A method, system, device, and medium for calculating the coordinated control rate of drug infusion.

Abstract

This invention relates to the field of medical data processing technology, and discloses a method, system, device, and medium for calculating the synergistic control rate of drug infusion. The invention acquires the patient's real-time bispectral index (BSE) and determines its deviation from a preset target range. A control algorithm is then used to calculate the required total effect intensity adjustment. Based on a preset fixed ratio of propofol and remifentanil effect-site concentrations, the total effect intensity adjustment is allocated to the target effect-site concentrations of each drug. Finally, the target infusion rates of propofol and remifentanil are calculated backward using the Schnider and Minto models, respectively. This invention achieves synergistic closed-loop control of sedative and analgesic drugs based on a single BIS feedback, solving the clinical problem of unquantifiable analgesia control, ensuring a dynamic balance between sedation and analgesia, and incorporating a built-in safety verification mechanism. This significantly improves the accuracy, stability, and safety of anesthesia depth control, while reducing clinical workload.

Description

Technical Field

[0001] This invention relates to the field of medical data processing technology, and in particular to a method, system, device and medium for calculating the coordinated control rate of drug infusion. Background Technology

[0002] In clinical anesthesia, the key to maintaining anesthesia lies in maintaining an appropriate depth of sedation and effective analgesia to ensure the patient is unaware and pain-free during surgery, while simultaneously ensuring stable vital signs and reducing postoperative complications. Currently, clinical studies have confirmed a negative correlation between propofol blood concentration and BIS (Bispectral Index) values. Based on this characteristic, closed-loop target-controlled infusion of propofol can be achieved through bispectral index (BIS) monitoring, thereby maintaining an appropriate depth of sedation. BIS, as a quantitative indicator of sedation depth, typically ranges from 0 to 100; a lower value indicates deeper sedation, providing an effective and reliable basis for controlling sedation depth. However, the biggest challenge currently lies in the inability to monitor the degree of analgesia. The infusion dose of remifentanil is often adjusted based on the anesthesiologist's experience, lacking precise quantitative indicators, resulting in low controllability and accuracy of anesthesia and analgesia.

[0003] Propofol is a commonly used intravenous sedative, characterized by rapid onset, strong controllability, and rapid and complete recovery. Remifentanil is a potent opioid analgesic with rapid onset and short duration of action. The combination of propofol and remifentanil is the most commonly used total intravenous anesthesia combination. However, in practical application, due to individual differences, different patients respond differently to these two drugs. Furthermore, due to the lack of analgesia monitoring methods, relying solely on experience to adjust remifentanil infusion results in poor precision in anesthesia and analgesia, and makes it difficult to achieve synergy with closed-loop target-controlled propofol infusion. This leads to poor matching between sedation and analgesia, and makes it impossible to automatically maintain the depth of anesthesia (including sedation depth and analgesic intensity). When the sedation depth is appropriate, insufficient analgesia may cause stress responses such as body movement, increased blood pressure, and increased heart rate; excessive analgesia may cause respiratory and circulatory depression, delayed postoperative recovery, and excessive remifentanil dosage may also induce hyperalgesia, leading to difficulties in postoperative pain management.

[0004] Although BIS-based closed-loop target-controlled infusion of propofol plays an important role in maintaining appropriate sedation depth, a synergistic closed-loop control scheme for propofol (sedative drug) and remifentanil (analgesic drug) has not yet been developed. This cannot compensate for the lack of monitoring of analgesia level, resulting in poor matching between sedation depth and analgesia intensity during anesthesia, failure to achieve automatic maintenance of anesthetic depth, and a need to improve the precision and controllability of anesthesia. Summary of the Invention

[0005] This invention provides a method, system, device, and medium for calculating the coordinated control rate of drug infusion, in order to overcome the deficiencies of the prior art.

[0006] This invention provides a method for calculating the synergistic control rate of drug infusion, comprising:

[0007] S1. Obtain the current BIS value of the target patient who is receiving drug infusion, wherein the target patient is receiving propofol and remifentanil, and the ratio of the effect-site concentration of propofol to the effect-site concentration of remifentanil is fixed at 1:2.

[0008] S2. Compare the current BIS value with the preset target range to obtain the target patient's drug infusion adjustment needs;

[0009] S3. When a drug infusion adjustment request indicates that the drug infusion rate needs to be adjusted, calculate the total effect strength adjustment amount that will bring the subsequent BIS value of the target patient back to the preset target range.

[0010] S4. Obtain the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculate the target effect-site concentrations of propofol and remifentanil based on the total effect strength adjustment.

[0011] S5. Based on the target effect-site concentration of propofol, the target infusion rate of propofol is inferred from the pre-set pharmacokinetic model of propofol applied to the target patient. Similarly, based on the target effect-site concentration of remifentanil, the target infusion rate of remifentanil is inferred from the pre-set pharmacokinetic model of remifentanil applied to the target patient.

[0012] According to the present invention, a method for calculating the synergistic control rate of drug infusion is provided, wherein S2 includes:

[0013] When the BIS value is within the preset target range, it is determined that there is no need to adjust the drug infusion rate.

[0014] When the BIS value is higher than the upper limit of the preset target range, the drug infusion adjustment requirement is determined to be an increase in the drug infusion rate.

[0015] When the BIS value is lower than the lower limit of the preset target range, the drug infusion adjustment requirement is determined to be that the drug infusion rate needs to be reduced.

[0016] According to the present invention, a method for calculating the synergistic control rate of drug infusion is provided, wherein S3 includes:

[0017] Calculate the deviation between the current BIS value and the midpoint of the preset target interval to obtain the BIS deviation value;

[0018] Based on the BIS deviation value, a control algorithm is used to obtain the total effect strength adjustment amount that brings the subsequent BIS value of the target patient back to the preset target interval.

