APPARATUS AND METHOD FOR DETECTING DISCONNECTION OF AN INTRAVASCULAR ACCESS DEVICE

Abstract

An apparatus and method are disclosed for detecting the disconnection of a vascular access device such as a needle, cannula or catheter from a blood vessel or vascular graft segment. A pair of electrodes is placed in direct contact with fluid or blood in fluid communication with the vascular segment. In one embodiment, the electrodes are incorporated into a pair of connectors connecting arterial and venous catheters to arterial and venous tubes leading to and from an extracorporeal blood flow apparatus. Wires leading from the electrodes to a detecting circuit can be incorporated into a pair of double lumen arterial and venous tubes connecting the blood flow apparatus to the blood vessel or vascular graft. The detecting circuit is configured to provide a low-voltage alternating current signal to the electrodes to measure the electrical resistance between the electrodes, minimizing both the duration and amount of current being delivered. Detection of an increase in electrical resistance between the electrodes exceeding a pre-determined threshold value may be used to indicate a possible disconnection of the vascular access device.

Claims

1-23. (canceled)

24. An apparatus for detecting vascular access disconnection in a pumping apparatus that pulls blood from a vascular access through an arterial conduit and returns blood to the vascular access through a venous conduit, the vascular access disconnection apparatus comprising: a detection circuit comprising: a first terminal and first line connected to the first terminal; a second terminal and second line connected to the second terminal; a switching circuit configured to apply alternating voltages across the first and second terminals; and a voltage sensor for measuring a voltage signal at a midpoint of the first line; a first and second connector, the first connector fluidly connecting the arterial conduit to an arterial needle, and the second connector fluidly connecting the venous conduit to a venous needle, the first connector including a first electrode in electrical contact with blood entering the arterial conduit and with the first line in the detection circuit, the second connector including a second electrode in electrical contact with blood exiting the venous conduit and with the second line in the detection circuit; and a controller that detects a vascular access disconnect based on the voltage signal.

25. The apparatus for detecting vascular access disconnection of claim 24, wherein the first line in the detection circuit further comprises a reference resistor between the first terminal and the midpoint.

26. The apparatus for detecting vascular access disconnection of claim 25, wherein the reference resistor has a resistance equal a mean value of resistance expected between the midpoint and the second terminal while a circuit is completed through the vascular access.

27. The apparatus for detecting vascular access disconnection of claim 24, wherein the first line includes a first capacitor between the midpoint and the first electrode and the second line includes a second capacitor between the second terminal and the second electrode.

28. The apparatus for detecting vascular access disconnection of claim 24, wherein the switching circuit alternates between: a) a first switch configuration wherein a first reference voltage V+ is applied at the first terminal, and a lower second reference voltage V− is applied at the second terminal, and; b) a second switch configuration wherein the first reference voltage V+ is applied at the second terminal, and the second reference voltage V− is applied at the first terminal.

29. The apparatus for detecting vascular access disconnection of claim 24, wherein the arterial and venous needles include a short tubing section, the short tubing section being less than half a length of the arterial and venous conduits.

30. The apparatus for detecting vascular access disconnection of claim 24, wherein the arterial needle includes a short tubing section, the short tubing section being less than a third of a length of the arterial conduit.

31. The apparatus for detecting vascular access disconnection of claim 24, wherein the arterial conduit and the vascular conduit are part of a hemodialysis blood flow circuit.

32. The apparatus for detecting vascular access disconnection of claim 24, wherein the vascular access is a blood vessel or graft.

33. The apparatus for detecting vascular access disconnection of claim 24, wherein the arterial conduit comprises a double lumen flexible tube having a first lumen for carrying blood, and a second lumen for carrying a wire connecting the first electrode to the first terminal.

34. The apparatus for detecting vascular access disconnection of claim 24, wherein the controller is programmed to determine a resistance based on the voltage signal and trigger an alert signal when the resistance exceeds a pre-determined threshold.

35. The apparatus for detecting vascular access disconnection of claim 24, wherein the pumping apparatus includes a mechanical occluder that when closed can prevent flow through the arterial and venous conduits; and wherein the controller is programmed to determine a resistance based on the voltage signal and close the occluder when the resistance exceeds a pre-determined value.

36. An apparatus for detecting vascular access disconnection in a pumping apparatus that pulls blood from a vascular access through an arterial conduit and returns blood to the vascular access through a venous conduit, the vascular access disconnection apparatus comprising: a detection circuit comprising: a first terminal and first line connected to the first terminal; a second terminal and second line connected to the second terminal; a switching circuit configured to apply alternating voltages across the first and second terminals; and a voltage sensor for measuring a voltage signal at a midpoint of the first line; a first and second connector, the first connector including a first electrode and attached to the arterial conduit and detachably connected to an arterial needle, the second connector including a second electrode and attached to the venous conduit and detachably connected to a venous needle, the first electrode in electrical contact with blood entering the arterial conduit and with the first line in the detection circuit, the second electrode in electrical contact with blood exiting venous conduit and with the second line in the detection circuit; and a controller configured to detect a vascular access disconnect based on the voltage signal.

37. The apparatus for detecting vascular access disconnection of claim 36, wherein the first line in the detecting circuit further comprises a reference resistor between the first terminal and the midpoint.

38. The apparatus for detecting vascular access disconnection of claim 36, wherein the first line includes a first capacitor between the midpoint and the first electrode and the second line includes a second capacitor between the second terminal and the second electrode.

39. The apparatus for detecting vascular access disconnection of claim 36, wherein the switching circuit alternates between: a) a first switch configuration wherein a first reference voltage V+ is applied at the first terminal, and a lower second reference voltage V− is applied at the second terminal and; b) a second switch configuration wherein the first reference voltage V+ is applied at the second terminal, and the second reference voltage V− is applied at the first terminal.

