JP4233717B2 - Online hemodiafiltration machine - Google Patents

Description

【００４６】
【発明の効果】
本発明に係わるオンライン血液透析濾過装置によると、（１）エンドトキシンなどの汚染を含まない透析液置換液を安定して供給することができる。（２）限外濾過フィルターを自動で管理することによりフィルターが汚染されることなく、除去性能が保持され、さらに耐久性も向上する。また、（３）安全機構により血液が補液系を逆流して透析液系を汚染することがない。（４）補液にローラーポンプを使用せず、よって高価なポンプセグメントを包含する補液回路も必要なくなり経済的にもメリットが大きい。（５）濾過条件を時間の関数として至適にプログラムできることから、過大なアルブミン損失を防止する一方で大分子量尿毒素の除去性能も向上する。
【００４７】
本発明では、オンライン血液透析濾過装置（Ｍ）内の水系の流路の汚染が生じない。いかなる工程においても２次限外濾過フィルターの濾液側（１２）から実際に補液を抽出する補液ポート部（１４）までの回路には、細菌の増殖ひいてはエンドトキシンレベルの増大につながる停滞が生じない。また、該部分には流路の内面に複雑な構造物を置くことを廃し、バルブも外部からチューブを圧迫するピンチバルブが採用され、流路に細菌汚染巣や無機物の沈着が生じないように工夫されている。
【００４８】
本発明に係わるオンライン血液透析濾過装置による治療の実践に当たっては、該装置に一定の水質基準（日本透析医学会誌３１：１１０７−１１０９、１９９８）を満たす清浄な透析液が供給されることが好ましい要件とされるが、該装置も高い透析液浄化能力を具備している。まず、該装置に供給された透析液は密閉系外に設置された１次限外濾過フィルターの透過水のみが、密閉系に供給される。また、間欠的に１次限外濾過フィルターの素通り側のコンパートメントを高速でフラッシングすることにより膜面に阻止された溶質の蓄積を予防し、フィルターの溶質阻止性能と透水性を長期に保持することができる。次に、密閉系内で２次限外濾過フィルターにより、さらに部分濾過処理を行い、安定的にエンドトキシン濃度が０の濾液が補液として血液回路に注入される。２次フィルターの素通り側コンパートメントは常に高流量が確保されているため、１次フィルター以上に、膜面に阻止された溶質の蓄積を予防し、フィルターの溶質阻止性能と透水性を長期に保持する効果を見込める。フィルターの性能が長期に維持されることはコスト削減にもつながる。
【００４９】
本発明に係わるオンライン血液透析濾過装置は、従来のオンライン血液透析濾過装置では必須とされた補液の駆動を目的とするローラーポンプを使用せず、したがって補液ラインにもポンプセグメントを必要としない。高価なローラーポンプや補液ラインが不要になったことで経済的メリットが大きくなるとともに、フィードバック制御により、従来のオンライン血液透析濾過装置よりも高い精度で濾過（補液）の条件設定が可能となっている。また、本発明では、血液汚染対策として、常に透析液水系回路の濾液部の圧力を血液回路圧よりも高く設定するとともに、不慮の事態に備え、血液逆流を検知する漏血センサーを補液ライン（Ｌ３またはＬ３′）もしくは濾液ライン（Ｌ９）に装着し、これと連動させて補液ライン（Ｌ３またはＬ３′）から濾液ライン（Ｌ９）を２重に遮断する安全機構を保有することにより、血液回路から血液が補液ライン（Ｌ３またはＬ３′）を逆流して透析液水系回路の濾液部に至り血液汚染を発生することがない。
【００５０】
従来のローラーポンプにより補液速度（濾過速度）を設定するオンライン血液透析濾過装置では、経時的なダイアフィルターの膜劣化や除水に伴う血液のヘマトクリット値の上昇による透水性能の低下により、ＴＭＰが経時的に大きく変動するという欠点が、本発明によるオンライン血液透析濾過装置では、プログラム圧制御ないしプログラム濾過速度制御により克服され、透析従事者による頻回のモニターや濾過条件の再設定という煩雑な操作が不要となった。特にプログラム圧制御では不意の血流低下にも濾過速度を瞬時に低下させて対応することが可能となっている。
【００５１】
本発明によるオンライン血液透析濾過装置では、プログラム圧制御ないしプログラム濾過速度制御により、治療初期の濾過条件を低レベルに設定し、経時的に徐々に濾過条件を高レベル（高濾過速度ないし高ＴＭＰ）にシフトさせることにより、治療初期の大量のアルブミン損失を抑制することができる。これにより、従来の血液透析濾過装置ではアルブミン損失が過大となるため使用できなかった大孔径の膜を用いることができ、さらにβ２ミクログロブリンやα１ミクログロビンのような大分子尿毒素の除去効率を高めることができる。また、治療後半の膜劣化を加味し、傾斜的にあるいは階段状にＴＭＰを漸増させたり、濾過速度を漸減させるというように濾過条件のプロフィールをプログラム設定できることも、β２ミクログロブリンやα１ミクログロビンのような大分子尿毒素の除去効率を至適に高めることに寄与する。
【００５２】
本発明によるオンライン血液透析濾過法を用いれば、慢性腎不全患者の維持治療のみならず、血行動態が極めて不良で通常の血液透析を行いがたい急性腎不全や多臓器不全の患者の治療も安定して行うことができる。
【図面の簡単な説明】
【図１】本発明の基本構成図
【図２】本発明による血液透析濾過実践の一実施例の図
【図３】本発明による血液濾過実践の一実施例の図
【図４】本発明による血液透析実践の一実施例の図
【図５】本発明における洗浄工程の一例
【図６】本発明における洗浄工程の一例
【図７】本発明によるプログラム従圧（ＴＭＰ制御）濾過の経時プロフィールの例
【図８】本発明によるプログラム従量（濾過速度制御）濾過の経時プロフィールの例
【符号の説明】
Ｂ，Ｂ′漏血センサー
Ｃ１ 動脈チャンバー
Ｃ２ 静脈チャンバー
Ｄ 血液浄化器（ダイアフィルター）
Ｆ１ 流量計（透析液送液ポンプ後）
Ｆ２ 流量計（透析液循環ラインの透析液送液ラインへの合流後）
