WO2018040324A1

WO2018040324A1 - Citrate anticoagulation device and application thereof

Info

Publication number: WO2018040324A1
Application number: PCT/CN2016/107678
Authority: WO
Inventors: 丁峰; 郑寅; 庄峰; 马帅; 俞雯艳; 陆伟; 卢建新
Original assignee: 上海交通大学医学院附属第九人民医院
Priority date: 2016-08-30
Filing date: 2016-11-29
Publication date: 2018-03-08
Also published as: CN206518724U

Abstract

Disclosed is a citrate anticoagulation device, comprising a control device (3), a first peristaltic pump (1) and a second peristaltic pump (2). The control device (3) comprises a peristaltic pump control module (100), a display module (200) and an input module (300). The input module (300) is connected to the peristaltic pump control module (100). The peristaltic pump control module (100) is connected to the first peristaltic pump (1) and the second peristaltic pump (2). The first peristaltic pump (1) is a citrate pump, and the second peristaltic pump (2) is a calcium pump. Using the inventive device, the automatic control of the citrate pump and the calcium pump can be realized, thereby saving labour and improving the accuracy.

Description

Tannic acid anticoagulant device and its application

Technical field

The invention relates to a citrate anticoagulant device and an application thereof.

Background technique

As shown in Figure 1, in vitro anticoagulation is the key to the smooth progress of blood purification. Regional citrate anticoagulation (RCA) is an ideal choice for extracorporeal circulation anticoagulation in patients with high risk of bleeding because of its anticoagulant effect, less bleeding complications, and prolonged service life of dialyzer 30. However, due to potential metabolic complications, the operation is complicated, and frequent monitoring is required during the period, which limits its clinical application.

The traditional local citrate anticoagulation technique is to inject the sodium citrate solution (disposed in the citrate reservoir 10) at a certain ratio according to the blood flow velocity at the extracorporeal circulation of the arterial end, and at the venous end (blood back) Calcium chloride (before the calcium chloride storage tank 20) is added to the patient to ensure normal levels of ionized calcium in the patient. Local citrate anticoagulation-CRRT principle: citrate is infused from the arterial end, the ionized calcium level in the extracorporeal circulation line is reduced to 0.2-0.4 mM/L, which exerts anticoagulation in vitro and chlorinate from the venous end. Calcium, the level of ionized calcium in the body remains normal without affecting the body's coagulation system.

In Figure 1, 4% sodium citrate is input from the venous end, so that the extracellular circulating ionized calcium is reduced to 0.2-0.4mmol/L to achieve anticoagulant effect, and calcium chloride is added from the vein end to restore the ionized calcium level in the body to 1.0-1.2 mmol/L.

According to the existing literature reports and the experience in practical work, the traditional RCA has the following problems in clinical application:

(1) It is necessary to add two precision infusion pumps for the infusion of citric acid solution and calcium solution on the basis of the original blood purification device, which is cumbersome to operate;

(2) The citrate infusion pump and the calcium supplemental infusion pump are two independent pumps. When the treatment parameters change or the dialysis machine stops the pump due to alarm, replacement of replacement fluid/dialysis solution, etc., the dialysis nurse needs to manually suspend the pump. / Start these two pumps, if the operation is not standardized, may cause excessive iatrogenic citrate infusion or hypercalcemia caused by anticoagulation failure of extracorporeal circulation;

(3) The traditional citrate anticoagulant program mainly adopts the “trial and error method” of monitoring-adjusting-re-monitoring, which is to set an initial calcium supplement rate according to experience, and then adjust the ion calcium level in the body and in vitro by frequent monitoring. Calcium supplementation rate, the results show that the level of ionized calcium in the body fluctuates greatly, and because the change of calcium lags behind the adjustment of calcium, it is difficult to accurately grasp the amount of calcium supplement;

(4) Manpower invested in RCA (at least one trained hemodialysis nurse and doctor familiar with citrate anticoagulant technology), material resources (requires monitoring of ionized calcium every 2-4 hours, cost per measurement) 150 yuan) The cost is huge.

Summary of the invention

In view of the above-discussed shortcomings of the prior art, it is an object of the present invention to provide a tantalum acid anticoagulant device capable of automatically adjusting the speed and an application thereof, which can realize automatic operation without manual trial and error.

To achieve the above and other related objects, the present invention provides a citrate anticoagulating device, the citrate anticoagulating device comprising at least: a first peristaltic pump, a second peristaltic pump, and a control device, the control The device comprises a peristaltic pump control module, a display module and an input module, the input module is connected to the peristaltic pump control module, the peristaltic pump control module is connected to the first peristaltic pump and the second peristaltic pump, the first peristaltic pump is tannic acid The pump, the second peristaltic pump is a calcium pump.

