Systems and / or methods for monitoring an intravenous procedure

Abstract

A system (10) for monitoring an intravenous procedure for a patient comprises a bio-impedance sensor (11) and an impedance measuring unit (20). The bio-impedance sensor (11) comprises at least a pair of supercutaneous electrodes (15a-15d) disposed in electrical contact with the skin of the patient proximate an insertion site (18, 350) for an injection device (300). The impedance measuring unit (20) is operatively coupled to the bio-impedance sensor (11) for generating a current, energising at least one electrode (15a) and measuring impedance values acquired, between the at least one pair of supercutaneous electrodes (15a-15d), proximate the injection device insertion site (350) when current is generated at multiple frequencies. A processor (30) coupled to the bio-impedance sensor (11) employs an algorithm to process the impedance values acquired at a plurality of selected frequencies. The algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysis of the acquired impedance values to determine presence of extravascular fluid.

Description

SYSTEMS AND / OR METHODS FOR MONITORING AN INTRAVENOUS PROCEDURETECHNICAL FIELD

[0001] The present disclosure relates to a system and / or methods for monitoring an intravenous procedure, in particular for detecting presence of extravascular fluid which may be indicative of intravenous (IV) infiltration and / or extravasation.BACKGROUND ART

[0002] The following discussion of the background art is intended to facilitate an understanding of the present disclosure only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.

[0003] Intravenous Therapy (IV) is a method of delivering lifesaving drugs, anaesthesia and nutrition, collectively “IV fluid”, directly into the bloodstream of a human or animal, typically by a catheter inserted into a peripheral vein. IV infiltration or extravasation is the unintended leakage of IV fluid that is being delivered outside the vein and into the surrounding tissues. Such infiltrated IV fluid or ‘extravascular fluid’, which may be toxic in nature (for example, chemotherapeutic agents), may cause chemical burn injuries or tissue necrosis that may be debilitating and have a lifelong impact.

[0004] These problems may be caused by infiltration or extravasation. “Infiltration” may be defined as leakage, from an injection device, of a non-vesicant or ‘noncaustic’ IV solution, such as saline, into tissue surrounding the IV site. By noncaustic, is intended ‘not burning’. While infiltration may not always result in visible or symptomatic injury, it can significantly compromise treatment delivery, reducing or halting the intended drug dose reaching the circulation.

[0005] “Extravasation” may be defined as leakage, from an injection device, into tissue, of a vesicant or otherwise damaging (e.g through being hyperosmotic or cytotoxic) IV solution, for example of a potentially therapeutically effective but harmful drug. Extravasation is typically a more urgent clinical concern thaninfiltration due to the potential for causing pain, inflammation and tissue necrosis when the IV solution escapes or is infused outside the desired vascular pathway.

[0006] Such IV infiltration and extravasation, which may be abbreviated ‘EVI’, has been reported to occur in 10-70% of IV therapies. The exact rate depends on a combination of factors such as the patient population, disease state and hospital reporting protocols. In some patient populations, such as prematurely born neonates, recipients of chemotherapy, and surgical patients requiring anaesthesia (including for plastic surgery), the injury may have a particularly severe impacts. Such impacts may include amputation, delay in critical drug delivery, additional hospital stay and awakening from anaesthesia during ongoing surgery as well as litigation.

[0007] Currently, an international standard for prevention of IV and extravasation injury is the periodic inspection of IV sites by attending nurses as per hospital protocol and / or patients alerting the nurses of discomfort. However, non-verbal populations like neonates and paediatric patients - as well as surgical patients under anaesthesia cannot communicate. In any event, nurses do not always have a clear line of sight to the IV site and infiltration may progress to injury faster than the interinspection intervals. Additionally, for prematurely born babies, visual inspection requires repeated handling of babies within the incubator increasing the chances of infection.

[0008] To avoid challenges such as the above, one approach to detect IV infiltration is by automatic continuous imaging of the IV insertion site for detecting infiltration of isotonic saline infusion. Light shone on the tissues surrounding the IV site is reflected by the tissue and captured in an image. These images are continuously analysed to detect changes in the tissue appearance due to infiltration. This method, however, requires somewhat bulky equipment which may interfere with the clinical workflow; and is susceptible to patient movement as motion alters the reflection of the light. Additional difficulties are posed by IV fluids that do not alter the reflectivity of tissues; and the narrow field of view. Thus, a high occurrence of false positive infiltration results may occur. Further, image analysis is computationally expensiveand does not ensure timely detection for the prevention of sequelae. Still further, this technique does not determine the amount of IV infiltration or leakage.

[0009] Another method of monitoring for, and detecting, IV infiltration includes medical imaging using X-ray or ultrasound as described, for example, in US Patent Application Publication No. US 20020172323. Such methods are only applicable for snapshot detection by a trained professional and are not suitable for continuous monitoring which is necessary for timely detection and prevention of infiltration and extravasation injuries.

[0010] It may also be possible to monitor the pressure and / or temperature of the IV insertion site. Such method may provide delayed information on occurrence of infiltration but is limited in efficacy for temperature controlled environments such as the inside of an incubator or in febrile patients.

[0011] It is against the above background that the present disclosure has been developed.SUMMARY

[0012] This summary is not intended to be limiting as to the embodiments disclosed herein and other embodiments are disclosed in this specification. In addition, limitations of one embodiment may be combined with limitations of other embodiments to form additional embodiments.

[0013] In at least one embodiment, the present disclosure provides a system for monitoring an intravenous procedure for a patient comprising: a bio-impedance sensor comprising at least a pair of super-cutaneous electrodes disposed in electrical contact with the skin of the patient proximate to an insertion site for an injection device for injecting a fluid to the patient; an impedance measuring unit, the impedance measuring unit being operatively coupled to the bio-impedance sensor for measuring impedance values acquired, between each electrode of the at least one pair of supercutaneous electrodes, when a current generated at multiple frequencies is directed between each electrode; anda processor coupled to the bio-impedance sensor and having a memory having stored therein an algorithm comprising electronic instructions that, when executed by the processor, process the impedance values acquired at a plurality of selected frequencies to determine presence of extravascular fluid in tissue due to the intravenous procedure, wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid. In preferred embodiments, the system is configured to detect early signs of infiltration or extravasation enabling inter alia physiological integrity and correct intravascular placement of an IV feed tube or line at the time of insertion and over time. Physiological changes may be identified within, or around, an accessed vein, including at or near an insertion site or injection device tip which indicate whether the IV line remains properly positioned, maintaining effective and safe therapy delivery and preventing local tissue damage.

[0014] The algorithm enables presence of intravenous (IV) infiltration and / or extravasation to be determined. Further, the algorithm will detect any break in integrity, for example due to mis-positioning of the injection device or lack of patency of injection device within vasculature, of the intravenous procedure. Desirably, the algorithm enables early detection of conditions such as, but not limited to, cannula displacement, tissue damage, vein perforation or vascular collapse to enable an efficacious therapeutic response.

[0015] The bioimpedance sensor may comprise at least two surface- contact electrodes (e.g. biopotential leads) configured for electrical coupling with the skin or tissue to enable bioimpedance and / or biopotential measurements. Examples are ECG, EEG, EMG or EIT electrodes. In some embodiments, the at least one pair of supercutaneous electrodes may be disposed, optionally as a configurable array, on a wearable patch. The bioimpedance sensor may communicate wirelessly with the impedance measuring unit, in particular the processor.

[0016] In at least one embodiment, at least one reference electrode is included in the bioimpedance sensor to provide a stable electrical baseline against which the physiological cause of any change in bioimpedance may be determined. Thereference electrode establishes a baseline signal. In embodiments where the at least one pair of supercutaneous electrodes are disposed on a wearable patch, the at least one reference electrode may be disposed on the wearable patch

[0014] The at least one pair of electrodes may be a first pair of electrodes forming part of a configurable array of supercutaneous electrodes. The configurable array may be deployed in a pattern on the wearable patch.

[0015] In at least one embodiment, the at least one pair of electrodes is disposed on the skin to run substantially parallel to, or longitudinally along, a path of a target vein and provide a first kelvin resistance circuit when connected to the impedance measuring unit. Each electrode of the pair is spaced by a distance, for example being selected with reference to the dimension of a limb on which the insertion site is located. Bioimpedance data measured in this way would typically fluctuate unilaterally with time from a baseline.

[0016] In such an embodiment, a second pair of electrodes may be disposed on the skin for a current path or line between the electrodes to run at an angle, conveniently perpendicularly, or substantially perpendicularly, though an acute angle may be acceptable in an alternative embodiment as described herein, to the path of the target vein and provide a second kelvin resistance circuit when connected to the impedance measuring unit. Bioimpedance data measured in this way would typically fluctuate bilaterally with time around a baseline, for example representative of mean or median bioimpedance. The first pair of electrodes allow collection of bioimpedance information useful for determining infiltration and / or extravasation events. This may be sufficient. However, use of both the first pair of electrodes and second pair of electrodes provides greater precision in characterisation of a physiological cause for changes in bioimpedance. Without wishing to be bound by theory, the first pair of electrodes accords with the path of electricity likely having the lowest resistance within the vein (i.e., within the blood) and the reference electrode(s) accords with the greatest capacitance on the electrical path running perpendicular or transverse to the vein as it crosses more cell membranes and the vein walls.

[0017] To save space in a typically small working area, a single reference electrode may be used. Such a reference electrode is disposed offset from each electrode of the first pair of electrodes and may be brought into electrical connection with either electrode providing an indication of capacitance on the electrical path aligned at an acute angle (or at 90 degrees) to the vein.

[0018] In embodiments using a wearable patch, additional electrodes may be disposed on the wearable patch outwardly of the first and / or second electrode pairs to provide further characterisation of infiltration and / or extravasation events. In certain embodiments, a higher resolution or sensitivity may be obtained, the greater the number of electrode pairs that are used. In certain embodiment, use of the first and second pair of electrodes, as described herein, may be used.

[0019] In some embodiments, a wearable patch may be configured, for example, being sized and / or shaped to fit a limb or different limbs, for example, leg / foot or wrist / fo rearm. The wearable patch may comprise a cuff, sock or sleeve portion for insertion of the limb. The wearable patch, including the cuff, sock or sleeve portion where provided, may be a flexible material, being elastic or stretchable to fit different limbs at least limiting the need for manufacture of a range of sizes of cuff, sock or sleeve portion. The wearable patch may also be configured, for example, being sized and / or shaped to accommodate patients according to anatomy, physiology, gestational age and so on. Similarly, the electrode array may be configured to suit a determined limb and / or to accommodate patients according to gestational age. The wearable patch may comprise a plurality of portions which - when combined in area even if spaced - form the wearable patch. The electrode array itself, as well as individual electrodes included within the array, may be stretchable to suit individual patients.

[0020] The wearable patch may include a transparent portion or window, whether or not formed of suitable material, allowing visual checking of the insertion site during the procedure with the injection device.