Ｌ１ 動脈側血液回路（１〜２）
Ｌ２ 静脈側血液回路（３〜４）
Ｌ３ 前希釈補液ライン（１４〜Ｃ１）
Ｌ３′後希釈補液ライン（１４〜Ｃ２）
Ｌ４ 透析液送液ライン（５〜６〜８〜９〜１３〜１５〜１６〜１７）
Ｌ５ 透析液排液ライン（１８〜１９〜２０〜２１〜２２）
Ｌ６ 除水ライン（２０〜２３）
Ｌ７ １次フィルター洗浄ライン（７〜２１）
Ｌ８ 透析液循環ライン（９〜１０〜１１〜１３〜９）
Ｌ９ 濾液ライン（１２〜１４〜１６）
Ｌ１０ 圧力逃がしライン（１５〜１９）
Ｍ オンライン血液透析濾過装置
Ｐ１ 血液ポンプ
Ｐ２ 透析液送液ポンプ
Ｐ３ 透析液排液ポンプ
Ｐ４ 透析液循環ポンプ
Ｐ５ 除水ポンプ
ＰＧ１ 動脈側血液回路圧モニター
ＰＧ２ 静脈側血液回路圧モニター
ＰＧ３ 透析液排液回路圧モニター
ＰＶ１ 流量調節用ピンチバルブ
ＰＶ２ 非常時遮断用ピンチバルブ
ＲＶ１ 圧リリーフ弁（透析液循環ライン（Ｌ８））
ＲＶ２ 圧リリーフ弁（圧力逃がしライン（Ｌ１０））
ＳＶ１ 電磁弁（１次フィルター洗浄ライン）
ＳＶ２ 電磁弁（透析液送液ライン）
ＳＶ３ 電磁弁（透析液送液ライン）
ＳＶ４ 電磁弁（濾液ライン）
ＵＦ１ 限外濾過フィルター（エンドトキシン除去フィルター）
ＵＦ２ 限外濾過フィルター（エンドトキシン除去フィルター）
ＵＶ 逆止弁（濾液ライン（Ｌ９））
１ 動脈側穿刺針と動脈側血液回路（Ｌ１）の接続点
２ 動脈側血液回路（Ｌ１）と血液浄化器（Ｄ）の接続点
３ 血液浄化器（Ｄ）と静脈側血液回路（Ｌ２）の接続点
４ 静脈側血液回路（Ｌ２）と静脈側穿刺針の接続点
５ 透析液監視装置への透析液供給点
６ 透析液送液回路（Ｌ４）のフィルター負荷部と限外ろ過フィルター（ＵＦ１）入口部の接続点
７ 限外ろ過フィルター（ＵＦ１）素通り出口部と１次フィルター洗浄ライン（Ｌ７）の接続点
８ 限外ろ過フィルター（ＵＦ１）濾液側と透析液送液ライン（Ｌ４）の接続点
９ 補液部透析液循環回路（Ｌ７）の透析液送液ライン（Ｌ４）からの分岐点
１０ 透析液循環回路（Ｌ８）のフィルター負荷部と限外ろ過フィルター（ＵＦ２）入口部の接続点
１１ 限外ろ過フィルター（ＵＦ２）素通り出口部と透析液循環回路（Ｌ８）の接続点
１２ 限外ろ過フィルター（ＵＦ２）濾液側と濾液ライン（Ｌ９）の接続点
１３ 透析液循環回路（Ｌ８）の透析液送液ライン（Ｌ４）への還流点
１４ 補液ポート（濾液ライン（Ｌ９）と補液ライン（Ｌ３またはＬ３′）の接続点
１５ 圧力逃がしライン（Ｌ１０）の透析液送液ライン（Ｌ４）からの分岐点
１６ 濾液ライン（Ｌ９）ドレーン部の透析液送液ライン（Ｌ４）への還流点
１７ 透析液送液ライン（Ｌ５）と血液浄化器（Ｄ）の接続点
１８ 血液浄化器と透析液排液ライン（Ｌ５）の接続点
１９ 圧力逃がしライン（Ｌ１０）の透析液排液ライン（Ｌ５）への合流点
２０ 除水ライン（Ｌ６）の透析液排液ライン（Ｌ５）からの分岐点
２１ １次フィルター洗浄ライン（Ｌ７）の透析液排液ライン（Ｌ５）の密閉系外への接続点
２２ 透析液排液ライン（Ｌ５）末端
２３ 除水ライン（Ｌ６）末端[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an on-line hemodiafiltration method which is a treatment method for removing toxic substances and waste products accumulated in blood due to renal failure or the like by applying ultrafiltration or diffusion using a separation membrane, More particularly, the present invention relates to an online hemodiafiltration device that improves safety and stability, reduces side effects, reduces manufacturing costs, and further improves removal efficiency, and a treatment method using the device.
[0002]
[Prior art]
Today, hemodialysis accounts for the majority of chronic renal failure treatment (reference book: Japan Dialysis Medical Association Statistical Survey Committee. Current status of chronic dialysis in Japan, Japan Dialysis Medical Association, 1998). In hemodialysis, blood and dialysate are flowed in opposite directions on both sides of a separation membrane called a dialysis membrane, and toxic and waste products in the blood are moved to the dialysate side by diffusion according to a concentration gradient, and removal is attempted. . Since the diffusion rate of a substance rapidly decreases with an increase in molecular or particle size, hemodialysis treatment based on the principle