40. The apparatus for detecting vascular access disconnection of claim 36, wherein the arterial needle includes a short tubing section, the short tubing section being less than a third of a length of the arterial conduit.

41. The apparatus for detecting vascular access disconnection of claim 36, wherein the arterial conduit comprises a double lumen flexible tube having a first lumen for carrying the fluid, and a second lumen for carrying a wire connecting the first electrode to the first terminal.

42. An apparatus for detecting vascular access disconnection in a pumping apparatus that pulls blood from a vascular access through an arterial conduit and returns blood to the vascular access through a venous conduit, the vascular access disconnection apparatus comprising: a detection circuit comprising: a first terminal and first line connected to the first terminal; a second terminal and second line connected to the second terminal; a switching circuit configured to apply alternating voltages across the first and second terminals; and a voltage sensor for measuring a voltage signal at a midpoint of the first line; a first electrode in contact with the blood in the arterial conduit, the first electrode electrically connected to the first line in the detection circuit via a first wire, the first wire in a second lumen of the arterial conduit; a second electrode in fluid contact with blood in the venous conduit, the second electrode electrically connected to the second line in the detection circuit via a second wire, the second wire in a second lumen of the venous conduit; and a controller configured to detect a vascular access disconnect based on the voltage signal.

43. The apparatus for detecting vascular access disconnection of claim 42, wherein the first line in the detecting circuit further comprises a reference resistor between the first terminal and the midpoint.

44. The apparatus for detecting vascular access disconnection of claim 42, wherein the first line includes a first capacitor between the midpoint and the first electrode, and the second line includes a second capacitor between the second terminal and the second electrode.

45. The apparatus for detecting vascular access disconnection of claim 42, wherein the switching circuit alternates between: a) a first switch configuration wherein a first reference voltage V+ is applied at the first terminal, and a lower second reference voltage V− is applied at the second terminal and; b) a second switch configuration wherein the first reference voltage V+ is applied at the second terminal, and the second reference voltage V− is applied at the first terminal.

46. The apparatus for detecting vascular access disconnection of claim 42, wherein the arterial needle includes a short tubing section, the short tubing section being less than a third of a length of the arterial conduit.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 is a schematic representation of a conductivity circuit in an illustrative embodiment;

[0013] FIG. 2 is a diagram of the electrical waveforms processed by the circuit of FIG. 1;

[0014] FIG. 3 is a representative graph of the noise/error sensitivity of the circuit of FIG. 1 plotted against the ratio of unknown/reference resistance in the circuit;

[0015] FIG. 4 is a schematic representation of an exemplary blood flow circuit of a hemodialysis system;

[0016] FIG. 5A is a side view of a connector that may be used in the blood flow circuit of FIG. 4;

[0017] FIG. 5B is a cross-sectional view of the connector of FIG. 5A;

[0018] FIG. 6 is a cross-sectional view of the connector of FIGS. 5A and 5B, with an attached wire and flexible tubing;

[0019] FIG. 7A is a perspective view of an alternate embodiment of a connector that may be used in the blood flow circuit of FIG. 4;

[0020] FIG. 7B is a top view of the connector of FIG. 7A;

[0021] FIG. 7C is a cross-sectional view of the connector of FIG. 7B;

[0022] FIGS. 8A-D are various cross-sectional views of a flexible tube incorporating a conductive wire;

[0023] FIG. 9 is a perspective view of a flexible double-lumen tube having a fluid-carrying lumen and a wire-carrying lumen;

[0024] FIG. 10 is a cross-sectional view of a connector similar to the connector of FIGS. 7A-C, with an attached wire and tubing;

[0025] FIG. 11 is a plan view of an extracorporeal blood flow circuit used in a representative hemodialysis system;

[0026] FIG. 12 is a perspective view of a hemodialysis apparatus configured to receive and operate the extracorporeal blood flow circuit of FIG. 11;

[0027] FIG. 13 is a representative plot of the resistance measured by the conductivity circuit of FIG. 1 under various conditions.

DETAILED DESCRIPTION

Conductivity Circuit

[0028] An exemplary electrical circuit shown in FIG. 1 can be used to measure the electrical conductivity or resistance of a subject fluid. In one embodiment, the fluid may be an electrolyte solution or dialysate fluid, and the circuit may ultimately provide a measurement of the conductivity of the fluid to ensure its compatibility for intravascular administration. In addition to monitoring the concentration of dissolved solutes in the fluid, the electrical circuit can also monitor for any interruption in the continuity of the fluid between the electrodes connected to the circuit. For example, it can be used to monitor an intravenous fluid line for the presence of air bubbles, or for the presence of a contaminating substance. In another embodiment, the fluid may be blood, and a change in the measured electrical resistance of a blood flow path (for example, in a conduit) may be used to indicate if a discontinuity occurs between the blood flow path and measuring electrodes. For example, the blood flow path may comprise a column of blood between two electrodes that includes indwelling needles or catheters in a segment of a blood vessel, arterio-venous fistula or graft. Vascular access disconnection can result in the introduction of air into the blood flow path, causing a change in the resistivity of the blood column between the electrodes. The electrical circuit can be readily modified (depending on its application) to adjust for the difference between the impedance of a blood flow path and that of dialysate fluid.