[0021] The system may a further sensor selected from the group consisting of: a temperature sensor for sensing patient skin temperature; optical sensors; motion or inertial sensors such as accelerometers, gyroscopes, magnetometers orcombinations thereof. The system may include one or more bio-sensors, for example, a glucose sensor. In embodiments using a wearable patch, the further sensor may be integrated, or at least in part integrated, with the wearable patch.

[0022] In at least one embodiment, the present disclosure provides a bioimpedance sensor comprising: a wearable patch adapted to be affixed to the skin of a patient proximate to an insertion site for an injection device for injecting a fluid to the patient; and at least a pair of supercutaneous electrodes disposed on the wearable patch for electrical contact with the skin of the patient for measurement of bioimpedance.

[0023] In at least one embodiment, the present disclosure provides a method for monitoring an intravenous procedure for a patient comprising: obtaining electrical signals from a bio-impedance sensor comprising: at least a pair of electrodes in electrical contact with the skin of the patient, at least one electrode being energisable when a current is generated at a selected frequency and directed to the at least one electrode; measuring impedance values acquired, by the bio-impedance sensor, proximate the injection device insertion site when the current is generated and directed between each electrode in said pair of electrodes at a plurality of selected frequencies; and processing, with an algorithm, the impedance values acquired at the plurality of selected frequencies to determine presence of extravascular fluid due to the intravenous procedure, wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid. In certain embodiments, an audible and / or visual alert is issued if impedance values exceed a permissible threshold, inparticular if impedance values exceed the permissible threshold for greater than a time period optionally selected with reference to a balance between benefit to an injection procedure and risk of injury to the patient. The permissible threshold may be selected with reference to toxicity or other properties of the fluid for injection.

[0024] As described above, at least one pair of electrodes may be disposed for a line between them to run substantially longitudinally along a path of a vein and / or for a line at an angle, in embodiments transverse or perpendicular to, the path of the vein. In certain embodiments, bioimpedance is monitored for both longitudinal and transverse electrode pairs. In one embodiment, where electrodes are in contact with a wrist of a patient, the vein may be the superficial dorsal vein.

[0025] Monitoring may include analysing bioimpedance fluctuations either unilaterally or bilaterally above a baseline, for example of mean bioimpedance values, to discriminate extravascular fluid which may be indicative of intravenous infiltration and / or extravasation from other causes, physiological or electrical, of bioimpedance fluctuations.

[0026] Acquired impedance values have associated noise. Therefore, the algorithm for processing the acquired impedance values may allow smoothing and reduction of noise. Examples of smoothing techniques that may be included within the algorithm include, without limitation, multistage median filtering along time and / or frequency axes, of raw data and its residual after fitting a time and / or frequency dependent bioimpedance model to the measurement along with computing moving average using various window functions and window size.

[0027] The algorithm may provide, as an output, a baseline impedance characteristic which takes account of patient and / or fluid parameters against which acquired impedance values may be analysed additionally to, or alternatively to, a baseline only taking account of measured impedance prior to injection. The baseline impedance characteristic may be therefore individually determined for each patient and not solely on tissue impedance prior to injection device insertion. The baseline impedance characteristic, even allowing for smoothing, is likely to be dynamic, for example changing during ongoing monitoring of a patient, and therefore adjusted accordingly, for example, at regular intervals. During monitoring, patient physiologyis likely to change and this in turn is likely to affect accuracy of determination of IV infiltration and / or extravasation. Monitoring, using the baseline as determined herein, may be commenced post injection device insertion.

[0028] In certain embodiments, fluid parameters may be included as inputs to the algorithm include the chemical and / or physical properties of the fluid, for example a drug. The algorithm may, for example, allow for inputs including infusion rate and / or different drugs having different burn rate. In certain embodiments, patient parameters may be included as inputs to the algorithm include physiological parameters for a selected patient such as body composition though there are a wide range of physiological patient features that may affect determination of the presence of extravascular fluid that the algorithm may take into account.

[0029] The algorithm may also take account of patient parameters including physiological and / or anatomical differences between the selected patient and a selected cohort of patients whether due to development and / or health status. Where the patient is a neonate, a patient parameter may include, without limitation, at least one of gestational age at birth, gestational age at the time of intravenous injection or therapy and weight of the baby. Such differences change across gestational ages and due to changes away from homeostasis which may occur due to a range of causes, for example injury, fever, oedema and so on.

[0030] In certain embodiments, the algorithm may allow quantification of at least one of the amount and rate of IV infiltration or extravasation for a given injected fluid, for example below 0.2 mL injected fluid, optionally below 0.15 mL injected fluid. Such quantification may be used to control the duration of an injection procedure, the procedure being terminated or adjusted after a determined duration correlated with the amount or rate of IV infiltration or extravasation. This allows optimisation of an injection procedure since other monitoring methods may result in a procedure being terminated too early or more likely too late after injury risk becomes significant.

[0031] In certain embodiments, the algorithm does not include an assumption that a particular patient is the same or other patients within a selected patient cohort, e.g., neonates, are the same. The algorithm may also take account of physiological variation or changes, including developmental changes, for a selected patient withtime. For example, the algorithm may take account of changes in body composition over time. The relevant time may include monitoring period or a period of time for example less than 48 hours, less than 24 hours, less than 12 hours or greater than 6 hours, for example the course of a disease, over which physiological change may have occurred. Such a physiological change may include vein composition and / or structure. In that case, the algorithm may take account of changes in vein composition and / or structure which may change continuously with recurrent drug therapy, for example with chemotherapy.

[0032] Based on such factors, and not necessarily limited to these, the algorithm may calculate a baseline for the patient and fluid parameters against which impedance values may be analysed for determination of IV infiltration and / or extravasation. This baseline is may be varied dependent on changes in patient physiology.

[0033] The patient may be a neonate, in particular, a prematurely born neonate, a context which has caused prior challenges for monitoring of IV infiltration and / or extravasation. In such cases, a patient parameter may include gestation age of a baby. Physiology changes over gestation so that a baby born at 24 weeks of gestation has a different body composition in terms of body fat content than that of a baby born at 32 weeks gestation. Gestation of baby at birth may be included as an input.

[0034] The baseline impedance is desirably impedance as measured after an injection device is inserted rather than pre-injection. Electrodes may be provided in pairs within the configurable electrode array with a first interrogating or excitation electrode of each pair energised with electrical energy, i.e. , current, and the second pick-up or sensing electrode of each pair receiving electrical energy, i.e. current, from the first electrode which, with knowledge of the potential difference (V) between the pick-up and sensing electrodes, allows an impedance measurement as calculated by Ohm’s law. The system may be provided with a range of baseline impedance values between respective pairs of electrodes as measured with a current generated at a plurality of frequencies.

[0035] In at least one embodiment, based on the fluid and patient parameters selected as inputs to the algorithm, the system determines monitoring parametersthat may affect IV infiltration or extravasation including - without limitation - frequency of impedance value acquisition, frequency at which impedance measurements are made, number of impedance values to be processed (for example by averaging) to achieve a selected sensitivity of detection of IV infiltration or extravasation. In certain embodiments the selected frequencies ranges may be between 1 to 100kHz, 1 to 50 kHz, 1 to 40 kHz, 1 to 20 kHz ,1 to 10 kHz, or 1 to 5 kHz. In certain embodiments, the system may measure between 1 to 8 frequencies, 1 to 10 frequencies, 1 to 20 frequences, 1 to 50 frequencies, or 1 to 100 frequences, at which electrodes are energised and impedance measurements are made. Frequency selection may also be determined by patient and fluid parameters as described herein. Impedance measurement may be at multiple frequencies of electrical energy application and / or with various selected waveforms, for example, sinusoidal, delta or square, for the application of energy to electrodes.

[0036] In certain embodiments, IV infiltration or extravasation is indicated when an impedance change exceeds a predetermined value. A convenient measurement is gradient of impedance change with time exceeding a threshold value, e.g. 0.5 Q / s. The predetermined value of impedance change may be determined empirically. Such empirically derived values may also be mapped against characteristics for selected patient cohorts, for example as described above, and used in determination of the baseline. Such determination may involve artificial intelligence or machine learning, for example using a neural network.

[0037] In certain embodiments, the disclosed methods may comprise processing motion or inertial sensor measurements to discriminate a limb movement of the patient from IV infiltration or extravasation.

[0038] In certain embodiments, the disclosed methods may comprise correlating temperature measurements with acquired impedance values; and discriminating temperature correlated changes in acquired impedance values from IV infiltration or extravasation.

[0039] The bioimpedance sensor, as described herein, may be used as a first pass success detector with the method comprising detecting first pass success. First pass success is correlated with an acceptable loss of drug activity close to an injection sitebefore that drug becomes therapeutically useful for the purpose for which it was injected. The first pass for IV insertion may be detectable if the at least one pair of super-cutaneous electrodes are placed on a patient’s skin prior to the first pass event with a successful first pass and unsuccessful first pass producing different signals over the following minutes after IV therapy has begun due to the difference in impedance when infiltration and extravasation are and are not present.

[0040] In certain embodiments, the present disclosure may be directed to the detection of oedema in a limb using that the bioimpedance sensor connected to the limb.

[0041] In at least one embodiment, the wearable patch disclosed above may be provided with an array of holes, each hole providing location for an electrode where selected for inclusion in the configurable array of electrodes. In other embodiments, the wearable patch may be provided with an array of holes, wherein a portion, or a substantial portion, of the holes in the array provides locations for a plurality of electrodes that were selected for inclusion in the configurable array of electrodes. The inclusion of electrodes within the array of holes may be determined based at least in part on the required precision of measurement of IV infiltration and / or extravasation. This may be influenced by selected fluid and / or patient parameters as described herein. In certain embodiments, use of two pairs of electrodes (four electrodes) may be suitable though the configuration of the electrode array, and electrode characteristics (e.g., electrode sizing), may change dependent on the patient parameters as described herein. For example, the configuration of the electrode array and electrode sizing would typically be different for a premature neonate than for a full-term baby.

[0042] The array of electrodes may be deployed in a pattern that may be selected from the group consisting of a line, a cross, a square, a circle, a rectangle, a hexagon, other suitable selected patterns or combinations thereof. The array of electrodes may be configured to acquire impedance values at multiple sites proximate to the array.

[0043] In certain embodiments, the system may be configured to avoid, or reduce, false positive indications of IV infiltration and / or extravasation. A false indication mayinvolve halting a procedure that does not require to be halted. Therefore, detecting presence of IV infiltration and / or extravasation is specific and / or non-responsive to other phenomena, for example a patient moving a limb, typically an arm, where the injection device is located. A change in impedance due to such movement may be empirically determined, taking fluid and / or patient parameters into account as described herein, and excluded from a determination of IV infiltration or extravasation.

[0044] The systems and methods, disclosure herein, may be used with a number of injection device designs including, but not limited to, catheters, needles, or cannulas. The injection device may be automatic and / or susceptible to automatic control. This permits an injection device to be switched off if IV infiltration and / or extravasation is detected.