[0019] According to the present invention, a method for calculating the coordinated control rate of drug infusion is provided, wherein the expression of the control algorithm is as follows:

[0020] E=Kp× BIS+Ki×∫ BISdt+Kd×d( BIS) / dt,

[0021] E represents the adjustment amount for the total effect intensity. BIS represents the BIS deviation value (Kp× BIS represents the scaling term, and Kp represents the preset scaling factor (Ki×∫). BISdt) represents the integral term, Ki represents the preset integral coefficient, (Kd×d( BIS) / dt) represents the differential term, and Kd represents the preset differential coefficient.

[0022] According to the present invention, a method for calculating the synergistic control rate of drug infusion is provided, wherein S4 includes:

[0023] The total effect intensity adjustment was converted into the concentration adjustment for propofol and remifentanil;

[0024] Based on the current effect-room concentrations of propofol and remifentanil, and combined with the concentration adjustment amounts of propofol and remifentanil, the target effect-room concentrations of propofol and remifentanil are obtained.

[0025] According to the present invention, a method for calculating the synergistic control rate of drug infusion, wherein converting the total effect intensity adjustment into concentration adjustments for propofol and remifentanil includes:

[0026] The concentration adjustment amount of propofol is obtained through the first expression, where the first expression is:

[0027] ΔC1 = ΔE / (a ​​+ 2b),

[0028] The concentration adjustment amount of remifentanil is obtained through the second expression, where the second expression is:

[0029] ΔC2 = 2×ΔC1 = 2×ΔE / (a ​​+ 2b),

[0030] In the formula, ΔC1 represents the concentration adjustment amount of propofol, and ΔC2 represents the concentration adjustment amount of remifentanil. E represents the adjustment amount for the total effect intensity, and a and b represent the preset weighting coefficients, respectively.

[0031] According to the present invention, a method for calculating the synergistic control rate of drug infusion, wherein the target effect-site concentrations of propofol and remifentanil are obtained based on the current effect-site concentrations of propofol and remifentanil, combined with the concentration adjustment amounts of propofol and remifentanil, include:

[0032] The target effect-compartment concentration of propofol is obtained through the third expression, which is:

[0033] C1_target = C1_current + ΔC1,

[0034] The target effect-cell concentration of remifentanil is obtained through the fourth expression, which is:

[0035] C2_target = C2_current + ΔC2,

[0036] In the formula, C1_target represents the target effect-room concentration of propofol, C1_current represents the current effect-room concentration of propofol, ΔC1 represents the concentration adjustment amount of propofol, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, and ΔC2 represents the concentration adjustment amount of remifentanil.

[0037] According to the present invention, a method for calculating the synergistic controlled infusion rate of propofol for the target patient is provided. The pre-defined pharmacokinetic model of propofol for the target patient adopts the Schnider model, which is a three-compartment model. The relationship between the effect-compartment concentration and the infusion rate is realized through the target-controlled infusion (TCI) algorithm. The expression for calculating the target infusion rate of propofol using the Schnider model is as follows:

[0038] R1=[(C1_target-C1_current)×V1×ke0+C1_target×CL] / C_prop,

[0039] In the formula, R1 represents the target infusion rate of propofol, C1_target represents the target effect-room concentration of propofol, C1_current represents the current effect-room concentration of propofol, V1 represents the central compartment distribution volume of propofol for the target patient, CL represents the central compartment clearance rate of propofol for the target patient, ke0 represents the transport rate constant between the effect-room and central compartment for propofol, and C_prop represents the propofol concentration.

[0040] According to the present invention, a method for calculating the synergistic control rate of drug infusion is provided. The pre-defined pharmacokinetic model for remifentanil applied to the target patient adopts the Minto model. The Minto model is a three-compartment model, and the relationship between the effect-compartment concentration and the infusion rate is realized through the target-controlled infusion (TCI) algorithm. The expression for calculating the target infusion rate of remifentanil using the Minto model is as follows:

[0041] R2=[(C2_target-C2_current)×V1_r×ke0_r+C2_target×CL_r] / C_prop_r,

[0042] In the formula, R2 represents the target infusion rate of remifentanil, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, V1_r represents the central chamber distribution volume of remifentanil for the target patient, CL_r represents the central chamber clearance rate of remifentanil for the target patient, ke0_r represents the transport rate constant between the effect-room and central chamber for remifentanil, and C_prop_r represents the concentration of remifentanil.

[0043] The method for calculating the synergistic control rate of drug infusion provided by the present invention further includes step S6:

[0044] According to the preset safety control mechanism, at least one of the following is verified: the target effect-site concentration of propofol, the target effect-site concentration of remifentanil, the adjustment range of propofol infusion rate, and the adjustment range of remifentanil infusion rate. Based on the verification results, the final drug infusion rate adjustment command is obtained.

[0045] According to the present invention, a method for calculating the coordinated control rate of drug infusion is provided, wherein the preset safety control mechanism includes:

[0046] When the target effect chamber concentration of propofol exceeds the first preset safety upper limit, the target effect chamber concentration of propofol is forcibly set to the first preset safety upper limit, and the target infusion rate of propofol is recalculated.

[0047] When the target effect chamber concentration of remifentanil exceeds the second preset safety upper limit, the target effect chamber concentration of remifentanil is forcibly set to the second preset safety upper limit, and the target infusion rate of remifentanil is recalculated.

[0048] When the infusion rate of propofol is adjusted by 20% or more, the target infusion rate of propofol will be adjusted to 1.2 times the current infusion rate. When the infusion rate of propofol is adjusted by less than 20%, the target infusion rate of propofol will be adjusted to 0.8 times the current infusion rate.

[0049] When the infusion rate of remifentanil is adjusted by 20% or more, the target infusion rate of remifentanil will be adjusted to 1.2 times the current infusion rate. When the infusion rate of remifentanil is adjusted by less than 20%, the target infusion rate of remifentanil will be adjusted to 0.8 times the current infusion rate.

