A device for obtaining an index of microcirculatory status

Abstract

The present invention relates to a device (1, 1') and a method for obtaining an indication of the microcirculatory status of a patient, the device (1, 1') comprising at least one first sensor (13) for measuring data indicative of a first carbon dioxide level, in particular a tissue carbon dioxide level, at least one second sensor (12) for measuring data indicative of a second carbon dioxide level, in particular a transcutaneously measured arterial blood carbon dioxide level, and a control unit (4) for determining a measure of the microcirculation, in particular changes in tissue perfusion, based on the tissue carbon dioxide level and the transcutaneously measured arterial blood carbon dioxide level, preferably in a septic patient.

Description

[Technical field]

[0001] The present invention relates to an apparatus and method for obtaining an indication of the microcirculatory status of a patient. [Background technology]

[0002] Several clinical conditions, such as sepsis, hemorrhage and cardiac arrest, cause a decrease in tissue perfusion, affecting even the smallest blood vessels. Long-term microcirculatory deterioration can eventually lead to functional impairment or even organ failure, which further worsens the patient's prognosis.

[0003] When bacteria enter the bloodstream and cause a systemic infection, the body responds to the infection with a condition called sepsis. Sepsis is one of the leading causes of morbidity and mortality in neonatal, pediatric and adult intensive care units (ICUs). The incidence of sepsis is approximately 25% in advanced neonatal ICUs. A number of factors, including prematurity, immunological defects and multiple insertion points such as lines / intravascular catheters, often lead to infiltration of organisms into the bloodstream.

[0004] Clinical monitoring provides continuous surveillance of patients. However, current monitoring techniques are unable to accurately detect sepsis, particularly its onset. Although the actual clinical signs of sepsis vary widely, sepsis is currently defined as a combination of clinical symptoms, deviant laboratory values, and positive blood cultures.

[0005] When sepsis is suspected, blood cultures are drawn. Due to the time required for microbial growth and identification in blood cultures, antibiotic treatment is initiated immediately after drawing, and blood cultures serve to confirm and evaluate the specific microbial characteristics found in the blood culture and tailor treatment. Unfortunately, the patient's clinical condition may be severely compromised by the time delay between blood drawing and confirmation of sepsis. Despite the immediate initiation of antibiotic treatment, mortality and morbidity are significant. Early detection of sepsis or even confirmation of its onset remains a challenge.

[0006] Sepsis is a systemic bloodstream infection by bacteria or other organisms that causes severe illness. In sepsis, dysfunction of the microcirculation appears in the early stages. Blood flow is shunted from arterioles to venules, leaving the microcirculation hypoxic and unable to remove carbon dioxide. Carbon dioxide levels in the skin increase significantly and oxygen levels decrease.

[0007] Several studies have pointed out that sepsis affects the microcirculation in the early stages. Continuous monitoring of the microcirculatory status has added value to detect possible changes in the microcirculatory status and to correlate these changes with sepsis. All cells of the body consume oxygen and produce carbon dioxide. Blood carries oxygen from the lungs to the tissues and facilitates the removal of carbon dioxide from the tissues, which are then exhaled. Due to lower oxygen and higher carbon dioxide concentrations in the peripheral tissues, oxygen diffuses from the circulating blood into the tissues.

[0008] Heating the skin increases blood flow to such an extent that oxygen levels rise and carbon dioxide levels decrease in the heated skin, a process called arterialization. When the skin is sufficiently heated and skin and microcirculatory conditions are permitted, oxygen and carbon dioxide levels can be measured at the skin surface, which correspond to arterial blood oxygen and carbon dioxide levels. This principle is applied to transcutaneous blood gas monitoring of a patient.

[0009] There are various techniques for transcutaneously measuring oxygen and carbon dioxide levels. Currently, optical and electrochemical sensors are widely used for transcutaneous oximetry and transcutaneous carbon dioxide measurement.

[0010] Typically, such a sensor contains a pH electrode, a reference electrode, an electrolyte solution, a membrane and a heating element.Other technologies for transcutaneous carbon dioxide measurement include optical techniques.

[0011] The sensor may be fixed to the skin. A heating element warms the skin to a temperature sufficient to improve perfusion, particularly above 40° C., more particularly between 42° C. and 45° C. Oxygen and carbon dioxide diffuse through the epidermis, through the semipermeable membrane of the sensor, and into the sensor chamber filled with an electrolyte solution.

[0012] In the case of an electrochemical sensor, a glass electrode measures the change in pH value. The output of the electrode is converted into a signal indicative of the partial pressure of carbon dioxide. The signal can be read out or displayed.

[0013] According to EP 2470066 B1, an index of tissue perfusion in a patient is measured by a carbon dioxide sensor, the skin carbon dioxide partial pressure (cPCO), without heating the sensor to a temperature above 37.5° C. 2 (hereinafter referred to as PcCO 2 ) and hereafter referred to as PaCO 2 Arterial pressure of carbon dioxide (aPCO 2 or PetCO below 2 End-tidal carbon dioxide partial pressure (EtPCO 2 It can be obtained by calculating the difference between

[0014] In patients with ventilation-perfusion imbalance, end-tidal carbon dioxide pressure may not be an appropriate reference. In these cases, end-tidal carbon dioxide pressure does not represent arterial carbon dioxide pressure.

