Antibacterial drug target control infusion system

Abstract

The invention discloses an antibacterial drug target control infusion system, and relates to the technical field of infusion instruments, and the system comprises an input unit which is used for inputting personal data of a patient; the data processing unit is used for determining target concentration data, a hypothetical infusion rate and a load dosage according to the personal data, inputting the hypothetical infusion rate into a pharmacokinetic model to obtain expected concentration data, and taking the hypothetical infusion rate as a command infusion rate if a difference value between the expected concentration data and the target concentration data is smaller than or equal to a threshold value; the infusion pump is used for infusing the antibacterial medicine to the patient according to the load dosage and then infusing the antibacterial medicine according to the command infusion rate. According to the method, the personalized infusion scheme is formulated according to the personal data of the patient, the method can adapt to the conditions of different patients, two-step drug administration is adopted during infusion, drug administration is performed according to the load dosage before the personalized infusion scheme is determined, and the continuity of antibacterial drug infusion is ensured.

Description

Technical Field

[0001] This application relates to the technical field of infusion devices, and particularly to an antibacterial drug target-controlled infusion system. Background Art

[0002] Infection is one of the most common causes of death in critically ill patients. Antibacterial drugs such as carbapenem antibiotics are the last line of defense in the anti-infection treatment of critically ill patients. However, there are long-term problems of "insufficient exposure" or "excessive exposure" in clinical applications, which seriously affect the efficacy of antibacterial drugs and even cause toxic and side effects. Although optimization strategies such as increasing the dosage, increasing the frequency of administration, and prolonging the infusion time can improve the efficacy, the conditions of each patient are different, resulting in drug resistance and pharmacokinetic differences to antibacterial drugs, making the fixed infusion administration plan unable to adapt to the conditions of different patients. Summary of the Invention

[0003] The embodiments of this application provide an antibacterial drug target-controlled infusion system to solve the problem that the fixed infusion administration plan in the prior art cannot adapt to different patients.

[0004] The embodiments of this application provide an antibacterial drug target-controlled infusion system, including:

[0005] An input unit, configured to input personal data of a patient;

[0006] A data processing unit, configured to determine corresponding target concentration data, hypothetical infusion rate, and loading dose according to the personal data, input the hypothetical infusion rate into a pharmacokinetic model, predict the expected concentration data in the patient's body, compare the expected concentration data with the target concentration data, if the difference between the expected concentration data and the target concentration data is less than or equal to a set threshold, use the hypothetical infusion rate as the commanded infusion rate, if the difference between the expected concentration data and the target concentration data is greater than the set threshold, adjust the hypothetical infusion rate, input the adjusted hypothetical infusion rate into the pharmacokinetic model, predict the updated expected concentration data, compare the updated expected concentration data with the target concentration data, until the difference between the updated expected concentration data and the target concentration data is less than or equal to the set threshold, and use the adjusted hypothetical infusion rate as the commanded infusion rate;

[0007] An infusion pump, configured to first infuse an antibacterial drug to the patient according to the loading dose within a set time, and then infuse the antibacterial drug to the patient according to the commanded infusion rate.

[0008] An antibacterial drug target-controlled infusion system in this application has the following advantages:

[0009] Formulating a personalized infusion plan based on the patient's personal data can adapt to the conditions of different patients. Moreover, two-step drug administration is adopted during infusion. Before determining the personalized infusion plan, the drug is administered according to the loading dose to ensure the continuity of antimicrobial drug infusion. Description of the Drawings

[0010] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present application. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0011] Figure 1 It is a schematic diagram of the functional modules of an antimicrobial drug target-controlled infusion system provided by an embodiment of the present application. Detailed Embodiments

[0012] The following will clearly and completely describe the technical solutions in the embodiments of the present application with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only some embodiments of the present application, rather than all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present application.

