Patent Application
20090264724
1. Field of the Invention
The invention relates to blood fluid sampling devices and associated methods.
2. Relevant Background
In 2001, Grete Van den Berghe, MD, published a seminal study (Van den Berghe G, et al. Intensive Insulin Therapy in Critically III Patients. NEJM, Vol. 345, No. 19, Nov. 8, 2001) that demonstrates the significant medical benefits derived by maintaining an Intensive Care Unit (ICU) patient's blood glucose levels between 80 and 110 mg/dl through highly managed insulin therapy. In the ICU, glucose levels commonly rise above 300 mg/dl as a consequence of stress, organ failure, infection, trauma, shock or other factors. Importantly, blood glucose levels increase dramatically even in patients without impaired glucose tolerance or diabetes (healthy, non-diabetics). Administering insulin to maintain blood glucose levels in the target range improves patient outcomes, perhaps due to the anti-inflammatory effects of insulin since seriously-ill individuals predominantly have elevated levels of inflammation. The Van den Berge study demonstrated very significant improvements in patient mortality, morbidity and length of hospitalization by aggressively using insulin to maintain low blood glucose levels and to decrease inflammation. Remarkably, intensive insulin therapy also has been found to reduce in-hospital mortality by 34%, acute renal failure by 41%, bacteremia by 46%, blood transfusions by 50%, and polyneuropathy by 44%.
Furthermore, patients receiving intensive insulin therapy are less likely to require prolonged mechanical ventilation and intensive care, an outcome also observed in patients with stroke, heart attack, and burn leading to the general concept of a “diabetes of injury” (Krinsley, J.: Effect of an intensive glucose management protocol on the mortality of critically ill adult patients, Mayo Clin. Proc. 79:992-1000, 2004, and Van den Berghe, G.: How does blood glucose control with insulin save lives in intensive care? J. Clin. Invest. 114:1187-1195, 2004). Dr. Van den Berghe's initial findings are corroborated by many other studies in settings ranging from surgical ICUs (Furnary, A P, Zurr K J, et al, Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 67:352-362, 1999) to general hospital wards (Newton, C A, Young, S, Financial implications of glycemic control, Endocrine Practice, Vol. 12, 7/8 2006, p. 43-48) to organ transplantations.
Based on the significant financial savings realized by hospitals when aggressively controlling blood glucose levels and the remarkable improvement realized in patient care from doing so, hospital use of aggressive insulin management protocol is not pursued simply due to cost.
Current techniques for measuring analytes such as blood glucose in seriously ill patients do not allow sufficiently frequent measurements and are expensive.
Conventional intensive blood glucose monitoring is expensive. For each new reading a glucose test strip, alcohol prep pad, cotton swab, lancet and gloves are used. While the single-use components may cost $1.50 in total on the open market, handling the components from a hospital's loading dock, through incoming inspection, into inventory, up to the ICU, onto a cart, to the patient's bedside and then disposed of after use, all the while complying with hospital tracking requirements, adds significantly to cost. An hourly glucose reading is then collected through one of two scenarios. The first involves dedicating one person per every 10 to 12 ICU beds to do nothing but collect blood glucose samples. The second uses the ICU nurse to take the reading. In the second scenario, the ICU nurse has one to two patients and collects an hourly blood glucose sample as part of standard care. Even for an experienced nurse, the test takes three to four minutes to prepare the site, make the blood stick, collect the blood sample, apply cotton, work the monitor, chart the value and dispose of the bloody material and wrapping materials. In either scenario, the fully burdened cost per glucose reading is $5 to $10, a new glucose value is generated only once every hour per patient and that value provides only a single data point of information from which to adjust insulin delivery rates. No method is known for real-time assessment of the glucose level's direction or rate of change, which is the critical information for aggressively and confidently managing insulin therapy.