Preferably, the peristaltic pump control module comprises:

a first peristaltic pump speed control sub-module for controlling a citrate infusion rate, connected to the first peristaltic pump;

A second peristaltic pump speed control sub-module for controlling the rate of calcium supplementation is coupled to the second peristaltic pump.

Preferably, the first peristaltic pump speed control submodule comprises:

a citrate infusion rate calculation unit for calculating a citrate infusion rate, connected to the input module;

A first peristaltic pump speed signal output unit for transmitting a first peristaltic pump infusion speed command is coupled to the capric acid infusion rate calculation unit and the first peristaltic pump.

Preferably, the citrate infusion rate calculation unit obtains a citrate infusion rate of Qcit,

Qcit=Qb×(1-Hct)×C ₀ mmol/Csolution;

C ₀ : 3 to 5;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity L/h,

Csolution: The amount of citric acid in 1 L of citric acid solution is mmol.

Preferably, the second peristaltic pump speed control submodule comprises:

a second peristaltic pump first stage speed calculation unit for calculating a sum of the amount of calcium removed by the in vitro dialysis and the amount of accumulated calcium in the body, connected to the input module and the citrate infusion rate calculation unit;

A second peristaltic pump second stage speed calculation unit for calculating the amount of calcium removed by the external dialysis is connected to the input module and the citrate infusion rate calculation unit.

A second creeping speed signal output unit for transmitting the second peristaltic pump speed is coupled to the second peristaltic pump first stage speed calculating unit, the second peristaltic pump second stage speed calculating unit, and the second peristaltic pump.

Preferably, the second peristaltic pump first stage speed calculation unit obtains the first stage calcium supplementation speed by using the following formula:

QCaCl ₂ = Qca/0.34

f: 0.80 to 0.90

Qca: the amount of calcium that should be replenished per unit time is mmol/h,

QCaCl ₂ : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): calcium supplement per unit time, mmol/h,

CcaT(art): total calcium concentration at the arterial end, equivalent to the total calcium concentration in the body, mmol/L,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qcit: citrate infusion rate L/h.

Preferably, the second peristaltic pump second stage speed calculation unit obtains the second stage calcium supplementation speed by using the following formula:

or:

Qca(phase II)=Qeffluent×Cca_effluent

QCaCl ₂ = Qca/0.34

Qeffluent: effluent speed L/h,

Cca_effluent: total calcium concentration in the effluent is mmol/L,

Qca (phase II): the second stage unit time calcium supplement mmol / h;

QCaCl ₂ : Infusion rate of 5% calcium chloride solution per unit time ml/h.

Preferably, the f is 0.87.

Preferably, the f is 0.80.

In the present invention, calcium supplementation is divided into two stages, and the process is as follows:

The core idea is that there is accumulation of tannic acid in the body during local anti-coagulation, and the accumulated tannic acid is mainly in the form of calcium salt. According to the pharmacokinetic parameters of tannic acid, the accumulation generally reaches about 3 hours after the start of treatment. Steady state, for example, Kramer et al reported that the half-life of citrate in critically ill patients with cirrhosis was 36 minutes. According to pharmacokinetic theory, the concentration of drug in vivo reached a steady state concentration after 5 half-lives, so the body citrate concentration in RCA - CRRT reaches steady state three hours after the start Degree, the time point at which the calcium supplementation rate was adjusted at the end of the third hour after the start of RCA-CRRT (Kramer L, Bauer E, Joukhadar C, et al. Crit Care Med, 2003, 31: 2450-2455.). Therefore, the calcium supplementation of local citrate anticoagulation also needs to be divided into two stages. The first stage needs to supplement the accumulation of calcium in the body and the extracorporeal circulation to remove calcium. In the second stage, it is only necessary to supplement the extracorporeal circulation to remove calcium.

It should be noted that the two-stage calcium supplement mathematical model proposed by the device is suitable for a low-clearing efficiency blood purification mode in which citrate accumulation exists, such as CRRT. For high-efficiency blood purification modes (such as conventional interstitial hemodialysis, etc.), since there is no cesium acid accumulation or accumulation negligible, it can be regarded as a special case of the above model, that is, directly entering the second stage of calcium supplementation, and There is no need to supplement the accumulated calcium fraction.

Preferably, the second peristaltic pump speed signal output unit comprises:

a switching time subunit for storing or setting the first phase and the second phase switching time of the second peristaltic pump;

a signal output subunit for transmitting a second peristaltic pump speed output signal according to a switching time, and a switching time subunit, a second peristaltic pump first stage speed calculation unit, a second peristaltic pump second stage speed calculation unit, and a second peristalsis The pump is connected.

Preferably, the citrate anticoagulating device further comprises a bubble detecting module, and the peristaltic pump control module further comprises: a module that receives the bubble detecting module signal and sends a pause peristaltic pump command, and is connected to the bubble detecting module.