[0015] In certain patient populations, such as neonates, low tidal volumes make end-tidal carbon dioxide measurement more difficult and less accurate. Summary of the Invention [Problem to be solved by the invention]

[0016] An object of the present invention is to avoid the drawbacks of the state of the art and to provide an apparatus and method for obtaining an indication of the microcirculatory state, in particular for indicating and / or predicting sepsis, which allows a non-invasive and reliable measurement that provides results within an acceptable reaction time. [Means for solving the problem]

[0017] According to the invention, this object is achieved by an apparatus and a method according to the independent claims. In particular, the apparatus is suitable for obtaining an indication of the microcirculatory state of a patient. The apparatus comprises at least one first sensor for measuring data indicative of a first carbon dioxide level, in particular a tissue carbon dioxide level, and at least one second sensor for measuring data indicative of a second carbon dioxide level, in particular an arterial blood carbon dioxide level.

[0018] The first sensor is preferably adapted for transcutaneous measurement at a first temperature, preferably kept below 38°C in the measurement area.

[0019] The second sensor is preferably adapted for transcutaneous measurement at a second temperature in the measurement area different from the first temperature. The second temperature is typically higher than the first temperature, for example higher than 38° C. Preferably, the second carbon dioxide level is measured by a heated transcutaneous sensor.

[0020] A control unit is provided for determining a measure of the microcirculatory condition based on the first carbon dioxide level, in particular a tissue carbon dioxide level, and the second carbon dioxide level, in particular a transcutaneous blood carbon dioxide level.

[0021] In particular, changes in tissue perfusion are sought for early detection of sepsis. The control unit has at least one input for receiving a measured or estimated first carbon dioxide level value, in particular a value corresponding to a tissue carbon dioxide level, at least one input for receiving a measured or estimated second carbon dioxide level value, in particular a value corresponding to an arterial blood carbon dioxide level, and at least one output interface for presenting an indication of the patient's microcirculatory status based on the received inputs.

[0022] In this application, "microcirculatory conditions" refers to the conditions of microcirculatory perfusion and gas diffusion.

[0023] A sensor that measures data indicative of arterial blood carbon dioxide level may be a sensor for an indicator of overall condition or systemic health.

[0024] The sensor that measures data indicative of tissue carbon dioxide levels may be a sensor that is indicative of a local condition found on the patient, for example a sensor that measures data indicative of skin carbon dioxide levels.

[0025] A sensor may detect one measured quantity or multiple measured quantities, either at once or sequentially. The measured data may correspond to one or more parameters, and / or a time series of the measured quantities.

[0026] Measures of microcirculation indicate the degree of vascularization, blood flow and tissue perfusion and thus the microcirculatory status.

[0027] In particular, the control unit is adapted to determine changes in tissue perfusion based on measurements of the two sensors.

[0028] The control unit is particularly adapted to determine measures of microcirculation in septic patients, where microcirculation is compromised due to reduced arterialization and reduced blood flow in the skin and other peripheral tissues.

[0029] The transcutaneously measured carbon dioxide levels correspond to arterial blood carbon dioxide levels when the skin is locally heated, resulting in sufficient arterialization to mitigate the effects on skin diffusion, even in the presence of sepsis, where oxygen and carbon dioxide diffusion through the skin is known to be affected by factors affecting the microcirculation.

[0030] It has been found that there is good correspondence between arterial blood carbon dioxide levels and heated transcutaneous carbon dioxide levels even when tissue perfusion is reduced, i.e., even in septic neonatal patients, carbon dioxide levels measured transcutaneously at elevated temperatures correspond to arterial blood carbon dioxide partial pressures in arterial blood samples.

[0031] In contrast, transcutaneous carbon dioxide measurements, with no or little application of heat to the skin, are sensitive to changes that directly affect skin diffusion, such as sepsis.

[0032] Without sufficient skin heating, transcutaneous carbon dioxide measurements estimate tissue carbon dioxide values ​​in the absence of arterialization. Thus, the combination of transcutaneous measurements, in which carbon dioxide is measured in both heated and unheated skin, allows for the measurement of cutaneous carbon dioxide diffusion and, in particular, the monitoring of its status.

[0033] The device detects a relationship between the first carbon dioxide level and the second carbon dioxide level and signals a change therein to indicate a change in microcirculatory condition, in particular using a difference measurement between a carbon dioxide level measured at a first temperature and a carbon dioxide level measured at a second temperature higher than the first temperature to detect the degree of microcirculatory deterioration caused by, for example, sepsis.

[0034] Independent measurements of heated transcutaneous and tissue carbon dioxide levels allow reliable detection of microcirculatory conditions.

[0035] Changes in the microcirculatory state may be a precursor of significant disturbances in blood flow, arterialization or tissue perfusion and therefore indicate possible subsequent problems depending on the time course of the changes. Thus, preferably the control unit is adapted for predicting measures of microcirculation, and preferably for predicting sepsis depending on the time trend of the measured changes.

[0036] The first sensor and / or the second sensor may include a chemical sensor, an optochemical sensor, an optical sensor, an electrical sensor, an electrochemical sensor, an optoelectric sensor, a pressure sensor, and / or a temperature sensor.