[0045] The systems and methods described herein allow a non-invasive monitoring of an intravenous procedure, including for detection of extravascular fluid indicative of IV infiltration and / or extravasation which takes patient physiology and parameters of the injected fluid into account including in cases where patient physiology varies with time. The present disclosure is directed to overcome and / or ameliorate at least one or more of the disadvantages of the prior art, as will become apparent from the discussion herein. The present disclosure also provides other advantages and / or improvements as discussed herein. In addition, the present disclosure is directed at least in part to providing embodiments with improved precision in measurements that (1) avoids, or reduces, false positive indications, (2) reduces risk of injury, (3) reduces the costs of injury, (4) reduces wasted therapeutic resources encountered with known current methods of measurement, (5) or combinations thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Further features of the systems and / or methods for monitoring an intravenous procedure of the present disclosure are further described in the following description of non-limiting embodiments thereof. This description is included for the purposes of exemplifying one or more embodiments of the present disclosure. It should not be understood as a restriction on the summary, disclosure or description providedherein. The description will be made with reference to the accompanying drawings in which:

[0047] Figure 1 is a block diagram of the system for monitoring an intravenous procedure with a bioimpedance sensor (‘bioimpedance monitoring system’) according to at least one embodiment of the present disclosure with the bioimpedance sensor placed on the arm and / or leg of a patient.

[0048] Figure 2 is a schematic showing a bioimpedance sensor according to at least one embodiment of the present disclosure is placed on the wrist of a patient.

[0049] Figure 3(a) is an exploded view of the bioimpedance sensor of Figure 2.

[0050] Figure 3(b) is a detail of the bottom of the sensing portion of the bioimpedance sensor of Figure 3(a).

[0051] Figure 4 provides a plan view of the sensing portion of the bioimpedance sensor of Figures 2 and 3(a) and (b).

[0052] Figure 5 is a top perspective view of a bioimpedance sensor according to at least one embodiment of the present disclosure.

[0053] Figure 6 is a top perspective part sectional view of the bioimpedance sensor of Figure 5.

[0054] Figure 7 is an exploded view of the bioimpedance sensor of Figures 5 and 6.

[0055] Figure 8 provides plots for bioimpedance measured against time (top plot or panel) and against frequency (bottom plot or panel) using a first pair of electrodes running along the vein through which a catheter is inserted during intravenous therapy according to a at least one embodiment of the present disclosure.

[0056] Figure 9(a) provides plots for bioimpedance measured against time for the frequency range 2 kHz to 5 kHz using the same data points from Figure 8.

[0057] Figure 9(b) provides plots for bioimpedance measured against time for the frequency range 6 kHz to 10 kHz using the same data points from Figure 8.

[0058] Figure 10 is a flowchart showing one mode for processing bioimpedance data collected by the bioimpedance monitoring system of Figure 1.

[0059] Figure 11(a) is a bioimpedance sensor of the system for monitoring IV infiltration of Figure 1 when applied to cannulation of the hand of a neonate.

[0060] Figure 11(b) shows a schematic view of the positioning of the bioimpedance sensor of Figure 11(a) relative to the body of the neonate.

[0061] Figure 12(a) is a bioimpedance sensor of the system for monitoring IV infiltration of Figure 1 when applied to cannulation of the foot of a neonate.

[0062] Figure 12(b) shows a schematic view of the positioning of the bioimpedance sensor of Figure 12(a) relative to the body of the neonate.

[0063] Figure 13 shows a bioimpedance sensor, according to at least one embodiment of the present disclosure.

[0064] Figure 14 shows a bioimpedance sensor, according to at least one embodiment of the present disclosure.

[0065] Figure 15 shows a bioimpedance sensor, according to at least one embodiment of the present disclosure.

[0066] Figures 16(a) and (b) provide views of an exemplary electrode placement: Longitudinal (Figure 16(a)) and transverse placement (Figure 16(b)), according to at least one embodiment.

[0067] Figure 17 illustrates a bilateral fluctuation of bioimpedance around a mean and / or median value (B) measured in transverse placement of the electrodes as shown in Figure 16(b).

[0068] Figure 18 illustrates a unilateral fluctuation of bioimpedance around a mean and / or median value (B) measured in transverse placement of the electrodes as shown in Figure 16(b).

[0069] Figure 19 (top panel and lower panel) show a realtime bioimpedance measurement at a frequency between 2-3 KHz with transverse placement of electrode as a function of time.

[0070] Figure 20 illustrates a configuration for monitoring intravenous (IV) infiltration and extravasation with a bioimpedance sensor according to at least one embodiment of the present disclosure, across Fitzpatrick skin type I -IV for both male and female participants.DETAILED DESCRIPTION

[0071] The subject headings used in the detailed description are included only for the ease of reference of the reader and should not be used to limit the subject matter found throughout the disclosure or the claims. The subject headings should not be used in construing the scope of the claims or the claim limitations.

[0072] As shown in Figure 1 , there is provided a system 10 for monitoring an intravenous procedure to determine presence of extravascular fluid potentially indicative of intravenous (IV) infiltration and / or extravasation (‘bioimpedance monitoring system’) by bioimpedance spectroscopy (BIS) in a patient. System 10 comprises a bioimpedance sensor 11 comprising a plurality of electrodes 15 arranged in an array 13. Electrodes 15 are electrically connected to a DAQ 20 for measuring and processing impedance signals received from the bioimpedance sensor 11 when a current is passed between at least one pair 15a, 15b; 15c, 15d of electrodes 15. DAQ 20 is connected to a computing device comprising monitor 40 allowing further impedance signal processing and clinical decision support in relation to IV infiltration, extravasation and - more particularly - a sensible risk of an extravasation injury (EVI) presenting an urgent clinical concern. These components of the system 10 are described in further detail herein.

[0073] Bioimpedance sensor 11 comprises, in the illustrated embodiment, a wearable patch 12 adapted to be affixed to the skin of a limb, here the wrist, arm and / or leg of a patient proximate to an insertion site for an injection device, for example, a catheter but not limited thereto, for injecting a fluid to the patient. It will be understood that, in other embodiments, the wearable patch 12 may be moved toother sites on the skin of the patient to assess IV infiltration and / or extravasation away from the injection device insertion site. The wearable patch 12 may be formed of a transparent material or may include a transparent portion or window 12A (as shown in Fig.15) to allow optical observation or visual checking of the injection site. The wearable patch 12 may be of a flexible material, for example, a flexible polymer material. Other suitable materials may also be used and are contemplated.

[0074] One embodiment of a wearable patch 12 of bioimpedance sensor 11 is shown in detail in Figures 2 to 4. This embodiment is non-limiting and other configurations of wearable patch comprising a selected number of electrodes, 4 electrodes in this exemplary embodiment, may be used instead. The wearable patch 12 is typically used under sterile conditions and therefore may be disposed of following use. The wearable patch 12 is a consumable item. Its size and / or shape may be selected with reference to patient limb and patient developmental stage amongst other desired patient parameters.

[0075] Bioimpedance sensor 11 , as shown in Figures 2 to 4, is elongate and, as supplied, generally planar, having a sensing portion 120 and an alignment portion 122 having a proximal end 123 contiguous with the sensing portion 120 and distal end 124 spaced from proximal end 123. In this exemplary embodiment, the geometry of the sensing portion 120 for holding electrodes 15 as contained in corresponding holes 14 is approximately rectangular in the embodiment. A circular or quadrilateral (e.g., square) geometry or other selected geometry, such as a chevron shape, may also be used.

[0076] Sensing portion 120 accommodates an array of 4 surface or supercutaneous electrodes, i.e., two pairs of electrodes 15a, 15b; 15c, 15d. Surface electrodes 15a- 15d, which in this example are planar and light weight relative to the patient, may be, for example, electrically conductive material, typically containing a conductive metallic or metallic salt accepted for use in clinical settings. Each electrode 15a-15d is coupled to the skin via an ionic or conductive medium, such as a hydrogel, conductive adhesive or electrolyte, reducing skin contact impedance. Signal quality is also higher than for dry electrodes.

[0077] In the embodiment, silver-silver chloride (AgCI) has been selected as both electrically conductive and biocompatible and known for use in medical electrodes for ECG and EEG methods. In alternative embodiments, ECG or EEG leads may be used to form the bioimpedance sensor. A circular geometry has been selected for electrodes 15a-d but this selection is not intended to be limiting, other geometries may be used.

[0078] The use of four surface electrodes 15a-15d allows a higher sensitivity, than 2 electrodes 15a and 15b which may be used in another embodiment, for obtaining tissue impedance values and a higher precision of measurement of impedance for use in determining the presence of intravenous (IV) infiltration and / or extravasation. Such sensitivity desirably corresponds with sensitivity of a particular patient to IV infiltration or extravasation. However, in other embodiments, other surface electrodes 15 may be included in the array 13, for example 2, 6 or 8, to obtain a bioimpedance signal capable of processing as described herein. An embodiment using an odd number of electrodes, three electrodes for economy of space, is described below with reference to Figs. 13 and 14. The array 13 may be configurable allowing the number of electrodes to be selected by the user, for example being inserted into holes 14 when required. The array 13 may have a fixed number of electrodes installed.

[0079] The first pair of electrodes 15a and 15b are arranged transversely to the sensing portion 120 and in a direction intended to accord with the path of a selected blood vessel 18, for example, a vein which may be the superficial dorsal vein, as shown by the blue line of Figure 2. The second pair of electrodes 15c and 15d are arranged in the longitudinal direction of the wearable patch 12 and perpendicular to a line 18 joining electrode 15a and 15b, i.e., perpendicularly to the vein path, as shown by the blue line of Figure 2, of the selected blood vessel or vein in this embodiment. It is to be understood that the straight path of vein 18 is schematic and a vein path may not be straight. In either event, the electrodes 15c and 15d will enable a longitudinal bioimpedance signal capture. By arranging electrodes 15a-15d in this manner, two contrasting bioimpedance signals, i.e., for electrode pair 15a and 15b and electrode pair 15c and 15d, are obtained with benefit for determination - asdescribed herein - of a patient as healthy or, alternatively, at substantial risk of an extravasation injury.

[0080] Spacing of the holes 14 and corresponding electrodes 15 is selected to be sufficient to distinguish electrical signals from each electrode 15 and reduce signal noise. Below each electrode 15 is disposed on a hydrogel pad 17 conveniently of the same geometry as electrode 15, i.e., circular as shown in Figures 2 to 4. Electrodes 15, in use, are in electrical contact - here ohmic contact - with the skin of the patient proximate the intravenous (IV) injection device insertion site. It will be understood that, in other embodiments, the surface electrodes 15 may be capacitively or inductively coupled with the skin of the patient.

[0081] The base 127 of sensing portion 120 has a biocompatible adhesive backing layer 128 to allow it to be adhered to the skin of a patient. The adhesive may be selected to be suitable for neonates with sensitive skin. Wearable patch 12 may be applied to and removed from the skin, the approximate duration of being fixed to the skin being about seven days. In certain embodiments, the wearable patch 12 may be replaced and another wearable patch of the same, or similar, configuration which may be placed either at the injection device insertion site or away therefrom where desired to measure remote IV infiltration and / or extravasation.