Preferably, the bubble detecting module includes a bubble detecting member and a warning member.

Preferably, the bubble detecting member is an ultrasonic detector, and the warning member comprises a plurality of indicator lights of different colors.

The ultrasonic detector may adopt the prior art, and the ultrasonic detector detects bubbles in the infusion tube on the first peristaltic pump and the second peristaltic pump by ultrasonic waves, and the principle is as follows: when the ultrasonic wave propagates in the medium, the acoustic impedance is encountered. Different interfaces produce scattered reflections that can cause attenuation of the ultrasound. When there is no air bubble in the infusion tube, the ultrasonic reflection coefficient is small, and there is almost no attenuation; when there is a bubble, since the acoustic impedance of the air and water differ greatly, the ultrasonic wave has a large reflection coefficient, and the ultrasonic attenuation is severe at this time.

Preferably, the citrate anticoagulating device is connected to an external infusion tube, the peristaltic pump control module further comprising a pre-filling unit for controlling pre-charging of the infusion tube, and the first peristaltic pump speed control sub-module and the The two peristaltic pump speed control sub-modules are connected.

Preferably, the display module is coupled to the input module and is selectively connectable to the peristaltic pump control module.

Preferably, the control device further comprises a self-detection module for detecting whether the parameter input by the input module meets a preset parameter range, and the self-detection module is connected to the input module.

Another aspect of the invention provides the use of the above-described citrate anticoagulant device for local citrate anticoagulation.

Another aspect of the present invention provides a method for anticoagulation of citric acid, which in turn comprises the following steps:

1) The first stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used. Calcium is added to the blood after anticoagulation, and the amount of calcium supplementation is the sum of the amount of calcium removed by in vitro dialysis and the amount of accumulated calcium in the body;

2) The second stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used to supplement calcium in the blood after anticoagulation, which is in vitro. The amount of calcium removed by dialysis. Preferably, the first stage of citrate anticoagulation is for 3 hours.

Preferably, in the first stage of citrate anticoagulation and the second stage of citrate anticoagulation, the rate of addition of citric acid to the blood to be anticoagulated is calculated as:

Qcit=Qb×(1-Hct)×C ₀ mmol/Csolution;

C ₀ : 3 to 5;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity L/h,

Csolution: The amount of citric acid in 1 L of citric acid solution is mmol.

Preferably, the formula for calculating the amount of calcium in the first stage of citrate anticoagulation is:

QCaCl ₂ = Qca/0.34

f: 0.80 to 0.90

Qca: the amount of calcium that should be replenished per unit time is mmol/h,

QCaCl ₂ : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): the amount of calcium in the first phase per unit time is mmol/h,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qcit: citrate infusion rate L/h.

Preferably, the formula for calculating the amount of calcium in the second stage of citrate anticoagulation is:

or:

Qca(phase II)=Qeffluent×Cca_effluent

QCaCl ₂ = Qca/0.34

Qeffluent: effluent speed L/h,

Cca_effluent: total calcium concentration in the effluent is mmol/L,

Qca (phase II): the second stage unit time calcium supplement mmol / h;

QCaCl ₂ : Infusion rate of 5% calcium chloride solution per unit time ml/h.

Preferably, the f is 0.87.

Preferably, the f is 0.8.

As described above, the tannic acid anticoagulant device of the present invention has the following beneficial effects:

Compared with the prior art, the invention has the following advantages: the device is specially designed for RCA anticoagulation, and the tannic acid pump and the calcium pump are integrated, and the double pump system can be linked with the dialysis machine arterial pump, and the tannic acid is embedded at the same time. Calcium infusion mathematical model, controlling the speed of the two pumps, without the need for medical staff to operate too much. In the past, it was necessary to monitor the body and pipeline ionized calcium every 2-4 hours in the RCA process. The 24-hour CRRT needs to be monitored frequently for 6-8 times. The calcium supplementation rate calculated by the software is calcium supplementation, the monitoring interval is extended, and the 24-hour treatment only needs to be detected. 2 to 3 times. To a certain extent, the labor load of medical staff is reduced, and safety is improved. Improve the success rate of blood purification treatment in patients with critically acute kidney injury, especially those with high risk of bleeding. The invention on the one hand reduces the labor intensity of the staff and on the other hand reduces the cost of treatment. It makes local citrate anticoagulation a simple anticoagulant technology and promotes its clinical application.

DRAWINGS

Figure 1 is a schematic view of the structure of the prior art;

Figure 2 is a schematic structural view of a first embodiment of the present invention;

Figure 3 is a schematic structural view of a second embodiment of the present invention;

Figure 4 is a schematic structural view of a third embodiment of the present invention;

Figure 5 is a schematic structural view of a fourth embodiment of the present invention;

Figure 6 is a schematic structural view of a fifth embodiment of the present invention;

Fig. 7 is a schematic view showing the application effect of the two-stage calcium supplement model in the treatment of long-term CVVH in the present embodiment.

