WO2021006785A1 - System and method for continuous transcutaneous blood gas monitoring - Google Patents

System and method for continuous transcutaneous blood gas monitoring Download PDF

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Publication number
WO2021006785A1
WO2021006785A1 PCT/SE2020/050549 SE2020050549W WO2021006785A1 WO 2021006785 A1 WO2021006785 A1 WO 2021006785A1 SE 2020050549 W SE2020050549 W SE 2020050549W WO 2021006785 A1 WO2021006785 A1 WO 2021006785A1
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Prior art keywords
blood gas
skin
transcutaneous blood
nerve stimulating
transcutaneous
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PCT/SE2020/050549
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French (fr)
Inventor
Anders Persson
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Fourth State Systems Ab
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Priority to SE1950854 priority
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Publication of WO2021006785A1 publication Critical patent/WO2021006785A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1491Heated applicators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14539Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring pH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14542Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1477Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means non-invasive
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/683Means for maintaining contact with the body
    • A61B5/6832Means for maintaining contact with the body using adhesives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient ; user input means
    • A61B5/742Details of notification to user or communication with user or patient ; user input means using visual displays

Abstract

The present invention relates to systems and methods for transcutaneous blood gas measurements. In particular the invention relates to continuous transcutaneous measurement of carbon dioxide in the blood of the patient wherein the skin of the patient is heated and to minimize the detrimental effects of the heating. A nerve stimulating element of the system for transcutaneous blood gas measurement is configured to transmit a continuous pulsed signal to the skin of the person wherein the continuous pulsed signal comprises nerve stimulating pulses and relaxation periods. The nerve stimulating pulses each has a duration of less than 3 minutes.

Description

System and Method for Continuous Transcutaneous Blood Gas Monitoring
Field of invention
The present invention relates to systems and methods for transcutaneous blood gas measurements. In particular the invention relates to continuous transcutaneous measurement of carbon dioxide in the blood of the patient wherein the skin of the patient is heated and to minimize the detrimental effects of the heating.
Background
Transcutaneous blood gas measurements (TBM) are pivotal in monitoring the health of prematurely born children. Blood gases refer to oxygen and carbon dioxide in the blood of the patient, and transcutaneous means to measure through the skin. About 75 % of all neonates are monitored by TBM during their hospitalization, making it one of the most widely used methods in a modern Neonatal Intensive Care Unit (NICU). [1]
Together with measurements of pulse, respiration rate, body temperature, and blood oxygen saturation, TBM forms the backbone of monitoring the basic health of a neonate, where TBM gives unique information about both respiratory and circulatory function. Many neonates, particularly those born into extreme prematurity, have organs that are far from sufficiently developed to support them outside the womb. Hence, both lungs and heart may struggle to achieve proper oxygenation, and the patient must be treated in an incubator with increased ambient oxygen levels. However, it is crucial to keep the added oxygen at a healthy level, since hyperoxia, i.e., too much oxygen in the patient’s blood, may cause morbidity by damaging the central nervous system and often causes blindness by hampering the development of the optic nerve. Hypoxia, i.e. too little oxygen in the patient’s blood, on the other hand, may cause both morbidity and even mortality from insufficient oxygenation of the brain and other vital organs.
In TBM, the measurements are typically achieved by placing a transcutaneous blood gas monitoring system (TBM system) on the patient's skin, which collects the minute amount of gas that diffuses from the cutaneous capillaries through the skin. The collected gas is analyzed by a sensor unit in fluid communication with the sampling unit. The majority of the existing TBM systems consist of two main parts, namely a sampling unit that collects the blood gases at the skin surface and conducts them to a sensor unit that analyses the respective gas contents. In order to keep the sampling rate at a maximum, the dead volumes in the system are minimized. Therefore, the sensor unit is typically integrated inside the sampling unit. Typically, the system is equipped with a third component, a heater connected to a power supply that continuously heat the skin beneath the sampling unit to temperatures between 42 °C and 45 °C. The elevated temperature increases the diffusion flux of both carbon dioxide and oxygen through the skin in a number of ways. Without this flux increase, i.e. without heating, the technique does not work, since the response time of the sensor is too long to detect changes in the patient’s health status. [2]
The cause of the increase transcutaneous blood gas flux due to the heating is manifold and somewhat different for the two gases. The local heating of the skin causes the cutaneous capillaries to dilate, which greatly increases the cutaneous blood flow. The increased blood flow lets a large fraction of arterial blood enter the capillaries, and, hence, the capillary oxygen and carbon dioxide pressures approaches arterial levels, which offers a methodological advantage, since the arterial values generally offers more clinical information than the capillary ones.