While intensive insulin therapy programs cost more in labor and material to implement, the resulting savings in terms of shortened length of stay and fewer complications have been shown to result in a net savings of $40,000 per ICU bed per year (The ACE/ADA Task Force on Inpatient Diabetes, American College of Endocrinology and American Diabetes Association Consensus Statement on Inpatient Diabetes and Glycemic Control, Diabetes Care, Vol. 29, No. 8, 8/2006). Despite the savings and the improved outcomes, many medical and surgical ICU's cannot embrace the approach because intensive insulin therapy is difficult to accomplish in terms of staffing, training, implementing and managing.
In accordance with embodiments of a serum measurement device, an analyte concentration measurement apparatus facilitates sampling and analysis of analytes in body fluid and includes an implantable serum sampling catheter comprising a biocompatible tubing enclosing a vacuum release lumen and a serum lumen that are interconnected by a port. The serum lumen is separated from a body fluid compartment by a membrane barrier. The sampling catheter is configured for drawing a serum sample from the body fluid compartment by creation of suction in the serum lumen.
The features of the described embodiments believed to be novel are specifically set forth in the appended claims. However, embodiments of the invention relating to both structure and method of operation, may best be understood by referring to the following description and accompanying drawings.
In accordance with embodiments of a serum measurement device, an analyte concentration measurement apparatus comprises an implantable serum sampling catheter, an analyte sensor configured for coupling to and receiving a sample of filtered serum from the sampling catheter, and a display and control device. The display and control device is coupled to the analyte sensor that controls acquisition of serum, measurement of analyte concentration in the serum, and display of measurement results.
Referring to
The implantable serum sampling apparatus 100 can further comprise an analyte sensor 124 configured for coupling to and receiving a sample of filtered serum from the sampling catheter 102 and a display and control device 144. The display and control device 144 is coupled to the analyte sensor and performs various operations including controlling serum acquisition, measuring analyte concentration in the serum, and displaying measurement results.
In an example implantable serum sampling apparatus 100, the display and control device 144 comprises at least one pump 156, a control module 152, a processor 150, an analog signal processing module 151, and a display 160. The control module 152 receives user commands from one or more input devices 154 and sends control signals to the analyte sensor 124 and controls one or more pumps 156. The processor 150 is interfaced to the control module 152 and processes absorption measurement data for display. The signal processing module 151 receives measurement signals from the analyte sensor 124 and passes digitized absorption measurement data to the processor 150. The display 160 is coupled to the processor 150 and displays the processed absorption data.
The display and control device 144 can be implemented to operate in at least four modes including calibrate, infuse, sample, and measure modes. The calibrate mode operation comprises infusing a known analyte concentration to the analyte sensor 124 and calibrating the sensor 124 according to the known solution. In the infuse mode operation, saline is infused through the sampling catheter into the body compartment. In the sample mode operation, a serum sample is effused from the body compartment to the analyte sensor 124. The measure mode operation comprises measuring the analyte concentration in the serum sample.
In an illustrative embodiment, the display and control device 144 is configured to generate a display of the analyte concentration measurement in the serum sample within less than one minute of measurement initiation.
The display and control device 144 can further comprise a waste receptacle 162 coupled to the serum sampling catheter 102 that is configured for evacuating a sample of serum from the analyte sensor 124.
The illustrative sampling catheter 102 can be configured for usage in fluid drainage, fluid injection, instrument access, and/or separation of serum from whole blood.
The serum sampling system 100 can be implemented with three basic components that can be supplied independently or in combination. The components include a sampling catheter 102, an analyte sensor 124 which can be called an optical bench, and a display and control device 144, as shown in
The sensor 124 can be an analyte sensor which is configured for connecting to the sampling catheter 102 and for mounting on a patient's body adjacent the sampling catheter 102. The illustrative sampling catheter 102 comprises a tubing 120 and a membrane barrier 118 which encases the tubing 120 and filters red blood cells from serum entering the tubing 120. The display and control device 144 draws a sample from filtered serum of less than 1 milliliter volume for measurement. Accordingly, the illustrative system 100 enables a small sample size since, in an illustrative implementation, less than 1 ml of serum can be removed from the patient for each measurement. The analyte sensor 124 typically uses on the order of 5 microliters (μl) of serum to make a measurement. The analyte sensor 124 is sufficiently small to be mounted on a patient's forearm, upper leg, shoulder or chest and the volume of serum within tubing 120 connecting the body to the analyte sensor 124 is less than approximately 0.45 ml.
