CN106267408A - A kind of full-automatic Regional Citrate Anticoagulation device - Google Patents

Abstract

The invention discloses a kind of full-automatic Regional Citrate Anticoagulation device, controller connects the first peristaltic pump, the second peristaltic pump and I/O control module respectively, I/O control module is connected with bubble detection module and alarm module respectively, described controller transmission of control signals is for controlling the first peristaltic pump and the feed liquor speed of the second peristaltic pump, the detection signal of bubble detection module is transferred to controller by described I/O control module, and described I/O control module controls the opening and closing of alarm module.Alleviate the work load of medical personnel to a certain extent, improve safety simultaneously.Carry the anticoagulation that the invention enables Regional Citrate Anticoagulation to become a kind of simplicity, promote it in clinical application.

Description

A kind of full-automatic Regional Citrate Anticoagulation device

Technical field

The present invention relates to a kind of automaton, in particular a kind of full-automatic Regional Citrate Anticoagulation device.

Background technology

External anticoagulant is the key that blood purification is smoothed out.Regional Citrate Anticoagulation (regional citrate Anticoagulation, RCA) definite because having anticoagulant effect, the advantages such as hemorrhage complication is few, dialyser prolongation in service life, Become the ideal chose of current highly accomplished cardiopulmonary bypass in patients anticoagulant.But, due to potential Metabolic complication, operation Complex, period needs the problems such as frequent monitoring, limits it in clinical application.

As it is shown in figure 1, traditional Regional Citrate Anticoagulation technology is to circulate arterial end in vitro, according to blood flow rate with a definite proportion Example infusion liquor sodii citratis, replenishes the calcium at vein end (before blood returns in the patient) simultaneously, thus ensure in the patient from Sub-calcium level is normal.Regional Citrate Anticoagulation-CRRT principle: citric acid is from arterial end infusion, the ion in extracorporeal circulation pipeline Calcium level is down to 0.2-0.4mM/L, plays anticoagulation effect in vitro, supplements calcium from vein end simultaneously, and internal ionized calcium level maintains Normally, and internal blood coagulation system is not affected.R (replacement): displacement liquid；UF (ultrafiltrate): ultrafiltrate.

In Fig. 1,4% sodium citrate inputs from vein end, makes extracorporeal circulation ionized calcium be down to 0.2-0.4mmol/L, reaches anticoagulant Effect, supplements calcium chloride from vein end simultaneously, makes internal ionized calcium level recover to 1.0-1.2mmol/L.

According to the experience in existing document report and real work, generally there is following asking in clinical application in traditional RCA Topic:

(1) need extra two precision transfusion pumps of increase on the basis of original apparatus for purifying blood molten for citric acid soln and calcium The infusion of liquid, complex operation；

(2) citric acid infusion pump and infusion pump of replenishing the calcium are two independent pumps, when treatment Parameters variation or dialysis machine because reporting to the police, Change the reason tremulous pulse pump terminations of pumping such as displacement liquid/dialysis solution, it is necessary to dialysis nurse manually suspends/start the two pump, if operation is not Specification, too much or hypercalcemia causes extracorporeal circulation anticoagulant failure to be likely to result in iatrogenic citric acid infusion；

(3) traditional citrate anticoagulation scheme mainly uses " trial-and-error method " of monitoring-adjustment-monitor again, the most first sets A fixed speed of initially replenishing the calcium, then internal by frequently monitoring and extracorporeal circulation ionized calcium level adjusts speed of replenishing the calcium.We are saturating Analysis center is initially also adopted by this empirical " trial-and-error method " scheme at application RCA, found that internal ionized calcium level fluctuates relatively Greatly, and owing to the change of calcium lags behind the adjustment of calcium, it is difficult to the accurate assurance amount of replenishing the calcium；

(4) input during RCA manpower (at least needs one by the hemodialysis nurse of strict training and to be familiar with citrate anticoagulation technology Doctor on the scene), material resources (needing every 2-4 hour monitoring ionized calcium, every time measure expense 150 yuan) cost puts into huge.

Summary of the invention

It is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of full-automatic Regional Citrate Anticoagulation device, it is achieved Low artificial automatization.