[0082] Wearable patch 12, as referenced above, has a window 12A allowing optical inspection or visual checking of the injection device insertion site (18). This visibility is indicated in Figs. 11, 12, 14 and 15 and a window or transparent wearable patch is useful to include in certain embodiments.

[0083] Sensing portion 120, as shown in Figures 2 to 4, may be provided with a dressing, for example, a hydrocolloid dressing with a mapping grid. One example is a dressing available under the Comfeel® brand from Coloplast for attachment to a patient’s skin. In alternative embodiments, each electrode may be provided with a dressing.

[0084] Sensing portion 120 may comprise a sock or sleeve portion for insertion of a limb of a patient as shown in Figs. 11(b) and 12(b). The wearable patch 12, including the sock or sleeve portion where provided, may be made from a flexible material,advantageously being elastic or stretchable to fit different limbs at least limiting the need for manufacture of a range of sizes of sock or sleeve portion.

[0085] The alignment portion 122 of wearable patch 12 contains electrical wiring 125 running from the electrodes 15a-15d toward distal end 124 and electrical contacts 126 proximate distal end 124 for connection to other components of system 10 as described further below. Alignment portion 122 is of a pliable biocompatible material making application to the patient, for example, wrapping around a substantially circular limb easier. It will be understood that alignment portion 122 and the electrical circuitry are flexible making the bioimpedance sensor 11 more robust than an equivalent rigid structure. At the same time, the alignment portion 122 easily bends, curves or folds into compact spaces. With resilience, alignment portion 122 will typically return to a flat shape after bending unless sharply creased.

[0086] Electrical wiring 125 extends from the holes 14 - and in use electrodes 15 - of the sensing portion 120 through the proximal end 123 of alignment portion 122 to the electrical contacts 126 at the distal end 124. The electrical wiring 125 may be a readily available electrically conductive material, typically metallic or metallic salt accepted for use in clinical settings. In this embodiment, electrical wiring 123 is formed from silver chloride. Similarly with electrical contacts 126, a readily available biocompatible electrically conductive material may be selected whether metallic or carbon based. In this embodiment, carbon contacts have been selected. The position of electrical contacts 123 at a distal end ensures electrical connection outside the sterile area expected to be bounded by sensing portion 120.

[0087] As shown in Figure 3, and the above description, bioimpedance sensor 11 has a flexible laminated and layered structure. Electrical wiring 125 is sandwiched between a lower polymer layer 122a and a dielectric upper layer 122b. Dielectric upper layer 122b is adhered to a polyester cover layer 122c. Polyester layer 122c is a durable and chemically resistant material, for example, being available from Autotype under the trademark Autotex XE. The polyester layer 122c may be thin, say 0.2 mm.

[0088] Another embodiment of bioimpedance sensor 211 is shown in Figures 5 to 7 and has the elements as described above with reference to the bioimpedancesensor 11 shown in Figures 2 to 4. The common elements between bioimpedance sensors 11 and 211 are prefixed with a “2” in Figures 5 to 7. The main structural difference is that alignment portion 222 is formed as an easy to grip handle. In other embodiments, the bioimpedance sensor may be provided as a probe.

[0089] Sensor portion 220 also comprises a laminate comprising a plurality of layers including a base layer 228 and a top layer 227 between which are disposed hydrogel electrodes 215a-215d. The electrodes 215a-215d may be disposed in the same way as described above.

[0090] Top layer 221 is a polymer film, for example, a polyester (PET) film, cover for protecting the electrodes. The adjacent layer 229a is a dielectric or insulating layer for insulating the electrical wiring 225 which is disposed below. On the opposite side of the electrical wiring 225 is a further polyester liner 229b acting as a substrate for the electrical wiring 225. Below polyester liner 229b is an adhesive layer 230 allowing, when protective liner 228 is removed, adhesion to the skin while enabling reliable signal transmission and preventing silver chloride hydrogel electrodes 215a- 215d from detaching. The adhesive layer 230 may be formed from a biocompatible adhesive.

[0091] At distal end 223 of the alignment portion 222, here formed as a flexible cable 216 for connection to DAQ 20 as described below. Cables 216 and 16 serve the same function. A ferrule 235, of thermoplastic polymer, for example, is over moulded over the distal end 223 of the alignment portion 222 to capture the cable 16 and hold it in electrical connection with wiring 225 and silver chloride-hydrogel electrodes 215a-215d. The ferrule 235 may be formed as a socket with the cable 216 being fitted to a plug, such as a four-pin connector, that may be electrically connect with that socket. Pushing the plug into socket 235 allows connection and pulling the plug from socket 235 allows disconnection. Figures 11(a) and 12(a) show a 4 connector plug 235A operable in this manner for joining sensor cable 216 to trunk cable 16.

[0092] The length of the wearable patch 12 or 212 is selected with reference to anthropometric considerations. For example, if system 10 is to be applied in a neonatal intensive care unit (NICU), the length of wearable patch 12, 212 is compactand may, for example, be 35mm in length. Sensor cable 100 may, for example, be about 100mm in length.

[0093] Bioimpedance sensor 11 (or 211) is serially connected, here by connections in the form of flexible electrical cables or leads 16, to an impedance measuring unit (DAQ) 20 which conveniently forms part of a computing device 100 such as a laptop or desktop computer which may be powered by a battery or through mains power by electrical outlet (GPO) via the region adapter and power input. Suitable electrical leads 16 include sterile cutaneous ECG leads readily available in a clinical setting. It will be understood that the connection may be a wireless connection or a connection other than a lead. In at least one embodiment, the connection is quick release in case of emergency.

[0094] DAQ 20 has capacity to generate pulses of electrical energy to be directed as a DC current at selected frequencies, through wiring 125 of bioimpedance sensor 11 , between pick up and sensing electrodes 15a and 15b of the first pair of electrodes, as well as pick up and sensing electrodes 15c and 15d of the second pair of electrodes. The resulting kelvin resistance circuits allow measurement and / or analysis of resulting impedance values for tissue around the catheter insertion site with resolution being provided by use of the two pairs of electrodes 15a-15d in this embodiment. It will be appreciated that injection devices other than catheters may be used in other embodiments.

[0095] As to selection of bioimpedance as a metric, IV infiltration and / or extravasation may cause a tissue volume change due to tissue swelling, typically caused by a tissue reaction to the fluid injected into the patient. The volume change further causes a conductivity change which, in combination with the volume change, may cause a change in impedance sensed by the second pick up electrode 132b. With exemplary system 10, change in bioimpedance may indicate IV infiltration and / or extravasation at a system 10 calculated fluid volume 0.1 mL, and therefore providing earlier indication of an extravasation injury (EVI) event. Such quantification allows control over the duration of an injection procedure, the procedure being terminated or adjusted after a determined duration correlated with the system 10 calculated amount of IV infiltration or extravasation for a given injected fluid whichmay be characterised as a permissible threshold of IV infiltration and / or extravasation above which an alarm should be issued or the injection procedure terminated. This allows optimisation of an injection procedure since other monitoring methods may result in a critical procedure being terminated too early or more likely too late after injury risk becomes significant.

[0096] The DC current may be supplied at 5v DC for safety purposes but subject to compliance with applicable standards, e.g., International Standard IEC 60601-1- 11:2015 ‘Medical electrical equipment’, may be varied within the regulated range. A waveform generator / amplifier 22 is also included within DAQ 20 to automatically generate various kinds of waveforms for the generated current. Here, the waveform generator / amplifier 22 generates a current having a sine waveform at a plurality of selected frequencies in the 1 to 10 kHz range. The frequency range may be wider, for example 1 to 40 kHz, dependent on firmware provided for waveform generator / amplifier 22. In certain embodiments, the frequency range may be 1 to 10 kHz. In certain embodiments, the frequencies used may be one or more of the following: 1 to 20 kHz, 1 to 40 kHz, 1 to 50 kHz or 1 to 100 kHz.

[0097] DAQ 20 further includes a signal measurement block 24 providing signal amplification, signal switching and analog to digital conversion (ADC). Here the ADC is 16-bit, operating at 800 kSPs.

[0098] The above-described functionality of DAQ 20 is provided by an analog front end system (AFE) or chip 25, in the embodiment - and for experimental purposes - an AD 5940 chip as available from Analog Devices. Operation of the AD5940 chip in bioelectric systems is described in the document Lambe, M, AN-1557: Implementing the AD5940 and AD8233 in a Full Bioelectric System available from Analog Devices and online at analog.com / en / resources / app-notes / an-1557.html and the contents of which are hereby incorporated by reference for in its entirety.

[0099] DAQ 20 or the computing device further includes a processor (MPU) 30 of a suitable type such as a microprocessor, a controller, a microcontroller, a central processing unit (CPU), a digital signal processor (DSP), a state machine, discrete logic or the like. The AFE system (AD5940 chip) of the embodiment includes a microcontroller. The processor 30 may be programmed to perform a range ofmeasurement, analysis, storage and control functions. The processor 30 also includes instructions for controlling acquisition of impedance measurements from the electrode array 13 via DAQ 20.

[0100] Processor 30 has a memory having stored therein an algorithm comprising electronic instructions that, when executed by the processor 30, cause the DAQ 20 to generate current in a selected waveform, for example, a sine wave form, at a plurality of selected frequencies through operation of waveform / generator 22. The processor 30 may select the frequencies automatically or a clinician may select the frequencies manually. In either case, the frequencies are selected having regard to patient and / or fluid parameters as described herein.

[0101] When the generated current is passed between a selected pair of electrodes 15, the processor 30 calculates the impedance between the electrodes for each frequency over a period of time. Bioimpedance monitoring involves cycling through a sequence or sweep of frequencies.

[0102] Thus, the processor 30 calculates, following signal processing by a discrete Fourier transform (DFT), the impedance values acquired by DAQ 20 at a plurality of selected frequencies to determine, on comparison with a determined baseline, presence of intravenous (IV) infiltration or extravasation above a permissible threshold. The DFT transformation involves transformation of both amplitude and phase components of the bioimpedance signal. As shown in Figures 5 and 6, the acquired impedance values include fluctuations due to noise. The algorithm for processing the acquired impedance values also smooths the measured impedance signal to remove such noise as described in detail below.

[0103] The algorithm for processing the acquired impedance values uses patient and fluid parameters to provide a context for analysing the acquired impedance values to determine presence of intravenous (IV) infiltration or extravasation above a selected threshold, for example impedance change more than 0.5 Q / s. Such values may be empirically determined and stored in a memory of processor 30. The algorithm may calculate an amount or rate of IV infiltration and / or extravasation for a given injection fluid based on the impedance change data. Asdescribed herein, such information may be used to optimise therapeutic efficacy of an injection procedure.

[0104] The processor 30 includes communications functionality such that information acquired from the processor 30 may be communicated to a monitor 40 forming part of the computing device 100. Monitor 40 thus has functionality including screen 42, USB port (allowing download or upload of data and / or software or firmware), battery and battery indicator, processor, power input and power button as well as a processor (PCBA) as shown in Figure 1. Monitor 40 may be provided with a speaker for audible alarm. Screen 42 allows display of a visual alarm. And as shown in Fig. 1, monitor 40, DAQ 20 and processor 30 may be accommodated within a single housing, for example, being in the form of a laptop computer, a tablet computer, a smart phone or other suitable smart devices. However, alternative layouts of monitor 40, DAQ 20 and processor 30 may be adopted, for example, if monitor 40 is to be viewed at a location remote to the patient.