[0013] Figure 1 It is a schematic diagram of the composition of an antimicrobial drug target-controlled infusion system provided by an embodiment of the present application. An embodiment of the present application provides an antimicrobial drug target-controlled infusion system, including:

[0014] An input unit for inputting the patient's personal data;

[0015] A data processing unit for determining corresponding target concentration data, hypothetical infusion rate, and loading dose according to the personal data, inputting the hypothetical infusion rate into a pharmacokinetic model to predict the expected concentration data in the patient's body, comparing the expected concentration data with the target concentration data. If the difference between the expected concentration data and the target concentration data is less than or equal to the set threshold, the hypothetical infusion rate is used as the commanded infusion rate. If the difference between the expected concentration data and the target concentration data is greater than the set threshold, the hypothetical infusion rate is adjusted, the adjusted hypothetical infusion rate is input into the pharmacokinetic model to predict the updated expected concentration data, and the updated expected concentration data is compared with the target concentration data until the difference between the updated expected concentration data and the target concentration data is less than or equal to the set threshold, and the adjusted hypothetical infusion rate is used as the commanded infusion rate;

[0016] An infusion pump is used to first infuse an antibacterial drug to a patient at a loading dose within a set time, and then infuse the antibacterial drug to the patient at a commanded infusion rate.

[0017] Exemplarily, the input unit can adopt a mechanical or touch keyboard. Of course, it can also be integrated with the display unit to form a touch display screen. Before infusing the patient, medical staff first obtain the patient's personal data by asking the patient or their family members, and then input the personal data into the data processing unit through the input unit. The data processing unit then completes subsequent calculation and control operations.

[0018] In an embodiment of the present application, the data processing unit can adopt a computer or a single-chip microcomputer. The patient's personal data includes age (Age), weight (WT), and height (HT). In addition, the personal data also includes the serum creatinine value (Scr), which can be obtained through biochemical detection of the blood.

[0019] The data processing unit includes a processing unit and a storage unit. A pharmacokinetic model is stored in the storage unit, and the personal data of the patient input by the medical staff will also be temporarily stored in the storage unit. After the input is completed and the medical staff starts the control process, the data processing unit first calculates the corresponding loading dose based on the personal data, and then controls the infusion pump to infuse the antibacterial drug to the patient at the loading dose within a set time, such as 5 minutes or 10 minutes, to perform antibacterial treatment before the data processing unit calculates and determines the commanded infusion rate, so that the patient can be treated in the first time.

[0020] Furthermore, the process of the data processing unit determining the target concentration data refers to the process of medical staff determining the target concentration data based on experience. Generally speaking, experienced medical staff can, based on experience, determine that when the antibacterial drug reaches the target concentration data in the patient, it will have a better therapeutic effect after learning the patient's personal data. After summarizing the experience of medical staff, a quantitative calculation formula is formed and stored in the data processing unit, so that the target concentration data can be calculated quickly and relatively accurately.

[0021] Meanwhile, the hypothetical infusion rate is also calculated based on personal data. However, the pharmacokinetic model and the formula summarized from the experience of medical staff are not the same. Therefore, there may be a deviation when calculating the concentration data. If the deviation between the two, that is, the difference value, is less than or equal to the pre-set threshold, then it can be considered that the target concentration data and the expected concentration data are consistent, and there is no need to adjust the hypothetical infusion rate. The hypothetical infusion rate can be directly used as the commanded infusion rate to control the operation of the infusion pump. If the difference between the target concentration data and the expected concentration data exceeds the threshold, it indicates that the deviation between the two is large, and the hypothetical infusion rate cannot meet the treatment needs of the patient. Therefore, it is necessary to adjust the hypothetical infusion rate. Specifically, the hypothetical infusion rate can be increased or decreased by a certain value, such as 0.01 mg / h or 0.1 mg / h, to obtain multiple adjusted hypothetical infusion rates.

[0022] Further, after adjusting the hypothetical infusion rate and obtaining multiple adjusted hypothetical infusion rates, each adjusted hypothetical infusion rate is input into the pharmacokinetic model to obtain multiple updated expected concentration data, forming multiple data groups. Each data group includes the adjusted hypothetical infusion rate and the corresponding updated expected concentration data. The data processing unit determines the differences between each data group, the hypothetical infusion rate, and the target concentration data, obtains the rate difference and concentration difference corresponding to the data group, and selects the adjusted hypothetical infusion rate that minimizes the sum of the rate difference and the concentration difference as the commanded infusion rate.