[0029] The circuit shown in FIG. 1 may be used to measure an unknown resistance R.sub.x of a subject media 1 using inexpensive electronic components, particularly where the unknown resistance involves a conductive path through an electrolytic fluid. A switching network 2 comprising a pair of multiplexers allows the connection of nodes V.sub.A and V.sub.B to reference voltages V+ and V−. The subject media 1 having unknown resistance R.sub.x is connected to terminals V.sub.TA and V.sub.TB 3, and forms a voltage divider with reference resistor R.sub.ref 4. To make a conductivity measurement, alternating voltages can be presented to the subject media 1 via switching network 2 to the voltage divider created by the known reference resistor R.sub.Ref 4 (680Ω, for example, in the case of dialysate fluid) and the unknown resistance R.sub.X of the subject media 1. The midpoint of the voltage divider 5 is measured. The signal V.sub.Sense at point 5 is buffered by amplifier 10 to make the input signal V.sub.in of the analog-to-digital converter (ADC) 11. V.sub.Sense switches between two values as the voltage divider is driven first one way and then the other way. This signal is valid only for a short period of time after switching because the fluid in the conductivity cell 1 is AC coupled into the circuit through capacitors C1 and C2 6. Thus DC-blocking capacitors C1 and C2 6 may be used to prevent DC currents from passing through the unknown resistance (which may include a conductive path through electrolytic fluid or blood). In an embodiment, series capacitors C can each comprise two capacitors in parallel, one having a value, e.g., of 0.1 uF, and the other having a value, e.g., of 10 uF. Series resistors 7 may be used to reduce exposure by the switch network and other sense circuitry to noise and surge voltages. ADC 11 can take multiple samples of the signal as the circuit is switched between the two configurations.

[0030] The switching network 2 can be driven by a pair of alternating binary control signals 13, 14 that connect V.sub.A to V+ and V.sub.B to V− during one half-cycle, and V.sub.B to V+ and V.sub.A to V− during the other half-cycle. This results in a waveform at the V.sub.sense node 5 that is similar to the waveform 20 shown in FIG. 2. In this embodiment, V.sub.Ref is 4 volts, resulting in a V.sub.sense amplitude of less than 4 volts, as shown in FIG. 2. A voltage divider 8 creates the voltages V+ and V− that are near the positive reference voltage V.sub.Ref and near ground, respectively. In one embodiment, R1 can have a value of 10 ohms, and R2 can have a value of 2K ohms When both multiplexers of switching network 2 are commanded to zero, the circuit is at rest and the lower voltage is presented to terminals V.sub.TA and V.sub.TB 3. When V.sub.A is high and V.sub.B is low, the higher voltage is presented to the reference resistor R.sub.Ref 4 and the lower voltage is presented to the subject media 1 having unknown resistance R.sub.x. When V.sub.B is high and V.sub.A is low, the higher voltage is presented to the subject media 1 having unknown resistance R.sub.x and the lower voltage is presented to the reference resistor R.sub.Ref 4.

[0031] A change in voltage ΔV.sub.sense before and after each square wave edge, can be shown to depend only on the reference resistance R.sub.ref 4, the unknown resistance R.sub.x of subject media 1, and any series resistance (including, e.g., R.sub.s 7), and is generally independent of series capacitance C1 or C2 6, since during this short time period the capacitor acts as an incremental short circuit. In particular,

Δα=ΔV.sub.sense/(V.sub.+−V.sub.−)=(R.sub.y−R.sub.ref−R.sub.th)/(R.sub.y+R.sub.ref+R.sub.th)=(ρ−1)/(ρ+1)

where R.sub.y=R.sub.x+2R.sub.s+R.sub.th, where R.sub.th=source series resistance from multiplexer 2 and voltage divider 8, and ρ=R.sub.y/(R.sub.ref+R.sub.th). (Source series resistance R.sub.th can be derived as the sum of the resistance of multiplexer 2 and the Thevenin equivalent resistance of the voltage divider 8. For example, for R1=10 ohms, R2=2K ohms, then R.sub.th=R1∥(R1+R2)=9.95 ohms). Thus, if R.sub.y is a short circuit, then ρ=0 and Δα=−1. The sense node's change in voltage ΔV.sub.sense is then equal to the voltage change at V.sub.B which has an amplitude opposite to the drive node at V.sub.A. If R.sub.y is an open circuit, then ρ=∞ and Δα=1. The sense node's change in voltage ΔV.sub.sense is then equal to the voltage change at the drive node V.sub.A. Accordingly, if this change in voltage is measured, the preceding equations can be solved for the unknown resistance R.sub.x:

R.sub.x=ρ(R.sub.ref+R.sub.th)−2R.sub.s−R.sub.th, where ρ=(1+Δα)/(1−Δα)

[0032] As shown in FIG. 1, a low-pass filter 9 can be formed by resistor R.sub.f and capacitor C.sub.f, to filter out high-frequency noise. In one exemplary arrangement, R.sub.F can have a value of 1KΩ, and C.sub.F can have a value of 0.001 uF. Buffer amplifier 10 and analog-to-digital converter (ADC) 11 can then measure the sensed voltage for a computer or digital signal processor (not shown).

[0033] The reference voltages V+ and V− may be advantageously derived from a voltage divider 8 so that V+ is close to the reference voltage V.sub.Ref of the ADC 11, and V− is close to the ground reference voltage of the ADC 11. For example, for R.sub.1=10Ω, R.sub.2=2 kΩ, and V.sub.ref=4.0V, then V+=3.980V, and V−=0.020V. This places both voltages within but near the edges of the active sensing region of the ADC 11, where they can be used for calibration (discussed below). Switch SW.sub.1 12 may be used to help calibrate the load resistance sensing.

[0034] Several improvements may decrease errors related to variations of component values. First, a calibration step can be introduced where V.sub.A is switched to V+ for a relatively long period of time, until V.sub.sense settles and is approximately equal to V+, at which point ADC 11 can take a measurement of V.sub.sense. A second calibration step can involve switching V.sub.A to V− for a relatively long period of time, until V.sub.sense settles and is approximately equal to V−, at which point ADC 11 can take another measurement of V.sub.sense. This allows the ADC 11 to measure both V+ and V−.