[0050] The present invention also provides a coordinated control rate calculation system for drug infusion, comprising:

[0051] The data receiving module is used to: receive the current BIS value of a target patient receiving medication from at least one terminal, wherein the medication being infused in the target patient includes propofol and remifentanil, and the ratio of the effect-site concentration of propofol to the effect-site concentration of remifentanil is fixed at 1:2.

[0052] The drug infusion adjustment need determination module is used to: compare the current BIS value with the preset target range to obtain the drug infusion adjustment needs of the target patient;

[0053] The first calculation module is used to: calculate the total effect intensity adjustment amount that makes the subsequent BIS value of the target patient return to the preset target range when the drug infusion adjustment demand indicates that the drug infusion rate needs to be adjusted;

[0054] The second calculation module is used to: obtain the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculate the target effect-site concentrations of propofol and remifentanil respectively based on the total effect intensity adjustment.

[0055] The third calculation module is used to: back-calculate the target infusion rate of propofol based on the target effect-site concentration of propofol using a preset pharmacokinetic model of propofol applied to the target patient; and back-calculate the target infusion rate of remifentanil based on the target effect-site concentration of remifentanil using a preset pharmacokinetic model of remifentanil applied to the target patient.

[0056] The data output module is used to send the target infusion rates of propofol and remifentanil to at least one terminal.

[0057] It should be noted that a terminal refers to an input / output device connected to a computer system. Depending on the function, terminals can be divided into various types: smart terminals or intelligent terminals, dumb terminals, interactive terminals or online terminals. Specifically, a terminal can be various mobile communication devices, such as mobile phones and tablets. This article aims to provide users with the function of inputting data and outputting data.

[0058] The present invention also provides an electronic device, including a processor and a memory storing a computer program, wherein the processor executes the computer program to implement any of the above-described methods for calculating the coordinated control rate of drug infusion.

[0059] The present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements any of the above-described methods for calculating the coordinated control rate of drug infusion.

[0060] The present invention also provides a computer program product, the computer program product comprising a computer program that can be stored on a non-transitory computer-readable storage medium, and when the computer program is executed by a processor, the computer is able to execute any of the above-described methods for calculating the coordinated control rate of drug infusion.

[0061] The present invention provides a method, system, device, and medium for calculating the coordinated control rate of drug infusion, which can bring at least the following beneficial effects:

[0062] This invention uses the BIS (Biological Intensity Sequencing) signal, a single sedation depth monitoring signal, as a common feedback variable for the synergistic regulation of two drugs: sedation (propofol) and analgesia (remifentanil). By fixing the effect-site concentration ratio of the two drugs (1:2) and establishing a mathematical model of BIS deviation and total effect intensity adjustment, the real-time target infusion rates of the two drugs can be calculated. This transforms the regulation of analgesics from an empirical operation into an automated process based on precise calculations, overcoming the limitation of not being able to directly monitor the degree of analgesia in clinical practice.

[0063] When the BIS value deviates from the preset target range, this invention first calculates the total effect intensity adjustment (ΔE) required to bring the BIS value back to its normal range. Then, using preset weighting coefficients and fixed concentration ratios (a, b, 1:2), this effect intensity adjustment is scientifically allocated to the respective "concentration adjustment amounts" (ΔC1, ΔC2) of propofol and remifentanil. This achieves synergy and linkage between the two drugs at the level of pharmacological effect coupling, ensuring that changes in sedation and analgesia intensity are synchronous and proportional at any adjustment time. This effectively avoids problems such as intraoperative awareness, body movement response, or excessive circulatory and respiratory depression caused by imbalance between the two, achieving truly automated maintenance of "balanced anesthesia."

[0064] This invention constitutes a multi-layered precision calculation system: Outer layer closed-loop control: employing advanced control algorithms such as PID to handle BIS deviations and dynamically calculate the total effect requirement, enabling rapid and stable response to changes in surgical stimulation and individual differences; Middle layer concentration allocation and conversion: through rigorous mathematical transformation, the effect intensity requirement is decomposed into the target effect-site concentrations of two drugs; Inner layer individualized pharmacokinetic calculation: utilizing widely validated individualized pharmacokinetic models such as Schnider (propofol) and Minto (remifentanil), the precise individualized target infusion rate is calculated by back-calculating the target effect-site concentration. This complete closed loop of "feedback-decision-individualized execution" significantly improves the ability to stably control the BIS value within the target range and reduces fluctuations in anesthesia depth.

[0065] This invention also integrates proactive safety protection strategies, including: effect-room concentration safety upper limit control: preventing the calculated target concentration from exceeding the clinically safe range; and infusion rate adjustment range limitation (e.g., no more than ±20% per adjustment): avoiding drastic rate changes caused by transient signal interference or calculation anomalies, ensuring stable infusion. Through these pre-verification mechanisms, potential risk values ​​can be automatically corrected before outputting instructions, greatly reducing the risk of drug overdose due to algorithm or equipment failure, making fully automated collaborative target-controlled infusion safer and more reliable in clinical applications.

[0066] This invention frees anesthesiologists from the tedious and experience-dependent task of remifentanil dosage titration, transforming the human-dominated "monitoring-experience judgment-manual adjustment" model into a system-dominated "monitoring-intelligent calculation-automatic adjustment" model. This not only reduces management deviations caused by human fatigue, experience differences, or distraction, but also helps to develop more standardized and replicable precision anesthesia protocols, thereby improving the overall quality of anesthesia. Attached Figure Description

[0067] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0068] Figure 1 This is one of the flowcharts illustrating a method for calculating the synergistic control rate of drug infusion provided by the present invention.