[0023] Specifically, after each adjusted hypothetical infusion rate is input into the pharmacokinetic model, a corresponding expected concentration data will be obtained. The expected concentration data and the corresponding adjusted hypothetical infusion rate will form a data group. Therefore, after each adjusted hypothetical infusion rate is input into the pharmacokinetic model, multiple data groups will be formed. For each data group, the difference between the expected concentration data and the target concentration data in it can be calculated, which is called the concentration difference, and the difference between the adjusted hypothetical infusion rate and the original hypothetical infusion rate, which is called the rate difference. Calculate the sum of the concentration difference and the rate difference corresponding to each data group respectively, select the smallest one among the multiple sums, and use the adjusted hypothetical infusion rate corresponding to the smallest sum as the commanded infusion rate to control the infusion pump.

[0024] Further, in addition to direct summation, a weighted summation method can also be used to determine the sum of the rate difference and the concentration difference. When performing weighted summation, the weights of the rate difference and the concentration difference can be set as needed, but it is necessary to ensure that the sum of the two weights is 1. Screening the expected infusion rate according to the sum of the rate difference and the concentration difference can consider both the concentration data determined according to the experience of medical staff and the infusion rate determined according to the pre-set formula, combining subjective and objective data, and improving the accuracy of the finally obtained commanded infusion rate.

[0025] In a possible embodiment, before determining the sum of the rate difference and the concentration difference, the rate difference and the concentration difference are normalized first.

[0026] Exemplarily, since both the rate difference and the concentration difference have specific physical meanings, in order to ensure that they can be summed, normalization is required to remove their respective dimensions and convert them into dimensionless data.

[0027] In a possible embodiment, the method for a pharmacokinetic model to predict the expected concentration data includes:

[0028] Determine the first-order rate constant by the following formula:

[0029]

[0030] where k 12 represents the first-order rate constant for the drug to be transported from the central compartment to the peripheral compartment, k 21 represents the first-order rate constant for the drug to be transported from the peripheral compartment to the central compartment, k 10 represents the first-order rate constant for the drug to be eliminated from the central compartment, Q represents the inter-compartment clearance rate, with the unit of L / h, V 1 and V 2 respectively represent the apparent volume of distribution of the central compartment and the apparent volume of distribution of the peripheral compartment, both with the unit of L, CL represents the clearance rate of the central compartment, with the unit of L / h;

[0031] Determine the second-order constant by the following formula:

[0032]

[0033] where α and β respectively represent the first second-order constant and the second second-order constant;

[0034]

[0035] where C and C' respectively represent the expected concentration data in the rising phase and the expected concentration data in the falling phase, both with the unit of mg / L, k 0 represents the imaginary infusion rate, with the unit of mg / h, e represents the natural constant, t and t' respectively represent the infusion time and the time after the infusion ends, both with the unit of h.

[0036] Exemplarily, after determining the patient's age, symptoms, and antibacterial drug, the inter-compartment clearance rate Q, the apparent volume of distribution of the central compartment V 1 , the apparent volume of distribution of the peripheral compartment V 2 and the clearance rate of the central compartment CL can all be obtained by looking up a table. For example, for children under 12 years old, when meropenem is used as the antibacterial drug, the value of Q is Q = 2.97×(Age / 3.17) 2.50 , V1 The value of V 1 = 2.62 × (WT / 13.5) 1.06 , V 2 The value of V 2 = 2.62 × (WT / 13.5) 0.3 , the value of CL is CL = 4.22 × (Ccr / 53.35) 0.29 × (WT / 13.5) 0.86 , while for other antibacterial drugs, such as imipenem, corresponding data need to be taken.