1 first peristaltic pump

2 second peristaltic pump

3 control device

100 peristaltic pump control module

110 first peristaltic pump speed control sub-module

111 citrate speed calculation module

112 first peristaltic pump speed signal output unit

120 second peristaltic pump speed control submodule

121 second peristaltic pump first stage speed calculation unit

122 second peristaltic pump second stage speed calculation unit

123 second peristaltic pump speed signal output unit

1231 Switching time subunit

1232 signal output subunit

200 display module

300 input module

400 self-test module

4 bubble detection module

401 bubble detector

402 warnings

10 tannic acid storage tank

20 sodium chloride storage tank

30 dialyzer

detailed description

The embodiments of the present invention are described below by way of specific embodiments, and those skilled in the art can readily understand other advantages and functions of the present invention from the disclosure.

Please refer to Figure 1 to Figure 7. It should be understood that the structures, the proportions, the sizes, and the like, which are illustrated in the specification of the present specification, are only used to clarify the contents disclosed in the specification for understanding and reading by those skilled in the art, and are not intended to limit the implementation of the present invention. The conditions are limited, so it is not technically meaningful. Any modification of the structure, change of the proportional relationship or adjustment of the size should remain in the present invention without affecting the effects and the achievable purposes of the present invention. The disclosed technical content is within the scope of the disclosure. In the meantime, the terms "upper", "lower", "left", "right", "intermediate" and "one" as used in this specification are also for convenience of description, and are not intended to limit the present. The scope of the invention can be implemented, and the change or adjustment of the relative relationship is considered to be within the scope of the invention.

Example 1 uses a local citrate anticoagulation method for long-term CVVH (continuous venous-venous hemofiltration) Perform local citrate anticoagulation, which in turn includes the following steps:

1) The first stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used to supplement calcium into the blood after anticoagulation, and the amount of calcium supplement is external to the body. The sum of the amount of calcium removed by dialysis and the amount of accumulated calcium in the body;

2) The second stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used to supplement calcium in the blood after anticoagulation, which is in vitro. The amount of calcium removed by dialysis.

The first stage of citrate anticoagulation time is 3 hours, and the speed of the citrate pump and the calcium pump is controlled by a control device.

In the first stage of citrate anticoagulation and the second stage of citrate anticoagulation, the citrate pump adds citric acid to the blood to be anticoagulated by using the following formula to obtain the citric acid addition rate Qcit,

Qcit=Qb×(1-Hct)×C ₀ mmol/Csolution;

C ₀ : 3;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity L/h,

Csolution: The amount of citric acid in 1 L of citric acid solution is mmol.

The amount of calcium supplemented in the first stage of citrate anticoagulation is obtained by the following formula:

QCaCl ₂ = Qca/0.34

f: 0.87,

Qca: the amount of calcium that should be replenished per unit time is mmol/h,

QCaCl ₂ : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): the amount of calcium in the first phase per unit time is mmol/h,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qcit: citrate infusion rate L/h.

The amount of calcium supplemented in the second stage of citrate anticoagulation is obtained by the following formula:

or:

Qca(phase II)=Qeffluent×Cca_effluent

QCaCl ₂ = Qca/0.34

Qeffluent: effluent speed L/h,

Cca_effluent: total calcium concentration in the effluent is mmol/L,

Qca (phase II): the second stage unit time calcium supplement mmol / h;

QCaCl ₂ : Infusion rate of 5% calcium chloride solution per unit time ml/h.

Example 2 Localized citrate anticoagulation in patients with prolonged CVVH (continuous venous-venous hemofiltration) using a local citrate anticoagulation method:

In the present embodiment, f is 0.9 and C ₀ is 5, and the others are the same as those in the first embodiment.

Embodiment 3 As shown in FIG. 2, the present invention provides a citrate anticoagulant device comprising a first peristaltic pump 1, a second peristaltic pump 2, and a control device 3, the control device comprising a peristaltic pump control module 100, a display module 200 and an input module 300, the input module 300 is connected to a peristaltic pump control module 100, the peristaltic pump control module 100 is connected to a first peristaltic pump 1 and a second peristaltic pump 2, the first peristaltic pump 1 being a crucible An acid pump, the second peristaltic pump 2 is a calcium pump.

In order to further optimize the design, the display module 200 can also be connected to the input module 300. The peristaltic pump control module 100 is also connected to the display module 200, and the display module can display the speed of the peristaltic pump.