Continuous heating of the patient’s skin over a period of a few hours, which for the above reasons is utilized in existing TBM systems, causes skin burns on the patient, also known as erythema. This is particularly problematic for neonates that have a more fragile skin and suffer from a high risk of infection. To avoid erythema the system is usually moved around to different locations on the patient’s body, which is not only time consuming for the caretakers but may also decrease the reliability of the measurements as well as potentially cause tearing of the skin with subsequent risk of infection.
WO 2016/008840 describes a method for TBM with less heating by intermittently warming up the skin to a temperature of 42 °C or more for a time period to monitor the transcutaneous partial pressure of oxygen, before lowering the temperature to a lower level. This facilitates an intermittent measurement, where reliable data is received while the temperature is at the higher level, and the skin can recover while the temperature is at the lower level. The application discloses time intervals comprising at least 10 minutes of heating up the skin, followed by 5 minutes of measuring the oxygen partial pressure, followed by 20 minutes at the lower temperature at which the skin recovers.
Given the importance of blood gas data at an NICU, intermittent monitoring with periods without any measuring to up to 20 minutes is not sufficient. Hence, there is still a need for a system and method for TBM measurements that neither heats the patient’s skin to the extent that there is a risk for erythema nor leave the patient without functioning monitoring of blood gases for extended periods of time. Summary
The object of the invention is to provide a system and a method for transcutaneous blood gas measurements that overcomes at least some of the drawbacks of the prior art. This is achieved by the system as defined in claim 1 and method defined in claim 8.
The system for transcutaneous blood gas measurement according to the invention comprises a sampling unit adapted to be placed on the skin of a person, a carbon dioxide sensor, and a nerve stimulating element. The nerve stimulating element is configured to transmit a continuous pulsed signal to the skin of the person, the continuous pulsed signal comprising nerve stimulating pulses and relaxation periods, wherein the nerve stimulating pulses each has a duration of less than 3 minutes.
According to one aspect of the invention the nerve stimulating element is a heater.
According to one aspect of the invention the carbon dioxide sensor is configured to measure the partial pressure of the extracted transcutaneous blood gas.
According to one aspect of the invention the transcutaneous blood gas monitoring system further comprises a signal generator in connection with and configured to, output a continuous pulsed signal to the nerve stimulating element. The signal generator is connected to and controlled by a control unit.
According to one aspect of the invention the transcutaneous blood gas monitoring system is configured to
-generate and transmit via the nerve stimulating element a continuous series of nerve stimulation pulses to the skin of the person, thereby inducing vasodilation in the cutaneous capillaries located underneath the transcutaneous blood gas monitoring system;
-continuously extract the transcutaneous blood gas from the patient into the transcutaneous blood gas monitoring system;
-continuously measure the extracted transcutaneous blood gas with the transcutaneous blood gas sensor; and
-continuously analyze the signals from the carbon dioxide sensor and determining and presenting a carbon dioxide blood gas value. According to one aspect of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses has a pulse width, PW, between 2 and 180 s and the relaxation period, RP, is between 105 and 180 s.
According to one aspect of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses has a pulse width, PW, between 2 and 15 s and the relaxation period, RP, is between 105 and 118 s.
According to one aspect of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses has a pulse width, PW, between 2 and 8 s and the relaxation period, RP, is between 120 and 180 s.
The method for continuous transcutaneous blood gas monitoring according to the invention utilizes a transcutaneous blood gas monitoring system, the transcutaneous blood gas monitoring system comprising a sampling unit provided with a nerve stimulating element and at least a carbon dioxide sensor. The method comprises concurrent steps of:
- continuously transmitting a continuous pulsed signal to a nerve stimulating element that transmits a continuous series of stimulation pulses to the skin of the person, thereby inducing vasodilation in the cutaneous capillaries located underneath the sampling unit;
- continuously extracting the transcutaneous blood gas from the patient into the transcutaneous blood gas monitoring system;
- continuously measuring the extracted transcutaneous blood gas with the transcutaneous blood gas sensor; and
- continuously analyzing the signals from the carbon dioxide sensor and determining and presenting a carbon dioxide transcutaneous blood gas value. According to one aspect of method of the invention the step of continuously transmitting a continuous pulsed signal the continuous pulsed signal is arranged to maintain the vasodilation in the cutaneous capillaries above a predetermined vasodilation threshold value.