The present invention is achieved by the following technical solutions, and the present invention includes controller, the first peristaltic pump, the second peristaltic pump, I/O Control module, bubble detection module, alarm module；Described controller connects the first peristaltic pump, the second peristaltic pump and I/O respectively Control module, I/O control module is connected with bubble detection module and alarm module respectively, and described controller transmission of control signals is used In controlling the feed liquor speed of the first peristaltic pump and the second peristaltic pump, described I/O control module is by the detection signal of bubble detection module Being transferred to controller, described I/O control module controls the opening and closing of alarm module.

Described bubble detection module detection process is: by ultrasound examination tube for transfusion, when the reflection coefficient of ultrasound wave is more than setting Scope, then detect in tube for transfusion have bubble, and the reflection coefficient of ultrasound wave in set point, then detects in tube for transfusion and do not has Bubble.

Described controller connects the first peristaltic pump, the second peristaltic pump and I/O control module by RS-485 bus respectively.

Described alarm module is the display lamp of three kinds of colors.

Described first peristaltic pump is citric acid pump, and the second peristaltic pump is chlorination calcium pump.

The speed of described first peristaltic pump and the second peristaltic pump is denoted as Qcit and Q respectively_CaCl2, the second corresponding peristaltic pump Q_CaCl2Control Process includes replenish the calcium first stage and second stage of replenishing the calcium, and within after anticoagulant starts three hour, enters second stage of replenishing the calcium,

The infusion velocity of the first peristaltic pump Qcit is obtained by formula:

Qcit=Qb × (1-Hct) × C₀mmol/Csolution；

Wherein, Qcit: unit interval citric acid infusion velocity ml/h,

Qb: blood flow rate ml/min,

Hct: packed cell volume %,

Csolution:1L citric acid soln contains amount mmol of citric acid,

C₀: 3～5mmol/L；

In described first stage 0～3 hours, the amount of replenishing the calcium per hour:

$Qca\left(phaseI\right)=\frac{0.80\×CcaT\left(art\right)\×Qpw\×Quf}{Qpw+Qcit+Qsub}+0.78\×Css\left(t\right)\×WT\×25\%$

QCaCl2=Qca/0.34

Described second stage is after 3 hours, the amount of replenishing the calcium per hour:

$Qca\left(phaseII\right)=\frac{0.80\×CcaT\left(art\right)\×Qpw\×Quf}{Qpw+Qcit+Qsub}$

Or:

Qca (phaseII)=Qeffluent × Cca_effluent

QCaCl2=Qca/0.34

Wherein, calcium amount mmol/h that Qca: the unit interval should supplement,

Qcacl₂: unit interval 5% calcium chloride solution infusion velocity ml/h,

Qca (phase I): the first stage unit time amount of replenishing the calcium mmol/h,

Qca (phase II): the second stage unit interval amount of replenishing the calcium mmol/h,

CcaT (art): the total calcium concentration of arterial end, is equivalent to internal total calcium concentration mmol/L,

Qpw: blood plasma water speed L/h,

Quf: ultrafiltrate speed L/h,

Qsub: displacement liquid speed L/h,

WT: body weight kg,

Css (t): internal citric acid Css mmol/L,

Csys: internal citric acid blood drug level mmol/L

Qeffluent: effluent speed L/h,

Cca_effluent: effluent total calcium concentration mmol/L.

Described internal citric acid blood drug level:

$Csys=C\left(0\right)\·e^{-\[(CLb+CLf)\·\frac{t}{V}\]}+\frac{G}{(CLb+CLf)}\×(1-{e^{-}}^{-\[(CLb+CLf)\·\frac{t}{V}\]})$

Wherein, G: the citric acid flow mmol/h in unit interval tube for transfusion,

C (0): basis citric acid concentration mmol/L,

CLb: body clearance rate L/h to citric acid,

CLf: dialyser clearance rate L/h to citric acid,

T: citric acid Infusion Time h,

V: internal citric acid apparent volume of distribution L.