[0037] The first sensor and the second sensor may be formed by the same sensing unit that operates under different conditions, in particular that operates intermittently under different conditions.

[0038] In this case, the sensing unit may be used, for example, as a sensor to measure data indicative of tissue blood carbon dioxide level at a first temperature, and as a sensor to measure data indicative of arterial blood carbon dioxide level at a second temperature higher than the first temperature.

[0039] The sensing unit may be a temperature controlled sensing unit, particularly for transcutaneous gas measurements, that may be suitable for use in temperature cycling, so that data indicative of a first carbon dioxide level may be obtained during a first period of time and data indicative of a second carbon dioxide level may be obtained during a second period of time. In this manner, the temperature may be cycled alternately.

[0040] The sensing unit may also include a combined oxygen and carbon dioxide transcutaneous sensor. In an alternative embodiment of the device, the sensor measuring data indicative of tissue carbon dioxide level is a first sensing unit and the sensor measuring data indicative of arterial blood carbon dioxide level is a second sensing unit different from the first sensing unit. The first sensing unit and / or the second sensing unit may be temperature controlled. The degree or nature of heating may be different for the two sensing units.

[0041] The first sensing unit and / or the second sensing unit may include a heating element. Two or more separate sensing units allow different data to be measured at the same time. Simultaneous or at least timed measured data allows for a reasonable comparison of the data.

[0042] In that case, the two or more sensing units are preferably spaced at a distance of at least 1 cm between each other to reduce interference with simultaneous measurements.

[0043] There are several alternative methods for determining arterial and tissue carbon dioxide levels.

[0044] The first and / or second sensor may be adapted to analyze a blood sample. The blood sample may be taken from a patient. The sample may be taken from an artery or a capillary. In the second sensor, the blood may also be Arterial catheter Alternatively, continuous intra-arterial or intravascular measurements may be taken.

[0045] Blood samples may also be taken to calibrate the transcutaneous measurements, as described below. The first sensing unit may include a microneedle together with the first sensor element. The microneedle may be applied to the tissue, preferably at a distance of 0.2 to 1 mm from the skin surface. The microneedle may reach the arteriole and / or capillary loops so that carbon dioxide reaches the needle tip.

[0046] The microneedles can be heated or non-heated. The body area surrounding the measurement site is either heated or not heated.

[0047] The microneedles may include optical fibers and / or may use fluoroscopy. The microneedle may include an optical fiber, a chemical sensor, or an electrochemical probe to measure the carbon dioxide concentration in the liquid.

[0048] The first sensing unit may also be adapted to use spectroscopy for assessment of tissue carbon dioxide levels. Spectroscopy may be performed in tissue and therefore as an invasive procedure.

[0049] Thus, in a preferred embodiment, the second sensor comprises a sensor adapted for transcutaneous measurement, in particular for heated transcutaneous measurement, of carbon dioxide levels.

[0050] In the context of this application, a "heated" measurement means that the measurement area is heated to a temperature above normal body temperature, for example above 38° C. During a "heated" measurement, the measurement area is specifically heated to a temperature that achieves skin arterialization to such an extent as to allow gas diffusion with carbon dioxide levels measurably close to blood levels.

[0051] Preferably, the sensing unit includes a heating element. The second sensing unit may include a pH electrode, a reference electrode, an electrolyte solution and a membrane. Preferably, the second sensing unit may include a heating element.

[0052] In a preferred embodiment, the first sensor measures the tissue (or transcutaneous) carbon dioxide partial pressure, PcCO 2 The sensor includes a sensor adapted for transcutaneous measurement of

[0053] Preferably, the device comprises a transcutaneous sensor adapted for non-heated or low-heated transcutaneous measurement of dioxide levels, for measuring data indicative of tissue carbon dioxide levels.

[0054] For "non-heated" measurements, the measurement area may be heated in the same way, but not to a temperature which would achieve arterialization of the skin; in particular, the measurement area may be heated up to 38°C.

[0055] The first sensing unit may include a pH electrode, a reference electrode, an electrolyte solution, and a membrane. Optionally, the first sensing unit may include a heating element. Stabilizing the temperature of the skin generally allows for reproducible data.

[0056] The difference between the skin carbon dioxide level measured by the non-heated transcutaneous sensor and the skin carbon dioxide level measured by the heated sensor (as an index of arterial blood carbon dioxide level) provides information about carbon dioxide diffusion in the skin, which is in turn a measure of the microcirculatory state. Sepsis deteriorates the microcirculatory state and can therefore be detected by the present invention as early as possible than with current methods.

[0057] In particular, the device may comprise a sensing unit for use as a heated transcutaneous sensor and as a non-heated or low-heated transcutaneous sensor.

[0058] Thus, the same sensor unit can be used to measure data indicative of tissue carbon dioxide levels without heating or with limited heating, and to measure data indicative of arterial blood carbon dioxide levels when heated.

[0059] Preferably, in addition to the first and second sensors, the device comprises at least one further sensor for measuring data indicative of further parameters for determining the patient's condition, such as blood temperature, oxygen level, pH value and / or another blood parameter, in particular for correction and / or calibration of transcutaneous blood carbon dioxide level and / or tissue carbon dioxide level.