[0037] According to the above calculation formulas of C and C’, the drug concentration change curve obtained by pharmacokinetic simulation can be obtained. For the sake of simple calculation, the curve can be simplified into a broken line formed by connecting multiple straight lines in sequence. Then, at a set time after the infusion ends, such as 8 h later, the drug concentration in the patient's body is determined, which is called the predicted drug concentration. The predicted drug concentration and the target drug concentration are compared to determine whether the hypothetical infusion rate is appropriate.

[0038] In a possible embodiment, the hypothetical infusion rate is determined by the following formula:

[0039] k 0 = CL · Css

[0040] where, k 0 represents the hypothetical infusion rate, with the unit of mg / h, CL represents the central compartment clearance rate, with the unit of L / h, and Css represents the loading concentration, with the unit of mg / L;

[0041] For patients less than or equal to 12 years old, the central compartment clearance rate CL is determined by the following formula:

[0042] CL = 4.22 × (Ccr / 53.35) 0.29 × (WT / 13.5) 0.86

[0043] where, Ccr represents the endogenous creatinine clearance rate, with the unit of μmol / L;

[0044] For patients older than 12 years old and less than or equal to 65 years old, the central compartment clearance rate CL is determined by the following formula:

[0045] CL = 14.6 × (Ccr / 83) 0.62 × (Age / 35) -0.34

[0046] For patients older than 65 years old, the central compartment clearance rate CL is determined by the following formula:

[0047] CL = 8.98×[1 + 0.0182×(Ccr - 55.3)].

[0048] Exemplarily, the loading concentration Css is 4 times the inhibitory concentration of the corresponding antibacterial drug, i.e., Css = 4MIC, and this inhibitory concentration can also be determined by looking up a table. For example, when the patient is infected with bacteria of the Enterobacteriaceae family and meropenem is used as the antibacterial drug, the inhibitory concentration is 1 μg / mL, while when imipenem or ertapenem is used as the antibacterial drug under the same bacteria, the inhibitory concentrations are 1 μg / mL and 0.5 μg / mL respectively.

[0049] It should be understood that the above formulas for calculating the central compartment clearance rate CL take meropenem as an example for the selection of antibacterial drugs. If other antibacterial drugs are used, the corresponding calculation formulas need to be selected.

[0050] In a possible embodiment, the endogenous creatinine clearance rate Ccr is determined by the following formula:

[0051] Cockcroft formula:

[0052] Male: Ccr = (140 - Age) × WT / (72 × Scr)

[0053] Female: Ccr = (140 - Age) × WT / (85 × Scr)

[0054] Durate formula:

[0055] Male: Ccr = 109.8 / Scr - 1.8

[0056] Female: Ccr = 77.65 / Scr + 2.2

[0057] Among them, Scr represents the serum creatinine value, with the unit of μmol / L. For general patients, the Cockcroft formula is used, and for critically ill patients, the Durate formula is used.

[0058] Exemplarily, when the user inputs the personal data of the patient, the status data will also be input simultaneously, and this status data indicates whether the patient is in a general state or a critically ill state. After obtaining the status data, the data processing unit will calculate the corresponding endogenous creatinine clearance rate Ccr according to the status data.

[0059] In addition, when calculating the endogenous creatinine clearance rate Ccr, the situation of newborns is also considered. Newborns are infants under 28 days old after birth. For newborns, the formula for calculating the endogenous creatinine clearance rate Ccr is:

[0060] Ccr = K × HT / Scr

[0061] Among them, K can take 0.55.

[0062] In a possible embodiment, the loading dose is determined by the following formula:

[0063] X 0 = Css·V

[0064] Css = 4MIC

[0065] V = V 1 + V 2

[0066] Wherein, X 0 represents the loading dose, in mg; Css represents the loading concentration, in mg / L; MIC represents the minimum inhibitory concentration, in mg / L; V represents the apparent volume of distribution, in L; V 1 and V 2 represent the apparent volume of distribution of the central compartment and the apparent volume of distribution of the peripheral compartment respectively, both in L;

[0067] For patients less than or equal to 12 years old, the apparent volume of distribution of the central compartment V 1 and the apparent volume of distribution of the peripheral compartment V 2 are determined by the following formulas respectively:

[0068] V 1 = 2.62×(WT / 13.5) 1.06

[0069] V 2 = 2.5×(WT / 13.5) 0.30

[0070] For patients older than 12 years old and less than or equal to 65 years old, the apparent volume of distribution of the central compartment V 1 and the apparent volume of distribution of the peripheral compartment V 2 are determined by the following formulas respectively:

[0071] V 1 = 10.8×(WT / 70) 0.99

[0072] V 2 = 12.6

[0073] For patients older than 65 years old, the apparent volume of distribution of the central compartment V 1 and the apparent volume of distribution of the peripheral compartment V 2 are determined by the following formulas respectively:

[0074] V 1 = 16.1

[0075] V 2 = 12.0.

[0076] Exemplarily, in addition to calculating the intercompartment clearance Q, the apparent volume of distribution in the central compartment V 1 , the apparent volume of distribution in the peripheral compartment V 2 and the clearance rate CL in the central compartment according to age, the above data for patients in other states can also be calculated based on the status data. The status data also includes fever and burns caused by neutropenia. For patients with fever caused by neutropenia, the calculation formulas for the above data are as follows:

[0077] CL = 9.7×(Ccr / 120)

[0078] V 1 = 14.6×(WT / 61)

[0079]

[0080] Q = CL×e CL

[0081] For burn patients, the calculation formulas for the above data are as follows:

[0082] CL = 4.51 + 10.4×(Ccr / 138)

[0083] V 1 = 17.0 + 10.8×OEDEMA

[0084] V 2 = 10.1

[0085] Q = 5.16

[0086] Wherein, OEDEMA represents whether there is edema. If there is edema, the value of OEDEMA is 1; otherwise, the value is 0.

[0087] Although the preferred embodiments of the present application have been described, those skilled in the art can make additional changes and modifications to these embodiments once they know the basic creative concepts. Therefore, the appended claims are intended to be interpreted to include the preferred embodiments as well as all changes and modifications falling within the scope of the present application.

[0088] Obviously, those skilled in the art can make various changes and variations to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalent technologies, the present application is also intended to include these modifications and variations.

Claims

1. An antimicrobial drug target-controlled infusion system, characterized in that: include: An input unit for entering the patient's personal data; a data processing unit, configured to determine corresponding target concentration data, a hypothetical infusion rate and a loading dose according to the personal data, and input the hypothetical infusion rate into a pharmacokinetic model, predict the expected concentration data in the patient, compare the expected concentration data with the target concentration data, and if the difference between the expected concentration data and the target concentration data is less than or equal to a set threshold, use the hypothetical infusion rate as a command infusion rate; if the difference between the expected concentration data and the target concentration data is greater than the set threshold, adjust the hypothetical infusion rate, input the adjusted hypothetical infusion rate into the pharmacokinetic model, predict the updated expected concentration data, compare the updated expected concentration data with the target concentration data, until the difference between the updated expected concentration data and the target concentration data is less than or equal to the set threshold, and use the adjusted hypothetical infusion rate as the command infusion rate; The infusion pump is used to first infuse the antibiotic into the patient according to the loading dose within a set time, and then infuse the antibiotic into the patient according to the command infusion rate.

2. The antimicrobial drug target-controlled infusion system according to claim 1, characterized in that: After adjusting the hypothetical infusion rate, a plurality of adjusted hypothetical infusion rates are obtained, and each of the adjusted hypothetical infusion rates is input into the pharmacokinetic model to obtain a plurality of updated expected concentration data to form a plurality of data groups, each of which includes the adjusted hypothetical infusion rate and the corresponding updated expected concentration data. The data processing unit determines the difference between each of the data groups and the hypothetical infusion rate and the target concentration data to obtain the rate difference and concentration difference corresponding to the data group, and selects the adjusted hypothetical infusion rate that minimizes the sum of the rate difference and the concentration difference as the command infusion rate.

3. The antimicrobial drug target-controlled infusion system according to claim 2, characterized in that: The sum of the rate difference and the concentration difference is determined by weighted summation.