Citric acid flow in described unit interval tube for transfusion:

G=Qp × Cinf × (1-Ecit),

Cinf: every liter blood plasma adds citric acid amount mmol/L,

Ecit: citric acid filtration fraction,

Qp: plasmaflux L/h.

According to internal citric acid, calcium principle of dynamics, speed of replenishing the calcium in RCA-CRRT therapeutic process can reach according to internal citric acid The Css time is divided into two benches.Kramer etc. report without citric acid half-life average out to 36 points in liver cirrhosis critical patient body Clock, according to pharmacokinetic theory, vivo medicine concentration reaches Css after 5 half-life, the most internal citric acid concentration Within three hours after RCA-CRRT starts, reach Css, RCA-CRRT is started after the 3rd hour as replenish the calcium speed adjustment time Between point.(Kramer L, Bauer E, Joukhadar C, et al.Crit Care Med, 2003,31:2450-2455.)

Css (t) is internal citric acid Css (mmol/L), can be with following citric acid pharmacokinetics mathematical model (concrete mathematical model is derived and is seen Zheng Yin, Xu Zhongye, Jiao Zheng etc. in prediction.Citric acid medicine generation during continuous renal replacementtherapy Thank to the structure of dynamics mathematical model.Chinese Journal of Nephrology 2010；26 (6): 432-437. citric acid pharmacokinetics numbers Modelling verification sees: 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. (the citric acid pharmacokinetics of critical patients with acute renal failure)

The present invention has the advantage that this device aims at RCA anticoagulant design compared to existing technology, by whole to citric acid pump and pump of replenishing the calcium Closing, this double pump system can link with dialysis machine tremulous pulse pump again, be simultaneously embedded in citric acid, calcium infusion mathematical model, controlled two The speed of pump, it is not necessary to medical personnel cross multioperation.Needed monitoring in every 2-4 hour internal during RCA and pipeline ionized calcium in the past, Within 24 hours, CRRT needs frequently monitoring 6～8 times, and is replenished the calcium by the speed of replenishing the calcium of computed in software, and monitoring interval extends, and 24 is little Time treatment only need to detect 2～3 times.Alleviate the work load of medical personnel to a certain extent, improve safety simultaneously.Improve Critical acute injury of kidney patient, especially merges high-risk bleeding risk patient, the salvage success rate of blood purification treatment.The present invention On the one hand alleviate the labor intensity of staff, on the other hand decrease medical expense.Regional Citrate Anticoagulation is made to become one Plant easy anticoagulation, promote it in clinical application.

Accompanying drawing explanation

Fig. 1 is the structural representation of prior art；

Fig. 2 is the structural representation of the present invention；

Fig. 3 is the application structure schematic diagram of this enforcement；

Fig. 4 be the present embodiment two benches replenish the calcium model long-time CVVH treat in application effect schematic diagram.

Detailed description of the invention

Elaborating embodiments of the invention below, the present embodiment is implemented under premised on technical solution of the present invention, Give detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.

As in figure 2 it is shown, the present embodiment includes that controller, the first peristaltic pump, the second peristaltic pump, I/O control module, bubble are examined Survey module, alarm module；Described controller connects the first peristaltic pump, the second peristaltic pump and I/O control module respectively, and I/O is controlled Molding block is connected with bubble detection module and alarm module respectively, and described controller transmission of control signals is for controlling the first peristaltic pump With the feed liquor speed of the second peristaltic pump, the detection signal of bubble detection module is transferred to controller by described I/O control module, institute State I/O control module and control the opening and closing of alarm module.

Traditional RCA scheme needs by " monitoring-adjust-monitoring " mode adjustment citric acid and the input of calcium, and the present invention is by Chinese holly Rafter acid infusion mathematical model, two benches mathematical model C# language of replenishing the calcium is written as software, is needed by man-machine dialog interface input Clinical indices and treatment parameter, by RS485 bus marco citric acid pump and the rotating speed of pump of replenishing the calcium, two pumps just can be according to setting Fixed rotating speed inputs citric acid and calcium in the extracorporeal circulation pipeline that trend connects.

The software principle that the present invention is applied to is as follows: software uses C# language to write, and Runtime Library is Microsoft.Net Framework 3.5.Software provides two kinds of modes of operation: automatically control and Non-follow control.