[0060] The additional sensor may be adapted to measure data indicative of arterial blood oxygen level and / or tissue oxygen level. The additional sensor indicative of oxygen level may include a transcutaneous electrochemical sensor, a chemical-optical sensor, an optical sensor, or an invasive sensor including a needle.

[0061] The additional sensor may be adapted to measure temperature, preferably the temperature of the skin. The additional sensor may also be adapted to measure fetal hemoglobin when the device is used in neonates.

[0062] The additional sensor may be adapted to measure heart rate and / or heart rate variability. The additional sensor may be adapted to measure pulse and / or pulse variability.

[0063] The additional sensors may be adapted to measure electrical activity, such as ECG values, and / or muscle movement and / or blood flow and / or respiratory gas flow.

[0064] The apparatus may include a heating element. The first sensor and / or the second sensor and / or, if applicable, the additional sensors may be adapted for continuous and / or intermittent and / or alternating measurements.

[0065] Continuous measurements allow for analysis of parameters over time. For parameters known to vary slowly or not involving rapid changes, continuous measurements may mean that data is collected at predetermined time intervals, such as every few seconds or minutes.

[0066] In a preferred embodiment, the second sensor and the first sensor are adapted for alternating measurements, preferably with a time lag that ensures a stable presence or absence of arterialization, for example a time lag of at least 10 minutes, in order to ensure undisturbed measurements, especially when measurements are performed alternately at different temperatures.

[0067] In another embodiment of the device, the first sensor and / or the second sensor and / or the additional sensor, if applicable, are accommodated within a common housing.

[0068] The device may include a sensor housing that may be placed on or within the patient, in particular on the skin. The sensor housing may house the first sensor, the second sensor, and, if applicable, the additional sensor. By positioning the sensor housing, all sensors may be properly positioned with respect to the patient, in particular all sensors may face the skin.

[0069] The sensors may be designed as composite sensors that use and / or share the same sensor element, such as a temperature sensor, and / or that use and / or share the same heating element.

[0070] Beneficially, the first sensor and the second sensor are adapted to be placed anywhere on the skin or other peripheral tissue, e.g., on a portion of the skin, in particular on the upper or lower limbs, earlobes, fingertips, palms, feet and / or chest.

[0071] Advantageously, the control unit is capable of providing a first carbon dioxide level measurement at a first temperature and a second carbon dioxide level measurement in which the measurement area is heated to a second temperature higher than the first temperature, in particular above 38°C.

[0072] Preferably, the control unit detects tissue PcCO 2 It is possible to provide a transcutaneous measurement of

[0073] Preferably, the control unit detects the arterial blood PaCO by the second sensor. 2 It is possible to provide a transcutaneous measurement of

[0074] Preferably, the control unit is capable of controlling the first sensor, the second sensor and at least one heating element that keeps the measurement side of the skin at a particular temperature.

[0075] Preferably, the control unit includes an output for controlling the heating element, the first sensor and / or the second sensor.

[0076] Advantageously, the control unit determines the arterial blood carbon dioxide partial pressure PaCO2, preferably based on the transcutaneous carbon dioxide partial pressure obtained by measurement with the second sensor. 2 and the measurement area is heated to above 38° C. or to a temperature which causes arterialization of the measurement area.

[0077] Advantageously, the control unit determines the tissue carbon dioxide partial pressure PcCO2, preferably based on the transcutaneous carbon dioxide partial pressure obtained by measurement by the first sensor. 2 The method is adapted for the evaluation of the blood flow rate and the measurement area is kept at a certain temperature, for example below 38° C., so that arterialization is not achieved in the measurement area.

[0078] In a preferred embodiment of the device, the control unit is adapted to determine a difference between the first carbon dioxide level and the second carbon dioxide level, in particular the difference between the tissue carbon dioxide level and the arterial blood carbon dioxide level, a ratio between the first carbon dioxide level and the second carbon dioxide level, in particular the ratio between the tissue carbon dioxide level and the arterial blood carbon dioxide level, and / or an index based on the first carbon dioxide level and the second carbon dioxide level, e.g. based on the tissue carbon dioxide level and the arterial blood carbon dioxide level, preferably the tissue carbon dioxide level and / or the arterial blood carbon dioxide level are measured transcutaneously.

[0079] The index may be calculated based on the first and second carbon dioxide levels, such as tissue and transcutaneous carbon dioxide levels, and optionally further measured or predetermined parameters.

[0080] The control unit may also be adapted to monitor, and in particular display, the first carbon dioxide level and the second carbon dioxide level, such as tissue carbon dioxide level, transcutaneous carbon dioxide level, difference, ratio and / or index, over time and to determine changes over time.

[0081] In particular, the control unit is adapted to receive, collect, store and process in particular time-dependent data.

[0082] In particular, the control unit is adapted to determine changes in tissue perfusion on a predetermined and / or selectable timescale.

[0083] Furthermore, the control unit may be adapted for extrapolation of time-dependent data and / or for prediction of, for example, tissue perfusion status.

[0084] The control unit may be adapted to average and / or filter the measured and / or determined values ​​and / or to determine a running average over a predetermined time interval.

[0085] The control unit may be adapted to compare the first and second carbon dioxide levels, differences, ratios, indices and / or estimates, such as tissue and transcutaneous carbon dioxide levels, with respective nominal values.