[0105] DAQ 20 is controlled via a serial interface to monitor 40 through a suitable program such as PuTTY (PC) or Serial 2 (MacBook, other a laptop computer, a tablet computer, a smart phone or other suitable smart devices. The user may select and program the frequencies for bioimpedance monitoring. In one mode, as used in the embodiment, up to x - for example 2<x<10 - discrete frequencies may be programmed in a sequence. In another ‘sweep’ mode, the DAQ 20 is configured using selected minimum and maximum frequencies and a total number of frequencies through which to sweep. Test frequencies may be automatically generated in a logarithmic sequence with an upper limit y of frequencies for the sweep. In the embodiment, 2<y<100. In another mode, the selected frequencies are automatically generated in a linear sequence.

[0106] The DAQ 20 may cause sequence or sweep of frequencies at which current is generated to be cycled repetitively.

[0107] The monitor 40 may collect or log output from DAQ 20 in a convenient format, for example, a spreadsheet format, such as csv format which makes for simple transfer to Excel, Python or other like programs for analysis. The monitor 40 may display the output on a screen 42 in the general format: frequency (kHz),impedance (ohms) and phase (degrees), e.g., frequency 5 kHz, impedance16134.82 ohms, phase 72.24 degrees. Screen 42 may be a touch screen.

[0108] The monitor 40 may be configured with an option of displaying historical bioimpedance data on screen 42 to help aid in earlier detection of infiltration and / or extravasation or confirm any alarms or notices given by system 10. The historical bioimpedance data may also be used to gauge the patient’s overall fluid retention and / or other physiological data (for example, from vital signs monitoring) to potentially help inform healthcare workers of the patient status and potentially other injuries and / or adverse statuses.

[0109] The screen 42 may be operated with both a clear cover (as commonly used on items for ease of sterilising) or with gloves by use of a membrane covering the screen 42 and its touch buttons, where a touch screen is used. Alternatively, the membrane may cover or house required operating buttons. The screen 42 may be at least 7 inches large and mounted to an IV stand if required.

[0110] The monitor 40 may be located proximate to the patient or at a remote location, enabling remote surveillance of impedance measurements. One form of monitor 40 that may be used is described in further detail herein.

[0111] In another embodiment, DAQ 20 may be built into or integrated with monitor 40. For example, DAQ 20 and monitor 40 may be integrated within a computing device, for example, a laptop computer, a tablet computer, a smart phone or other suitable smart devices connected to the wearable patch 12. The foregoing description of DAQ 20 and monitor 40, as well as processing with processor 30, is also applicable where the bioimpedance sensor omits the above wearable patch 12, for example using other forms of supercutaneous electrodes such as provided by ECG or EEG leads or wirelessly connected electrodes.

[0112] Referring to Figure 8, the top panel shows a bioimpedance signal (Zmag in ohms) as a function of time (x axis, time in seconds) in a human wrist before, during and after cannula insertion across 9 selected discrete frequencies between 2 and 10 kHz. The selection of 9 discrete frequencies is selected here but is not intended to be limiting as described in the description of DAQ 20.

[0113] The bottom panel of Figure 8 shows a plot of bio-impedance across the 9 selected frequencies of the presently described embodiment. The bioimpedance signals are raw data which include statistical noise, such as Gaussian noise, as well as fluctuations, e.g. corresponding with movements of the limb where an injection device is inserrted, shaking / moving of a feed (IV) tube to the injection device, spikes, outliers and other noise inducing factors, in the measured data. As a result, each bioimpedance signal trace - as shown for each selected frequency as shown in Figs. 9(a) and 9(b) - has differences from the others, especially at the selected low frequencies (2 kHz and 3 kHz c.f. the illustrated 4 and 5 kHz frequencies). The algorithm determined outlier data points using a statistical method, e.g. median filtering, polynomial filtering, median polynomial filtering etc. but not limited to these to provide resulting data as shown by the black curve. A smoothing algorithm was then applied to remove statistical noise to provide bioimpedance data as shown by the blue curve. A variety of smoothing algorithms may be used including, but not limited to one or more of the following: bin smoothing, simple moving average, running line, locally estimated scatterplot smoother, and smoothing splines. In the embodiment, a moving average smoothing algorithm was used as shown in Figure 10.

[0114] Referring further to Figure 10, the flowchart shows the steps in processing of bioimpedance data by processor 30. In step S1 , bioimpedance data is loaded to the processor with data for different frequencies - as for example shown above - being extracted in step S2. In step S3, root-mean-square (RMS) and statistical metrics are computed. In step S4, the bioimpedance data is filtered for noise reduction. Outliers are detected and residuals computed in step S5. In step S6, a model for trend analysis is fitted to the filtered data. Moving average smoothing is performed in step S7. At step S8, the algorithm supports clinical decision making by determining whether an extravasation injury, i.e., EVI, is occurring. Such determination may be expressed as a probability of an extravasation injury occurring. Result of the determination is displayed on screen 42 in step S9 and results recorded to enable monitoring over time. This flowchart is then repeated for as long as cannulation is maintained. It is to be understood that system 10 collects and processes tissue bioimpedance data whether or not extravasation injury is present.

[0115] Determination of impermissible IV infiltration and / or extravasation requires a baseline impedance characteristic output against which such determination may be made where bioimpedance data is matched by the algorithm with a database containing a map or table of extravasation events (or absence of extravasation events) against patient and / or injection fluid parameters as described herein. In some embodiments, artificial intelligence or machine learning techniques may be used for this purpose. Such a database may be based on bioimpedance, patient and / or fluid data from accepted clinical studies which allow accurate comparison between extravasation as determined by the system 10 and / or extravasation as determined by other accepted techniques as described herein. An alarm is then sounded if predicted injury and / or cost to a patient is above a determined threshold level.

[0116] In some prior proposals, the baseline has simply been set as tissue impedance before injection. However, this approach is not followed in the present embodiment because such a baseline may provide misleading results for certain patients, particularly neonates or patients undergoing physiological change, for example due to disease. Such a baseline may also provide misleading results dependent on the characteristics of fluid injected into a particular patient.

[0117] In certain embodiments, with a view toward more precise measurement, the baseline may be desirably individually determined for each patient taking physiological and / or injection fluid parameters into account.

[0118] Injection fluid parameters to be included as inputs to the algorithm desirably include the chemical and / or physical properties of the fluid, for example a drug. The algorithm may, for example, allow for inputs including infusion rate and / or different drugs having different burn rate. Patient parameters to be included as inputs to the algorithm desirably include physiological parameters such as body composition including vein composition and disease state though there are a wide range of physiological patient features that affect measurement of IV infiltration and / or extravasation and which the algorithm may take into account.

[0119] In certain embodiments, the algorithm also takes account of the physiological differences between patients and does not include an assumption thatpatients are the same or that patients within a cohort, e.g. neonates, are the same. The algorithm also takes account of physiological variation for a particular patient with time. For example, the algorithm may take account of changes in body composition over time. The relevant time may include monitoring period or a period of time, for example the course of a disease, over which physiological change may occur and which may be taken into account in setting the baseline. The baseline may be varied dependent on actual and / or anticipated changes in patient physiology.

[0120] Such a physiological change may include change in vein composition and / or structure. In that case, the algorithm may take account of changes in vein composition and / or structure which may change continuously with recurrent drug therapy particularly chemotherapy.

[0121] Based on such factors, and not necessarily limited to these, the algorithm calculates a baseline for the patient and fluid parameters against which impedance values are analysed to determine presence of IV infiltration and / or extravasation. The baseline may be dynamic being adapted by the algorithm in response to changes in patient physiology and / or change in the physical or chemical characteristics of the injection fluid. An example of a physical characteristic is injection fluid flow. An example of a chemical characteristic is the chemical composition, including the active ingredient, of the injection fluid.

[0122] In certain embodiments, precision monitoring of an intravenous catheter site and / or detection of one or more of the following: deterioration of the vein’s physiological integrity, IV leakage, IV extravasation, occlusion, phlebitis and sepsis may be done using bioimpedance measurement of the IV site. An understanding of the equivalent electrical circuit of vein and surrounding tissue is useful in monitoring of an intravenous catheter site. Biological tissue may be nonlinear, dispersive dielectric which is a mix of resistors and capacitors depending on frequency.

[0123] Table 1 below shows the electrical nature of various components.Table 1

[0124] At frequencies <10 kHz, current mainly travels through extracellular and / or blood pathways, giving higher impedance. At frequencies (>10 kHz), capacitive coupling across membranes increases, reducing impedance. A vein’sphysiological integrity, IV leakage, IV extravasation, occlusion and / or phlebitis may impact one or more of these equivalent circuit parameters in different but connected ways.

[0125] Without wishing to be bound by theory, in certain embodiments, electrode placements on the IV site may result in useful detectability of IV leakage in the measured data. For example, transverse electrode placement may be useful in certain embodiments. When electrodes are placed across the vein perpendicular to blood flow, for example the superficial dorsal vein for an electrode placement on the wrist, the measured bioimpedance may be dominated by skin, vessel wall, blood and vein wall which are in series - a tissue tomography in 1D. The measurement reflects contribution from one or more of the following: the blood volume, vein wall characteristics, extravasated fluids.

[0126] In certain embodiments one or more of the following signal characteristics may be considered:Baseline: The mean impedance (|Z|) reflects total layered resistance.Dynamic changes:Infiltration (fluid leak) — > decrease in mean impedance (more conductive path in subcutaneous region).Vasoconstriction I collapse — > increase in impedance (blood replaced by less conductive tissue).

[0127] The data has bilateral fluctuation i.e., fluctuates symmetrically above and below the mean baseline (both positive and negative excursions).

[0128] Figures 16(a) and 16(b) provide an exemplary electrode placement using ECG leads as an alternative to wearable patch 12: Longitudinal (Figure 16(a) and transverse placement (Figure 16(b)) of electrodes on the wrist / hand of an adult volunteer with Fitzpatrick skin types l-ll. The longitudinal placement illustrates electrodes that are placed along the vein along the direction of the blood flow, the measured bioimpedance is dominated by the axial impedance of blood + vein wall in the measurement segment.

[0129] With respect to the signal characteristics the following is observed:Baseline: The minimum impedance (|Z|) is the same as the mean impedance as given by transverse electrode placement.Dynamic changes:Infiltration (fluid leak) — > Occurs due to puncture of the vein which decreases the capacitive reactance of the vein and therefore the minimum impedance (more conductive path in subcutaneous region).Vasoconstriction and / or collapse — > transient increase in impedance due to injury of the vein as seen as a pulse in Figure 8 - top panel at the frequencies of measurement when an IV catheter is inserted into the vein the first time.