[0035] Secondly, as shown in FIG. 2, while the square wave is switching, ADC 11 readings before and after both edges of the switching waveform may be used to compute the dimensionless quantity Δα:

Δα=ΔV.sub.Sense/(V+−V−)=[(V2−V1)+(V3−V4)]/2(V+−V−)

As a result, both edges of the waveform can be used to measure
ΔV.sub.Sense=[(V2−V1)+(V3−V4)]/2, so that asymmetric responses to the circuit are likely to be canceled out. Alternatively, an average voltage at about the midpoint of the waveform may be used; so that, for example, Δα=ΔV.sub.Sense/(V+−V−)=[(V7−V6)+(V7−V8)]/2(V+−V−), and ΔV.sub.Sense=[(V7−V6)+(V7−V8)]/2. In addition, only differential measurements of the input signal V.sub.in of the ADC 11 can be used. Thus, any offset errors of the buffer amplifier 10 and ADC 11 can be canceled out. Also, Δα is a ratiometric quantity based on measurements using the same signal path. Thus, any gain errors of the ADC 11 can also be canceled out.

[0036] The reference resistor R.sub.Ref 4 may be optimally chosen to be equal to the geometric mean of the endpoints of the desired range of unknown resistances, taking series resistances R.sub.s 7 into account. For example, if R.sub.s=100Ω and R.sub.x varies from 100Ω to 3000Ω, then R.sub.y=R.sub.x+2R.sub.s varies from 300Ω to 3200Ω, and R.sub.ref should be approximately the square root of (300Ω.Math.3200Ω)=980Ω. To measure an unknown resistance in the range of 100 k-300 k ohms (as in, for example, a column of blood extending from one electrode to another via an arterio-venous fistula), the reference resistor R.sub.ref 4 can be changed to approximately 200 k ohms and the filter capacitor R.sub.F of low pass filter 9 at the input to the buffering amplifier 10 can be removed completely.

[0037] Because a voltage divider's output is a nonlinear function of its resistance ratio, errors or noise in readings from the ADC 11 produce their lowest fractional error (sensitivity) in the resultant calculation of R.sub.y when it is equal to R.sub.ref, and the sensitivity increases the more R.sub.y diverges from the reference resistance R.sub.ref. Specifically, it can be shown that the sensitivity in resistance ratio is as follows:

S.sub.ρ=(1/ρ).Math.δρ/δΔα=2/[(1+Δα)(1−Δα)]=2/[1−(Δα).sup.2]

When R.sub.y=R.sub.ref, ρ=1, Δα=0 and S.sub.ρ=2. Thus, for a change in Δα of 0.001 (0.1% of the ADC full-scale) around this point, the calculated resistance R.sub.y changes by 0.002 or 0.2%. The sensitivity increases as ρ diverges from 1, as shown in Table 1.

TABLE-US-00001 TABLE 1 ρ Δα S.sub.ρ 1 0 2 2, 0.5 ±0.333 2.25 4, 0.25 ±0.6 3.13 5.83, 0.172 ±0.707 4 10, 0.1 ±0.818 6.05 20, 0.05 ±0.905 11.03
FIG. 3 shows that the noise/error sensitivity doubles at about a 6:1 ratio of unknown/reference resistance, and triples at a 10:1 ratio. Resistance measurements outside this range may suffer in their increased sensitivity to noise and error.

[0038] For calibration purposes, a switch SW.sub.1 12 can be used to make resistance measurements to calibrate out a point at R.sub.x=0. Preferably this switch 12 should be placed across the terminals V.sub.TA and V.sub.TB 3, or as close to the terminals as feasible, which would give a true zero-point calibration. In practice, however, locating the switch 12 close to the terminals V.sub.TA and V.sub.TB 3 may make the switch 12 prone to external noise and surge voltages, and may introduce DC leakage current into the subject media 1.

[0039] The series capacitances C1 and C2 6, and the use of square waves are important for unknown resistances that include an electrolytic conductive path. There are at least two reasons for this. First, it may be important in many applications to prevent DC current from flowing through an electrolyte solution or a bodily fluid having similar properties; otherwise electroplating and/or electrolysis of electrodes at the terminals V.sub.TA and V.sub.TB 3 can occur. In this circuit, the capacitors C1 and C2 6 block DC currents. Furthermore, because the capacitors may allow very small currents to flow (microamps or less), using an alternating square wave voltage may help to limit the average current further.

[0040] Secondly, in the event that a small electrochemical DC voltage is induced in the subject media 1 (for example, the electrodes in a fluid path may oxidize over time at different rates), this DC voltage can be blocked by the capacitors C1 and C2 6. Because the method for calculating resistance takes differential measurements, any residual DC voltage may be canceled out through the process of calculating the unknown resistance Rx of subject media 1.

Vascular Disconnect Detector

[0041] With the appropriate modifications of a conductivity measurement circuit such as the one described above, it is possible to detect the conductivity and changes in the conductivity of blood. More specifically, it is possible to detect the change that occurs in the conductivity of a volume of blood when air enters the volume. This situation can occur, for example, when an intravascular access site becomes dislodged in an extracorporeal blood circuit.

[0042] The circuit shown in FIG. 1 can be used to measure the resistance of a volume of fluid in a conductivity cell or conduit 1. For measurements of R.sub.x of a conductivity cell 1 representing the resistance or conductivity of a volume of dialysate solution, a convenient value for the reference resistor R.sub.Ref 4 can be chosen to be approximately 680 ohms. For measurements of R.sub.x of a conduit 1 representing the resistance or conductivity of a column of blood extending from a first cannula or needle, through an arterio-venous fistula, to a second cannula or needle, a convenient value for the reference resistor R.sub.Ref 4 can be chosen to be approximately 200 k ohms.

[0043] The advantages of using this circuit to monitor the continuity of a column of a bodily fluid such as blood or plasma include the following:

[0044] Capacitive coupling to the conductivity cell or conduit 1 blocks DC current which could cause plating and corrosion of electrodes at terminals VTA and VTB;

[0045] Voltages and current levels are very low and decoupled for patient safety;

[0046] Current only flows briefly while the measurement is being taken. No current flows between measurements.