[0086] The control unit may be adapted to receive data by means of an input device, such as a control panel, console or data carrier reader.

[0087] In particular, the control unit may be adapted to receive, store and process algorithms, correction parameters, nominal values ​​and trigger values.

[0088] The correction parameters may be used to process the measured and / or derived data in accordance with rules, for example, drug, vascular tone factors, and chemical drift of the sensor may be taken into account when analyzing the measured data.

[0089] The control unit may be adapted to indicate a sensor disturbance, a need for maintenance, or a need for a new sensor calibration.

[0090] If the difference between the measured and / or determined value and the respective nominal value exceeds a predefined trigger value, the control unit may generate a respective output information.

[0091] The control unit may analyze the time course of tissue carbon dioxide levels, transcutaneous carbon dioxide levels, differences, ratios, indices and / or estimates and may detect clinical or potential clinical conditions in the microcirculatory conditions.

[0092] The control unit may provide a warning signal if a clinical condition is present or may be expected in the microcirculation.

[0093] The device may provide a result based on a current measured and / or determined value. The device may provide a result based on a time evolution of the measured and / or determined values.

[0094] The control unit may be adapted to determine the difference, ratio and / or index based on the measured data during the time interval. Preferably, the control unit may be adapted for continuous measurements based on stored data of a running time interval. To this end, the apparatus may include a storage device for storing the measurement data and / or the reference data.

[0095] Thus, the device allows for retrospective analysis of the data. The changes due to sepsis are caused by a slow process. Therefore, the desired results take some time, typically minutes to hours. However, the device can provide an indication of the microcirculatory status, and therefore of sepsis, potentially earlier than clinical symptoms indicate clinical signs of sepsis.

[0096] In a preferred embodiment of the apparatus, the control unit is preferably connected or connectable to an output device such as a monitor or display for displaying measures of microcirculation and / or for displaying signals generated by the control unit.

[0097] The output device may be part of the appliance. The output device may be adapted to emit an acoustic signal and / or an optical signal.

[0098] The output device may be adapted to display the measured and / or determined values ​​and / or time-dependent representations of the measured and / or determined values.

[0099] The output device may be adapted to indicate a measure of microcirculation. For example, the output device may comprise a display designed to include a three-level scale, with a first level indicating "no problem", a second level indicating "potential problem", and a third level indicating "Caution: problem".

[0100] The output device may be adapted to display a measure of the quality of the measured and / or determined values, such as an estimated measurement error or a standard deviation of the mean.

[0101] The output device may be adapted to display a measure of the quantity of the microcirculation measure, such as a reliability index, which may be based on the amount of data used. The more data used, the more reliable the results. Such a reliability index may be derived from the deviation of the measurement data over a period of time, i.e., if the deviation is relatively low over a sustained period of time, the reliability index will be high.

[0102] The values ​​measured by the described sensors can be displayed by an output device, thus providing the user with additional information and the ability to control the amount of microcirculation measurement.

[0103] The device can be a stand-alone device that is placed at the patient's bedside, or it can be a hook-up element for an existing system.

[0104] The apparatus may be formed in part by components of an existing system, for example sharing sensors or output devices with the existing system.

[0105] The present invention also provides a device for obtaining an indication of the microcirculatory status of a patient, preferably as described above, comprising at least one first sensor for measuring data indicative of a first carbon dioxide level, in particular a tissue carbon dioxide level.

[0106] The device further comprises at least one second sensor for measuring data indicative of a second carbon dioxide level, in particular an arterial blood carbon dioxide level.

[0107] The apparatus further comprises a control unit for determining a measure of microcirculation, in particular a change in tissue perfusion, preferably in a septic patient, based on a first carbon dioxide level, in particular a tissue carbon dioxide level, and a second carbon dioxide level, in particular an arterial blood carbon dioxide level.

[0108] The control unit has at least one input for receiving a measured or estimated first carbon dioxide level value, in particular a tissue carbon dioxide level value, and at least one input for receiving a measured or estimated second oxygen level value, in particular an arterial blood carbon dioxide level value.

[0109] The control unit has at least one output interface that outputs an indication of the patient's microcirculatory status based on the input received.

[0110] For the sensor, as explained above, there are several possible embodiments, as for each sensing unit.

[0111] The first sensor preferably measures tissue carbon dioxide partial pressure, PcCO 2 The sensor may include a sensor for transcutaneous measurement adapted to transcutaneously measure a first temperature, more preferably less than 38°C.

[0112] The second sensor preferably measures arterial blood PaCO 2The second sensor is preferably adapted for transcutaneous measurement at a second temperature higher than the first temperature, where the measurement area is preferably heated to above 38° C. In particular, the sensor may be adapted for heated transcutaneous measurement.

[0113] The object of the present invention is also achieved by a method for obtaining an index of tissue perfusion, comprising the following steps:

[0114] A first carbon dioxide level, in particular a tissue carbon dioxide level, of the patient is provided, preferably a transcutaneously measured tissue PcCO 2 A value is provided.

[0115] A second carbon dioxide level, in particular an arterial blood carbon dioxide level, of the patient is provided, preferably a transcutaneously measured arterial blood carbon dioxide value tcPCO 2 A value is provided.

