Search

EP-4742252-A1 - A METHOD FOR COMPENSATING THE EFFECTS OF TIME DELAY FROM SAMPLING TO MEASUREMENT IN A BLOOD SAMPLE

EP4742252A1EP 4742252 A1EP4742252 A1EP 4742252A1EP-4742252-A1

Abstract

The invention relates to a method for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample from a subject, such as a human patient. A mathematical model is simulating time development in the blood sample, the mathematical model having 1) a first sub-model describing red blood cell metabolism, and 2) a second sub-model describing the effect of the red blood cell metabolism on the whole blood acid-base chemistry. The mathematical model calculates from a time of measurement (Tm) to the time of sampling (Ts) a modified set of blood variables to compensate for a time delay (TD), e.g. by calculating backwards in time 0.5-3 hours. The invention can simulate the biochemical processes occurring in blood, and demonstrates the ability to simulate changes in measured blood variables over time. This may simplify transport and/or storage constraints of blood samples, and improve quality and accuracy of blood gas measurements.

Inventors

  • REES, STEPHEN EDWARD
  • THOMSEN, Lars Pilegaard
  • Nevirian, Bahareh
  • Fagerberg, Steen Kåre

Assignees

  • Aalborg Universitet

Dates

Publication Date
20260513
Application Date
20241111

Claims (16)

  1. A computer-implemented method for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample from a subject, the method comprising: - providing a blood sample with a known or estimated time of sampling (Ts), - performing a blood gas measurement of said blood sample at a later time of measurement (Tm) resulting in a set of blood variables (BV'[Tm]) indicative of acid-base, oxygenation and/or electrolyte status in said blood sample, - providing a mathematical model based on a plurality of physiological sub-models simulating time development in blood, the mathematical model comprising: o a first sub-model describing red blood cell metabolism, and o a second sub-model describing the effect of said red blood cell metabolism on the whole blood acid-base chemistry, and - applying said mathematical model to calculate from the time of measurement (Tm) to the time of sampling (Ts) a modified set of blood variables (BV[Ts]) indicative of the corresponding acid-base, oxygenation and/or electrolyte status of said blood sample so as to at least partly compensate for said time delay (TD) between sampling and actual measurement.
  2. The computer-implemented method according to any of the preceding claims, wherein the first sub-model describes red blood cell metabolism as a rate of strong acid production in whole blood (ΔAcid), preferably with a rate of change of lactate concentration (ΔLA) in whole blood being substantially equal to the acid production.
  3. The computer-implemented method according to claim 2, wherein the first sub-model describing red blood cell metabolism further assumes that glucose diffuses passively between plasma and RBCs so that concentrations can be assumed to be substantially equal in the plasma and the erythrocyte fractions of blood.
  4. The computer-implemented method according to any of the preceding claims, wherein the second sub-model describing the effect of said red blood cell metabolism on the whole blood acid-base chemistry comprises one, or more, of the following elements: - the plasma and red blood cell buffering including - mass conservation equations, - mass action/reaction equations, and - physiochemical properties, - an empirical or biochemical relationship for the link between plasma and erythrocyte pH and/or, - a description of plasma and erythrocyte fractions from haemoglobin concentration.
  5. The computer-implemented method according to any of the preceding claims, wherein the second sub-model describing the effect of said red blood cell metabolism on the whole blood acid-base chemistry comprises incorporating the effect of acid addition to whole blood by modifying the total buffer base concentration (BB), or strong ion difference (SID), and reducing this according to the acid addition (ΔAcid) at a point in time so as to calculate one, or more, values of oxygenation and acid-base status according to, or substantially according, to the equation: pH p , PCO 2 , p , PO 2 , p , SO 2 , p = acid base model BB − Δ Acid , tCO 2 , tO 2 , tHb , Atot , wherein the acid base model refers to a biochemical mathematical model of the acid-base chemistry of blood.
  6. The computer-implemented method according to any of the preceding claims, wherein the mathematical model comprises one, or more, model parameter(s) chosen from the group consisting of: - the total non-bicarbonate buffer, Atot, - the red blood cell (RBC) acid production (ΔAcid), - a parameter describing the degree to which Cl - reduction occurs in the blood sample (CLmp), and - a water distribution fraction., preferably said one, or more, model parameter(s) being substantially unchanged from one subject to another.
  7. The computer-implemented method according to any of the preceding claims, wherein the mathematical model takes into account a dependency on temperature of the sample during the time delay (TD), preferably a known or an estimated variable temperature profile during the time delay.
  8. The computer-implemented method according to any of the preceding claims, wherein the mathematical model further comprises a sub-model describing electrolyte distribution between plasma and erythrocyte fractions.
  9. The computer-implemented method according to any of the preceding claims, wherein the mathematical model further comprises a sub-model describing gas diffusion across plastic syringes with blood sample.
  10. The computer-implemented method according to any of the preceding claims, wherein said time delay (TD) from sampling to actual measurement is larger than 20 min., 30 min., 40 min., 50 min., 60 min., 70 min., 80 min., 90 min., 100 min., 110 min., 120 min, 150 min., or 180 min.
  11. The computer-implemented method according to any of the preceding claims, wherein the set of blood variables (BV) are chosen from the group consisting of: pH, PCO 2 , PO 2 , SO 2 , Hb, FMetHb, COHb, glucose, lactate, Na + , Cl - , Ca 2+ , and/or K + .
  12. The computer-implemented method according to any of the preceding claims, wherein the mathematical model calculates backwards in time blood variables (BV'[Tm]) in the measured blood to blood variables (BV[Ts]) in the sampled blood.
  13. The computer-implemented method according to any of the preceding claims, wherein the mathematical model calculates forwards in time from blood variables (BV[Ts]) in the sampled blood to blood variables (BV'[Tm]) in the measured blood.
  14. A computer-implemented system for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample from an associated subject, the system being arranged for: - receiving a blood sample with a known or estimated time of sampling (Ts), - performing a blood gas measurement of said blood sample at a later time of measurement (Tm) resulting in a set of blood variables (BV'[Tm]) indicative of acid-base, oxygenation and/or electrolyte status in said blood sample, - operating a mathematical model based on a plurality of physiological sub-models simulating time development in blood, the mathematical model comprising: o a first sub-model describing red blood cell metabolism, and o a second sub-model describing the effect of said red blood cell metabolism on the whole blood acid-base chemistry, and - applying said mathematical model to calculate from the time of measurement (Tm) to the time of sampling (Ts) a modified set of blood variables (BV[Ts]) indicative of the corresponding acid-base, oxygenation and/or electrolyte status of said blood sample so as to at least partly compensate for said time delay (TD) between sampling and actual measurement.
  15. A computer program product being adapted to enable a computer system comprising at least one computer having data storage means in connection therewith to control a system according to claim 14, such as a computer program product comprising instructions which, when the program is executed by a computer, cause the computer to carry out the steps of the method of claim 1.
  16. The use of the method and/or the system according to any of claims 1-15 for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample from a subject.