[0047] With the lower reference resistor R.sub.ref 4 value (e.g. 680 ohms), this circuit is appropriately configured for dialysate conductivity measurements. With a much higher reference resistor R.sub.ref 4 value (e.g. 200 k ohms) this circuit is appropriately configured for measuring the resistance between an arterial needle and a venous needle to detect vascular needle dislodgement from an arterio-venous fistula.

Electrode Placement

[0048] The continuity of a fluid column leading from a fluid delivery apparatus to a patient's blood vessel or vascular graft can be monitored using the electronic circuit described above. The fluid being delivered may include blood or any electrolyte solution, including dialysate fluid. Although the following discussion will involve a hemodialysis system, the same principles of operation of the invention can apply to any device that is configured to deliver a fluid to a patient via a vascular access. In an embodiment illustrated by FIG. 4, the conductivity of a volume of blood or other fluid within a fluid flow circuit 100 of a hemodialysis machine 200 can be monitored electronically, using electrodes on each end of the volume that make direct contact with the blood or other fluid. Using an electrical circuit such as the one shown in FIG. 1, one electrode can be connected to the V.sub.TA terminal, and the other electrode can be connected to the V.sub.TB terminal of the circuit. The voltages applied to the electrodes by the circuit can be sufficiently small (e.g., about 4 volts or less), sufficiently brief, and with DC voltages sufficiently decoupled so as to prevent any harm to the patient. In this example, a fluid flow circuit 100 is shown, including an arterial access needle 102, an arterial catheter tubing 104, an arterial catheter tubing connector 106, arterial blood circuit tubing 108, a transition 110 between the blood circuit tubing 108 and hemodialysis machine 200, a blood pump inlet line 112, a blood pump 114, a blood pump outlet line 116, a dialyzer 118, a dialyzer outlet line 120, air trap 122, a transition 124 between hemodialysis machine 200 and venous blood circuit tubing 126, a venous catheter tubing connector 128, a venous catheter tubing 130, a venous access needle 132, and the intraluminal volume of that portion of the patient's blood vessel or fistula 134 that lies between the arterial access needle 102, and the venous access needle 132. It should be noted that the invention described herein also encompasses circumstances in which the arterial access needle may reside in one blood vessel of a patient, while the venous access needle may reside in a separate blood vessel some distance away from the arterial access site. Furthermore, the circuit described above may be used to monitor the integrity of a vascular access in a fluid delivery system that does not have the venous return line shown in FIG. 4. In that case, for example, an electrode at location B could be paired with an electrode in contact with fluid in a dead-end line communicating with a second needle or cannula accessing the blood vessel or vascular graft. In another example, an indwelling hollow cannula or solid trocar in the vascular segment can be equipped with a conductive wire which could then serve as the second electrode in the monitoring system. The vascular segment being accessed may be a surgically constructed arterio-venous fistula, and may also include an artificial conduit such as a Gortex vascular graft. The term ‘arterial’ is used herein to denote the portion of the blood flow circuit that conducts blood away from the patient and toward the hemodialysis machine 200. The term ‘venous’ is used to denote the portion of the blood flow circuit that conducts blood away from the hemodialysis machine 200 and back toward the patient. The term ‘access needle’ is used to denote a needle or catheter device that penetrates the patient's vascular segment or fistula. In different embodiments it may be permanently fused or reversibly connected to a corresponding catheter tubing 104, 130.

[0049] The continuity of any segment of the fluid flow circuit 100 can be monitored by positioning two electrodes in contact with the fluid on either side of the fluid and blood-containing segment of interest. In order to monitor for a disconnection of the arterial access needle 102, or the arterial catheter tubing 104, or the venous access needle 132 or venous catheter tubing 130, one electrode can be placed in continuity with the lumen of the venous side of the blood flow circuit, while a second electrode is placed in continuity with the lumen of the arterial side of the blood flow circuit. In one embodiment, the two electrodes can be positioned on or near the dialysis machine 200, with an electrode in contact with blood upstream of blood pump 110, and a second electrode in contact with blood downstream of the dialyzer 118 and/or air trap 122. For example, the electrodes can be incorporated into transition locations 110 and 124.

[0050] In another embodiment, one of the electrodes can be positioned to be in contact with the fluid in the fluid flow circuit 100 at a point that is closer to the vascular access site 134 than it is to the equipment (e.g. a dialysis machine) used to deliver fluid flow to the accessed blood vessel or vascular graft. In a preferred embodiment, both electrodes can be positioned to be nearer to the patient's blood vessel or vascular graft than the equipment associated with the dialysis machine 200. This may further reduce electrical interference associated with the dialysis machine 200. An electrode A can be conveniently placed at or near the arterial catheter tubing connector 106 and a second electrode B can be conveniently placed at or near the venous catheter tubing connector 128. In this arrangement, the electrical continuity pathway from the first electrode through the patient's vascular access to the second electrode is much shorter—and the electrical resistance lower—than the pathway extending back toward the dialysis machine 200. In some cases, the access catheters 104 and 130 can be as short as about a foot, whereas the arterial and venous tubings 108 and 126 can be about six feet long. Because of the electrical conductive properties of the fluid in the circuit, the electrical resistance associated with the pathway incorporating tubing 108 and 126, and components of the dialysis machine 200, can be many times greater than the electrical resistance associated with the pathway through the patient's blood vessel or fistula 134.

[0051] Electrical interference associated with the dialysis machine 200 is thus reduced, and a change in electrical resistance due to an access-related disconnection can more easily be detected. Preferably, the electrodes A and B are positioned to be more than 50% of the distance from the dialysis machine to the patient. More preferably (and more conveniently), the electrodes A and B are located near the last disengageable fluid connection before reaching the patient. In one embodiment of a hemodialysis system, the blood tubing 108 and 126 is approximately 6 feet in length, and the arterial and venous catheter tubes 104, 130 are about two feet or less in length. A convenient location for electrodes A and B would then be at the arterial line and venous line connectors 106, 128 (which can be, e.g. Luer type connectors or modifications thereof) that connect the arterial and venous blood circuit tubes 108, 126 with the arterial and venous catheter tubes 104, 130.