According to one aspect of the method of the invention the step of continuously measuring the extracted transcutaneous blood gas includes continuously measuring the carbon dioxide in the extracted transcutaneous blood gas with a carbon dioxide sensor configured to measure the partial pressure of the extracted transcutaneous blood gas.
According to one aspect of the method of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 180 s and the relaxation period, RP, is between 105 and 180 s.
According to one aspect of the method of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 15 s and the relaxation period, RP, is between 105 and 118 s.
According to one aspect of the method of the invention the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 8 s and the relaxation period, RP, is between 120 and 180 s.
It is an advantage with the invention that the TBM system can remain attached to the same site for long periods of time, i.e. without having to be relocated after a few hours to avoid the formation of skin burns. Avoiding relocation saves both time and labor. This is a particular advantage for neonates since the total number of locations on the body suitable for attachment of a TBM system are more or less limited the torso where it competes for space with ECG electrodes etc.
It is a further advantage with the invention that it increases the safety for the patient. The system must be glued very tightly to the skin to avoid gas leakages. Hence, removing it from the skin risk causing tears that in turn might cause infections. Neonates are particular sensitive to infections and minimizing this risk by avoiding relocation of the TBM system will consequently improve the safety and quality of their care.
It is an advantage with the invention that the measurement can be performed continuously without the need for interruptions. A current system for TBM must either be relocated or turned off to allow the skin beneath the system to recover and not be burnt. If the system is relocated, the sensor unit needs to be recalibrated, and the whole process typically takes between 20 and 30 minutes. If the system, or its heater, is instead turned off, it needs to stay off for at least 20 minutes for the skin to recover. Both these measures cause a pause in the measurement.
It is further advantage with the method of the invention that it facilitates continuous measurement of the patient’s blood gas status and hence provides the care-takers with real-time data.
It is a further advantage that the duty cycle of the continuous pulsed signal may be precisely controlled that not only lower the risk of skin burns, but also minimizes spurious signals arising from increased metabolism in the heated tissue, and, hence, offers a more precise measurement of the arterial blood gases.
Description of drawings
Figure 1 is a schematic drawing of a TBM system according to the invention;
Figure 2 is a schematic illustration of a continuous pulsed signal;
Figure 3 a) is a graph showing a continuous pulsed signal for axon reflex stimulation, and b) is a graph showing relative blood flow and fraction arterial gas content of cutaneous capillaries as a function of time;
Figure 4 a) is a graph showing relative transcutaneous gas signal as a function of time., and b) is a graph showing relative transcutaneous gas signal as a function of time.
Detailed description
The following terms are defined and used throughout the description and claims:
Cutaneous - located close to the skin; erythema - redness of the skin or skin burns; stimulation pulse - continuous series of pulses transmitted to the small cutaneous nerve fibers;
TBM - transcutaneous blood gas measurement;
TBM system - system for transcutaneous blood gas monitoring; transcutaneous -through the skin; and vasodilation - widening of blood vessels’ cross section.
Heating is used in TBM in order to increase the capillary blood flow by causing vasodilation of the cutaneous capillaries. Although vasodilation is the body’s natural way of cooling, it is not directly caused by an increased temperature, but by signaling from the nervous system. In the case of local heating, temperature sensitive small nerve fibers close to the skin mediate axon reflex-related vasodilation, creating a local increase in the capillary blood flow, i.e. the physical effect that makes TBM feasible.