of removing diffusion is not suitable for removing a large molecular weight uremic toxin having a molecular weight of tens of thousands of daltons. It has long been known theoretically and empirically that hemofiltration based on the principle of ultrafiltration is more advantageous than hemodialysis based on the principle of removing diffusion for removing large molecular weight substances. It was. However, blood filtration, on the other hand, has an extremely poor ability to remove important small-molecular-weight uremic toxins such as urea. Also, the preparation of replacement fluids to supplement the loss of body fluids due to filtration and the replacement operation are complicated. Hemofiltration has not been accepted as a general treatment because of the high cost of the liquid and the limitations of insurance-affected diseases (Reference: Yasunari Kanari. On-line HDF --- Next-generation artificial kidney As an artificial organ, 26: 905-912, 1997).
[0003]
In recent years, on-line hemodiafiltration has been devised, which purifies the dialysate used for hemodialysis and uses part of it as a replacement fluid in hemodiafiltration treatment that takes advantage of both hemodialysis and hemofiltration. Although it has been tried to put it into practical use, it has been proven to have a high clinical effect (reference book: dialysate water quality management & online HDF, Yasunari Kanari, Medical Review, Osaka, 1996). There is room for improvement in stability, operability, removal performance and economy.
[0004]
In the current on-line hemodiafiltration method, the same amount is automatically applied to the diafilter in the closed system by injecting dialysate into the blood circuit outside the closed system with a roller pump from inside the closed system of the dialysate water system circuit. A system is adopted in which ultrafiltration of blood occurs and the fluid replacement rate and the filtration rate are balanced. Since the flow rate of the liquid pump at the inlet of the closed system and the flow rate of the drainage pump at the outlet are strictly matched, the drainage flow rate is obtained by ultrafiltering the shortage extracted as replacement fluid in the middle. Is kept equal to the feed flow rate. Although it is cheaper than the conventional hemodiafiltration method using a replacement liquid filled in a commercially available bottle or bag, it is necessary to install a relatively expensive roller pump for replacement fluid. In addition, the use of a replacement fluid circuit having a pump segment in every treatment causes a cost increase.