[0069] Figure 2 This is the second flowchart illustrating a method for calculating the synergistic control rate of drug infusion provided by the present invention.

[0070] Figure 3This is one of the structural schematic diagrams of a collaborative control rate calculation system for drug infusion provided by the present invention.

[0071] Figure 4 This is the second schematic diagram of a collaborative control rate calculation system for drug infusion provided by the present invention.

[0072] Figure 5 This is a schematic diagram of the structure of the electronic device provided by the present invention. Detailed Implementation

[0073] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, embodiments of this invention, and should not be construed as limiting the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention. In the description of this invention, it should be understood that the terminology used is for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0074] Figure 1 and Figure 2 This is a flowchart illustrating a method for calculating the coordinated control rate of drug infusion provided by the present invention. The executing entity of this method can be any applicable terminal-side device or network-side device, such as a coordinated control rate calculation device for drug infusion.

[0075] See Figure 1 and Figure 2 The present invention provides a method for calculating the synergistic control rate of drug infusion, which may include:

[0076] S1. Obtain the current BIS value of the target patient who is receiving infusion of drugs. The infusion drugs for the target patient include propofol and remifentanil. The ratio K of the effect-site concentration of propofol (C1) and the effect-site concentration of remifentanil (C2) is fixed at 1:2, specifically 1 μg / mL: 2 ng / mL.

[0077] In one embodiment, the current BIS value of the target patient receiving drug infusion can be obtained by acquiring real-time electroencephalogram (EEG) signals, processing them, and obtaining continuous BIS monitoring values. Furthermore, the current effect-site concentrations of propofol and remifentanil can be calculated using pharmacokinetic models (Schnider model for propofol and Minto model for remifentanil).

[0078] S2. Compare the current BIS value with the preset target range (40-60 in this embodiment) to obtain the drug infusion adjustment requirements of the target patient.

[0079] In one embodiment, S2 may include:

[0080] When the BIS value is within the preset target range, it is determined that there is no need to adjust the drug infusion rate; the current drug infusion rate can be maintained.

[0081] When the BIS value is higher than the upper limit of the preset target range, the sedation is determined to be too shallow, and the drug infusion adjustment requirement is to increase the drug infusion rate.

[0082] When the BIS value is lower than the lower limit of the preset target range, it is determined that the sedation is too deep, and the drug infusion adjustment needs to be adjusted by reducing the drug infusion rate.

[0083] S3. When the drug infusion adjustment request indicates that the drug infusion rate needs to be adjusted, calculate the total effect intensity adjustment amount that will bring the subsequent BIS value of the target patient back to the preset target range.

[0084] The total effect intensity (E) is a comprehensive indicator reflecting the synergistic effect of "sedation + analgesia". Its change (ΔE) is determined by the deviation between the BIS value and the preset target range. It can be calculated by the control algorithm (in this embodiment, a PID controller is used). The PID controller can calculate ΔE by combining the three parts of "proportional (P), integral (I), and derivative (D)".

[0085] In one embodiment, S3 may include:

[0086] Calculate the deviation between the current BIS value (BIS_current) and the midpoint of the preset target interval (BIS_target) (in this embodiment, the preset target interval is 40-60, and the midpoint is 50) to obtain the BIS deviation value. BIS, the calculation formula is: BIS = BIS_current - BIS_target;

[0087] Based on the BIS deviation value, a control algorithm is used to obtain the total effect strength adjustment that brings the subsequent BIS value of the target patient back to the preset target interval. The expression of the control algorithm is as follows:

[0088] E=Kp× BIS+Ki×∫ BISdt+Kd×d( BIS) / dt,

[0089] E represents the adjustment amount for the total effect intensity. BIS represents the BIS deviation value (Kp× BIS represents the proportional term, and Kp represents the preset proportional coefficient (determined through clinical adjustments, such as 0.02), which directly responds to the current deviation. The larger the deviation, the greater the adjustment of ΔE. (Ki×∫) BISdt) represents the integral term, and Ki represents the preset integration coefficient (e.g., 0.005), used to eliminate long-term steady-state deviations (e.g., the cumulative error of BIS consistently slightly exceeding the target). The integration time range is the first 5-10 minutes, (Kd×d( BIS / dt) represents the differential term, and Kd represents the preset differential coefficient (e.g., 0.01), which reflects the rate of change of the deviation (e.g., BIS rapidly increases from 55 to 65, indicating a large rate of change). This is used to suppress over-adjustment and avoid drastic fluctuations in the depth of anesthesia.

[0090] If ΔBIS is positive (sedation is too shallow), then ΔE is positive, and the total effect intensity needs to be increased.

[0091] If ΔBIS is negative (sedation is too deep), then ΔE is negative, and the total effect intensity needs to be reduced.

[0092] Example: If Kp=0.02, Ki=0.005, Kd=0.01, BIS_current=65 (ΔBIS=15), the integral ∫ΔBISdt=40 for the first 5 minutes, and the rate of change of deviation d(ΔBIS) / dt=2 (BIS increases by 2 per minute), then:

[0093] ΔE = 0.02 × 15 + 0.005 × 40 + 0.01 × 2 = 0.3 + 0.2 + 0.02 = 0.52 (The total effect intensity needs to be increased by 0.52 units).

[0094] S4. Obtain the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculate the target effect-site concentrations of propofol and remifentanil based on the total effect strength adjustment.

[0095] In one embodiment, S4 may include:

[0096] S401. Convert the total effect intensity adjustment into the concentration adjustments for propofol and remifentanil. Specifically, obtain the concentration adjustments for propofol and remifentanil using the first and second expressions. The first expression is:

[0097] ΔC1 = ΔE / (a ​​+ 2b),

[0098] The second expression is:

[0099] ΔC2 = 2×ΔC1 = 2×ΔE / (a ​​+ 2b),

[0100] In the formula, ΔC1 represents the concentration adjustment amount of propofol, and ΔC2 represents the concentration adjustment amount of remifentanil. E represents the adjustment amount for the total effect intensity, and a and b represent the preset weighting coefficients, respectively.