Connector Electrodes

[0052] As shown in FIGS. 5A and 5B, in one embodiment, a blood line connector for the blood circuit of a hemodialysis system may incorporate electrodes that can make contact with any liquid within the lumen of the connector. In one aspect, the electrode can comprise an annular conductive cap 310 placed at the tube-connection or proximal end 302 of any suitable connector, such as, for example connector 300. The electrode is preferably constructed from a durable and non-corrosive material, such as, for example, stainless steel. The distal coupling end 304 of connector 300 can be constructed to make a sealing engagement with a corresponding Luer-type connector of an arterial or venous catheter, for example. The inner annular surface 312 of the cap 310—in part or in whole—can make contact with any liquid present within the lumen 314 of the connector. As shown in FIG. 5B, an O-ring 316 or a suitable sealant can be placed between the cap electrode 310 and the proximal end 302 of the connector to maintain a fluid-tight connection between the connector and any flexible tubing attached to the connector.

[0053] An elastomeric O-ring may be particularly useful in hemodialysis or other extracorporeal systems in which the blood-carrying components are subjected to disinfection or sterilization using heated liquids. The thermal coefficients of expansion of the plastic components of a connector may be sufficiently different from that of an incorporated metal electrode that a permanent seal may not be preserved after one or more sterilization or disinfection procedures. Adding an elastomeric component such as an O-ring at the junction between an electrode and the connector seat on which it is positioned may preserve the seal by accommodating the different rates of expansion and contraction between the electrode and the connector.

[0054] As shown in FIG. 6, in one embodiment, a conductive electrode 310 (constructed of, e.g., stainless steel) can be incorporated into a portion of a connector 300 (either at its proximal end 302, or alternatively at its distal connecting end 304), over which the end of a flexible tubing 318 can be placed. In this embodiment, the electrode 310 is generally cylindrical, and has a taper 320 on a proximal end to permit an easier slip-fit attachment of the end of a segment of flexible tubing 318 over the outside surface of the electrode 310. As shown in FIG. 6, the internal surface of the electrode 310 has an internal ledge 322 that allows the electrode cap 310 to slip over and abut a proximal end 302 of connector 300. Connector 300 can be constructed of any suitable hard material, including metal or more typically a plastic material. The ledge 322 helps to ensure that a smaller diameter inner surface 312 of electrode 310 is properly positioned to make contact with any liquid (e.g. blood) that passes through the lumen 314 of connector 300. The connections between connector 300 and electrode 310, and electrode 310 and the termination of an overlying flexible tubing 318 can be made air tight or permanent with any suitable adhesive compatible with the compositions of the components.

[0055] To ensure a more secure seal to prevent blood leakage between the connector and electrode, and to limit the area under the electrode where blood elements may migrate and become lodged, an O-ring 316 can be incorporated into the inner surface of electrode 310 near the electrode internal ledge 320. This is seen in enlarged detail in FIG. 6. In this example, the O-ring 316 seals between the stainless steel electrode 310 and the distal end 302 of connector 300. A barb element 324 on the proximal end 302 of connector 300 can be incorporated in the connector design in order to hold the stretched end of the flexible tubing 313 onto the proximal end 302 of connector 300. In an embodiment, the electrode 310 is held in place by the portion of the flexible tube that is stretched over both the electrode 310 and the barb 324 of connector 300.

[0056] A wire 326 can be soldered, welded or otherwise secured onto the outer surface of electrode 310, and can travel under the overlying stretched tubing 318 until exiting more distally along the connector 300. The wire can thus conduct electrical signals to and from the electrode 310 as the internal surface 312 makes contact with the intraluminal fluid (e.g. blood). In the example shown, wire 326 is soldered to a distal portion of electrode 310 and travels under tubing 318, to emerge at the abutment of tubing 318 with a corresponding stop 326 of connector 300.

[0057] In another embodiment as shown in FIGS. 7A-7C, a connector 400 as described in U.S. Patent Application Publication No. 2010/0056975 (the contents of which are hereby incorporated by reference) has been modified so that a mid-portion 406 of the connector 400 can incorporate an electrode. Placement of the electrode along the mid-portion 406 of the connector 400 avoids having to alter the distal coupling end 404 of the connector, and avoids any alteration of the interaction between the termination of the flexible tubing and the proximal end 402 of the connector. In this example, the blood line connector 400 is constructed to make two different types of sealing connections on its distal coupling end 404, including an internal screw-type connection 405 for a Luer-type connector of a patient access line, and an external press-in type connection 407 with a dialysis machine port for recirculation of priming and disinfecting fluid through the blood carrying components of a dialysis system. The press-in feature 407 is formed having a frustoconical shape on the outside surface of the distal end 404 of the connector 400, while the Luer-compatible screw-type feature 405 is formed on the corresponding internal surface of the distal end 404 of the connector 400. The outside surface of the frustoconical member is constructed to make sealing engagement with the seat of a mating connector of a dialysis machine 200 or other device. A pair of locking arms 408 extending proximally from the distal coupling end 404 of the connector 400 can each have a barbed portion 409 to engage a corresponding locking feature on a mating connector on the dialysis machine, and a finger depression portion 410 to aid in disengaging the barbed portions 409 from the dialysis machine. The barbed portion 409 helps to lock the frustoconical member in sealing engagement with its mating connector on the dialysis machine when making a press-in type of connection. The distal ends of the locking arms can be constructed to attach to the connector via a flange 411 located proximal to the frustoconical portion 407 of the connector 400. The connector 400 has a proximal tubing attachment end 402 to sealingly engage a flexible tube. The tubing attachment end 402 may have one or more barb features 412 to help prevent disengagement of the end of a flexible tube from the connector 400.