The sampling catheter 118 has pores of diameter in a range of approximately 0.005-0.1 micrometers whereby blood components larger than the pore size are rejected by the membrane 118.
The display and control device 144 includes a controller 150 that displays a venous or arterial sample concentration measurement within less than one minute of measurement initiation. Accordingly, the illustrative system 100 enables acquisition with a short duration lag time.
The illustrative system 100 further enables frequent analyte measurements, such as glucose measurements. For example, glucose measurements can occur as frequently as about once every two minutes.
The implantable serum sampling apparatus 100 can further comprise a waste receptacle 162 coupled to the sampling catheter 102 that evacuates a sample of serum.
The system 100 enables complete avoidance of blood products waste since all fluids deposited in the waste receptacle are either calibration solution or saline, thus reducing or minimizing handling of biohazard materials.
The system 100 also can eliminate loss of red blood cells. Avoiding loss of red blood cells is particularly useful for patients with anemia, pulmonary disease, and the like.
In an illustrative embodiment, the display and control device 144 can comprise a control module 152 that receives user commands from one or more user input devices 154, sends control signals to the sensor 124 and sends pneumatic controls to one or more pumps 156, the signal processing module receives measurement signals from the sensor 124, and generates digitized absorption measurements. The display and control device 144 further comprises a processor 150 interfaced to the control module 152 that receives the digitized absorption measurements from the control module 152 and processes absorption data for display. A display 160 coupled to the processor 150 displays the processed absorption data.
Referring to
In some embodiments, the sampling catheter 202 can further comprise a porous support 270 configured to support the membrane 218 and prevent membrane collapse.
The illustrative implantable serum sampling apparatus 200 has two lumens in the double lumen sampling catheter 202, including the vacuum release lumen 264 and the serum lumen 266. The vacuum release lumen 264 has an air intake 267 coupled to a connecting passageway 268 to the serum lumen 266 near the tip section 204 of the double lumen sampling catheter 202. The serum lumen 206 includes a porous support 270 within the serum lumen 266 and is circumferentially encased by the membrane 218. The tip section 204 comprising a plastic cap 274 sealing the interior lumen 272 of both the serum and vacuum release lumen. The exit section 208 and a connector section at the proximal end 210 are formed of a biocompatible tubing 220.
In an illustrative implementation, the tubular membrane 218 has pores with diameter in a range of approximately 0.005-0.1 micrometers so that components in body fluid larger than the pore size are rejected.
In an illustrative embodiment, an implantable serum sampling apparatus 200 comprises a sampling catheter 202 that functions as a catheter for fluid drainage, fluid injection, and/or instrument access, and functions as a blood separator that separates serum from whole blood.
In accordance with another embodiment of an implantable serum sampling apparatus 200, a sampling catheter 202 comprises a biocompatible tubing 220 with an serum lumen 266 coupled to the biocompatible tubing 220 that is configured to separate the serum lumen from an artery, vein or other body compartment such brain ventricles or bladders. The sampling catheter 202 is configured to acquire an analyte by pulling serum from body fluid through the membrane barrier 218 with a pump connected to the serum lumen 266. Cross-flow filtering is accomplished by creating suction in the serum lumen 266. The serum flow rate in cross-flow filtering is significantly higher than dead-end filtering with no air inlet at the distal end, because no vacuum exists to overcome to pull the serum sample out. Dead-end filtering also results in a low serum flow rate because the pores in the membrane become obstructed. Accordingly, the sampling catheter 202 does not function in the manner of a conventional dialysis catheter which passes fluid through a membrane and acquires an analyte by osmosis. In contrast, the illustrative sampling catheter 202 passes air rather than a fluid that dilutes the sample. Accordingly, the illustrative implantable serum sampling apparatus 200 improves sampling accuracy over a dialysis system because the exact concentration of analytes in the blood is measured. The dilution which occurs in dialysis catheters is avoided, enabling a far smaller sample volume. For example, in an example configuration an accurate measurement can be made by sampling only a 3-5 microliter sample.