[0101] Based on a fixed ratio K (1:2), the total effect intensity adjustment ΔE is allocated to propofol and remifentanil, transforming it into effect-site concentration adjustments for both. The core logic is that "the concentration change ratio is consistent with K." Specifically, the derivation process may include the following steps:

[0102] 1) Derivation of the proportional relationship: From K=C1:C2=1:2, we can get C2=2×C1. Therefore, the concentration change must satisfy ΔC2=2×ΔC1 (to ensure that the synergistic ratio is maintained after adjustment).

[0103] 2) The relationship between total effect and concentration: The relationship between the total effect intensity E and C1, C2 is described by a "synergistic effect model" (such as a linear model based on clinical data fitting: E=a×C1 + b×C2, where a and b are weighting coefficients determined by a large number of cases, such as a=1, b=0.5, which can be fine-tuned according to the type of surgery). Therefore, the relationship between ΔE and ΔC1, ΔC2 is:

[0104] ΔE = a×ΔC1 + b×ΔC2.

[0105] 3) Substituting proportions to solve for ΔC1 and ΔC2: Substituting ΔC2 = 2 × ΔC1 into the above formula, we get:

[0106] ΔE = a×ΔC1 + b×2×ΔC1 = ΔC1×(a + 2b).

[0107] Therefore, the formula for calculating the propofol concentration adjustment amount ΔC1 is:

[0108] ΔC1 = ΔE / (a ​​+ 2b).

[0109] The formula for calculating the remifentanil concentration adjustment ΔC2 is as follows:

[0110] ΔC2 = 2×ΔC1 = 2×ΔE / (a ​​+ 2b).

[0111] Example: If ΔE = 0.52, a = 1, b = 0.5, then:

[0112] ΔC1=0.52 / (1 + 2×0.5)=0.52 / 2=0.26 (μg / mL);

[0113] ΔC2=2×0.26=0.52 (ng / mL).

[0114] This means that the concentration of propofol in the effect cell needs to be increased by 0.26 μg / mL, and the concentration of remifentanil needs to be increased by 0.52 ng / mL.

[0115] S402. Based on the current effect-room concentrations of propofol and remifentanil, and combined with the concentration adjustment amounts of propofol and remifentanil, the target effect-room concentrations of propofol and remifentanil are obtained through the third and fourth expressions. The third expression is:

[0116] C1_target = C1_current + ΔC1,

[0117] The fourth expression is:

[0118] C2_target = C2_current + ΔC2,

[0119] In the formula, C1_target represents the target effect-room concentration of propofol, C1_current represents the current effect-room concentration of propofol, ΔC1 represents the concentration adjustment amount of propofol, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, and ΔC2 represents the concentration adjustment amount of remifentanil.

[0120] Example: If C1_current = 2.5 μg / mL and C2_current = 5 ng / mL, then:

[0121] C1_target=2.5 + 0.26=2.76 (μg / mL);

[0122] C2_target=5 + 0.52=5.52 (ng / mL).

[0123] The verification ratio is 2.76:5.52 = 1:2, which meets the requirements of K.

[0124] S5. Based on the target effect-site concentration of propofol, the target infusion rate of propofol is calculated using a pre-defined pharmacokinetic model for propofol applied to the target patient. Similarly, based on the target effect-site concentration of remifentanil, the target infusion rate of remifentanil is calculated using a pre-defined pharmacokinetic model for remifentanil applied to the target patient. The calculated target infusion rates can be transmitted to a display terminal for anesthesiologists' reference and can also be used to send drug infusion commands to the drug infusion device.

[0125] In one embodiment, the pre-set pharmacokinetic model for propofol applied to the target patient adopts the Schnider model, and the pre-set pharmacokinetic model for remifentanil applied to the target patient adopts the Minto model. Through the Schnider model of propofol and the Minto model of remifentanil, the "target effect-site concentration (C1_target, C2_target)" is back-calculated into the "actual infusion rate (R1, R2, unit: mL / h)". The core is to use the "effect-site concentration-infusion rate" correlation formula of the pharmacokinetic model.

[0126] In one embodiment, the core parameters of the Schnider model (including central ventricular distribution volume (V1) and central ventricular clearance rate (CL), where ke0 is a fixed value) can be pre-calculated using the target patient's age (Age), height (Ht), and weight (Wt). The Schnider model is a three-compartment model, and the relationship between effect room concentration (C1) and infusion rate (R1) is realized through the target-controlled infusion (TCI) algorithm. The expression for calculating the target infusion rate of propofol in the Schnider model is as follows (in the TCI algorithm, the infusion rate R1 must satisfy "to increase C1 from C1_current to C1_target at time t (e.g., within the next minute)":

[0127] R1=[(C1_target-C1_current)×V1×ke0+C1_target×CL] / C_prop,

[0128] In the formula, R1 represents the target infusion rate of propofol, C1_target represents the target effect-room concentration of propofol, C1_current represents the current effect-room concentration of propofol, V1 represents the central compartment distribution volume of propofol for the target patient, V1=4.27+(0.0267×Age)-(0.0015×Ht)+(0.0163×Wt) (unit: L), CL represents the central compartment clearance rate of propofol for the target patient, CL=1.89+(0.045×Age)-(0.015×Ht)+(0.013×Wt) (unit: L / h), and ke0 represents the transport rate constant between the effect room and central compartment for propofol (fixed at 0.46 min). - ¹ (i.e., 27.6 h) - ¹, reflecting the rate of drug transport from the central compartment to the effect compartment), C_prop represents the concentration of propofol (clinically commonly 10mg / mL=10000μg / mL, which needs to be adjusted according to the actual drug specifications), and the unit conversion needs to be consistent (e.g., C1_target is in μg / mL, V1 is in L=1000mL, and CL is in L / h).

