypothermia.
However, some studies indicate that the systemic complications of prolonged whole-body hypothermia (also called whole body cooling, or WBC) are a major barrier to the effectiveness of this therapy in either stroke or trauma in humans. As a result, some investigators have focused on a human strategy of selective brain cooling (also called SBC). Unfortunately, SBC is very difficult to achieve in large animals such as humans. Compared with smaller animals, the human head has a low surface area-to-volume ratio and a high degree of thermal inertia. The human brain is insulated from the surface of the head by approximately 2.5 cm of highly vascular scalp, bone, meninges and cerebrospinal fluid (CSF). In addition, the brain receives constant thermal input in the form of 20% of the cardiac output, or 1 L/min of blood at 37° C. Because of this, reduction of the surface temperature of the human head has been shown to be ineffective as a method of SBC.
An alternative to surface cooling is intra-arterial cooling using either bypass-cooled blood or intra-arterial cooling probes. Intra-arterial approaches suffer from the major inherent risk of endovascular instrumentation of the cranial arteries; that of precipitating stroke. To minimize this risk, such instrumentation is normally done under full dose heparin anticoagulation, which may be contraindicated in both trauma and stroke due to the risk of bleeding.
It has been taught to withdraw cerebrospinal fluid (CSF), cool it, and return the cooled CSF to a patient.
U.S. Pat. No. 4,904,237 (Janese, 1990) discloses a CSF exchange system which removes CSF from the lumbar cistern, filters out blood contaminants, cools, pH adjusts and performs diagnostic measurements, then returns the CSF to the lumbar cistern by reversal of flow using a single reciprocating pump. This system seems intended primarily for the removal of subarachnoid blood from the CSF in the context of subarachnoid hemorrhage. In the preferred embodiment, 10 ml of CSF are exchanged in 25 s cycles, giving a flow rate of 24 ml/min. If the temperature of the returned CSF is at 4° C., this flow rate may not be adequate to achieve significant cooling in the spinal cord, where published flows of approximately 30 ml/min were required in a human trial (Davison et al, 1994).
U.S. Pat. No. 6,379,331 (Barbut, 2002) discloses another medical device for intrathecal cooling of the spinal cord in which separate inflow and outflow catheters are inserted into the CSF spaces of the spinal cord such that their tips are at the extremities of the cavity to be cooled. CSF is extracted from one catheter, cooled, and returned to the second catheter by means of a single pump without automated feedback control. The flow rate of the single pump is adjusted to keep intraspinal pressure (as estimated from the pressure of the extracorporeal fluid, and not from measurement within the cavity) below a safe level. This system is intended primarily for the special case of intraoperative spinal cord cooling in the context of abdominal aortic aneurysm surgery and provides no means of continued cooling over 24 h or more, as required for delayed hypothermia to be effective. Alternate placement of one of the catheters into the lateral ventricle of the brain is disclosed as a method of cooling the brain, although practical brain cooling would seem unlikely due to flow rate limitations. A difficulty with any catheter arrangement in which the catheter tips are separated in space is that pressure differentials may occur between the inflow and outflow regions at higher flow rates. Hence, the maximal flow is limited by the maximal safe pressure in the region of the inflow catheter, where pressure is high, and minimal safe pressure in the region of the outflow catheter, where pressure is low. Placement of two catheters in the brain ventriclular system such that their tips are relatively close together suffers from the disadvantage of having to pierce the brain twice, doubling the risk of intraparenchymal hemorrhage due to catheter placement.
U.S. Pat. No. 4,445,500 (Osterholm) discloses a treatment for stroke involving the recirculation of an oxygenated perfluorocarbon emulsion in the subarachnoid (CSF) space. This system is intended to counteract ischemic injuries of the central nervous system by providing sufficient oxygen in the perfusate to allow continued tissue metabolism in the face of insufficient blood flow. The system depends on an involved process for the manufacture and maintenance of the perfluorocarbon emulsion, which is a fluid whose biocompatibility would need to be established. As in the previously discussed patent, a single pump is again used for circulation of the fluid within the subarachnoid space, which precludes active pressure modulation, and the inflow and outflow catheters are separated. The low flow rates possible under this configuration (<60 ml/min) are disclosed as sufficient for adequate brain oxygentation with the emulsion used. Intracranial pressure measurements are made by means of a double lumen catheter in which one lumen is devoted to pressure measurements. The infusion rate into the brain is adjusted manually to keep the pressure below a safe limit. The temperature of the emulsion may be adjusted extracorporeally, but no measurements of temperature are made within the CNS. Together with the low flow rates, this would seem to preclude practical and precise therapeutic temperature modulation. Precise control of temperature is required in hypothermic therapy, particularly during the dangerous rewarming stage, and to an even greater extent in therapeutic hyperthermia, in which overheating can severely damage normal tissue. Finally, with regard to the removal of contaminants, the Osterholm system calls for microfiltration of the emulsion as a means of removing bacteria, but discloses no means of removal of other contaminants, such as proteins or blood products.
Liquid in Non-CNS Body Cavities
Devices for recirculation of liquids in the peritoneal cavity have been disclosed in, for example, U.S. Pat. Nos. 6,254,567, 6,409,699, and 5,141,493. These devices are dialysate circulators for the purpose of continuous flow-through intraperitoneal dialysis (CFPD) used in the treatment of kidney or liver failure. Many of these designs incorporate a heater whose purpose is to warm the dialysate to body temperature before it enters the body, but therapeutic temperature modulation is not encompassed. They generally feature a means of maintaining constant pressure of the dialysate fluid extracorporeally, but do not accomplish pressure modulation within the cavity by use of independent inflow and outflow pumps. These devices are also not intended for the delivery of drugs or the removal of contaminants such as blood or pus.
Foam Fractionation
Foam fractionation is a technique for the removal of proteins and other contaminants from a liquid. This technique is used in marine aquaculture, where it is commonly known as ‘protein skimming’. Dissolved amphipathic (partly water soluble and partly non-water soluble) molecules such as proteins tend to accumulate at an air/water interface since part of the molecule is more stable when dissolved in aqueous solution and part is more stable in air. Such molecules can be removed with high efficiency from liquids with favorable physical properties by saturation of the solution with fine bubbles. The bubbles accumulate proteins at the air/water interface and the resulting foam rises to the top of the liquid, where it may be collected or skimmed off. As an additional benefit, the intimate contact of air or of a gas mixture containing oxygen can oxygenate the liquid. Contact of an oxygen-carbon dioxide gas mixture with a bicarbonate-buffered solution, for example, can both oxygenate and pH balance the solution. U.S. Pat. Nos. 6,436,295, 5,562,821, 5,554,280, 5,122,267, 5,665,227, and 5,380,160, for example, describe devices for foam fractionation in marine aquariums. Foam fractionation is also used in the purification of proteins and drugs in the pharmaceutical industry. Foam fractionation has apparently not been disclosed for use in the purification of a bulk liquid for recirculation within a body cavity.