Bubble detection module detection process is: by ultrasound examination tube for transfusion, when the reflection coefficient of ultrasound wave is more than set point, Then detecting in tube for transfusion have bubble, the reflection coefficient of ultrasound wave in set point, then detects in tube for transfusion do not have bubble.

Described controller connects the first peristaltic pump, the second peristaltic pump and I/O control module by RS-485 bus respectively.

Described alarm module is the display lamp of three kinds of colors.

If there is bubble in tube for transfusion, then bubble detection module will detect this bubble, and by RS485 bus notification controller Stop the injection of this two pumps.When system runs well, display lamp green light；During pipeline preliminary filling, amber light is bright；In infusion process Will report to the police when having bubble, display lamp when red, two pumps shut down simultaneously.Bubble detection module uses ultrasound detection bubble former Reason, i.e. when ultrasound wave is propagated in media as well, runs into the different interface of acoustic impedance and can produce scatter reflections, thus can cause ultrasonic The decay of ripple.When not having bubble in tube for transfusion, ultrasonic reflection coefficient is the least, almost without decay；When having bubble, due to The acoustic impedance difference of air and water is relatively big, and ultrasound wave has the biggest reflection coefficient, and now ultrasonic attenuation is serious.When bubble is examined When survey module is not detected by bubble, export logic level 0；When bubble being detected, export logic level 1.

I/O control module is multi-channel module, carries out data interaction, major control also by RS-485 communication modes and controller The display lamp of three colors and bubble detection module.Multichannel I/O module can control the open and close of three lamps, also may be used simultaneously Read the state of bubble detection module, and this state is sent in time to controller.

Described first peristaltic pump is citric acid pump, and the second peristaltic pump is chlorination calcium pump.

In order to be calculated infusion flow, the parameter of needs: total calcium concentration CcaT_art (mmol/L), displacement liquid speed Qsub (L/h), citric acid infusion velocity Qcit (L/h), ultrafiltrate speed Quf (L/h), blood flow velocity Qb (L/h), erythrocyte Specific volume Hct, total protein concentration TP (g/L), patient body weight WT (kg).

Citric acid infusion velocity mathematical formulae is as follows:

Qcit=Qb × (1-Hct) × 4mmol/L

Qcit represents citric acid infusion velocity L/h,

Hct: hematocrit value.

Two benches process of replenishing the calcium is as follows:

Citric acid accumulation in body when its core concept is Regional Citrate Anticoagulation, the citric acid of accumulation is mainly deposited with calcium salt forms , according to citric acid pharmacokinetic parameter, accumulation typically reaches stable state in about 3 hours after treatment starts.Therefore, locally Replenishing the calcium of citrate anticoagulation is also required to be divided into two stages, and the first stage requires supplementation with body accumulation calcium and calcium is removed in extracorporeal circulation, Second stage has only to added body outer circulation and removes calcium.It should be noted that the two benches that this device proposes replenish the calcium mathematical model fit For there is the low elimination efficiency blood purification pattern of citric acid accumulation, such as CRRT etc..And for the blood purification of high elimination efficiency Pattern (such as conventional Intermittent hemodialysis etc.), is negligible owing to there is not citric acid accumulation or accumulation, can regard as State the special case of model, be i.e. directly entered second stage and replenish the calcium, without supplementary accumulation calcium part.Equipment under automatic control mode Possessing and automatically adjust speed function of replenishing the calcium, speed of i.e. replenishing the calcium divides two-part.RCA starts latter 3rd hour, and system can point out entrance Replenishing the calcium to second stage, relevant parameter can be carried out resetting with flow velocity.Once arrange successfully, system can automatically according to Second stage parameter directly changes the exploitation speed of two pumps, it is not necessary to doctor's troublesome operation.Simultaneity factor arranges Autonomous test with parameter Function, after i.e. input arranges parameter, system will arrange parameter the most rationally by automatic decision, if unreasonable it would appear that prompting is believed Breath, prevents doctor from inputting the maloperation in parametric procedure.