[0005]
In the situation where blood is being filtered, the blood circuit side of the membrane of the diafilter is at a positive pressure, whereas the dialysate circuit system in the closed system is at a relatively negative pressure. Since the roller pump extracts the dialysate from the negative pressure part of the dialysate circuit and ejects it against the positive blood circuit against the pressure, the actual ejected flow rate is several% to several percent of the set value of the pump. It is inaccurate because it is reduced to the order of 10%. Further, there is a concern that a reverse flow may occur instantaneously when the plurality of rotating rollers are switched, and blood may flow back to the dialysate water system circuit, resulting in a blood contamination accident. Although a method of installing a small ultrafiltration filter in the replacement fluid circuit has been devised (AK100Ultra: manufactured by Gambro, Sweden), it is rarely used in Japan because of a considerable increase in cost.
[0006]
The online hemodiafiltration method is based on the premise of stable supply of ultrapure water quality dialysate, and usually the apparatus has two or more ultrafiltration filters (hereinafter also simply referred to as filters) arranged in series. An ultrafiltration membrane is a separation membrane capable of blocking endotoxin almost completely (blocking rate of 99.9% or more). However, if it is used inappropriately, sufficient performance cannot be obtained. For example, when the flow rate of the filter is not filtered to ensure a flow through (also referred to as total filtration or dead end filtration), solutes such as endotoxin blocked on the membrane surface are concentrated and exceed the threshold for blocking performance of the membrane. And lead to endotoxin leaks. When a filter is used for total filtration, air mixed in the circuit is stored in the filter, reducing the effective membrane area of the filtration, reducing water permeability, or creating bacterial or fungal contamination in the air retention area. May form. When installing a filter, it is indispensable to maintain sufficient blocking performance and water permeability by adopting a partial filtration method that secures a flow path, but it is essential to maintain blocking performance and water permeability. Wearing and management was insufficient.
[0007]
If the dialysate water system is stagnant and aquatic bacteria are mixed, it will grow explosively in the stagnant space, causing an increase in the level of contamination and biofilm (a complex of sugar, sugar, organic and inorganic substances secreted by bacteria and bacteria). ) And other permanent contamination sources. In particular, when complex structures are introduced into the circuit, bacteria, organic matter, and inorganic matter are likely to adhere. Once a biofilm is formed, it is difficult to remove it even with a cleaning disinfectant, and it is important to prevent its formation. However, in conventional online hemodiafiltration devices, the dialysate water system circuit, especially the water system circuit for extracting the ultra-pure replacement fluid, is not always sufficient, and measures for preventing stagnation are not necessarily sufficient, causing endotoxin contamination of several EU / L levels. There was also.
[0008]
In general, blood filtration treatment causes membrane degradation and blood concentration due to water removal over time, resulting in a decrease in the water permeability of the diafilter, and the initial filtration rate cannot be maintained. sell. An excessive load on the membrane was observed as an increase in TMP. When TMP reached 300 mmHg, the actual rate of the conventional hemodiafiltration apparatus was that the filtration rate was reduced by manual operation. Even when the blood flow was temporarily reduced due to the patient changing his / her posture, TMP rapidly increased, and manual operation to temporarily reduce the filtration rate was unavoidable. The point which requires the monitoring of TMP which fluctuates dynamically, and the countermeasure at the time of fluctuation became extra labor and was complicated.
[0009]
The pore size of the diafilter membrane when not in use is extremely large, and albumin having a molecular weight of 66 kD also allows considerable permeation (permeability is about 0.01 to 0.1%). It is thought that the plasma protein is sorbed or adsorbed on the membrane surface or pores by contact with blood, so that the pores are relatively narrowed to have a pore diameter suitable for blood filtration. That is, since the filtration flux in the initial adsorption non-equilibrium phase contains a considerable amount of albumin, it is preferable to set the initial filtration rate to a low value. It was ignored. Since albumin loss leads to lower blood pressure and worsening nutritional status, there is a tolerance limit for the living body, and from the viewpoint that albumin loss must be kept within a certain range, large pore membranes have high removal performance of large molecule uremic toxins Even if it was known, it was difficult to select. In addition, when an excessive filtration speed or TMP is loaded on the membrane, the risk of deterioration due to rapid clogging or a large amount of albumin loss due to the concentration effect has been overlooked.
[0010]
Even though the usefulness of hemofiltration has decreased, hemofiltration is still evaluated as the first choice in pathologies such as glaucoma, dialysis dysfunction, acute stroke, and heart failure. However, in the conventional online hemodiafiltration apparatus, it is difficult to perform hemofiltration treatment due to insufficient mechanical function.