[0058] FIG. 7B shows a side view of connector 400, bringing into view an access feature or port 420 that can permit placement of an electrode in direct communication with the lumen of connector 400. In other embodiments, the access feature may house an elastomeric stopper—with or without a septum—to permit sampling of fluid from within the lumen 414 of connector 400 using a syringe with a sharp or blunt needle. Alternatively, the feature may serve as a port to allow connection of another fluid line to the lumen 414 of connector 400.

[0059] In yet another embodiment, the mid-portion 406 of connector 400 may have two access ports, as shown in the cross-sectional view of FIG. 7C. A fluid access port 420a can serve as a sampling port, and an electrode port 420b can serve as an electrode cradle. An elastomeric stopper 422 within sampling port 420a can be shaped to extend to the lumen 414 of connector 400, simultaneously permitting sampling of fluid in the lumen 414 with a needle, while maintaining an air-tight seal. Alternatively, a Luer-type connector having a separated cap or seal can be incorporated into the port, which is capable of connecting with a syringe or catheter having a mating Luer-type connector. An electrode port 420b can serve as a seat or cradle for an electrode 424. In can be press-fit or cemented into position, and sealed with an adhesive, or with an O-ring 416 as shown. A wire 426 can be soldered, welded or otherwise secured onto the outer surface of electrode 424, and can travel proximally toward dialysis machine 200 with the arterial tubing 108 or venous tubing 126 to which connector 400 is attached.

[0060] In any of the above electrode embodiments, the electrodes may be replaced by a suitably sized thermistor, or combination of a thermistor and electrical conductor, for the additional purpose of monitoring the temperature of the fluid passing through connector 300, 400 or variants thereof.

Wire Assembly

[0061] In one embodiment, the wires carrying electrical signals to or from a pair of electrodes on connectors 106, 128 (one on the arterial side and one on the venous side of the blood flow circuit) can travel separate and apart from the blood tubing 108, 126 back toward dialysis machine 200, where they ultimately terminate and connect to a conductivity detecting circuit, such as the conductivity circuit shown in FIG. 1. The conductivity circuit, in turn, provides an appropriately configured signal to a processor on the dialysis machine to determine whether a change in fluid conductivity consistent with an access disconnection has occurred. If so, the processor can trigger an alarm condition, or can initiate a shut-down of blood pump 114, and trigger a mechanical occlusion of blood tubing 108 and/or 126, for example.

[0062] Wires that extend together or separately between the dialysis machine and the patient are at risk of getting tangled, broken or becoming disconnected. Therefore, preferably, each wire 326 or 426 can be attached, fused, or otherwise incorporated into its associated tubing 103, 123. Incorporating a wire into its associated tubing provides a convenient way of protecting the wires and connections, and simplifying the interface between the patient and the dialysis apparatus. Exemplary methods of achieving this are shown in FIGS. 8A-8D. In a preferred embodiment, the tubing is comprised of a flexible material (e.g., silicone) that can be formed in an extrusion process. As shown in FIG. 8A, a loose wire mesh may be embedded in the flexible silicone tubing as it is formed and extruded, similar to fiber reinforcement of flexible tubing. As shown in FIG. 5A, a wire mesh 500 can be embedded within the wall of the flexible tubing 502 during extrusion, in a manner similar to the construction of a fiber-reinforced tube. As shown in FIG. 81, an insulated wire 504 can be joined to the external surface of its adjacent tubing 506, either during a secondary extrusion process, or a process in which the two structures are joined by an adhesive, for example. As shown in FIG. 8C, a second extrusion producing a secondary concentric layer of tubing material 503 can be made to capture a wire running along the external surface of the tubing after the primary extrusion. As shown in FIG. 8D, the tubing 510 during formation can also be co-extruded with a wire 512 embedded in the wall of the tubing.

[0063] In some of the above methods, the resulting tube-wire combination may have a tendency to curl because of the difference in thermal coefficients of expansion between the wire and the silicone material of the tubing. As the material cools after extrusion, the silicone may capture the embedded wire tightly, causing the cooled tube-wire bundle to curl. In a preferred embodiment, the wire lumen of the extrusion die is constructed to be large enough to accommodate a cross-sectional area significantly larger than the cross-sectional area of the wire to be embedded. Then as the silicone cools, the passageway surrounding the wire does not shrink to the point of tightly encasing the wire. A co-extrusion process incorporating an insulated wire can generate a tube-wire bundle as shown in FIG. 9. In this example, flexible tubing 514 is a co-extrusion of a fluid-carrying lumen 516 and a wire-carrying lumen 518. Preferably, the wire 520 is multi-stranded for flexibility and durability, and is coated or sheathed in a durable, flexible synthetic insulating material 522, such as, for example, PTFE. A PTFE-based sheath 522 of the stranded wire 520 can sustain the high temperatures associated with the silicone tubing extrusion process, so that its integrity is maintained along the section 524 of the wire that ultimately exits the tubing for connection either to the dialysis machine 200 or the patient line connectors 106, 128. A coating or sheathing may also help prevent the wire from adhering to the side walls of the wire-carrying lumen after extrusion and during cooling.

[0064] FIG. 10 shows a cross-sectional view of an exemplary connector-wire-tubing assembly. The proximal tubing connection end of a connector 400 is shown with the end of a double-lumen tubing 514 attached. The fluid-carrying lumen 516 is press-fit and/or cemented to the proximal end of connector 400, allowing for fluid flow through the central lumen 414 of connector 400. Stranded wire 520 is soldered or otherwise attached to electrode 424, which is in conductive contact with any fluid present within the lumen 414 of connector 400. The non-connecting portion of the wire 520 that travels outside tubing 514 is preferably sheathed in an insulating synthetic coating, such as, for example, PTFE. Optionally, this portion of both the exposed and sheathed wire may also be sealed with a sealant, such as RTV. The sheathed wire 522 enters the wire-carrying lumen 518 of tubing 514 near its termination onto connector 400. The wire/tubing bundle then makes its way toward the dialysis machine 200, where the wire emerges from the tubing to make a connection to a conductivity circuit such as the one shown in FIG. 1.