Vasodilation and contraction is rather slow processes. Once the capillaries have been stimulated by the small nerve fibers, they dilate in the matter of seconds, but it takes several minutes before they contract back to their original cross section. In other words, the relationship between skin temperature and blood flow is hysteretic, where a short nerve stimuli can result in a long period of increased blood flow in the cutaneous capillaries. [3]
The present invention relates to a system and method for continuous TBM that does not require continuous heating of the patient’s skin. The TBM system of the invention is schematically described in Figure 1. It should be noted that the figure does not show the system according to any scale, external or internal. The TBM system 100 comprises a sampling unit 101 which is configured to be applied to the skin 102 of a patient. The sampling unit 101 comprises a sensor system, or probe 104, performing the gas analysis and a membrane 103. The probe 104 comprises two sensors, an oxygen sensor 105 and a carbon dioxide sensor 106. Alternatively the probe 104 is provided a distance from the sampling unit. The sampling unit 101 collects the blood gases from the skin 102 that has passed via the membrane 103 and the gas is transferred to the oxygen sensor 105 and a carbon dioxide sensor 106 of the probe 104. The sensors can be measuring cells of the Clark type, be based on measuring the pH of a liquid solution, measure absorption of infra-red, visible or ultra-violet light, be based on emission or optogalvanic spectroscopy, or any other optical or electrochemical detection method. The sensors may be of the kind that analyses the partial oxygen pressure (pO2) and the partial carbon dioxide pressure (pCO2). The sampling unit 101 may also be designed without utilizing a membrane in which cases a gas flow drawn from outside the sampling unit and passing the skin 102 is utilized. The system further consists of a nerve stimulating element 107 capable of stimulating a local axon reflex in small, cutaneous nerve fibers in order to increase the diffusion of gases through the skin 102. The nerve stimulating element 107 is connected to a signal generator 108 that is connected to a control unit 109. The control unit 109 is configured to control the signal generator 108 to output a continuous pulsed signal to the nerve stimulating element 107. Thereby, in operation, the nerve stimulating element 107 will transmit a corresponding continuous pulsed nerve stimulating signal. The oxygen sensor 105 and the carbon dioxide sensor 106 are connected to a control and analysis unit (not shown) comprising or connected to a display monitor 111. The TBM system 100 may further be provided with an input/output device as well as communication unit for remote control and/or supervision. Such arrangements are well known in the art. The sampling unit 101 of the TBM system 100 is during use attached to the skin of the patient 102 using glue 110 or the like, and the results from the measurement are displayed on the display monitor 111. The display monitor 111 is preferably continuously updated to show real-time data of the patient’s blood gas status.
The nerve stimulating element 107 is any element capable of stimulating a local axon reflex in small nerve fibers close to the skin underneath the sampling unit 101. In one embodiment of the invention the nerve stimulating element 107 is a heater that heats at least a portion of the skin surface covered by and underneath the sampling unit 101. Due to the continuous pulsed signal transmitted by the TBM system 100 the heating is not continuous but pulsed, and hence the risk of skin burns is reduced, since the skin 102 has time to recover between the pulses. The heater may for example be a resistive heater, a thermoelectric heater or an IR-heater and the generated pulse an electrical pulse with a current/voltage that matches the characteristics of the resistive heater. Suitable resistive or thermoelectric heaters are commercially available, e.g., Heating Rings from Bach Resistor Ceramics GmbH or MC04-series thermoelectric controllers from TEC Microsystems Inc., and the heating element may be custom made to fit a specific sampling unit 101. The nerve stimulating element 107 may alternatively be an electrode that stimulates the small nerve fibers electrically or any other suitable stimulation element.
The TBM system 100 is adapted to transmit a continuous pulsed signal, i.e. a continuous series of stimulating pulses, to the skin of the patient 102 inducing a local axon reflex in small nerve fibers located underneath the sampling unit 101. The signal generator 108 is configured to generate a continuous pulsed signal, for example and typically electrical pulses which by the nerve stimulating element 107 are transmitted to the skin of the patient as a continuous series of pulses, hereinafter referred to as stimulation pulses. The local axon reflex induced by the stimulation pulses induces vasodilation which enables the blood gas measurement.
The continuous pulsed signal can be described by a pulse-scheme 200, which is schematically illustrated in Figure 2, and comprises stimulation pulses SP and relaxation periods, RP. The stimulation pulse SP has a maximum power level, MPL, and a pulse width, PW, the relaxation periods, RP, has a power level, the relaxation power level, RPL. The amplitude, A, is the difference between the maximum power level, MPL, for the stimulation pulse SP and the power level, RPL, for the relaxation period RP. The area under the curve of a stimulation pulse SP represents the submitted energy to the skin during one simulation pulse. The shape of the simulation pulses are illustrated as essentially rectangular, which represents typical stimulation pulses SP. As realized by the skilled person other shapes of the stimulation pulses SP are possible and ramping up and/or down the power in a predetermined manner may be advantageous or required for certain heaters, for example. The maximum power level, MPL, of the stimulation pulse SP and its pulse width, PW, should be chosen to correspond to a heating of the skin underneath the sampling unit 101 of the TBM system 100 to a temperature of 42 to 45 °C. The relaxation power level, RPL, should be selected to give an effective relaxation, typically cooling down. According to one embodiment the relaxation power level, RPL, is zero.