In the present invention, the control device can transmit a signal to the first peristaltic pump and the second peristaltic pump through the RS485 bus by using a computer. The display module and the input module are configured to provide a dialog box on the computer display device to form a human-computer interaction interface, and the user can input parameters and/or instructions by using a computer keyboard or a touch screen display. Both the first peristaltic pump and the second peristaltic pump are commonly used peristaltic pumps, which are commercially available to those skilled in the art.

For example, as shown in FIG. 3, the control device 3 further includes a self-detection module 400 for detecting whether the input parameter of the input module 300 meets the preset parameter range, and is connected to the input module 300 and the display module 200. That is, after the input module 300 inputs the parameters, the self-test module 400 will automatically determine whether the set parameters or the input parameters are reasonable. If it is unreasonable, the display module 200 displays the prompt information to prevent the doctor from inputting the parameters during the error operation. Regarding a reasonable range of parameters, industry standards in the field can be employed. For example, the general range of hematocrit is male: 0.40 to 0.50, female: 0.35 to 0.45. If the user inputs a hematocrit of 0.8, the display module will pop up a dialog box prompting the user to make an error.

To further optimize the design, the peristaltic pump control module 100 as shown in FIG. 4 includes a first peristaltic pump speed control sub-module 110 for controlling the citrate infusion rate, and a second peristaltic pump speed control for controlling the calcium supplementation speed. The sub-module 120 controls the speeds of the first peristaltic pump 1 and the second peristaltic pump 2, respectively. To further optimize the design, the first peristaltic pump speed control sub-module 110 can control a 4% citrate anticoagulation rate or an ACDC anticoagulation rate. The speed of the second peristaltic pump is respectively recorded as QCaCl ₂ , and the speed of calcium supplementation by the second peristaltic pump is divided into two stages, which are a first stage and a second stage, respectively, and the first stage is calcium supplementation 0～ Between 3h (the first 3 hours), the second phase begins with the fourth hour of calcium supplementation.

As shown in FIG. 5, the first peristaltic pump speed control sub-module 110 includes a citrate infusion rate calculation unit 111 for calculating a citrate infusion rate, which is connected to the input module and passes the input parameters. The value is further calculated to obtain a citrate infusion rate; a first peristaltic pump speed signal output unit 112 for transmitting a first peristaltic pump infusion speed command, and the citrate infusion rate calculation unit and the first peristaltic pump 1 is connected, and the speed signal command is sent to the first peristaltic pump 1.

The mathematical formula for the citrate infusion rate can be calculated by the prior art, preferably by the following method:

Qcit=Qb×(1-Hct)×C ₀ mmol/Csolution;

C ₀ : 3 to 5;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity (L/h)

Csolution: 1L of citric acid in a 1L citric acid solution,

The above parameters Hct and Qb can be measured by the prior art before the start of dialysis, and the user inputs with the input module, and C ₀ can be preset.

As shown in FIG. 5, the second peristaltic pump speed control sub-module 120 includes: a second peristaltic pump first-stage speed calculation unit 121 for calculating the sum of the amount of calcium removed by the external dialysis and the amount of accumulated calcium in the body, and the input The module is connected to the citrate infusion rate calculation unit; the second peristaltic pump second stage speed calculation unit 122 is configured to calculate the amount of calcium removed by the external dialysis, and is connected to the input module and the citrate infusion rate calculation unit; A second creeping speed signal output unit 123 for transmitting the second peristaltic pump speed is connected to the second peristaltic pump first stage speed calculating unit, the second peristaltic pump second stage speed calculating unit, and the second peristaltic pump 2. Therefore, the second creeping speed signal output unit 123 can transmit the speed signal required by the second peristaltic pump obtained from the second peristaltic pump first stage speed calculating unit 121 and the second peristaltic pump speed second creeping speed signal output unit 122. Give the second peristaltic pump 2.

As shown in FIG. 5, in order to further optimize the design, the second peristaltic pump speed signal output unit 123 includes: a switching time subunit 1231 for storing or setting the first and second phase switching times of the second peristaltic pump; a signal output subunit 1232 for transmitting a second peristaltic pump speed output signal according to the switching time, and a switching time subunit, a second peristaltic pump first stage speed calculation unit, a second peristaltic pump second stage speed calculation unit, and a second peristalsis The pump is connected. User can The switching time points of the first stage and the second stage are set by the input module. For example, after 3 hours of dialysis, the second peristaltic pump directly enters the second stage from the first stage, and the signal output is performed during the dialysis period of 0-3 hours. The unit transmits the obtained speed signal from the first stage speed calculation unit of the second peristaltic pump to the second peristaltic pump, and after the start of the fourth hour, the signal output unit is obtained from the second stage speed calculation unit of the second peristaltic pump The speed signal is transmitted to the second peristaltic pump.