[0011]
[Problems to be solved by the invention]
In the present invention, steadily increasing complications of dialysis patients and prolongation of dialysis history will result in intractable complications that cannot be dealt with by further normal hemodialysis (nutrient disorders, arteriosclerosis, dialysis amyloidosis, dialysis dysfunction, pigmentation, skin pruritus). The goal is to develop a versatile online hemodiafiltration treatment that can replace conventional hemodialysis. In other words, high-performance online hemodialysis that is as easy to operate as or better than conventional hemodialysis machines, is excellent in stability and safety, is labor-saving and economical, and can expect high treatment efficiency. By providing a filtering device, we will create a medical environment that allows patients to practice hemodialysis treatment on a large number of patients simultaneously, and ultimately contribute to improving the prognosis and quality of life of patients being treated. I am aiming.
[0012]
In addition, the present invention seeks to solve the problem of minimizing the removal of substances essential to a living body while making the most of the characteristics of substance removal by filtration by program-controlling filtration conditions over time. It also describes the methodology. In other words, considering that the pore size of the membrane is large when not in use and the pore size gradually decreases due to protein adhesion, the filtration flux applied to the membrane is initially reduced, and the filtration flow is gradually or stepwise. It is intended that a program that raises the bundle or conversely reduces the filtration flux according to the membrane deterioration that progresses as the treatment progresses can be performed by both pressure filtration (TMP control) and volumetric filtration (filtration speed control). Optimum filtration conditions so as not to reduce solute removal performance and water permeability by loading excessive filtration flux on the membrane and accelerating membrane deterioration, and not causing a large amount of protein loss Establish a monitoring mechanism that will be maintained throughout the course of treatment. Further, as a variation of treatment, it is also an object that hemofiltration applied to special conditions such as glaucoma, dialysis dysfunction, acute stroke, and heart failure can be carried out as easily as hemodiafiltration.
[0013]
[Means for Solving the Problems]
In the present invention, (1) a primary filter washing line connected to a passage side of a primary ultrafiltration filter provided outside a closed system, which is not found in existing hemodialysis apparatuses and hemodiafiltration apparatuses; (2) dialysis Dialysate circulation line that keeps the secondary ultrafiltration filter in the liquid feed line locally at a positive pressure above a certain pressure, (3) Replacement fluid that extracts dialysate filtrate from the secondary ultrafiltration filter A filtrate line that has a port and merges with the liquid feeding line, (4) a dialysate circulation line, and a dialysate liquid feeding line connected thereto, which is a safety mechanism when an abnormally high pressure is reached, and a bypass line for blood filtration (5) Mechanisms such as a blood leakage sensor provided in the vicinity of the blood circuit merging portion of the replacement fluid line, and a plurality of transmission control programs (fm) for controlling a plurality of these mechanisms in conjunction with each other By It has solved the serial problems.
[0014]
Hereinafter, a hemodiafiltration method using an on-line hemodiafiltration device according to the present invention will be described in detail with reference to the drawings. FIG. 1 is a diagram showing components of an on-line hemodiafiltration device according to the present invention and piping of the device. The dialysate supplied to the hemodiafiltration apparatus according to the present invention is prevented from impurities on the membrane surface by a primary ultrafiltration filter (UF1) mounted outside the sealed system, and only the dialysate filtered by the membrane is sealed system. It is taken in. Impurities blocked on the membrane surface of the filter are washed away into the dialysate drainage line (L5) using the primary filter washing line (L10) provided on the passage side of the filter. In other words, taking a device with a chamber type dialysate ejection system as an example, one of the two chambers (usually 500 ml capacity) on the liquid feed side received dialysate from outside the closed system and became full. The electromagnetic valve (SV1) attached to the primary filter cleaning line is opened during the waiting time (usually about 10 to 15 seconds) from the time point until the actual delivery of liquid to the outside of the closed system, and the filter passage side is flushed. Thus, the film surface deposit is washed away (transmission control system f), and the filter removal performance and water permeability performance can be maintained over a long period of time. Moreover, the air mixed in the piping does not accumulate in the filter, reduce the effective membrane area, or form a dead space to become a contamination source. In an apparatus having a double pump (double plunger pump) dialysate ejection system instead of the chamber system, there is no waiting time for the chamber system, so a separate flush time must be provided in the cleaning process. In the case of the dual pump system, the chamber system is preferable because total filtration is performed during treatment.
[0015]
The dialysate circulation line (L8) provided in the form of being inserted into the dialysate feed line is a dialysate circulation pump (P4) that is a water flow pump, a secondary ultrafiltration filter (UF2), a flow-through side passage, and a pressure relief valve. (RV1), and the secondary ultrafiltration filter passage side is positive pressure (usually 1 kg / cm2) due to the performance of dialysate circulation pump (P4) and pressure relief valve (RV1). ² This pressure is the driving force when the filtrate is injected from the replacement fluid line into the blood circuit. Accordingly, the roller pump and the replacement fluid line pump segment used in the conventional on-line hemodiafiltration apparatus are not required, and the economy and operability are excellent.