[0130] In the example of Figure 16, the data has unilateral fluctuation, i.e., fluctuates asymmetrically above the minimum baseline values (only positive excursions). Figure 17 shows a bilateral fluctuation of bioimpedance around a mean and / or median value (B) measured in transverse placement of the electrodes as shown in the right panel (Figure 16(b). Figure 18 shows unilateral fluctuation of bioimpedance around a mean / median value (B) measured in transverse placement of the electrodes as shown in the left panel (Figure 16(b)).

[0131] Figure 19: Top Panel - Realtime bioimpedance measurement at a frequency between 2-3 KHz with transverse placement of electrodes as a function of time. The measurement shows bilateral fluctuations around the mean value of 7340 Ohm from the onset of measurements until 567 seconds when 0.1ml of fluid is injected (bolus) into the transcutaneous space between the electrodes. The mean impedance drops to 7320 Ohm and remains stable at that value while still showing bilateral excursions around the mean. This represents system’s sensitivity to a detection of 0.27% change in the mean impedance value.

[0132] Figures 9(a) and 9(b) show the bioimpedance measurements with longitudinal placements of electrodes in a Fitzpatrick skin type II I— IV. In the raw data (Grey), besides the Gaussian system noise (bi-lateral), the other excursions are unilateral. When a 0.2ml of fluid is injected (bolus) into the transcutaneous spacearound the electrodes at around 225 sec, the mean (min) impedance drops by 0.8% at the frequencies between 2-3KHz and by 1% at all higher frequencies.

[0133] In certain embodiments, the algorithm does not require skin tone as an input patient parameter. In such embodiments, determination of presence of extravascular fluid has equal sensitivity across a Fitzpatrick skin tone range and specific account need not be taken of skin tone by the algorithm.

[0134] In certain embodiments, simultaneous transverse and longitudinal bioimpedance measurements and their bilateral and unilateral variabilities may be used in combination to characterise the changes in the bioimpedance that are nondegenerate with the physiological changes due to vein decomposition and / or IV leakage such as movement of fingers, arms, moving / shaking IV line, changes in the fluid flow etc. For example, if both the minimum of a unilateral bioimpedance dataset is reducing simultaneously with the mean / medium / average of the bilateral dataset reducing this provides confidence that intravenous infiltration and / or extravasation (‘EVI event’) is occurring. Combining the two datasets enables discrimination of an EVI event from a plurality of other possible causes for bioimpedance fluctuation including, for example and without limitation, one or more of the following: cardiac output including heart rate, respiration rate, oxygen saturation, motion, and oedema. This results in a high confidence detection IV leakage even when the drop of local bioimpedance is visually missed.

[0135] Based on the fluid and patient parameters selected as inputs to the algorithm, the system 10 determines monitoring parameters that may affect IV infiltration and / or extravasation including - without limitation - frequency of impedance value acquisition, frequency at which impedance measurements are made, number of impedance values to be processed (for example by averaging) by processor 30 to achieve a selected sensitivity of detection of IV infiltration or extravasation. System 10, through the algorithm, may calculate an amount of IV infiltration or extravasation based on the impedance measurements.

[0136] Through determination of a baseline impedance characteristic as described herein, the system 10 has a particular benefit for a particular patient cohorts and, more particularly, specific patients within such patient cohorts.

[0137] In one embodiment, the algorithm relates an X change in tissue bioimpedance to Y amount of infiltrated and / or extravasated fluid. X and Y may be calculated by the algorithm for a patient using patient and fluid parameters. For example, and without limitation, patient parameters may include one or more of the following: gestational age, weight, limb girth, pathologies or physical features that change impedance, topical agents being used and so on). Fluid parameters may include one or more of the following: infusion rate, osmolality and type of fluid (Z) being administered for Y amount of a given fluid, e.g., a drug. The algorithm may predict an extravasation injury or injury risk once Z amount of fluid as infiltrated, extravasated. At this point, system 10, may issue an alarm by monitor 40 display and / or audible alarm. However, the algorithm may further process tissue bioimpedance data to determine whether leakage is increasing, decreasing or accelerating and may issue an alarm based on such further processing.

[0138] For example, the patient may be a neonate, in particular a prematurely born neonate. In such cases, a patient parameter may include one or more of the following: gestational age of a baby at birth, gestational age at the time of the intravenous injection or therapy, weight of the baby and gender. Physiology changes over gestation so that a baby born at 24 weeks of gestation has a different body composition in terms of body fat content than that of a baby born at 32 weeks gestation. Gestation of baby at birth may be included as an input to the algorithm.

[0139] Continuous calculations of tissue impedance may be by system 10 during the injection procedure and these may be filtered for noise and averaged to provide an impedance value for comparison with the baseline. The electrode patch 12 (or other electrode arrangement) remains affixed to the patient during monitoring. Monitoring continues over time, and the measured and stored impedance values are compared to the stored baseline values. Impedance values may be mapped over a two-dimensional and / or three-dimensional space.

[0140] System 10 determines the presence or absence of extravascular fluid potentially indicative of IV infiltration and / or extravasation above the selected threshold based on comparison between measured impedance values and the baseline as above calculated and communicates the results to a screen 42 or otherways for alerting a clinician or care giver. An alert 36 is provided if impedance values are over a threshold indicating unacceptable IV infiltration and / or extravasation which may, for example, be due to mispositioning of catheter or other injection device. Fluid injection may be manually or automatically stopped at this time.

[0141] The electrode array 13 comprises electrodes 15a-15d which enable both longitudinal and transverse tissue bioimpedance signal capture and processing by processor 30 on the basis of the algorithm as above described. By arranging electrodes 15a-15d in this manner, two contrasting bioimpedance signals are obtained with benefit for determination - as described below - of a patient as healthy or, alternatively, at substantial risk of an extravasation injury. To illustrate this, some example scenarios follow. In a first example, fluid retention in a limb may be distinguished from extravasation injury to the vein 18, for example the superficial dorsal vein of the wrist. Where fluid is retained in the limb, both pairs of electrodes 15a, 15b; 15c, 15d would provide a similar bioimpedance signal. In contrast, an extravasation injury to vein 18 would show a larger change, from baseline, in bioimpedance for the longitudinal electrode pair 15a, 15b than for the perpendicular or transverse electrode pair 15c, 15d. Time length of the deviation of the bioimpedance signal from baseline is also a relevant parameter which may also be included in the algorithm. With extravasation, vein smooth muscle reacts fast like a spasm while physiological fluid buildup in a limn is generally relatively very slow, slower than leakage. Such physiological response is predictable being generally uniform across a human population. Thus, machine learning and / or advanced signal processing techniques may be used to categorise various conditions following appropriate clinical studies allowing mapping of such conditions against bioimpedance traces for a range of patient and fluid parameters. Without limitation, such categories may include extravasation injury (EVI) signal, oedema signal and limb movement. Determined event category may be displayed on screen 42 of monitor 40.

[0142] System 10 and its operation, as described in detail above, allow an application of monitoring of babies admitted to neonatal intensive care units (NICUs). Duration of intravenous cannulation for nutritional support or administration ofmedications and / or fluids depends on the severity of underlying illness and may range from a few days to several weeks.

[0143] Typically, for neonates in an NICU, peripheral veins are used for short term intravenous access, say for 3 to 7 days. However, venous access may be needed for 3 to 6 weeks for conditions such as meningitis or osteomyelitis or extreme prematurity. The alternative in such cases is the use of central venous catheters. Extravasation and consequential injury have been common complications of intravenous catheters in NICUs despite expert nursing care and use of devices such as automated backpressure alarms set on medication infusion pumps. Such backpressure alarms may be triggered only after a significant volume of the administered fluid or medication has extravasated. This may be caused, at least in part, because the inadequate subcutaneous fat and muscle tissue, especially in premature babies, allows continued extravasation given the low resistance limb compartment where the cannula is inserted.

[0144] System 10 addresses the NICU issues described above by allowing continuous monitoring of an intravenous needle insertion site for early detection of extravasation. Such monitoring is expected to enable healthcare professionals to stop an infusion within a few minutes, or less, of the occurrence of extravasation to prevent an imminent injury (EVI).

[0145] Monitoring of babies involves collecting data on transcutaneous bioelectrical impedance (TcBI) in the upper and lower limbs (typical sites for intravenous cannulation) of premature babies. The TcBI may be measured and analysed using system 10 as described above. Such measurement of TcBI using supercutaneous electrodes 15 and ECG leads 16 involves use of a low power signal allowing conformance with the IEC 60601-1 medical device safety standard (mgp need a date for standard), the contents of which are hereby incorporated by reference by reference in its entirety. System 10 may be configured to not adversely interfere with the communication or function of the intensive care equipment.

[0146] A workflow for use of system 10 in the case of a NICU is now described. An existing workflow for an IV procedure includes the following steps:1) Needle insertion with needle being applied to the wrist or foot;2) Securing needle, with tape, to the skin of the baby at wrist or foot dependent on needle;3) Applying dressing, such as an adhesive bandage (e.g., 3 M Tegaderm transparent film dressing), over the IV insertion point; and4) Optionally, taping a splint to the baby’s wrist or foot dependent on the selection of the needle insertion site.

[0147] Where system 10 is used, the bioimpedance sensor 11, 211 is applied to the baby’s wrist or foot, dependent on needle insertion site, either:(a) prior to needle insertion step 1) to enable a baseline bioimpedance reading following the bioimpedance monitoring process as described above; or(b) after securing needle step 2) to enable a baseline bioimpedance reading following the bioimpedance monitoring process as described above.

[0148] Referring to Figs. 11(a) and 11(b), a neonate 500 is monitored with head and chest EEG sensors 522 through sensor lines 520 attached to monitoring equipment which may, in some embodiments, be monitor 40 given that space constraints are typical. The wrist 540 of neonate 500 is cannulated with cannula 300 for delivery of an IV fluid through IV line 310. Bioimpedance sensor 211, forming part of IV monitoring system 10 - as described above - is used for monitoring IV infiltration or extravasation as described above. The wearable patch 212 of bioimpedance sensor 211 here comprises a stretchable cuff, sock or sleeve to fit a range of wrist 540 (or other limb, for example foot) sizes of neonate 500 making fitting easier by avoiding need for selection between a range of sock or sleeve sizes which would be typical for an inelastic sock or sleeve.

[0149] Sensor cable 216 is connected to sensor cable 16 by a 4-pin connector 235A. Label 240 provides identification of the source of the sensor cable 216 and bioimpedance sensor 211. Injection site 350 is located between electrodes 215a- 215d and is visible due to the broad field of view given by the spacing of electrodes215a-215d and the window 12A allowing optical inspection or visual checking. In other embodiments, such visual checking may be facilitated by fabricating the bioimpedance sensor 211 from a transparent material.