Referring to
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Characteristics and operation of the sampling catheter 102 enable a compact configuration of the analyte sensor 324A that is suitable for mounting on a patient's limb, even for chronic monitoring. For example, the analyte sensor 324A can be configured for connecting to the sampling catheter 102 and accepting a sample of serum of less than 0.005 milliliter volume.
The analyte sensor 324A shown in
Referring to
In an illustrative configuration, the hollow fibers 480 circumferentially contain pores with diameter in a range of approximately 0.005-0.1 micrometers so that body fluid components larger than the pore size are rejected.
Referring to
The controller 150 can operate the system 100 to apply suction to the serum lumen 466 so that serum is drawn into the serum lumen 166 through pores in the hollow fibers 480 from the body fluid lumen 467, and release suction through the vacuum release lumen 464.
The perspective pictorial views shown in
Referring to
The analyte sensor 324B is configured for connecting to the sampling catheter 402 and accepting a sample of serum of less than 0.005 milliliter volume.
Referring to
In the illustrative implantable serum sampling apparatus 500, the hypodermic tubing 520 extending longitudinally from a proximal end 582 to a distal tip 584 and includes an outer tubing 590 and an inner tubing 592 which is positioned internal to the outer tubing 590. The distal tip 584 of the hypodermic tubing 520 is configured for implanting in the artery, vein, or body fluid compartment. In the illustrative example, the vacuum release lumen 564 is enclosed between the outer tubing 590 and the inner tubing 592 with both distal tips sealed from the body fluid. The one or more hollow fibers 580 are positioned internal to the inner tubing 592. The serum lumen 566 is enclosed between the inner tubing 592 and the hollow fiber(s) 580. The medial serum lumen 566 and outer vacuum release lumen 564 are connected by the port 568 at the distal tip 584, enabling air flow between the serum lumen 566 and the vacuum release lumen 564. The one or more body fluid lumens 567 are contained within the one or more hollow fibers 580 and are configured to enable flow of body fluid from the artery, vein, or body fluid compartment. The one or more hollow fibers 580 function as a cross-flow separator that separates and filters body fluid from serum.
In an example embodiment, the hollow fibers 580 contain pores with diameter in a range of approximately 0.005-0.1 micrometers so that body fluid components larger than the pore size are rejected.
Referring to
Referring again to
In another aspect, a method can further comprise implanting the sampling catheter 102 into a patient's vein, artery, or body fluid compartment, and connecting the sampling catheter 102 to a sensor 124. During operation, the method can further comprise calibrating the sensor 124, acquiring an analyte, measuring the analyte in a serum sample, and flushing the sensor 124. The sensor 124 can be calibrated by infusing a known solution to the sensor 124 and calibrating the sensor 124 according to the known solution. The analyte can be acquired by effusing a body fluid sample from the vein or artery to the sensor 124. The sensor 124 can be flushed after each calibration and each measurement by infusing saline through the sensor 124 and the sampling catheter 102 into the vein or artery.
According to a further aspect and according to
While the invention has been described with reference to various embodiments, it will be understood that these embodiments are illustrative and that the scope of the invention is not limited to them. Many variations, modifications, additions and improvements of the embodiments described are possible. Those skilled in the art will readily implement the steps necessary to provide the structures and methods disclosed herein, and will understand that the process parameters, materials, and dimensions are given by way of example only and can be varied to achieve the desired structure as well as modifications which are within the scope of the invention. Variations and modifications of the embodiments disclosed herein may be made based on the description set forth herein, without departing from the scope and spirit of the invention as set forth in the following claims.
In the claims, unless otherwise indicated the article “a” is to refer to “one or more than one”.