[0116] Preferably, the first carbon dioxide level and the second carbon dioxide level, such as a tissue carbon dioxide level and an arterial blood carbon dioxide level, are provided by independent measurements.

[0117] A measure for microcirculation is determined, preferably in a septic patient, based on a first carbon dioxide level and a second carbon dioxide level, such as a tissue carbon dioxide level and an arterial blood carbon dioxide level.

[0118] Preferably, measures of microcirculation are displayed in real time. The first and second carbon dioxide levels may be provided by data collection or, preferably, may be measured by transcutaneous measurement. Other measurement principles may also be used, as explained above.

[0119] Preferably, a first carbon dioxide level is measured at a first temperature and a second carbon dioxide level is measured by heating the measurement area to a second temperature higher than the first temperature, preferably above 38°C.

[0120] Preferably, the second carbon dioxide level, in particular the arterial blood carbon dioxide level, is arterial PaCO 2 is measured by transcutaneously measuring the temperature of the skin, the measurement area being heated to a temperature above 38°C, preferably above 40°C, preferably by a heating element of the detection unit and / or located in the sensor head, such that arterialization of the skin is achieved.

[0121] Preferably, the first carbon dioxide level, in particular the tissue carbon dioxide level, is determined by measuring the tissue PcCO 2 The temperature of the skin is measured by measuring the temperature of the skin percutaneously. Preferably, the measurement area is kept at the patient's body temperature, e.g., below 38° C. and / or 37.5° C. The measurement area is kept at a temperature that does not cause arterialization of the skin. When heat is applied, metabolic activity changes and arterialization begins.

[0122] The measurements can be performed simultaneously or, preferably, alternated with a time lag that ensures the steady presence or absence of arterialization, for example a time lag of at least 10 minutes.

[0123] The object of the present invention is also achieved by a computer program product, directly loadable into a digital internal memory, comprising software code portions which, when said product is executed on a computer, perform the steps of the method for obtaining an index of tissue perfusion as described above.

[0124] The computer program can be loaded into and / or executed on a control unit of an apparatus as described above.

[0125] The computer program may be loaded into and / or executed on a central computer device, or alternatively may be loaded into and / or executed on a measurement device which measures the patient's arterial blood carbon dioxide level and / or tissue carbon dioxide level.

[0126] The invention will now be further described with reference to preferred embodiments and the accompanying drawings. [Brief description of the drawings]

[0127] [Figure 1] FIG. 1 is a schematic diagram of a first example of an apparatus. [Diagram 2] FIG. 2 is a schematic diagram of a second example of the device. [Diagram 3] FIG. 11 is a schematic diagram of a sensor head of a third example of the device. [Figure 4] FIG. 4 is a schematic cross-sectional view of the sensor head of FIG. [Diagram 5] FIG. 13 is a schematic diagram of a fourth example of the device. [Figure 6] FIG. 11 is a schematic cross-sectional view of a sensor head of a fourth example of the apparatus. [Figure 7] FIG. 2 is a schematic diagram of an example of the microcirculatory conditions as measured by the device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0128] 1 shows a schematic diagram of a first example of an apparatus 1 for obtaining an indication of the microcirculatory status of a patient. The apparatus 1 comprises a first sensor 13 for measuring data indicative of tissue carbon dioxide levels and a second sensor 12 for transcutaneously measuring data indicative of arterial blood carbon dioxide levels.

[0129] The second sensor 12 is formed by a second sensing unit, and the first sensor 13 is formed by a first sensing unit different from the second sensing unit.

[0130] The second sensor 12 and the first sensor 13 are arranged in a common housing 6 forming a sensor head 8 .

[0131] The device 1 comprises a control unit 4 which determines a measure of microcirculation, in particular a change in tissue perfusion or a change in microcirculatory state, based on the values ​​measured by the first sensor 13 and the second sensor 12, in particular based on the tissue carbon dioxide level and the heated and transcutaneously measured carbon dioxide level.

[0132] The device 1 comprises an additional sensor 5 which measures data indicative of further parameters, such as blood temperature, oxygen level, pH value and / or another blood parameter, in particular for correcting the arterial blood carbon dioxide level and / or the tissue carbon dioxide level.

[0133] The sensor head 8 may be connected to an instrument base 9 by a cable 10. The control unit 4 may be located within the instrument base 9.

[0134] The control unit 4 is connected to an output device 7, such as a monitor or display for displaying measures of microcirculation. The output device 7 may also be located within the device base 9.

[0135] The sensor head 8 comprises a contact surface 11 which is orientable towards a measuring side, in this case an area on the patient's skin.

[0136] FIG. 2 shows a schematic diagram of a second example device 1' for obtaining an indication of the microcirculatory status of a patient. The device 1' comprises a sensor head 8 with a single sensing unit 14 including a first sensor 13 and a second sensor 12, respectively. Depending on the temperature, the sensing unit 14 is controlled to transcutaneously measure data indicative of the arterial blood carbon dioxide level or indicative of the tissue carbon dioxide level. The skin temperature is regulated by a heating element 15 controlled by the control unit 4. Thus, the sensing unit 14 serves as a sensor for measuring data indicative of the arterial blood carbon dioxide level at a first temperature and as a sensor for measuring data indicative of the tissue carbon dioxide level at a second temperature.