A common way to describe a pulsed signal is with the parameter duty cycle, D, defined as
D=PW/T [1]
Wherein PW is the pulse width of the stimulation pulse SP and T is the period, i.e. the pulse width PW of the stimulation pulse added with the relaxation period RP.
The method for transcutaneous blood gas measurement according to the invention enables continuous measurement of the blood gases (oxygen and carbon dioxide) without continuous heating of the patient’s skin 102. The method utilizes a TBM system 100 comprising a sampling unit 101 provided with a nerve stimulating element 107, and a signal generator 108. The signal generator 108 transmits a continuous pulsed signal 200 to the nerve stimulating element 107 that transmits a continuous series of stimulation pulses SP to the skin of the patient 102. The continuous series of stimulation pulses SP induces vasodilation in the cutaneous capillaries underneath the TBM system 100.
The TBM method according to the invention comprises the main concurrent steps of:
a) continuously transmitting a continuous pulsed signal 200 to the nerve stimulating element 107 that transmits a continuous series of stimulation pulses to the skin 102 of the patient , thereby inducing vasodilation in the cutaneous capillaries located underneath the sampling unit 101 and maintaining the vasodilation in the cutaneous capillaries in order to achieve a continuous transcutaneous blood gas flux; b) continuously extracting the transcutaneous blood gas from the patient into the sampling unit 101; c) continuously measuring the oxygen concentration and/or the carbon dioxide in the extracted transcutaneous blood gas with an oxygen sensor 105 and/or a carbon dioxide sensor 106; and d) continuously analyzing the signals from the oxygen sensor 105 and/or a carbon dioxide sensor 106 and determining oxygen and/or and carbon dioxide levels in the extracted transcutaneous blood gas and continuously presenting the results for example on a display monitor 111.
In order for the TBM system 100 to provide the continuous measurement the vasodilation needs to be above a threshold value, referred to as the vasodilation threshold value, VTV. This vasodilation threshold value, VTV, corresponds to a capillary cross section that is sufficiently wide to allow enough arterial blood to enter the cutaneous capillaries for the arterial blood gas levels to dominate the measured signal. A suitable maximum power level, MPL, of the stimulation pulse SP giving a vasodilation above the vasodilation threshold value, VTV, will depend on the specific configuration of the TBM system 100 and may without undue burden be determined by a person skilled in the art. For example, in the embodiment using a heater as the nerve stimulating element the designer given the instructions that the maximum power level, MPL, should correspond to a maximum temperature of the skin of 42-45 °C, would establish appropriate parameters for the heater with only a few tests.
An exemplary suitable pulse scheme is schematically illustrated in Figure 3a by a graph that shows a continuous pulsed signal that corresponds to a method according to the invention. The pulse width is 2 s and the subsequent relaxation time is 118 s. Figure 3b shows the calculated relative blood flow and fraction of arterial blood gas in the cutaneous capillaries arising from the axon stimuli that occurs when the signal in Figure 3a feeds the nerve stimulating element 107, which in this case is a heater that heated the skin to 43 °C. The left y axis shows relative blood flow (dashed and dotted lines) where 1 corresponded to the blood flow in the undilated (unstimulated) capillaries, and the right y axis shows the fraction of arterial blood gas in the cutaneous capillaries (solid and dash-dotted lines). Of these lines, the solid and dashed ones show the situation when the method according to the invention is employed, resulting in a significantly increased cutaneous blood flow, as well as a high and stable fraction of arterial blood gas in the capillaries. The dotted and dash-dotted lines, on the other hand, show the situation when the skin is only subjected to the initial 40 s of heat but none of the subsequent pulses. In the latter case, or when the continuous pulsed signal is discontinued, the cutaneous capillaries contract back to their original cross-section after a time period of typically 300-600 s. An example of a vasodilation threshold value VTV is shown by the thin solid line.