[0016]
In the secondary ultrafiltration filter, the filtrate is extracted by the partial filtration method, and the compartment on the passing side is the flow path of the dialysate circulation line (L8). The dialysate circulation pump (P4) is a water flow pump. Since it circulates at a high flow rate (usually 1 L / min or more), obstructions are not deposited on the membrane surface, and the membrane inhibition performance and water permeation performance are maintained for a long time. The dialysate supplied to the blood circuit is subjected to two stages of ultrafiltration in series in the online hemodiafiltration apparatus according to the present invention, and the endotoxin concentration is always below the detection limit, so that a stable supply of ultrapure replacement fluid can be provided. Is possible. In the present invention, a method of once filtering the entire amount of dialysate loaded on the secondary ultrafiltration filter and distributing it to the replacement fluid and the dialysate sent to the diafilter can be used. Care must be taken that the blocking solute concentrates on the membrane surface during the course.
[0017]
The filtrate of the secondary ultrafiltration filter is extracted by the filtrate line (L9). By finely adjusting the patency state (flow path cross-sectional area) of the flow path with the flow rate adjusting pinch valve (PV1), the replacement fluid speed (that is, the filtration speed) can be freely adjusted. The fluid replacement speed is a function of TMP. Generally, as TMP increases, the filtration speed increases proportionally at first, but the increase in the filtration speed slows down from a certain point, and eventually reaches a plateau (blood filtration). In general, TMP is about 300 to 500 mmHg, and the filtration rate usually reaches a plateau). The method of monitoring the TMP and feedback-controlling the flow rate adjusting pinch valve (PV1) so as to keep the TMP at a predetermined TMP is the pressure filtration (TMP control, transmission control system h). The method of feedback control of the flow rate adjustment pinch valve so as to keep the flow rate constant is the metered filtration (filtration speed control, transmission control system i), but any selection including midway switching is possible. TMP is obtained by calculating the difference between the average of arterial blood circuit pressure (PG1) and venous blood circuit pressure (PG2) and dialysate drainage circuit pressure (PG3). The filtration speed, ie, the replacement fluid speed, is determined by the flow rate of the dialysate feed pump (the value of the flow meter F1) and the flow rate downstream of the confluence to the dialysate feed channel of the dialysate circulation circuit (the value of the flow meter F2). Equal to the difference. In order to adjust the cross-sectional area of the replacement fluid flow path, the purpose of using a pinch valve that compresses the tube from the outside is to consider the possibility of becoming a contamination source if there is a complicated structure inside the flow path It is. The replacement fluid must be completely endotoxin free. In a time zone other than the time when the replacement fluid is being used (for example, during treatment in the hemodialysis treatment mode or a washing step), the electromagnetic valve (SV4) of the filtrate line (L9) is opened and the secondary ultrafiltration filter (UF2). ) Passes through the replacement fluid port (14), and finally joins the dialysate feeding line (L5). At least in the operating state of the apparatus, there is no stagnation up to the point of the replacement port of the filtrate line (12 to 14), so that secondary contamination of bacteria does not occur. When not in use, fill with disinfectant solution to prevent contamination.
[0018]
In the present invention, there are two methods for performing hemofiltration treatment. Blood filtration is a technique in which only dialysate and fluid replacement are performed without perfusing dialysate through a diafilter and without removing substances by diffusion. (1) In the main method, the solenoid valves (SV3 and SV4) located in the flow path leading to the diafilter are closed, the dialysate reaching the diafilter is shut off, and the dialysate feed pump (P2) is used to send the solution. Of the flow rate of the dialysate, the dialysate not used for the replacement fluid is bypassed from the pressure relief line (L10) to the dialysate drainage line (L5). Filtration can be adjusted by either controlled pressure (TMP) control or controlled volume control. (2) In another method, the ejection speed of the dialysate pump (P2) is monitored by a flow meter (F1) and feedback control is performed so that the actual ejection amount becomes equal to the set value. (Speed control) m (transmission control system m), and if the ejection amount of the dialysate feed pump (P2) is adjusted so that a predetermined TMP value is achieved, pressure filtration (TMP control) is achieved.