[0137] The device 1 shown in Figures 3 and 4 has a surface 30 on which, in the embodiment shown, is placed a membrane 50 with a thin layer of electrolyte 51 in between. The membrane 50 is placed on the skin at a location on the human body that has good blood flow, for example the skin on the finger, forehead or earlobe (see Figure 4).

[0138] The illustrated device 1 comprises a sensor unit 19 adapted for transcutaneous measurement of first and second tissue carbon dioxide levels by electrochemical detection. To this end, the device 1 preferably comprises a micro pH electrode 24 and an Ag / AgCl reference electrode 25 (see FIG. 3). The carbon dioxide level can be measured potentiometrically in that the pH of a thin layer of electrolyte solution 51 is measured, which communicates with the skin via a hydrophobic membrane 50 with good gas permeability. A change in the carbon dioxide value at the skin surface causes a pH change in the electrolyte solution. The pH is measured in that the potential is measured between the miniature pH electrode 24 and the reference electrode 25. The micro pH electrode 24 is conductively connected to the control unit 4 via an electrical internal deflector 16.

[0139] The device 1 comprises a heating element 26 and a temperature sensor 27 . The sensor unit 19 is adapted for transcutaneous measurements at a first temperature, where the measurement area is kept below 38°C.

[0140] The sensor unit 19 is also adapted for transcutaneous measurements at a second temperature higher than the first temperature, where the measurement area is heated by the heating element 26 to above 38°C.

[0141] The sensor unit 19 is thus a first sensor that measures data indicative of a first carbon dioxide level, in particular a tissue carbon dioxide level, and a second sensor that measures data indicative of a second carbon dioxide level, in particular an arterial blood carbon dioxide level.

[0142] FIG. 5 shows a schematic diagram of a fourth example of a device 1 for obtaining an indication of the microcirculatory status of a patient. The first sensing unit 13 , the second sensing unit 12 , the additional sensor 5 , the housing of the processor or control unit 4 and the output device 7 may be arranged within a common housing 6 .

[0143] Preferably, the housing allows for the combination, integration and proper separation of the components.

[0144] The first sensing unit 13 may be a first transdermal measurement device. The second sensing unit 12 may be a second transdermal measurement device and may include a heating element.

[0145] Additional sensors 5 include temperature, transcutaneous CO 2 may be detected and / or may include input for external values.

[0146] The output device 7 may include a display that shows digital or analog output. FIG. 6 shows a schematic cross-sectional view of a sensor head 8 for obtaining an indication of the microcirculatory condition of a patient in a fourth example of the device 1.

[0147] The sensor head 8 is placed in contact with the skin 103 of the patient. A first sensing unit 13 for measuring data indicative of tissue carbon dioxide level, an additional sensor 5, a second sensing unit 12 for measuring data indicative of arterial blood carbon dioxide level, and a heating element 15 are arranged in a common housing 6. The sensing unit 13 is adapted for transcutaneous carbon dioxide measurement at a first temperature, where the measurement area is kept below 38° C. The sensing unit 12 is adapted for transcutaneous carbon dioxide measurement at a second temperature higher than the first temperature, where the measurement area is heated above 38° C. A processor or control unit 4 and an output device 7 (see FIG. 4), not shown in this figure, may be arranged in the housing 6 as well. The processor 4 is programmed to detect changes in skin perfusion and has an input for receiving a first measured or estimated carbon dioxide level value, in particular a tissue carbon dioxide level value, from the first sensor 13, an input for receiving a second measured or estimated carbon dioxide level value, in particular an arterial blood carbon dioxide level value, from the second sensor 12, and at least one output interface for presenting an indication of the microcirculatory state of the patient based on the received inputs.

[0148] The sensor head 8 is connected to an output connection 20, which may establish a connection with an external processor or controller and may act as a power source.

[0149] The skin 103 is permeated with arteries 101 and capillaries 102 . FIG. 7 shows a schematic diagram of an example of the microcirculatory conditions measured by the first sensor 13 and the second sensor 12 under septic and normal conditions.

[0150] The blood supply in the cutaneous artery 101 remains intact during sepsis. However, the blood supply in the capillaries 102 may be compromised in a septic state, and therefore a significantly different amount of carbon dioxide diffuses from the skin surface, which can be detected by transcutaneous measurements without heating the skin.

[0151] Surprisingly, skin heating, even in the presence of sepsis, results in sufficient arterialization to reduce the effects on skin diffusion, and thus the transcutaneously measured carbon dioxide levels correlate with arterial blood carbon dioxide levels.

[0152] The sepsis status indicator may for example be output by the processor by outputting a difference between the first carbon dioxide level and the second carbon dioxide level, e.g. the difference between the tissue carbon dioxide level and the arterial carbon dioxide oxygen level, a ratio between the first carbon dioxide level and the second carbon dioxide level, e.g. the ratio between the tissue carbon dioxide level and the arterial carbon dioxide level, and / or an index based on the first carbon dioxide level and the second carbon dioxide level, e.g. based on the tissue carbon dioxide level and the arterial carbon dioxide level, preferably for predicting sepsis.