Figure 4a is a graph of a measurement of relative transcutaneous gas signal as a function of time using a TBM system 100 described with reference to Figure 1 with a thermoelectric heater. From t=0 the TBM system 100 is monitoring the capillary blood gas level, indicated by the dotted line. At t=6.5 minutes, the heater is activated with a continuous pulsed signal 200 that comprises a series of stimulation pulses SP with an maximum power level, MPL, corresponding to a temperature of 45 °C. The stimulation pulses SP each have a pulse length, PW, of 15 s and the following relaxation periods, RP, each are 465 s long, making up a total period, T, of 480 s and duty cycle, D, of 3.1%. The relaxation power level, RPL, was 0 W. The timing of the pulses is indicated by vertical dashed lines in the graph. Directly after a stimulation pulse SP, the signal rises to the arterial level, indicated by the dash-dotted line, and remains there for about 180 s. It then relaxes back to the capillary level, before being raised again by the second pulse.
Figure 4b illustrates a measurement with the same equipment as in Figure 4a and is a graph of a relative transcutaneous gas signal as a function of time for a continuous pulsed signal 200 with a shorter period, T. Here, the continuous pulsed signal 200 has the same maximum power level MPL (45 °C) and pulse length, PW, (15 s) as in Figure 4a, but the relaxation periods, RP, each are 105 seconds long, making up a total period, T, of 120 s and duty cycle, D, of 12.5%. The first stimulation pulse SP of the continuous pulsed signal 200 raises the signal from the capillary blood gas level (dotted line) to the arterial blood gas level (dash-dotted line) and the following pulses keeps the signal at the latter, hence, enabling continuous monitoring of arterial blood gases without continuous heating. Figure 4b illustrates that the method according to the invention facilitates the continuous measurements without continuous heating.
In the process of continuously transmitting a continuous pulsed signal to the nerve stimulating element 107, during the stimulation pulse SP the nerves are stimulated so that the local axon reflex induces vasodilation to a sufficient degree that enables the measurement of the oxygen concentration and/or the carbon dioxide concentration in the extracted gas. According to one embodiment vasodilation is induced by applying heat and the stimulation pulse SP comprises applying heat in an amount so that the temperature of the skin during the stimulation pulse SP rises to in-between 42 and 45 °C. During the relaxation period, RP, the applied amount of heat is lowered or completely turned off so that the temperature of the skin is lowered to the temperature of the skin prior to receiving the first stimulation pulse SP.
The requirements regarding measurability of the carbon dioxide concentration in the extracted gas without risk for erythema is fulfilled for a continuous pulsed signal with a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses SP having a pulse width, PW, between 2 and 180 s and the relaxation period, RP, being between 105 and 180 s, which corresponds to one embodiment of the invention. This corresponds to a duty cycle, D, of at the most 50 %.
According to one embodiment of the invention the system and method is optimized for providing high accuracy, by increasing the vasodilation threshold value, VTV, hence, keeping the arterial blood gas fraction in the cutaneous capillaries at a higher and steadier fraction, however, still complying with the requirements of the heating. According to this embodiment the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses SP has a pulse width, PW, between 2 and 15 s and the relaxation period, RP, is between 105 and 118 s. This corresponds to a duty cycle, D, of at the most 13 %.
According to one embodiment of the invention the system and method is optimized for minimizing the heating effect further by minimizing the pulse width, PW, which could be used for extremely sensitive patients. In this case the accuracy of the measurement may be lower, however acceptable in most monitoring situations. According to this embodiment the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses SP has a pulse width, PW, between 2 and 8 s and the relaxation period, RP, is between 120 and 180 s. This corresponds to a duty cycle, D, of at most 6 %.
The embodiments described above are to be understood as illustrative examples of the system and method of the present invention. It will be understood that those skilled in the art that various modifications, combinations and changes may be made to the embodiments. In particular, different part solutions in the different embodiments can be combined in other configurations, where technically possible.
References
[1] I. Bromley, "Transcutaneous monitoring - understanding the principles”, Infant, vol. 4, p.
95-98, 2008.
[2] "Transcutaneous Blood Gas Monitor", http://www.who.int/medical devices/en/index.html
World Health Organization.
[3] W. Mager land R. D. Treede, Heat-evoked vasodilation in human hairy skin: axon reflexes due to low-level activity of nociceptive afferents. Journal of Physiology, 497.3, pp. 837-848, 1996.