The second peristaltic pump first stage speed calculation unit and the second peristaltic pump second stage speed calculation unit may be obtained by using the prior art, preferably by the following formula (f=0.80):

The first stage calculation formula:

QCaCl2=Qca/0.34

The second stage calculation formula:

or:

Qca(phaseII)=Qeffluent×Cca_effluent

QCaCl2=Qca/0.34

Among them, Qca: the amount of calcium that should be replenished per unit time,

QCaCl ₂ : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): the amount of calcium in the first phase per unit time is mmol/h,

Qca (phase II): the second stage unit time calcium supplementation mmol/h,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qeffluent: effluent speed L/h,

Cca_effluent: Total calcium concentration in the effluent is mmol/L.

Qcit: citrate infusion rate L/h,

The above parameters CcaT(art), Qpw, Quf, Qsub, WT, Css(t), Qeffluent, Cca_effluent, etc. can be measured by the prior art before the start of dialysis, and the user inputs with the input module.

Among them, Css(t) is the steady state concentration of citrate in the body (mmol/L), which can be predicted by the following mathematical model of citrate pharmacokinetics (see Zheng Zheng, Xu Zhongyu, Jiao Zheng et al., Continuity). Construction of mathematical model of citrate pharmacokinetics during renal replacement therapy, Chinese Journal of Nephrology 2010;26(6):432-437.) Validation of mathematical model of citrate pharmacokinetics See: Yin Zheng, Zhongye Xu, Qiuyu Zhu, Junfeng Liu, Jing Qian, Huaizhou You, Yong Gu, Chuanming Hao, Zheng Jiao, Feng Ding. Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury. PLoS ONE 2013,8(6):e65992.(Citrate pharmacokinetics in patients with critically acute renal failure); Csys (in vivo citrate plasma concentration mmol/L) is generally about 3 hours of niacin Steady state, the concentration does not change, you can get it, this time is Css(t).

C(0): basic citric acid concentration mmol/L;

CLf: in vitro citrate dialysis clearance rate L/h;

CLb: body citrate clearance rate L/h;

t: citrate infusion time h;

V: apparent volume L of citric acid;

G: The amount of citric acid in the body per unit time is mmol.

G=Qp×Cinf×(1-Ecit),

Cinf: The amount of citric acid added per liter of plasma is mmol/L.

Ecit: citrate filtered fraction,

Qp: plasma flow rate L/h.

Css(t) is obtained by obtaining C(0), CLf, CLb, V, Cinf, Ecit, and Qp using the prior art.

As described in Figure 7, the application in CVVH treatment (n = 10). The CVVH treatment time was longer than 24 hours and the data was displayed up to 24 hours. The calcium supplementation rate in the first stage was 6.24±0.43 mmol/h, and the second stage was reduced to 5.10±0.22 mmol/h. The ionized calcium concentration in the patient's body and in the dialysis tubing is smoothly controlled within the desired range.

As shown in FIG. 6, in order to further optimize the design, the citrate anti-coagulation device in this embodiment further includes a bubble detecting module 4, and the bubble detecting module 4 is connected to the peristaltic pump control module 100, and the bubble detecting module 4 includes air bubbles. The detecting member 401 and the warning member 402 are ultrasonic detectors (commercially available), and the warning members include three different color indicator lights (red, yellow, green).

In another embodiment, the bubble detecting module includes an I/O control unit, and the I/O control unit is in a multi-channel mode, and also performs data interaction with the control device through RS-485 communication mode, and mainly controls three color indicators and air bubbles. Test piece. Multipass The track I/O unit can control the opening and closing of the three lamps, and can also read the state of the bubble detecting member and send the state to the peristaltic pump control module 100 in time.

The citrate anticoagulant device is connected to the external infusion tube. If there is a bubble in the infusion tube, the ultrasonic detector will detect the bubble and send it to the peristaltic pump control module 100 through the RS485 bus, and the peristaltic pump control module 100 further includes a module that receives the bubble detection module signal and sends a pause peristaltic pump command, and is connected to the bubble detection module 4, and receives a signal from the bubble detection module, for example, prompting a bubble signal, accepting and signaling, causing the first creep The pump 1 and the second peristaltic pump 2 are stopped. When the system is running normally, the indicator light is green; when there is air bubble in the infusion process, it will alarm, the indicator light will be red, and the two pumps will stop running at the same time.

In order to further optimize the design, the peristaltic pump control module further includes a pre-charging unit, and the pre-charging unit is connected to the first peristaltic pump speed control sub-module and the second peristaltic pump speed control sub-module, and the user controls the pre-use before use. The charging unit pre-charges the infusion tube with the first peristaltic pump and the second peristaltic pump, respectively, and the indicator light is illuminated.

Those skilled in the art are aware of the process of obtaining the first peristaltic pump speed signal calculation process, the process of transmitting the first peristaltic pump speed signal, the second peristaltic pump speed signal calculation process, and the process of transmitting the second peristaltic pump speed signal as described above. The self-test module determines the parameter operation process, and can be implemented by using a computer, an integrated circuit module, a programmable logic device, other hardware or an existing software module in the prior art.