As it is shown on figure 3, as a example by continuous venovenous hemofiltration (CVVH) illustrate, in figure 1～9 be respectively formula 1～ 9。

Eq1: unit of account time blood plasma discharge Qpw (L/h):

Eq1:Qpw=Qb × (1-Hct) × (1-Cprotein/100)

Qb: blood flow L/h；

Hct: hematocrit %；

Cprotein: total protein concentration of serum g/L.

Eq2: total calcium concentration CcaT_in (mmol/L) before filter after calculating citric acid infusion:

Eq2: $CcaT\_in=\frac{C\mathrm{caT}\_\mathrm{art}\×Qpw}{(Qpw+Qcit+Qsub)}$

CcaT_art: internal total calcium concentration mmol/L；

Qcit: citric acid infusion velocity L/h；

Qsub: displacement liquid flow L/h.

Eq3: calculating after citric acid infusion before filter can disperse calcium concentration CcaF_in (mmol/L):

Eq3: $CcaF\_in=\frac{fa\×CcaT\_art\×Qpw}{(Qpw+Qcit+Qsub)}$

Fa: total ca proportion % can be accounted for by disperse calcium.

Eq4: calcium amount Caflux (mmol/h) that calculating extracorporal dialysis is removed:

S: sieve coefficient ≈ 1.

Eq4:Caflux=Quf × S × CcaF_in.

Eq5:Eq3 and Eq4 merges.

Eq5: $\mathrm{Caflux}=\frac{fa\×CcaT\_art\×Qpw\×Quf}{(Qpw+Qcit+Qsub)}.$

Eq6: calculating body accumulation calcium concentration Ca_bound (t) (mmol/L):

Eq6: Δ Cca_bound (t)=fb × Csys (t)

Fb: accumulation calcium concentration and citric acid concentration correlation coefficient；

Csys (t): concentration mmol/L during citric acid point.

Eq7: citric acid Pharmacokinetics Formula:

$Csys=C\left(0\right)\·e^{-\[(CLb+CLf)\·\frac{t}{V}\]}+\frac{G}{(CLb+CLf)}\×(1-e^{-\[(CLb+CLf)\·\frac{t}{V}\]})$

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

Kf: external citric acid dialysis clearance rate L/h；

Kb: internal citric acid clearance rate L/h；

T: citric acid Infusion Time h；

V: citric acid apparent volume L；

G: the citric acid flow mmol in unit interval tube for transfusion, i.e. the citric acid flow of internal injection in the unit interval.

Eq8: calculating body accumulation calcium total amount Qca (mmol):

Eq8:Qca=fb × Csys (t) × Body Weight × 25%

Body Weight: body weight kg；

25%: extracellular fluid volume.

Eq9: before citric acid reaches stable state, the first stage replenishes the calcium loading Qca1 (mmol):

$Qca\left(phaseI\right)=\frac{0.80\×CcaT\left(art\right)\×Qpw\×Quf}{Qpw+Qcit+Qsub}+0.78\×Css\left(t\right)\×WT\×25\%/3$

QCaCl2=Qca/0.34

Css (cit): internal citric acid Css mmol/L.

Fig. 4 be the present embodiment two benches replenish the calcium equipment long-time CVVH treat in application (n=10).CVVH treatment time is equal It is longer than 24 hours, the data of display to 24 hour.First stage speed of replenishing the calcium is 6.24 ± 0.43mmol/h, second stage It is reduced to 5.10 ± 0.22mmol/h.In the patient and dialysis pipeline intermediate ion calcium concentration the most smoothly control in the ideal range.

The foregoing is only presently preferred embodiments of the present invention, not in order to limit the present invention, all spirit in the present invention and former Any amendment, equivalent and the improvement etc. made within then, should be included within the scope of the present invention.

Claims (8)

1. a full-automatic Regional Citrate Anticoagulation device, it is characterised in that include controller, the first peristaltic pump, the second wriggling Pump, I/O control module, bubble detection module, alarm module；Described controller connects the first peristaltic pump, the second wriggling respectively Pump and I/O control module, I/O control module is connected with bubble detection module and alarm module respectively, the transmission control of described controller Signal processed is for controlling the first peristaltic pump and the feed liquor speed of the second peristaltic pump, and described I/O control module is by bubble detection module Detection signal is transferred to controller, and described I/O control module controls the opening and closing of alarm module.