Claims

Claims
1. A system for transcutaneous blood gas measurement (100) comprising a sampling unit (101) adapted to be placed on the skin of a person, a carbon dioxide sensor (106), and a nerve stimulating element (107), characterized in that the nerve stimulating element (107) is configured to transmit a continuous pulsed signal to the skin of the person, the continuous pulsed signal comprising nerve stimulating pulses and relaxation periods, wherein the nerve stimulating pulses each has a duration of less than 3 minutes.
2. The transcutaneous blood gas monitoring system (100) of claim 1, wherein the nerve
stimulating element (107) is a heater.
3. The transcutaneous blood gas monitoring system (100) according to claim 1 or 2, wherein the carbon dioxide sensor (106) is configured to measure the partial pressure of the extracted transcutaneous blood gas.
4. The transcutaneous blood gas monitoring system (100) according to any of claim 1 to 3, further comprising a signal generator (108) in connection with and configured to, output a continuous pulsed signal to the nerve stimulating element (107), wherein the signal generator (108) is connected to and controlled by a control unit (109)
5. The transcutaneous blood gas monitoring system (100) according to any of claims 1 to 4, wherein the transcutaneous blood gas monitoring system (100) is configured to
-generate and transmit via the nerve stimulating element (107) a continuous series of nerve stimulation pulses to the skin (102) of the person, thereby inducing vasodilation in the cutaneous capillaries located underneath the transcutaneous blood gas monitoring system (100);
-continuously extract the transcutaneous blood gas from the patient into the
transcutaneous blood gas monitoring system (100);
-continuously measure the extracted transcutaneous blood gas with the transcutaneous blood gas sensor (105; 106); and
-continuously analyze the signals from the carbon dioxide sensor (106) and determining and presenting a carbon dioxide blood gas value.
6. The transcutaneous blood gas monitoring system (100) of claim 5, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 180 s and the relaxation period, RP, is between 105 and 180 s.
7. The transcutaneous blood gas monitoring system (100) of claim 5, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 15 s and the relaxation period, RP, is between 105 and 118 s.
8. The transcutaneous blood gas monitoring system (100) of claim 5, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 8 s and the relaxation period, RP, is between 120 and 180 s.
9. A method for continuous transcutaneous blood gas monitoring of a person using a
transcutaneous blood gas monitoring system (100) comprising a sampling unit (101) placed on the skin of a person, the a sampling unit (101) comprising a nerve stimulating element (107) and at least a carbon dioxide sensor (106), the method comprising concurrent steps of: a) continuously transmitting a continuous pulsed signal (200) to a nerve stimulating element (107) that transmits a continuous series of stimulation pulses to the skin (102) of the person, thereby inducing vasodilation in the cutaneous capillaries located underneath the transcutaneous blood gas monitoring system (100); b) continuously extracting the transcutaneous blood gas from the patient into the sampling unit (101); c) continuously measuring the extracted transcutaneous blood gas with the transcutaneous blood gas sensor (105; 106); and d) continuously analyzing the signals from the carbon dioxide sensor (106) and
determining and presenting a carbon dioxide transcutaneous blood gas value.
10. The method according to claim 8, wherein in the step of continuously transmitting a continuous pulsed signal (300) the continuous pulsed signal (200) is arranged to maintain the vasodilation in the cutaneous capillaries above a predetermined vasodilation threshold value.
11. The method according to claim 8 or 9, wherein the step of continuously measuring the
extracted transcutaneous blood gas (302) further includes continuously measuring the carbon dioxide in the extracted transcutaneous blood gas with a carbon dioxide sensor (106) configured to measure the partial pressure of the extracted transcutaneous blood gas.
12. The method according to any of claims 9 to 11, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 180 s and the relaxation period, RP, is between 105 and 180 s.
13. The method according to any of claims 9 to 11, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45
°C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 15 s and the relaxation period, RP, is between 105 and 118 s.
14. The method according to any of claims 9 to 11, wherein the continuous pulsed signal has a maximum power level, MPL, corresponding to a maximum temperature of the skin of 42-45 °C and the nerve stimulating pulses (SP) has a pulse width, PW, between 2 and 8 s and the relaxation period, RP, is between 120 and 180 s.
PCT/SE2020/050549 2019-07-05 2020-06-01 System and method for continuous transcutaneous blood gas monitoring WO2021006785A1 (en)

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