[0019]
When blood flows back through the replacement fluid line (L3 or L3 ′) and reaches the filtrate line (L9), there is a possibility that a serious nosocomial infection accident due to hepatitis virus or the like will occur. A safety mechanism is provided. (1) Dialysate circulation circuit (L8) is positive pressure (usually 1 kg / cm) by dialysate circulation pump (P4) and pressure relief valve (RV1). ² Above). For this reason, the pressure of the filtrate line (L9) located on the opposite side of the membrane of the secondary ultrafiltration filter (UF2) is a value obtained by subtracting the pressure loss of the filter from the pressure of the filter passage part of the dialysate circulation line ( Usually 0.75kg / cm ² more than). Therefore, when the pressure of the blood circuit is taken into consideration, the backflow of blood cannot occur in the operating state of the device according to the present invention. In the event that the positive pressure maintenance is disturbed for some reason and a blood regurgitation occurs, the following mechanism operates. (2) The fluid replacement line (L3 or L3 ') is instantaneously synchronized with the signal detected by the blood leakage sensor (B or B') installed in the vicinity of the blood circuit junction of the fluid replacement line (L3 or L3 '). Alternatively, the emergency shutoff pinch valve (PV2) attached to the filtrate line (L9) is closed to shut off the flow path (transmission control system g). (3) Similarly, the flow rate adjusting pinch valve (PV1) also shuts off the flow path in conjunction with the operation of the blood leakage alarm (transmission control system g). (4) Provide a check valve (UV) in the filtrate line. Although the above mechanism does not cause a back flow of blood into the filtrate line, it is essential to fully disinfect and clean the entire flow path of the device before proceeding to the next patient treatment.
[0020]
In hemodiafiltration or hemofiltration of controlled volume control (filtration rate control) that tries to keep the filtration rate constant at a high value, due to the deterioration of water permeability due to blood concentration due to membrane deterioration over time and dehydration of patient excess body fluid, As the treatment progresses, TMP increases, and the filtration rate cannot be maintained. This problem can be easily avoided by employing pressure-dependent (TMP) control. From the viewpoint of the stability of the filtration operation state, the sub pressure control is superior to the sub amount control. However, according to the present invention, even in the case of metered amount control, the filtration rate in the latter half of the treatment is automatically gradually decreased linearly, curvilinearly or stepwise over time by a program (FIG. 8). The treatment can be performed stably even in the case of metered control by using a control mechanism that automatically reduces the filtration rate when the TMP reaches a certain threshold (usually about 300 mmHg).
[0021]
A large amount of albumin loss at the beginning of treatment when the membrane pore size of the diafilter is large can be avoided by setting the initial filtration conditions lower and gradually increasing in a linear, curved, or stepped manner (Fig. 7, 8). Increasing the filtration conditions gradually has the effect of minimizing membrane deterioration, and contributes to the improvement of the removal efficiency of large molecule uremic toxins. In particular, in the controlled pressure control, when a high value (200 to 300 mmHg) of TMP is set from the start of the treatment, the filtration flux becomes excessive, leading to a large amount of albumin loss and also the deterioration of the membrane.
[0022]
The profile of assisted pressure filtration (TMP control) with the highest removal efficiency is such that the starting TMP is set low (for example, 50 mmHg or less), and the optimum TMP value (usually 100 to 100) over a certain period of time (usually about 60 minutes). 200mmHg) and gradually increase until the TMP reaches the maximum allowable value (usually about 300mmHg) as the membrane permeability decreases from the latter half of the treatment (usually after 2 to 3 hours). It is programmed to gradually increase (3-point sigmoid method or 4-point broken line method). Even if the TMP is set to exceed the maximum allowable value, the albumin loss is exponentially in spite of the fact that effective filtration flux and large molecule uremic solute flux cannot be increased due to membrane degradation. Since it increases, it is not preferable. As the gradual increase mode, a straight line, a curved line, or a stepped shape can be selected.
[0023]
On the other hand, the profile of optimum filtration conditions in metered filtration (filtration rate control) is set to a low filtration rate at the start (for example, 20 ml / min or less) and is optimum over a certain time (usually about 15 minutes). The filtration rate is gradually increased and maintained until the filtration rate (about 80 ml / min for blood flow of 250 ml / min), and the filtration rate is reduced according to the decrease in membrane permeability from the latter half of treatment (usually after 2 to 3 hours). Is programmed to gradually decrease to the final decrease value (usually 60 to 70 ml / min) toward the end (four-point broken line method). As the gradual increase and decrease modes, any of straight line, curved line, and stepped shape can be selected.