[0065] FIG. 11 shows an exemplary extracorporeal circuit 210 that may be used as a removable, replaceable unit in a hemodialysis apparatus 220 as shown in FIG. 12. In this embodiment, the extracorporeal circuit comprises a blood pump cassette 114, dialyzer 118, venous return air trap 122, arterial blood tubing 108, venous blood tubing 126, arterial catheter connector 106, and venous catheter connector 128. The arterial 106 and venous 128 connectors may be of a type similar to the connector 300 shown in FIGS. 5A and 5B, or similar to the connector 400 shown in FIGS. 7A-7C, or variants thereof. The arterial 103 and venous 126 blood tubes may be of a type shown in FIGS. 8A-8D, or FIG. 9. Wires forming terminal connections to electrodes on connectors 106 and 128 may exit arterial 106 and venous 126 tubes as segments 524A and 524B to make a connection with a connector that ultimately passes the connection through on the dialysis apparatus to terminals associated with a conductivity circuit such as that shown in FIG. 1. In the embodiment shown, the connector 526 is mounted to a support structure 212 for the blood pump 114 and air trap 122.

[0066] FIG. 12 shows an exemplary hemodialysis apparatus 220 that is configured to receive the extracorporeal circuit 210 shown in FIG. 11. In this illustration, the dialyzer 118 is already mounted onto the apparatus 220. A base unit 220 receives the control ports of a mating blood pump cassette 114. Sets of raceways or tracks 222 help to organize the pair of arterial 106 and venous 126 blood tubes when not extended out and connected with a patient. A connector 224 receives and passes through the connections made between wire segments 524A and 524B and connector 526 to the terminal connections of a conductivity circuit such as that shown in FIG. 1. A tubing occluder 226 is positioned to receive venous blood tube 126 after it exits air trap 122, and arterial blood tube 108 before it reaches blood pump cassette 114. The occluder 226 may be actuated pneumatically or electromechanically, for example, whenever an alarm condition occurs that requires cessation of extracorporeal blood flow. A set of arms of occluder 226 can be configured to rotate against the walls of the flexible tubes, constricting or stopping fluid flow within them. Thus, a controller installed within apparatus 220 can receive a signal from a conductivity circuit similar to FIG. 1, the signal representing the electrical resistance of the column of fluid or blood between the electrodes mounted on connectors 106 and 128. Because the connectors are positioned much closer fluidically to the patient's blood vessel or fistula 134 than to the blood pump 114, dialyzer 118 and air trap 122, the signal associated with the fluid path through the blood vessel or fistula 134 can discriminate between an intact and an interrupted column of blood or fluid between the connectors 106/128 and the patient's blood vessel or fistula 134. The controller can be programmed to respond to an electrical resistance detected by the conductivity circuit found to exceed a pre-determined value. Depending on the circumstances, the controller may then-trigger an alarm to alert the patient to a possible disconnection of blood flow, and may also optionally command the occluder 226 to cease extracorporeal flow to and from the patient.

Operation of the Disconnect Detection Circuit

[0067] FIG. 13 shows test results utilizing the disconnect detection circuit described above and shown in FIG. 1. In this case, a hemodialysis blood circuit and apparatus was employed that is similar to that disclosed in U.S. Patent Application Publication Nos. 2009/0114582 and 2010/0056975, (the contents of which are hereby incorporated by reference). The extracorporeal circuit 210 shown in FIG. 11, comprises a blood pump 114, dialyzer 118, air trap 122, venous blood circuit tubing 126, and arterial blood circuit tubing 108. Extracorporeal circuit 210 mates to a hemodialysis apparatus 220 similar to the one shown in FIG. 12. The blood flow circuit tested included a pair of membrane-based blood pumps arranged on a blood pump cassette 114 shown in FIG. 11, a dialyzer 118, a venous return air trap 122, an arterial blood tubing set 163, a venous blood tubing set 126, arterial and venous connectors 106 and 128, and catheter tubing sets 104, 130 connected to vascular access needles 102, 132 as shown in FIG. 4. The needles 102, 132 were placed in a container holding anticoagulated bovine blood. The blood tubing set 108 and 126 was approximately six feet long, and the catheter tubing sets 104 and 130 were approximately two feet long or less. The needles were alternately manually placed in or withdrawn from the container during blood flow to simulate disconnection of a needle from a fistula or blood vessel. Periods A, C and F in FIG. 13 represent the times during which the needles were submerged in the blood in the container. The electrical resistance measured by the disconnect detection circuit shown in FIG. 1 during these periods averaged between 120,000 and 130,000 ohms. Periods B and E in FIG. 13 represent the times during which the venous return needle 132 (under positive pressure from the blood pumps) was withdrawn several centimeters above the surface of the blood within the container, forming a stream of blood mixed with air as the blood exited the venous return needle and entered the container of blood below. The electrical resistance measured during these periods averaged between 140,000 and 150,000 ohms. Period D represents the time during which one of the needles was completely removed from the container, creating a fully open electrical circuit. The electrical resistance measured during this period averaged between about 160,000 and 180,000 ohms. Thus a controller can be readily programmed to distinguish the difference in the monitored resistance of the electrical circuit between an uninterrupted and an interrupted flow of blood. These results showed that an interruption of the continuity of the blood between the arterial 102 and venous 132 needles can reliably produce a detectible change in the measured electrical resistance between two electrodes when placed relatively closer to the arterial and venous access sites than to the blood processing components 114, 118 and 122 of the extracorporeal blood circuit. Furthermore, even a partial interruption of the continuity of blood flow (as in the streaming of blood through air) can be reliably detected, albeit with a smaller change in the measured electrical resistance.