4. The antimicrobial drug target-controlled infusion system according to claim 2, characterized in that: Before determining the sum of the rate difference and the concentration difference, the rate difference and the concentration difference are first normalized.

5. The antimicrobial drug target-controlled infusion system according to claim 1, characterized in that: The method for obtaining the expected concentration data by predicting the pharmacokinetic model includes: The first-order rate constant was determined by the following equation: Among them, k 12 represents the first-order rate constant for drug transport from the central compartment to the peripheral compartment, k 21 represents the first-order rate constant for drug transport from the peripheral compartment to the central compartment, k 10 represents the first-order rate constant of drug elimination from the central compartment, Q represents the inter-compartmental clearance rate, the unit is L / h, V1 and V2 represent the apparent distribution volume of the central compartment and the apparent distribution volume of the peripheral compartment, the unit is L, CL represents the central compartment clearance rate, the unit is L / h; The secondary constant is determined by the following formula: Where α and β represent the first and second order constants, respectively; Wherein, C and C' represent the expected concentration data in the ascending stage and the expected concentration data in the descending stage, respectively, both in mg / L, k0 represents the hypothetical infusion rate, in mg / h, e represents the natural constant, t and t' represent the infusion time and the time after the end of infusion, respectively, both in h.

6. The antimicrobial drug target-controlled infusion system according to claim 1, characterized in that: The personal data includes age Age and weight WT, and the hypothetical infusion rate is determined by the following formula: k0=CL·Css Wherein, k0 represents the hypothetical infusion rate, in mg / h, CL represents the central compartment clearance, in L / h, and Css represents the loading concentration, in mg / L; For patients aged 12 years or less, the central compartment clearance CL is determined by the following formula: CL=4.22×(Ccr / 53.35) 0.29 ×(WT / 13.5) 0.86 Wherein, Ccr represents endogenous creatinine clearance, in μmol / L; For patients aged greater than 12 years and less than or equal to 65 years, the central compartment clearance CL is determined by the following formula: CL=14.6×(Ccr / 83) 0.62 ×(Age / 35) -0.34 For patients older than 65 years, the central compartment clearance CL is determined by the following formula: CL=8.98×[1+0.0182×(Ccr-55.3)].

7. The antimicrobial drug target-controlled infusion system according to claim 6, characterized in that: The endogenous creatinine clearance Ccr is determined by the following formula: Cockcroft formula: Male: Ccr=(140-Age)×WT / (72×Scr) Female: Ccr=(140-Age)×WT / (85×Scr) Durate formula: Male: Ccr = 109.8 / Scr - 1.8 Female: Ccr = 77.65 / Scr + 2.2 Among them, Scr represents the blood creatinine value, the unit is μmol / L. The Cockcroft formula is used for general patients, and the Durate formula is used for critically ill patients.

8. The antimicrobial drug target-controlled infusion system according to claim 1, characterized in that: The personal data include age and weight WT, and the loading dose is determined by the following formula: X0=Css·V Css=4MIC V=V1+V2 Wherein, X0 represents the loading dose, in mg, Css represents the loading concentration, in mg / L, MIC represents the inhibitory concentration, in mg / L, V represents the apparent distribution volume, in L, V1 and V2 represent the apparent distribution volume of the central compartment and the apparent distribution volume of the peripheral compartment, respectively, in L; For patients aged 12 years or less, the central compartment apparent distribution volume V1 and the peripheral compartment apparent distribution volume V2 are determined by the following formulae: V1=2.62×(WT / 13.5) 1.06 <h2 style=";text-align:left;direction:ltr">V2=2.5×(WT / 13.5)<h2 style=";text-align:left;direction:ltr"> 0.30 For patients aged greater than 12 years and less than or equal to 65 years, the central compartment apparent distribution volume V1 and the peripheral compartment apparent distribution volume V2 are determined by the following formulae, respectively: V1=10.8×(WT / 70) 0.99 V2＝12.6 For patients older than 65 years old, the central compartment apparent distribution volume V1 and the peripheral compartment apparent distribution volume V2 are determined by the following formulae: V1＝16.1 V2＝12.0。

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