[0150] Referring to Figs. 12(a) and 12(b), a neonate 500 is monitored with chest and abdominal sensors 522 through sensor lines 520 attached to monitoring equipment which may, in some embodiments, be monitor 40 given that space constraints are typical. The foot 550 of neonate 500 is cannulated with cannula 300 for delivery of an IV fluid through IV line 310. Bioimpedance sensor 211, forming part of IV monitoring system 10 - as described above - is used for monitoring IV infiltration or extravasation as described above. The wearable patch 212 of bioimpedance sensor 211 here comprises a stretchable cuff, sock or sleeve (as shown in Fig. 12(b)) to fit a range of foot 550 (and other limb, for example wrist) sizes of neonate 500 making fitting easier by avoiding need for selection between a range of sock or sleeve sizes which would be typical for an inelastic sock or sleeve. Indeed, the same wearable patch may be used in this embodiment as in the embodiment of Figs. 11(a) and (b). In other embodiments, the electrode array may itself be stretchable, analogously to a stretchable printed circuit, to suit the neonate 500.

[0151] Sensor cable 216 is connected to sensor cable 16 by a 4-pin connector 235A. Label 240 provides identification of the source of the sensor cable 216 and bioimpedance sensor 211. Injection site 350 is located between electrodes 215a- 215d and is visible due to the broad field of view given by the spacing of electrodes 215a-215d and the transparent material from which bioimpedance sensor 211 is fabricated.

[0152] An objective for integrating system 10 with an NICU workflow is a non- disruptive and easy to use system which readily accommodates an already complex clinical workflow. Bioimpedance sensors 11, 211 has a '+’ shaped array of electrodes 215a-215d which surrounds the injection site 350. In further embodiments of bioimpedance sensor 311 , 411, as respectively shown in Figures 13 and 14, further economy is achieved in the space occupied by the bioimpedance sensor 311, 411 each of which comprises three electrodes.

[0153] Referring to Figure 13, bioimpedance sensor 311 comprises three electrodes 315a, 315b and 315e arranged on a semi-circular shaped wearable patch 312. In another embodiment, bioimpedance sensor 311 may have the first pair of electrodes 315a and 315b arranged simply in the longitudinal direction of vein 318. However, bioimpedance sensor 311 allows a higher sensitivity of bioimpedance monitoring to be achieved because pairing, i.e., electrical connection, of reference electrode 315e with electrode 315a or 315b, from which it is offset at an acute angle to vein 318, allows a bioimpedance reading in a transverse direction allowing selectivity and sensitivity to IV infiltration and / or extravasation as opposed to patient movement or other potentially false positive indications for IV infiltration and / or extravasation.

[0154] Referring to Figure 14, bioimpedance sensor 411 comprises three electrodes 415a, 415b and 415e arranged on a chevron or V shaped wearable patch 412. In another embodiment, bioimpedance sensor 411 may have the first pair of electrodes 415a and 415b arranged simply in the longitudinal direction of vein 418. However, bioimpedance sensor 411 allows a higher sensitivity of bioimpedance monitoring to be achieved because pairing, i.e., electrical connection, of reference electrode 415e with electrode 415a or 415b, from which it is offset at an acute angle to vein 418, in embodiments being the superficial dorsal vein of the wrist, allows a bioimpedance reading in a transverse direction allowing selectivity and sensitivity to IV infiltration and / or extravasation as opposed to patient movement or other potentially false positive indications for IV infiltration and / or extravasation.

[0155] Referring to Figure 15, bioimpedance sensor 511 comprises four electrodes 515a-515d arranged on a square shaped wearable patch 512. In both Figures 14(a) and 14(b), a window 12A is included to enable optical inspection or visual checking at a cannula insertion site. Given the nature of the procedure, the field of view is broad. Cannulation is described in additional detail above with reference to Figs. 12(a) and 12(b).

[0156] Although the above description has focussed on monitoring for IV infiltration and / or extravasation, the system and method may be used to monitor conditions including one or more of the following: oedema, first pass success,internal bleeding such as after blood vessel surgery and / or injuries causative of, and caused by, IV extravasation.

[0157] In system 10 the reading of bioimpedance along and across a vein or artery at different angles (i.e. both parallel and perpendicular to vessel path) may also be used to measure heart rate, blood pressure, and / or monitor for oedema. When placed across an injury, system 10 may be used to monitor changes in inflammation and oedema in a large portion or small portion of tissue containing the injury allowing tracking a healing process of an injury through the changes in water composition over time. Measuring bioimpedance of injuries such as burns or lacerations is a non-invasive way of monitoring the healing process without disturbing the dressings or the injury itself. In embodiments, the systems and / or methods of the disclosure identify early signs of local physiology of the vein to which IV fluid is injected, either at the insertion site or around of the tip of the injection device. The systems and / or methods also identify infiltration (leakage of nonvesicant fluid) or extravasation (leakage of vesicant or caustic fluid causing tissue injury) enabling continued venous access by the injection device and effective delivery of therapy while preventing local tissue damage.

[0158] Further advantages and / or features of the claimed subject matter will become apparent from the following examples describing certain embodiments of the disclosed subject matter.1. A system for monitoring an intravenous procedure for a patient comprising: a bio-impedance sensor comprising at least a pair of super-cutaneous electrodes disposed for electrical contact with the skin of the patient proximate to an insertion site for an injection device for injecting a fluid into the patient ; an impedance measuring unit, the impedance measuring unit being operatively coupled to the bio-impedance sensor for generating a current, energising at least one electrode and measuring impedance values acquired, between each electrode of the at least one pair of supercutaneous electrodes, proximate the injection device insertion site when current is generated at multiple frequencies; anda processor coupled to the bio-impedance sensor and having a memory having stored therein an algorithm comprising electronic instructions that, when executed by the processor, process the impedance values acquired at a plurality of selected frequencies to determine presence of extravascular fluid due to the intravenous procedure, wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid, for example caused by intravenous (IV) infiltration or extravasation. The system of example 1 , wherein at least one reference electrode is included to provide greater sensitivity in characterising the cause of a change in bioimpedance. The system of example 1 or 2, wherein said at least one pair of electrodes is disposed on a wearable patch. The system of example 3, wherein said at least one pair of electrodes is a first pair of electrodes forming part of a configurable array of supercutaneous electrodes which are deployed in a pattern on the wearable patch. The system of any one of the preceding examples, wherein the at least one pair of electrodes is disposed to run substantially parallel to, or along, a path of a target vein and provide a first kelvin resistance circuit when connected to the impedance measuring unit; and wherein each electrode of the pair is spaced by a selected distance. The system of example 5, wherein a second pair of reference electrodes is disposed for a line between the electrodes to run at an angle to the path of said target vein and provide a second kelvin resistance circuit when connected to the impedance measuring unit. The system of example 6, wherein said angle is perpendicular to the path of said target vein.The system of example 6, wherein said angle is an acute angle to said target vein. The system of example 3, wherein a single reference electrode is disposed on said wearable patch, said reference electrode being disposed offset from each electrode of the first pair of electrodes, said single reference electrode being brought into electrical connection with either electrode of the providing an indication of capacitance on the electrical path aligned at an acute angle to the vein. The system of example 3, wherein the wearable patch is configured to fit a limb, optionally selected from the group consisting of leg, foot, wrist and forearm. The system of example 10, wherein the wearable patch is made from a flexible material, optionally being elastic or stretchable to fit different limbs. The system of example 3, 10 or 11 , wherein the wearable patch comprises a plurality of portions which - when combined - form the wearable patch. The system of examples 3 or 10 to 12, wherein the wearable patch includes a transparent portion or window allowing visual checking of the insertion site during the procedure with the injection device. The system of any one of the preceding examples, including a further sensor selected from the group consisting of a temperature sensor for sensing patient skin temperature; optical sensors; motion or inertial sensors optionally accelerometers, gyroscopes and magnetometers; and bio-sensors. A bioimpedance sensor when used in the system of any one of the preceding examples comprising: a wearable patch adapted to be affixed to the skin of a patient; and at least a pair of supercutaneous electrodes disposed on the wearable patch and in contact with the skin of the patient for measuring bioimpedance.A method for monitoring an intravenous procedure for a patient comprising: obtaining electrical signals from a bio-impedance sensor comprising at least a pair of electrodes in electrical contact with the skin of the patient proximate to an insertion site for an injection device for injecting a fluid to the patient, at least one electrode being energisable when a current is generated at a selected frequency and directed to the at least one electrode; measuring impedance values acquired, by the bio-impedance sensor, proximate the injection device insertion site when the current is generated and directed between each electrode in said pair of electrodes at a plurality of selected frequencies; and processing, with an algorithm, the impedance values acquired at the plurality of selected frequencies to determine presence of extravascular fluid due to the intravenous procedure, wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid, for example caused by intravenous (IV) infiltration or extravasation. The method of example 16, comprising issuing at least one of an audible and visual alert if acquired impedance values exceed the permissible threshold. The method of example 17, comprising issuing said alert if impedance values exceed the permissible threshold for greater than a selected time period. The method of any one of examples 16 to 18, wherein said acquired impedance values have associated noise and the algorithm for processing the acquired impedance values allows smoothing and reduction of noise. The method of any one of examples 16 to 19, wherein the algorithm provides, as an output, a baseline impedance characteristic which takes account of patient and fluid parameters against which acquired impedance values are analysed.The method of example 20, wherein the baseline impedance characteristic is individually determined for each patient. The method of example 21, wherein said baseline impedance characteristic is dynamic and adjusted, at regular intervals, during monitoring. The method of any one of examples 20 to 22, wherein monitoring commences post injection device insertion. The method of any one of examples 16 to 23, wherein fluid parameters to be included as inputs to the algorithm include at least one of the chemical and physical properties of the fluid, optionally a drug. The method of example 24, wherein the algorithm allows for an input selected from the group consisting of infusion rate and different drugs having different burn rate. The method of any one of examples 16 to 25, wherein patient parameters to be included as inputs to the algorithm include physiological parameters. The method of example 26, wherein said physiological parameters are for a selected patient. The method of example 27, wherein said physiological parameters comprise a physiological and / or anatomical difference between the selected patient and a selected cohort of patients. The method of any one of examples 16 to 28, wherein said patient is a neonate and said patient parameters include gestational age. The method of any one of examples 16 to 29, wherein the algorithm allows quantification of at least one of the amount and rate of IV infiltration or extravasation for a given injected fluid. The method of example 30, comprising using said quantification to control the duration of an injection procedure, the procedure being terminated or adjustedafter a determined duration correlated with the amount or rate of IV infiltration or extravasation. The method of any one of examples 16 to 31 , wherein the algorithm takes account of physiological change for a selected patient with time, time optionally being selected from the group consisting of a monitoring period and a period of time over which physiological change has occurred. The method of example 32, wherein the algorithm takes account of changes over time in at least one of body composition, vein composition and vein structure over time. The method of any one of examples 16 to 33, wherein monitoring is conducted during recurrent drug therapy, optionally chemotherapy. The method of any one of examples 16 to 34, wherein said plurality of frequencies is selected from the 1 to 40 kHz range, optionally the 1 to 10 kHz range. The method of example 35, wherein frequency selection is determined by patient parameters and fluid parameters. The method of any one of examples 16 to 36, comprising determining monitoring parameters that may affect IV infiltration or extravasation, said monitoring parameters being selected from the group consisting of frequency of impedance value acquisition, frequency at which impedance measurements are made, number of impedance values to be processed (for example by averaging) to achieve a selected sensitivity of detection of IV infiltration or extravasation. The method of any one of examples 16 to 37, wherein IV infiltration or extravasation is indicated when an impedance change, optionally gradient of impedance change with time, exceeds a predetermined value. The method of example 38, wherein said predetermined value is an empirically derived value which is mapped against characteristics for a selected patient cohort and used in determination of the baseline.40. The method of any one of examples 16 to 39, comprising processing motion or inertial sensor measurements to discriminate a limb movement of the patient from IV infiltration or extravasation.41. The method of any one of examples 16 to 40, comprising correlating temperature measurements with acquired impedance values; and discriminating temperature correlated changes in acquired impedance values from IV infiltration or extravasation.42. The method of any one of examples 16 to 41 , comprising detecting first pass success.43. The method of any one of examples 16 to 42, comprising detecting oedema in a limb that the bioimpedance sensor is connected to.44. One or more computer-readable non-transitory storage media embodying software that is operable when executed using any of the systems or methods in examples 1 to 43.