Description

FIELD OF THE INVENTION The present invention relates to a computer-implemented method for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample. The invention also relates to a corresponding system for measurement of blood, a corresponding computer programme product, and corresponding use of the method and/or the system. BACKGROUND OF THE INVENTION Measurements of blood acid-base status are usually performed quickly after blood sampling to avoid errors and to minimize physiological changes before sampling. This necessitate rapid transport of samples and therefore may be problematic in situations where the patient is far from the analyser, either because the patient is far from a clinic having appropriate blood measurement facilities - or because transportation and/or working procedures in a large hospital makes it difficult to transport the sample from the patient to the point of blood measurement in the hospital quickly enough. Thus, it is generally accepted in this field that measurements of acid-base, oxygenation, and electrolyte status of blood should be performed quickly after sampling, and typically with a maximum delay between 25 to 40 minutes. This may present clinical problems if blood gas analysis devices are remote from sampling site such as in pre-hospital or telemedical settings, ambulance transport or where delays in processing are inherent, such as taking of samples from multiple patients on a ward round. Most studies emphasize the unsuitability of results obtained from blood samples analyzed after the allowable storage time, and postulate mechanisms of change of individual variables. US 6,859,738 to Becton, Dickinson and Company suggests a solution to the delay problem with e.g. blood measurements. Thus, a method is provided for estimating the initial level of an analyte in a blood sample based on an actual level observed, a time of storage of the blood sample, a storage temperature, and a type of container in which said blood sample is stored. Equations are presented for a particular analyte based on observations of actual analyte levels initially after a blood sample is drawn, as well as at various times thereafter. The time of storage, the temperature of storage, and the type of container are observed along with actual analyte level in each observation. These equations are considered useful if the estimated initial values are more accurate than the actual observed final values. The equations thereby represent the time development of blood parameters, which is made based on collected data, cf. Figs. 2 & 5 for some examples. However, these equations are based on purely statistical tests and models, such as a polynomial regression model with the square of the time and the square of the storage temperature. For systems where variables are tightly related by physiochemical processes, modelling using statistical approaches may not be appropriate or even adequate. Blood oxygen, acid-base and electrolytes are such a system, where values are tightly coupled and changes over time require consideration of the whole system for quantifying the effects of delay in blood analysis. Hence, an improved method for compensating the effects of time delay (TD) from sampling to actual measurement of for example acid-base, oxygenation and/or electrolyte status in a blood sample would be advantageous, and in particular a more efficient and/or reliable method for compensating this time delay would be advantageous. OBJECT OF THE INVENTION It is a further object of the present invention to provide an alternative to the prior art. In particular, it may be seen as an object of the present invention to provide a method that solves the above-mentioned problems of the prior art having for example an approach based on statistical analysis of blood samples measured over time. SUMMARY OF THE INVENTION Thus, the above described object and several other objects are intended to be obtained in a first aspect of the invention by providing a computer-implemented method for compensating the effects of time delay (TD) between sampling and actual measurement of acid-base, oxygenation and/or electrolyte status in a blood sample from a subject, the method comprising: providing a blood sample with a known or estimated time of sampling (Ts),performing a blood gas measurement of said blood sample at a later time of measurement (Tm) resulting in a set of blood variables (BV'[Tm]) indicative of acid-base, oxygenation and/or electrolyte status in said blood sample,providing a mathematical model based on a plurality of physiological sub-models simulating time development in blood, the mathematical model comprising: o a first sub-model describing red blood cell metabolism, ando a second sub-model describing the effect of said red blood cell metabolism on the whole blood acid-base chemistry, andapplying said mathematical model to calculate from