Claims

1. 1. An apparatus for obtaining an indication of the microcirculatory status of a patient, comprising: A heating element; at least one first sensor (13) for measuring data indicative of a first carbon dioxide level, the at least one first sensor (13) including a first measurement area for contacting tissue of the patient, the first measurement area being adapted for transcutaneous carbon dioxide measurement at a first temperature less than 38°C; at least one second sensor (12) for measuring data indicative of a second carbon dioxide level, the at least one second sensor (12) including a second measurement area for contacting tissue of the patient, the second measurement area being heated by the heating element, the second measurement area being adapted for transcutaneous carbon dioxide measurement at a second temperature higher than the first temperature, the second measurement area being greater than 38° C.; A control unit (4) for detecting changes in skin perfusion, at least one input for receiving a first measured or estimated carbon dioxide level value from said first sensor (13); and at least one input for receiving a second measured or estimated carbon dioxide level value from the second sensor (12); a control unit (4) adapted to determine the indicator of the patient's microcirculatory status based on a difference between the first carbon dioxide level and the second carbon dioxide level, a ratio between the first carbon dioxide level and the second carbon dioxide level, and / or an index based on the first carbon dioxide level and the second carbon dioxide level; at least one output interface that outputs said indicator of the patient's microcirculatory status based on the input received; and an output device adapted to display a confidence index, the confidence index being derived from a deviation of measurement data over a period of time based on an amount of data used, the confidence index being high if the deviation is relatively low over a duration period.

2. The device described in claim 1, wherein the first sensor (13) and the second sensor (12) are formed by the same detection unit that operates under various conditions.

3. 2. The apparatus of claim 1, wherein the first sensor (13) is a first sensing unit (13) and the second sensor (12) is a second sensing unit (12) different from the first sensing unit (13).

4. The device (1, 1') according to any one of claims 1 to 3, comprising at least one additional sensor (5) adapted to measure a second carbon dioxide level and / or data indicative of a temperature, an oxygen level or a pH value of blood in order to correct the first carbon dioxide level.

5. The device according to any one of claims 1 to 4, wherein the sensors (12, 13, 5) are adapted for continuous and / or intermittent and / or alternating measurements.

6. The device according to any one of the preceding claims, wherein the first sensor (13) and the second sensor (12) are arranged in a common housing (6).

7. The device according to any one of claims 1 to 6, wherein the first sensor (13) and the second sensor (12) are adapted to be placed on an earlobe, a fingertip, a palm, a foot and / or a chest.

8. the control unit (4) is adapted to provide the first carbon dioxide level measurement at the first temperature and to provide the second carbon dioxide level measurement where the second measurement area is heated to the second temperature, the second temperature being higher than the first temperature; the control unit is adapted to control at least one heating element that maintains the measurement side of the skin at a specific temperature; An apparatus according to any one of the preceding claims, wherein the control unit comprises an output for controlling the heating element, the first sensor and / or the second sensor.

9. The control unit (4) is configured to measure the transcutaneous carbon dioxide partial pressure (tcPCO) obtained by the measurement using the second sensor (12). ２ Arterial blood carbon dioxide partial pressure PaCO ２ 9. The device according to claim 1 , wherein the second measurement area is heated to a temperature above 38° C. and / or to a temperature which achieves arterialization.

10. The control unit (4) is configured to detect the transcutaneous carbon dioxide partial pressure (tcPCO) obtained by measuring the transcutaneous carbon dioxide partial pressure (tcPCO) by the first sensor (13). ２ Tissue carbon dioxide partial pressure PcCO ２ An apparatus according to any one of claims 1 to 9, adapted for the evaluation of:

11. The control unit The difference between tissue carbon dioxide level and arterial blood carbon dioxide level, the ratio of tissue carbon dioxide level to arterial carbon dioxide level; and / or An index based on tissue and arterial carbon dioxide levels The apparatus according to any one of claims 1 to 10, adapted to determine said indicator of the microcirculatory status of a patient based on:

12. Apparatus according to any one of the preceding claims, wherein the output interface of the control unit (4) is connected or connectable to an output device such as a monitor or display.

13. 1. A method for obtaining an index of tissue perfusion by a computer, comprising: providing a first carbon dioxide level from a first sensor; providing a second carbon dioxide level from a second sensor; determining a measure for microcirculation based on the first carbon dioxide level and the second carbon dioxide level by determining the index of the patient's microcirculatory status based on a difference between the first carbon dioxide level and the second carbon dioxide level, a ratio between the first carbon dioxide level and the second carbon dioxide level, and / or an index based on the first carbon dioxide level and the second carbon dioxide level; displaying said indicator of the patient's microcirculatory status based on the input received and displaying a confidence index, said confidence index being based on the amount of data used and derived from the deviation of the measurement data over a period of time, said confidence index being high if said deviation is relatively low over a sustained period of time; A method comprising:

14. measuring the first carbon dioxide level at a first temperature; measuring said second carbon dioxide level while a measurement area is heated to a second temperature, said second temperature being higher than said first temperature; The method of claim 13, comprising:

15. The method of claim 13 or 14, wherein data indicative of oxygen level, pH level and / or temperature is provided.

16. A computer program product directly loadable into an internal digital memory comprising software code portions which, when said product is executed on a computer, performs the steps of the method according to any one of claims 13 to 15.

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