[0159] In this specification, the word “comprising” is to be understood in its “open” sense, that is, in the sense of “including”, and thus not limited to its “closed” sense, that is the sense of “consisting only of’. A corresponding meaning is to be attributed to the corresponding words “comprise”, “comprised” and “comprises” where they appear.

[0160] It is to be understood that the present disclosure is not limited to the disclosed embodiments and is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the present disclosure. Also, the various embodiments described above may be implemented in conjunction with other embodiments, e.g., aspects of one embodiment may be combined with aspects of another embodiment to realize yet other embodiments. Further, independent features of a given embodiment may constitute an additional embodiment. In addition, a single feature or combination of features in certain of the embodiments may constitute additional embodiments.

[0161] Specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a representative basis for teaching one skilled in the art to variously employ the disclosed embodiments and variations of those embodiments.

[0162] Modifications and variations to the systems and / or methods for monitoring and intravenous procedure described in this specification will be apparent to the skilled reader. Such modifications and variations are deemed within the scope of the present disclosure. For example, system 10 may enable control over an electronic injection device or infusion pump 120 as a function of acquired impedance values. For example, processor 30 may disable an electronic injection device or infusion pump 120 by instruction sent through a wireless connection 90 if measured IV infiltration or extravasation is above a permissible threshold. Further, while discussion above concerns bioimpedance measurement, a bioimpedance related property such as reactance, phase angle or conductivity may be used in processing by processor 30 to detect IV infiltration or extravasation.

Claims

CLAIMS1. A system for monitoring an intravenous procedure for a patient comprising: a bio-impedance sensor comprising at least a pair of super-cutaneous electrodes disposed in electrical contact with the skin of the patient proximate to an insertion site for an injection device for injecting a fluid into the patient; an impedance measuring unit, the impedance measuring unit being operatively coupled to the bio-impedance sensor for generating a current, energising at least one electrode and measuring impedance values acquired, between each electrode of the at least one pair of supercutaneous electrodes, proximate the injection device insertion site when current is generated at multiple frequencies; and a processor coupled to the bio-impedance sensor and having a memory having stored therein an algorithm comprising electronic instructions that, when executed by the processor, process the impedance values acquired at a plurality of selected frequencies to determine presence of extravascular fluid in tissue due to the intravenous procedure, wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid.

2. The system of claim 1, further comprising at least one reference electrode is to provide greater sensitivity in characterising the cause of a change in bioimpedance.

3. The system of claim 1 or 2, wherein said at least one pair of electrodes is disposed on a wearable patch.

4. The system of any one of the preceding claims, wherein said at least one pair of electrodes is a first pair of electrodes forming part of a configurable array of supercutaneous electrodes which are deployed in a pattern.

5. The system of any one of the preceding claims, wherein the at least one pair of electrodes is disposed to run substantially parallel to, or longitudinally along, a path of a target vein and provide a first kelvin resistance circuit when connected to the impedance measuring unit; and wherein each electrode of the pair is spaced by a selected distance.

6. The system of claim 4 or 5, wherein a second pair of reference electrodes is disposed for a line between the electrodes to run at an angle to the path of said target vein and provide a second kelvin resistance circuit when connected to the impedance measuring unit.

7. The system of claim 6, wherein said angle is perpendicular to the path of said target vein.

8. The system of claim 6, wherein said angle is an acute angle to said target vein.

9. The system of claim 3, wherein a single reference electrode is disposed on said wearable patch, said reference electrode being disposed offset from each electrode of the first pair of electrodes, said single reference electrode being brought into electrical connection with either electrode of the providing an indication of capacitance on the electrical path aligned at an acute angle to the vein.

10. The system of any one of the preceding claims, as dependent from claim 3, wherein the wearable patch is configured to fit a limb, optionally selected from the group consisting of leg, foot, wrist and forearm.

11. The system of claim 10, wherein the wearable patch is made from a flexible material, optionally being elastic or stretchable to fit different limbs.

12. The system of any one of the preceding claims, as dependent from claim 3, wherein the wearable patch comprises a plurality of portions which - when combined - form the wearable patch.

13. The system of any one of the preceding claims, as dependent from claim 3, wherein the wearable patch includes a transparent portion or window allowingvisual checking of the insertion site during the procedure with the injection device.

14. The system of any one of the preceding claims, including a further sensor selected from the group consisting of a temperature sensor for sensing patient skin temperature; optical sensors; motion or inertial sensors optionally accelerometers, gyroscopes and magnetometers; and bio-sensors.

15. A bioimpedance sensor when used in the system of any one of the preceding claims comprising: a wearable patch adapted to be affixed to the skin of a patient proximate to an insertion site for an injection device for injecting a fluid to the patient; and at least a pair of supercutaneous electrodes disposed on the wearable patch and in contact with the skin of the patient for measuring bioimpedance.

16. A method for monitoring an intravenous procedure for a patient comprising: obtaining electrical signals from a bio-impedance sensor comprising at least a pair of electrodes in electrical contact with the skin of the patient proximate to an insertion site for an injection device for injecting a fluid to the patient, at least one electrode being energisable when a current is generated at a selected frequency and directed to the at least one electrode; measuring impedance values acquired, by the bio-impedance sensor, proximate the injection device insertion site when the current is generated and directed between each electrode in said pair of electrodes at a plurality of selected frequencies; and processing, with an algorithm, the impedance values acquired at the plurality of selected frequencies to determine presence of extravascular fluid in tissue due to the intravenous procedure,wherein said algorithm for processing the acquired impedance values uses patient and fluid parameters as inputs for analysing the acquired impedance values to determine presence of extravascular fluid.

17. The method of claim 16, comprising disposing a pair of electrodes to run substantially parallel to, or longitudinally along, a path of a target vein and measuring bioimpedance values.

18. The method of claim 16 or 17, comprising disposing a pair of electrodes for a line between the electrodes to run at an angle to the path of a target vein and measuring bioimpedance values.

19. The method of claim 18, wherein the line runs transversely and perpendicularly to the path of the target vein.

20. The method of any one of claims 16 to 19, comprising monitoring whether bioimpedance fluctuates either unilaterally or bilaterally relative to a baseline.

21. The method of any one of claims 16 to 20, comprising issuing at least one of an audible and visual alert if acquired impedance values exceed the permissible threshold.

22. The method of claim 21 , comprising issuing said alert if impedance values exceed the permissible threshold for greater than a selected time period.

23. The method of any one of claims 16 to 22, wherein said acquired impedance values have associated noise and the algorithm for processing the acquired impedance values allows smoothing and reduction of noise.

24. The method of any one of claims 16 to 23, wherein the algorithm provides, as an output, a baseline impedance characteristic which takes account of patient and fluid parameters against which acquired impedance values are analysed.

25. The method of claim 24, wherein the baseline impedance characteristic is individually determined for each patient.

26. The method of claim 24 or 25, wherein said baseline impedance characteristic is dynamic and adjusted, at regular intervals, during monitoring.

27. The method of any one of claims 24 to 26, wherein monitoring commences post injection device insertion.

28. The method of any one of claims 16 to 27, wherein fluid parameters to be included as inputs to the algorithm include at least one of the chemical and physical properties of the fluid, optionally a drug.

29. The method of claim 28, wherein the algorithm allows for an input selected from the group consisting of infusion rate and different drugs having different burn rate.

30. The method of any one of claims 16 to 29, wherein patient parameters to be included as inputs to the algorithm include physiological parameters.

31. The method of claim 30, wherein said physiological parameters are for a selected patient.

32. The method of claim 32, wherein said physiological parameters comprise a physiological and / or anatomical difference between the selected patient and a selected cohort of patients.

33. The method of any one of claims 16 to 32, wherein said patient is a neonate and said patient parameters include gestational age.

34. The method of any one of claims 16 to 33, wherein the algorithm allows quantification of at least one of the amount and rate of IV infiltration or extravasation for a given injected fluid.

35. The method of claim 34, comprising using said quantification to control the duration of an injection procedure, the procedure being terminated or adjusted after a determined duration correlated with the amount or rate of IV infiltration or extravasation.

36. The method of any one of claims 16 to 35, wherein the algorithm takes account of physiological change for a selected patient with time, time optionally being selected from the group consisting of a monitoring period and a period of time over which physiological change has occurred.

37. The method of claim 36, wherein the algorithm takes account of changes over time in at least one of body composition, vein composition and vein structure over time.

38. The method of any one of claims 16 to 37, wherein monitoring is conducted during recurrent drug therapy, optionally chemotherapy.

39. The method of any one of claims 16 to 38, wherein said plurality of frequencies is selected from the 1 to 50 kHz range, optionally the 1 to 20 kHz range.

40. The method of claim 39, wherein frequency selection is determined by patient parameters and fluid parameters.

41. The method of any one of claims 16 to 40, comprising determining monitoring parameters selected from the group consisting of frequency of impedance value acquisition, frequency at which impedance measurements are made, number of impedance values to be processed (for example by averaging) to achieve a selected sensitivity of detection of IV infiltration or extravasation.

42. The method of any one of claims 16 to 41 , wherein IV infiltration or extravasation is indicated when an impedance change, optionally gradient of impedance change with time, exceeds a predetermined value.

43. The method of claim 42, wherein said predetermined value is an empirically derived value which is mapped against characteristics for a selected patient cohort and used in determination of the baseline.

44. The method of any one of claims 16 to 43, comprising processing motion or inertial sensor measurements to discriminate a limb movement of the patient from IV infiltration or extravasation.

45. The method of any one of claims 16 to 44, comprising correlating temperature measurements with acquired impedance values; and discriminating temperature correlated changes in acquired impedance values from IV infiltration or extravasation.

46. The method of any one of claims 16 to 45, comprising detecting first pass success.

47. The method of any one of claims 16 to 46, comprising detecting oedema in a limb that the bioimpedance sensor is connected to.

48. One or more computer-readable non-transitory storage media embodying software that is operable when executed using any of the systems or methods in claims 1 to 47.

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