The citrate anticoagulant device of the present invention provides two modes of operation: an automatic control mode and a manual control mode. The automatic control mode means that the user (mostly a doctor) inputs the parameters required in the anticoagulation process through the input module, for example: total calcium concentration CcaT_art (mmol/L), replacement fluid velocity Qsub (L/h), citrate loss Injection speed Qcit (L / h), ultrafiltrate velocity Quf (L / h), hematocrit (Hct), total protein concentration TP (g / L), patient weight WT (kg), through the peristaltic pump control module Calculate the speed of the two peristaltic pumps and transmit the speed signal to the peristaltic pump.

In the automatic control mode, the device has the function of automatically adjusting the calcium supplement speed, that is, the calcium supplementation speed is divided into two sections. After the RCA starts for 3 hours, the system will prompt to enter the second stage of calcium supplementation, and the relevant parameters and flow rate can be reset. Once the setting is successful, the system will automatically change the operating speed of the two pumps according to the parameters of the second stage, without the cumbersome operation of the doctor.

The manual control mode refers to inputting the speed signals of the first peristaltic pump and the second peristaltic pump to the peristaltic pump control module through the input module, the first peristaltic pump speed signal transmitting unit and the second peristaltic pump speed in the peristaltic pump control module The signal transmitting unit transmits the speed signals to the first peristaltic pump and the second peristaltic pump, respectively.

Therefore, the present invention effectively overcomes various shortcomings in the prior art and has high industrial utilization value.

The above-described embodiments are merely illustrative of the principles of the invention and its effects, and are not intended to limit the invention. Modifications or variations of the above-described embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention. Therefore, all that is accomplished by those of ordinary skill in the art without departing from the spirit and scope of the invention disclosed herein Modifications or modifications are still covered by the claims of the present invention.

Claims

A citrate anticoagulant device, characterized in that the citrate anticoagulant device comprises at least: a first peristaltic pump, a second peristaltic pump, and a control device, the control device comprising a peristaltic pump control module and a display module And an input module, the input module is connected to the peristaltic pump control module, the peristaltic pump control module is connected to the first peristaltic pump and the second peristaltic pump, the first peristaltic pump is a tannic acid pump, and the second peristaltic pump is Calcium pump.
The citrate anticoagulant device according to claim 1, wherein the peristaltic pump control module comprises:

a first peristaltic pump speed control sub-module for controlling a citrate infusion rate, connected to the first peristaltic pump;

A second peristaltic pump speed control sub-module for controlling the rate of calcium supplementation is coupled to the second peristaltic pump.
The citrate anticoagulant device according to claim 2, wherein the first peristaltic pump speed control submodule comprises:

a citrate infusion rate calculation unit for calculating a citrate infusion rate, connected to the input module;

A first peristaltic pump speed signal output unit for transmitting a first peristaltic pump infusion speed command is coupled to the capric acid infusion rate calculation unit and the first peristaltic pump.
The citrate anticoagulant device according to claim 3, wherein the citrate infusion rate calculation unit obtains a citrate infusion rate Qcit by using the following formula:

Qcit=Qb×(1-Hct)×C 0 mmol/Csolution;

C 0 : 3 to 5;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity L/h,

Csolution: The amount of citric acid in 1 L of citric acid solution is mmol.
The citrate anticoagulant device according to claim 2, wherein the second peristaltic pump speed control submodule comprises:

a second peristaltic pump first stage speed calculation unit for calculating a sum of the amount of calcium removed by the in vitro dialysis and the amount of accumulated calcium in the body, connected to the input module and the citrate infusion rate calculation unit;

a second peristaltic pump second stage speed calculation unit for calculating the amount of calcium removed by the external dialysis, and connected to the input module and the citrate infusion rate calculation unit;

A second creeping speed signal output unit for transmitting the second peristaltic pump speed is coupled to the second peristaltic pump first stage speed calculating unit, the second peristaltic pump second stage speed calculating unit, and the second peristaltic pump.
The citrate anticoagulant device according to claim 5, wherein the second peristaltic pump is calculated in the first stage speed The unit uses the following formula to obtain the first stage calcium supplementation rate:

QCaCl 2 = Qca/0.34

f: 0.80 to 0.90

Qca: the amount of calcium that should be replenished per unit time is mmol/h,

QCaCl 2 : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): the amount of calcium in the first phase per unit time is mmol/h,

CcaT(art): total calcium concentration at the arterial end, equivalent to the total calcium concentration in the body, mmol/L,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qcit: citrate infusion rate L/h.
The citrate anticoagulant device according to claim 6, wherein the second stage speed calculation unit of the second peristaltic pump obtains the second stage calcium supplementation speed by using the following formula:

or:

Qca(phase II)=Qeffluent×Cca_effluent

QCaCl 2 = Qca/0.34

Qeffluent: effluent speed L/h,

Cca_effluent: total calcium concentration in the effluent is mmol/L,

Qca (phase II): the second stage unit time calcium supplement mmol / h;

QCaCl 2 : Infusion rate of 5% calcium chloride solution per unit time ml/h.
The citrate anticoagulant device according to claim 7, wherein said f is 0.87 or 0.80.
The citrate anticoagulant device according to claim 5, wherein the second peristaltic pump speed signal output unit comprises:

a switching time subunit for storing or setting the first phase and the second phase switching time of the second peristaltic pump;

a signal output subunit for transmitting a second peristaltic pump speed output signal according to a switching time, and a switching time subunit, The second peristaltic pump first stage speed calculation unit, the second peristaltic pump second stage speed calculation unit and the second peristaltic pump are connected.
The citrate anticoagulant device according to claim 1, wherein the citrate anticoagulant device further comprises a bubble detecting module, and the peristaltic pump control module further comprises:

A module that receives the bubble detection module signal and sends a pause peristaltic pump command is coupled to the bubble detection module.
The citrate anticoagulant device according to claim 10, wherein the bubble detecting module comprises a bubble detecting member and a warning member.
The citrate anticoagulant device according to claim 11, wherein the bubble detecting member is an ultrasonic detector, and the warning member comprises a plurality of indicator lights of different colors.
The citrate anticoagulant device according to claim 1, wherein the citrate anticoagulant device is connected to an external infusion tube, and the peristaltic pump control module further comprises a method for controlling prefilling of the infusion tube. The pre-filling unit is connected to the first peristaltic pump speed control sub-module and the second peristaltic pump speed control sub-module.
The citrate anticoagulant device of claim 1 wherein said display module is coupled to the input module and is selectively connectable to the peristaltic pump control module.
The citrate anticoagulant device according to claim 1, wherein the control device further comprises a self-detection module for detecting whether an input parameter of the input module meets a preset parameter range, the self-detection module and the input module And the display module is connected.
The use of the citric acid anticoagulant device according to any of claims 1-15 for local citrate anticoagulation.
A method for anticoagulation of citric acid, which in turn comprises the following steps:

1) The first stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used to supplement calcium into the blood after anticoagulation, and the amount of calcium supplement is external to the body. The sum of the amount of calcium removed by dialysis and the amount of accumulated calcium in the body;

2) The second stage of citrate anticoagulation: a tannic acid pump is used to add citric acid to the blood to be anticoagulated, and a calcium pump is used to supplement calcium in the blood after anticoagulation, which is in vitro. The amount of calcium removed by dialysis.
The citrate anticoagulant method according to claim 17, wherein the first stage citrate anticoagulation is 3 hours.
The citrate anticoagulant method according to claim 17, wherein the calculation formula for the rate Qcit added to the blood to be anticoagulated is:

Qcit=Qb×(1-Hct)×C 0 mmol/Csolution;

C 0 : 3 to 5;

Qcit: citrate infusion rate L/h,

Hct: hematocrit,

Qb: blood velocity L/h,

Csolution: The amount of citric acid in 1 L of citric acid solution is mmol.
The method for anticoagulation of citric acid according to claim 17, wherein the formula for calculating the amount of calcium in the first stage citrate anticoagulation is:

QCaCl 2 = Qca/0.34

f: 0.80 to 0.90

Qca: the amount of calcium that should be replenished per unit time is mmol/h,

QCaCl 2 : 5% calcium chloride solution infusion rate per unit time, ml/h,

Qca (phaseI): the amount of calcium in the first phase per unit time is mmol/h,

CcaT(art): total calcium concentration at the arterial end, equivalent to the total calcium concentration in the body, mmol/L,

Qpw: plasma water velocity L/h,

Quf: ultra-filtrate speed L/h,

Qsub: replacement fluid speed L/h,

WT: weight kg,

Css(t): the steady state concentration of citrate in the body is mmol/L,

Qcit: citrate infusion rate L/h.
The citrate anticoagulant method according to claim 20, wherein the calculation formula of the calcium supplement amount in the second stage citrate anticoagulation is:

or:

Qca(phase II)=Qeffluent×Cca_effluent

QCaCl 2 = Qca/0.34

Qeffluent: effluent speed L/h,

Cca_effluent: total calcium concentration in the effluent is mmol/L,

Qca (phase II): the second stage unit time calcium supplement mmol / h;

QCaCl 2 : Infusion rate of 5% calcium chloride solution per unit time ml/h.
The citrate anticoagulant method according to claim 19, wherein the f is 0.87 or 0.80.