One the most according to claim 1 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described bubble detects Module detection process is: by ultrasound examination tube for transfusion, when the reflection coefficient of ultrasound wave is more than set point, then detect defeated Having bubble in liquid pipe, the reflection coefficient of ultrasound wave in set point, then detects in tube for transfusion do not have bubble.

One the most according to claim 1 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described controller divides Do not connect the first peristaltic pump, the second peristaltic pump and I/O control module by RS-485 bus.

One the most according to claim 1 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described alarm module It it is the display lamp of three kinds of colors.

One the most according to claim 1 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described first wriggles Pump is citric acid pump, and the second peristaltic pump is chlorination calcium pump.

One the most according to claim 5 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described first wriggles The speed of pump and the second peristaltic pump is denoted as Qcit and Q respectively_CaCl2, the second corresponding peristaltic pump Q_CaCl2Control process includes replenishing the calcium first Stage and second stage of replenishing the calcium, enter second stage of replenishing the calcium in after anticoagulant starts three hour,

The infusion velocity of the first peristaltic pump Qcit is obtained by formula:

Qcit=Qb × (1-Hct) × C₀mmol/Csolution；

Wherein, Qcit: unit interval citric acid infusion velocity ml/h,

Qb: blood flow rate ml/min,

Hct: packed cell volume %,

Csolution:1L citric acid soln contains amount mmol of citric acid,

C₀: 3～5mmol/L；

In described first stage 0～3 hours, the amount of replenishing the calcium per hour:

$Qca\left(phaseI\right)=\frac{0.80\×CcaT\left(art\right)\×Qpw\×Quf}{Qpw+Qcit+Qsub}+0.78\×Css\left(t\right)\×WT\×25\%$

QCaCl2=Qca/0.34

Described second stage is after 3 hours, the amount of replenishing the calcium per hour:

$Qca\left(phaseII\right)=\frac{0.80\×CcaT\left(art\right)\×Qpw\×Quf}{Qpw+Qcit+Qsub}$

Or:

Qca (phaseII)=Qeffluent × Cca_effluent

QCaCl2=Qca/0.34

Wherein, calcium amount mmol/h that Qca: the unit interval should supplement,

Qcacl₂: unit interval 5% calcium chloride solution infusion velocity ml/h,

Qca (phase I): the first stage unit time amount of replenishing the calcium mmol/h,

Qca (phase II): the second stage unit interval amount of replenishing the calcium mmol/h,

CcaT (art): the total calcium concentration of arterial end, is equivalent to internal total calcium concentration mmol/L,

Qpw: blood plasma water speed L/h,

Quf: ultrafiltrate speed L/h,

Qsub: displacement liquid speed L/h,

WT: body weight kg,

Css (t): internal citric acid Css mmol/L,

Csys: internal citric acid blood drug level mmol/L,

Qeffluent: effluent speed L/h,

Cca_effluent: effluent total calcium concentration mmol/L.

One the most according to claim 6 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described internal citron Acidemia concentration:

$Csys=C\left(0\right)\·e^{\[(CLb+CLf)\·\frac{1}{V}\]}+\frac{G}{(CLb+CLf)}\×(1-e^{{}^{\[(CLb+CLf)\·\frac{1}{V}\]}})$

Wherein, G: the citric acid flow mmol/h in unit interval tube for transfusion,

C (0): basis citric acid concentration mmol/L,

CLb: body clearance rate L/h to citric acid,

CLf: dialyser clearance rate L/h to citric acid,

T: citric acid Infusion Time h,

V: internal citric acid apparent volume of distribution L.

One the most according to claim 7 full-automatic Regional Citrate Anticoagulation device, it is characterised in that described unit interval Citric acid flow in tube for transfusion:

G=Qp × Cinf × (1-Ecit),

Cinf: every liter blood plasma adds citric acid amount mmol/L,

Ecit: citric acid filtration fraction,

Qp: plasmaflux L/h.