[0129] Example: Patient Age = 50 years, Ht = 170cm, Wt = 70kg, C_prop = 1000ug / mL, C1_current = 2.5μg / mL, C1_target = 2.76μg / mL:

[0130] Calculate V1: 4.27 + (0.0267 × 50) - (0.0015 × 170) + (0.0163 × 70) = 4.27 + 1.335 - 0.255 + 1.141 = 6.5 L = 6500 mL;

[0131] Calculate CL: 1.89 + (0.045×50) - (0.015×170) + (0.013×70) = 1.89 + 2.25 - 2.55 + 0.91 = 2.5 L / h;

[0132] Substitute into the model expression:

[0133] R1=[(2.76-2.5)×6500×27.6 + 2.76×2.5×1000] / 10000

[0134] (Note: C1_target×CL needs to be converted to units. CL=2.5L / h=2500mL / h, C1_target=2.76μg / mL, so 2.76×2500=6900μg / h).

[0135] Step-by-step calculation:

[0136] ①(0.26×6500×27.6)=0.26×179400=46644μg / h

[0137] ②46644 + 6900 = 53544 μg / h

[0138] ③R1=53544 / 10000=5.3544mL / h≈5.4mL / h.

[0139] In one embodiment, the core parameters of the Minto model (including central compartment distribution volume (V1_r) and central compartment clearance rate (CL_r), where ke0_r is a fixed value) can be pre-calculated using the target patient's age (Age), height (Ht), weight (Wt), and sex (Sex). The pre-defined pharmacokinetic model for remifentanil applied to the target patient is the Minto model. The Minto model is a three-compartment model, and the relationship between effect room concentration and infusion rate is realized through the target-controlled infusion (TCI) algorithm. The expression for calculating the target infusion rate of remifentanil using the Minto model is as follows:

[0140] R2=[(C2_target-C2_current)×V1_r×ke0_r+C2_target×CL_r] / C_prop_r,

[0141] In the formula, R2 represents the target infusion rate of remifentanil, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, V1_r represents the central chamber distribution volume of remifentanil for the target patient (V1_r = 0.33 + (0.005 × Wt) for males and V1_r = 0.28 + (0.005 × Wt) for females (unit: L), CL_r represents the central chamber clearance rate of remifentanil for the target patient (CL_r = (0.013 × Wt) + (0.0002 × Age) + (0.015 × Sex) (Sex = 1 for males, 0 for females, unit: L / h), and ke0_r represents the transport rate constant between the effect-room and central chamber for remifentanil, fixed at 1.2 min. - ¹ (i.e., 72 h) - ¹), C_prop_r represents the concentration of remifentanil (clinically commonly 1mg / 50mL=20μg / mL=20000ng / mL).

[0142] Example: Same patient as before (male, Wt=70kg, Age=50 years), C_prop_r=20000ng / mL, C2_current=5ng / mL, C2_target=5.52ng / mL:

[0143] Calculate V1_r: 0.33 + (0.005×70) = 0.33 + 0.35 = 0.68 L = 680 mL;

[0144] Calculate CL_r: (0.013×70)+(0.0002×50)+(0.015×1)=0.91+0.01+0.015=0.935L / h=935mL / h;

[0145] Substitute into the model expression:

[0146] R2 = [(5.52-5)×680×72 + 5.52×935] / 20000.

[0147] Step-by-step calculation:

[0148] ①(0.52×680×72)=0.52×48960=25459.2ng / h

[0149] ②5.52×935=5161.2ng / h

[0150] ③25459.2 + 5161.2=30620.4ng / h

[0151] ④R2=30620.4 / 20000=1.53102mL / h≈1.5mL / h.

[0152] S6. According to the preset safety control mechanism, verify at least one of the following: the target effect-site concentration of propofol, the target effect-site concentration of remifentanil, the adjustment range of propofol infusion rate, and the adjustment range of remifentanil infusion rate, and obtain the final drug infusion rate adjustment command based on the verification results.

[0153] In one embodiment, the preset security control mechanism may include:

[0154] When the target effect-site concentration of propofol exceeds the first preset safety upper limit (e.g., 6 μg / mL), the target effect-site concentration of propofol is forcibly set to the first preset safety upper limit, and the target infusion rate of propofol is recalculated.

[0155] When the target effect-community concentration of remifentanil exceeds the second preset safety upper limit (e.g., 12 ng / mL), the target effect-community concentration of remifentanil is forcibly set to the second preset safety upper limit, and the target infusion rate of remifentanil is recalculated.

[0156] When the adjustment range of propofol infusion rate (infusion rate adjustment range = |target infusion rate - current infusion rate| / current infusion rate) is greater than or equal to 20%, the target infusion rate of propofol will be adjusted to 1.2 times the current infusion rate; when the adjustment range of propofol infusion rate is less than 20%, the target infusion rate of propofol will be adjusted to 0.8 times the current infusion rate.

[0157] When the infusion rate of remifentanil is adjusted by 20% or more, the target infusion rate of remifentanil will be adjusted to 1.2 times the current infusion rate. When the infusion rate of remifentanil is adjusted by less than 20%, the target infusion rate of remifentanil will be adjusted to 0.8 times the current infusion rate.

[0158] In one embodiment, the BIS value can also be monitored, and an abnormal BIS value alarm can be issued when it continuously exceeds a preset range.

[0159] The method for calculating the synergistic control rate of drug infusion provided by this invention has the following significant advantages:

[0160] By fixing the effect-site concentration ratio of the two drugs, the synchronization and matching of sedation and analgesia are fundamentally ensured, avoiding the risks caused by the excessively strong or weak effects of a single drug, and achieving true automation of "balanced anesthesia".

