System and method for site specific therapy

Abstract

A system, including catheter apparatus, and related method for performing site specific therapy. The catheter apparatus can include one or more semipermeable microcatheters for use in performing site specific microdialysis. The system and method are particularly suited for use in addressing cerebral edema by affecting the osmolar relationship between fluids making up the brain tissue.Also disclosed is an apparatus having a delivery / recovery mechanism in the form of a pump reservoir and one or more catheters in the form of semipermeable microcatheters, for use in delivering and / or recovering fluid to and / or from a tissue site or for performing tissue engineering outside of the body. The apparatus can be used in a method to perform site specific microtherapy, including for the treatment of avascular necrosis, compartment syndrome, cerebral edema, and to improve skin flap survival in the course of reconstructive surgery.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of U.S. patent application filed 24 Mar. 2003 and assigned Ser. No. 10 / 395,573, which is a continuation of U.S. patent application filed 17 May 1999 and assigned Ser. No. 09 / 313,341, which is a continuation of an international patent application filed 7 Aug. 1998 and assigned Serial No. PCT / US98 / 16416 which is a continuation-in-part of U.S. patent application filed 8 Aug. 1997 and assigned Ser. No. 08 / 908,555, the entire disclosure of which is incorporated herein by reference.TECHNICAL FIELD[0002]In one aspect, the present invention relates to methods and apparatuses for treating microcirculatory problems, including transient and reversible conditions that do no involve structural injury, as well as permanent or chronic conditions that do involve structural injury to the microcirculation. In another aspect, the invention relates to methods and apparatuses for augmenting normal microcirculation. In...

AI Technical Summary

Benefits of technology

[0040]Applicant has found that the distribution of fluids within or between portions of a tissue, including the delivery of fluids and any solutes contained therein, can be significantly enhanced by the present apparatus, which can serve to artificially replicate the hydrostatic forces and / or solute delivery characteristics of the microcirculatory system. In such a preferred embodiment the present invention employs microfibril technology to deliver and / or remove fluid, solutes, or specific agents to and / or from a tissue space. In particular, the apparatus permits the infusion of fluids and / or therapeutic agents, and the corresponding removal of tissue fluids and / or biological factors, with the optional ability to simultaneously monitor physiologic parameters. In turn, the invention further provides a commercially viable in vitro tissue engineering technique based on the principle of microdialysis.

[0061]In turn, the preferred method and system have an indirect effect, in that they can be used to achieve a result in a remote (first) fluid, for instance, by lessening its volume, and in turn, its pressure. This indirect effect can be achieved by direct contact with (and the affirmative manipulation of) a second fluid, which is directly or indirectly separated from the first fluid by an osmotic barrier. The method and system can achieve such results in any suitable manner, e.g., by altering the absolute and / or relative volumes or osmolarities of one or more fluids, and / or by simply controlling or maintaining the volumes and / or osmolarities in order to prevent further edema.

Problems solved by technology

A number of conditions involve poor blood supply to the bone, leading to bone necrosis.

There is no treatment presently available that can predictably alter the natural history of the disorder.

Several technical barriers to the treatment of AVN of the femoral head and neck include the limited blood supply of the site, difficult surgical access, and the accelerated progression of the disease due to biomechanical demands of walking on the hip joint.

Acute compartment syndrome generally involves impaired circulation within an enclosed fascial space, leading to increased tissue pressure and necrosis of muscle and nerves.

Direct trauma, ischemia, or excessive, unaccustomed exercise can result in hemorrhage and swelling inside the anterior compartment.

In addition, the prolonged compression of nerves can destroy their ability to function.

These symptoms must be identified quickly, since misdiagnosis can lead to permanent neuromuscular damage and physical disability.

The characteristics of acute tissue edema are well known, and the condition continues to be a clinical problem, particularly since edema can be detrimental to the tissue as a result of disruption of the microcirculation.

Tissue swelling results in increased diffusion distances, which in turn decreases interstitial nutrient delivery.

Irreversible disruption of the microcirculatory system can occur as a result of unresolved acute injury.

Resolution of tissue edema is problematic since natural mechanisms by which edema resolves are also affected by the edema.

Pharmacologic treatment is often not effective since blood borne agents have difficulty reaching their target tissue.

Opening the skull generally cannot be done to relieve pressure, because the brain tissue would herniate out the opening causing significant tissue damage.

Giving intravenous treatments is also not effective because the brain microcirculation is disrupted so deilivery to the brain is impaired.

Brain swelling leading to dangerously elevated ICP develops in 40-50% of TBI patients with a Glascow Coma Scale (GCS) of 8 or less, and higher ICP levels have been repeatedly shown to lead to poor prognosis or outcome.

While the placement of an ICP monitor is invasive, the benefits of ICP monitoring are felt to offset this factor, carry a relatively small risk of complications (e.g., infection, hemorrhage, malfunction, obstruction or malposition), and rarely result in increased patient morbidity.

As fluid is removed, however, brain swelling often progresses to the point where the ventricular system is compressed and the ability to drain CSF can be compromised.

This may be exacerbated by overdrainage, leading to the ventricular walls or the choroid plexus actually collapsing in a manner that occludes the orifices of the catheter.

The therapeutic efficacy of convective CSF drainage by conventional ventriculostomy catheters, therefore, is limited.

Also, ventriculostomy catheters can become occluded with tissue debris and clots during convective fluid removal.

As briefly outlined below, it can be seen that each of these therapeutic strategies is a “double-edged sword” since each treatment is typically associated with potential adverse consequences and each has limited efficacy.Hyperventilation: Prophylactic hyperventilation of TBI patients is currently questioned since it has been reported to worsen outcomes, does not consistently reduce ICP, and may cause loss of autoregulation and potentiate secondary ischemia due to its actions on reducing cerebral blood flow.Mannitol: This osmotic diuretic is currently the most widely used, and probably the safest, treatment for short-term control of elevated ICP in patients with TBI.

Although it has become the cornerstone for control of elevated ICP after severe TBI, mannitol administration is not without risks.

Although the use of mannitol affects osmolarity within the site, this approach is not site-specific, rather, it is systemically administered.

Since this approach is also chemically based, rather than device based, it does not employ a device that is itself provides an osmotic barrier.Barbiturates: Prophylactic barbiturate therapy is currently discouraged, due to variable and unpredictable positive effects on ICP.

While edema can be controlled in many patients by the use of drug treatments, there are many patients for whom such treatment is not effective.

To date, however, Applicant is unaware of any description of the use of such dialysis techniques or apparatuses in the treatment of cerebral edema or ICP.

In the course of inserting microdialysis probes into brain parenchyma, in order to monitor neurochemical alterations in patients, it has been found that there is minimal trauma to brain tissue and that complications are extremely rare.

However, most, if not all, current microdialysis procedures rely on the slow, pump-driven infusion of dialysis fluid which travels through inlet lines past the dialysis fiber and then through outlet lines to enable collection of the dialysate.

These techniques, however, continue to be plagued by problems having to do with survival of the skin flaps, which in turn, is believed to rely, at least in part, on efficient revascularization of the site.

To Applicant's knowledge, however, there is no present teaching, let alone clinically acceptable approach for the application of tissue microdialysis in site specific therapy, or in particular, a microdialysis apparatus useful for prolonged periods, difficult sites, and in clinical settings.

In turn, current therapies for treating elevated ICP and cerebral edema, in humans with severe traumatic brain injury, have limited efficacy and continue to be associated with serious risks (particularly with prolonged use).

In some patients, cerebral edema simply remains untreatable or nonresponsive to treatment.

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