[0161] Closed-loop control based on real-time BIS feedback can quickly respond to individual differences and changes in surgical stimulation, so that the BIS value is more stably controlled within the target range, reducing fluctuations in the depth of anesthesia.

[0162] This significantly reduces the workload of anesthesiologists during the maintenance period of anesthesia and reduces management deviations caused by differences in human experience and fatigue.

[0163] Built-in multiple safety protection mechanisms (concentration limit, rate limit, and abnormal alarm) can effectively avoid the risks caused by drug overdose or equipment failure, greatly improving the safety of the automatic infusion process.

[0164] The following describes the collaborative control rate calculation system for drug infusion provided by the present invention. The collaborative control rate calculation system for drug infusion described below can be referred to in correspondence with the collaborative control rate calculation method for drug infusion described above.

[0165] See Figure 3 The present invention provides a collaborative control rate calculation system for drug infusion, which may include:

[0166] The data receiving module is used to: receive the current BIS value of a target patient receiving medication from at least one terminal, wherein the medication being infused in the target patient includes propofol and remifentanil, and the ratio of the effect-site concentration of propofol to the effect-site concentration of remifentanil is fixed at 1:2.

[0167] The drug infusion adjustment need determination module is used to: compare the current BIS value with the preset target range to obtain the drug infusion adjustment needs of the target patient;

[0168] The first calculation module is used to: calculate the total effect intensity adjustment amount that makes the subsequent BIS value of the target patient return to the preset target range when the drug infusion adjustment demand indicates that the drug infusion rate needs to be adjusted;

[0169] The second calculation module is used to: obtain the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculate the target effect-site concentrations of propofol and remifentanil respectively based on the total effect intensity adjustment.

[0170] The third calculation module is used to: back-calculate the target infusion rate of propofol based on the target effect-site concentration of propofol using a preset pharmacokinetic model of propofol applied to the target patient; and back-calculate the target infusion rate of remifentanil based on the target effect-site concentration of remifentanil using a preset pharmacokinetic model of remifentanil applied to the target patient.

[0171] The data output module is used to send the target infusion rates of propofol and remifentanil to at least one terminal.

[0172] See Figure 4 The present invention provides a collaborative control rate calculation system for drug infusion, which may include:

[0173] BIS monitoring module: used to collect and process the electroencephalogram (EEG) signals of the target patient and output the BIS value;

[0174] Target-controlled infusion pump: Includes two independent, high-precision infusion pump channels, used for infusing propofol and remifentanil respectively. Each channel has an adjustable infusion rate control function and receives instructions from the central control unit to adjust the rate in real time.

[0175] Central Control Unit: This is the core processing component, responsible for receiving data from the BIS monitoring module, executing the steps of the collaborative control rate calculation method for drug infusion provided by this invention, sending rate adjustment commands to the infusion pump, and possessing data storage and abnormal alarm functions. Specifically, it includes:

[0176] Data processing subunit: used to receive and process BIS signals;

[0177] Pharmacokinetic Model Library: Stores parameters for pharmacokinetic models of propofol and remifentanil;

[0178] Control algorithm subunit: Built-in PID and other control algorithms are used to execute the steps of the collaborative control rate calculation method for drug infusion provided by this invention;

[0179] Security monitoring subunit: used to execute security control logic;

[0180] Communication interface: Used to send rate control commands to the infusion pump.

[0181] Audible and visual alarm device: Receives abnormal signals from the central control unit and provides dual alerts for faults or risks through sound and light (flashing red).

[0182] Figure 5 An example is a schematic diagram of the physical structure of an electronic device, such as... Figure 5As shown, the electronic device may include a processor 810, a communications interface 820, a memory 830, and a communication bus 840, wherein the processor 810, the communications interface 820, and the memory 830 communicate with each other via the communication bus 840. The processor 810 can call logical instructions in the memory 830 to execute the above steps S1-S5 or S1-S6.

[0183] Furthermore, the logical instructions in the aforementioned memory 830 can be implemented as software functional units and, when sold or used as independent products, can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, or the part that contributes to the prior art, or a part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of the present invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0184] On the other hand, the present invention also provides a computer program product, the computer program product including a computer program, the computer program being stored on a non-transitory computer-readable storage medium, and when the computer program is executed by a processor, the computer is able to perform the above steps S1-S5 or S1-S6.

[0185] In another aspect, the present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, is implemented to perform the above steps S1-S5 or S1-S6.

[0186] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs. Those skilled in the art can understand and implement this without any creative effort.

[0187] Through the above description of the embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus necessary general-purpose hardware platforms, and of course, it can also be implemented by hardware. Based on this understanding, the above technical solutions, in essence or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, magnetic disk, optical disk, etc., and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute the methods described in the various embodiments or some parts of the embodiments.

[0188] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A synergistic controlled rate calculation system for drug infusion, characterized by, include: The data receiving module is used to: receive the current BIS value of a target patient receiving medication from at least one terminal, wherein the medication being infused in the target patient includes propofol and remifentanil, and the ratio of the effect-site concentration of propofol to the effect-site concentration of remifentanil is fixed at 1:

2. The drug infusion adjustment need determination module is used to: compare the current BIS value with the preset target range to obtain the drug infusion adjustment needs of the target patient; The first calculation module is used to: calculate the total effect intensity adjustment amount that makes the subsequent BIS value of the target patient return to the preset target range when the drug infusion adjustment demand indicates that the drug infusion rate needs to be adjusted; The second calculation module is used to: obtain the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculate the target effect-site concentrations of propofol and remifentanil respectively based on the total effect intensity adjustment. The third calculation module is used to: back-calculate the target infusion rate of propofol based on the target effect-site concentration of propofol using a preset pharmacokinetic model of propofol applied to the target patient; and back-calculate the target infusion rate of remifentanil based on the target effect-site concentration of remifentanil using a preset pharmacokinetic model of remifentanil applied to the target patient. The data output module is used to: send the target infusion rates of propofol and remifentanil to at least one terminal; The step of obtaining the current effect-site concentrations of propofol and remifentanil infused in the target patient, and calculating the target effect-site concentrations of propofol and remifentanil based on the total effect strength adjustment, includes: The concentration adjustment amount of propofol is obtained through the first expression, where the first expression is: ΔC1 = ΔE / (a ​​+ 2b), The concentration adjustment amount of remifentanil is obtained through the second expression, where the second expression is: ΔC2 = 2×ΔC1 = 2×ΔE / (a ​​+ 2b), In the formula, ΔC1 represents the concentration adjustment amount of propofol, and ΔC2 represents the concentration adjustment amount of remifentanil, E represents the total effect intensity adjustment amount, and a and b represent preset weight coefficients, respectively. The target effect-compartment concentration of propofol is obtained through the third expression, which is: C1_target = C1_current + ΔC1, The target effect-cell concentration of remifentanil is obtained through the fourth expression, which is: C2_target = C2_current + ΔC2, In the formula, C1_target represents the target effect-room concentration of propofol, C1_current represents the current effect-room concentration of propofol, ΔC1 represents the concentration adjustment amount of propofol, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, and ΔC2 represents the concentration adjustment amount of remifentanil. The pre-defined pharmacokinetic model for propofol in target patients is the Schnider model, a three-compartment model. The expression for calculating the target infusion rate of propofol using the Schnider model is as follows: R1=[(C1_target-C1_current)×V1×ke0+C1_target×CL] / C_prop, In the formula, R1 represents the target infusion rate of propofol, C1_target represents the target effect room concentration of propofol, C1_current represents the current effect room concentration of propofol, V1 represents the central compartment distribution volume of propofol for the target patient, CL represents the central compartment clearance rate of propofol for the target patient, ke0 represents the transport rate constant between the effect room and the central compartment for propofol, and C_prop represents the propofol concentration. Furthermore, the pre-defined pharmacokinetic model for remifentanil in target patients is the Minto model, a three-compartment model. The expression for calculating the target infusion rate of remifentanil using the Minto model is as follows: R2=[(C2_target-C2_current)×V1_r×ke0_r+C2_target×CL_r] / C_prop_r, In the formula, R2 represents the target infusion rate of remifentanil, C2_target represents the target effect-room concentration of remifentanil, C2_current represents the current effect-room concentration of remifentanil, V1_r represents the central chamber distribution volume of remifentanil for the target patient, CL_r represents the central chamber clearance rate of remifentanil for the target patient, ke0_r represents the transport rate constant between the effect-room and central chamber for remifentanil, and C_prop_r represents the concentration of remifentanil.

2. The synergistic controlled rate calculation system for drug infusion of claim 1, wherein, The step of comparing the current BIS value with a preset target range to obtain the target patient's drug infusion adjustment needs includes: When the BIS value is within the preset target range, it is determined that there is no need to adjust the drug infusion rate. When the BIS value is higher than the upper limit of the preset target range, the drug infusion adjustment requirement is determined to be an increase in the drug infusion rate. When the BIS value is lower than the lower limit of the preset target range, the drug infusion adjustment requirement is determined to be that the drug infusion rate needs to be reduced.

3. The synergistic controlled rate calculation system for drug infusion of claim 2, wherein, When a drug infusion adjustment request indicates a need to adjust the drug infusion rate, the calculation of the total effect strength adjustment that brings the target patient's subsequent BIS value back to the preset target range includes: Calculate the deviation between the current BIS value and the midpoint of the preset target interval to obtain the BIS deviation value; Based on the BIS deviation value, a control algorithm is used to obtain the total effect strength adjustment amount that brings the subsequent BIS value of the target patient back to the preset target range. The expression for the control algorithm is as follows: E = Kp x BIS + Ki x ∫ BIS dt + Kd x d( BIS) / dt, E represents a total effect intensity adjustment amount, BIS represents a BIS deviation value, (Kp x BIS) represents a proportional term, Kp represents a preset proportional coefficient, (Ki x ∫ BISdt) represents an integral term, Ki represents a preset integral coefficient, (Kd x d( BIS) / dt) represents a differential term, and Kd represents a preset differential coefficient.

4. A synergic control rate calculation system for drug infusion according to any of claims 1-3, characterized in that, It also includes a verification module, which is used to: verify at least one of the target effect-site concentration of propofol, the target effect-site concentration of remifentanil, the infusion rate adjustment range of propofol, and the infusion rate adjustment range of remifentanil according to a preset safety control mechanism, and obtain the final drug infusion rate adjustment command based on the verification result. The preset security control mechanism includes: When the target effect chamber concentration of propofol exceeds the first preset safety upper limit, the target effect chamber concentration of propofol is forcibly set to the first preset safety upper limit, and the target infusion rate of propofol is recalculated. When the target effect chamber concentration of remifentanil exceeds the second preset safety upper limit, the target effect chamber concentration of remifentanil is forcibly set to the second preset safety upper limit, and the target infusion rate of remifentanil is recalculated. When the adjustment range of propofol infusion rate is greater than or equal to the first preset range threshold, the target infusion rate of propofol is adjusted to X1 times the current infusion rate; when the adjustment range of propofol infusion rate is less than the first preset range threshold, the target infusion rate of propofol is adjusted to X2 times the current infusion rate. When the adjustment range of the remifentanil infusion rate is greater than or equal to the second preset range threshold, the target infusion rate of remifentanil is adjusted to X3 times the current infusion rate. When the adjustment range of the remifentanil infusion rate is less than the second preset range threshold, the target infusion rate of remifentanil is adjusted to X4 times the current infusion rate.

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