[0024]
DETAILED DESCRIPTION OF THE INVENTION
The present invention is a kind of blood purification device for purifying waste accumulated in blood in a pathological state such as renal failure by membrane separation, and includes a basic that a so-called hemodialysis device (also referred to as a dialysis monitoring device) includes (A) a roller-type blood pump for circulating blood through a diafilter and blood circuits on the arterial and venous sides for blood flow; (b) dialysis stock solution or bulk powder with water A mixing device for diluting to prepare a dialysate of a predetermined concentration (necessary only for personal devices, not required for the central method), (c) a liquid feed line for feeding dialysate to the blood purifier, ( d) A drainage line for draining dialysate in which waste products are dissolved by substance exchange with blood, (e) a closed system that keeps the flow rate of the liquid supply line and the drainage line equal (an inlet / outlet flow rate balancing mechanism), (F) Vein Pressure monitor in the vicinity of the blood purifier in the chamber, arterial chamber and dialysate drainage line; (g) water removal to remove excess body fluid accumulated in the body from the blood by ultrafiltration at a precise and constant rate A drainage line having a pump and a drain to the outside of the system, and further, as a characteristic feature of the present invention, (h) dialysate drainage outside the sealed system from the passage side of the primary ultrafiltration filter provided outside the sealed system Primary filter washing line connected to bypass line, (i) Secondary ultrafiltration filter section in dialysate feeding line is locally maintained at a positive pressure above a certain pressure and a high circulation flow rate is maintained. Dialysate circulation line, (j) extract the dialysate filtrate for replacement fluid from the secondary ultrafiltration filter, and have a replacement fluid port in the middle and join the fluid feed line, (k) dialysate circulation line and this Ream As a safety mechanism when the dialysate delivery line that reaches the abnormally high pressure locally, it is a flow path that releases pressure to the dialysate drainage line, and does not send dialysate to the blood purifier during blood filtration Pressure relief line that also serves as a bypass line to the dialysate drainage line, (1) a replacement fluid line for connecting the filtrate line and the blood circuit, and leading the secondary ultrafiltration filter to the blood circuit, (m) a replacement fluid line Equipped with at least a blood leakage sensor provided in the vicinity of the blood circuit junction.
[0025]
The dialysate circulation circuit has a dialysate circulation pump (P4) which is a water flow pump, a pressure relief valve (RV1), and a solenoid valve (SV2). The dialysate circulation pump (P4) and the pressure relief valve (RV1) Between the positive pressure (usually 1kg / cm ² This pressure serves as a driving force for the replacement fluid and prevents blood backflow in the replacement fluid lines (L3 to L3 ′). For this reason, the fluid replacement circuit which has the roller pump and pump segment which were essential by the conventional online hemodialysis is not required. By maintaining a high flow rate in the dialysate circulation line (L8), the membrane surface of the secondary ultrafiltration filter (UF2) is flushed and works as an effective cleaning action.
[0026]
A flow rate adjusting pinch valve (PV1) that can freely adjust the flow path from fully open to fully closed is provided in the filtrate line (L9), and the replacement fluid speed (that is, the filtration speed) can be arbitrarily set. A transmission control system (h and i) capable of monitoring the TMP or the filtration speed in real time and feedback-controlling the closed state of the flow rate adjusting pinch valve (PV1) so as to have a predetermined value is provided. The reason why the pinch valve that presses the tube from the outside is used to adjust the cross-sectional area of the flow path is that if a protruding type valve is provided in the flow path, the filtrate may be contaminated.
[0027]
Emergency shut-off pinch capable of instantaneously shutting off the flow path from fully open to fully closed immediately downstream of the flow control pinch valve (PV1) in the replacement fluid line (L3 or L3 ') or filtrate line (L9) A valve (PV2) is provided to prevent any further blood backflow by immediately shutting off the filtrate line or the replacement fluid line in the event of an unexpected situation where the blood flows back through the replacement fluid line (L3). An unexpected situation in which blood flows back through the replacement fluid line (L3 or L3 ′) is detected by the blood leakage sensor in the next section. Pinch valve for flow adjustment
(PV1) has the same function, but this is suitable for fine adjustment of the blockage of the flow path and may not be able to cope with the instantaneous blockage mechanism, so an emergency shut-off pinch valve (PV2) is provided separately It is preferable. In other steps, the emergency shut-off pinch valve (PV2) is interlocked and closed when the flow rate adjusting pinch valve (PV1) is completely closed.
[0028]
As a safety mechanism for preventing blood from flowing into the filtrate line (L9) and causing contamination, a junction of the replacement fluid line (L3 or L3 ′) to the arterial blood circuit (L1) or the venous blood circuit (L2) A blood leakage sensor (B or B ′) is provided in the vicinity, and a signal is transmitted when blood mixture (back flow) into the fluid replacement line (L4) is detected, and a pinch valve (PV2) and a flow control pinch valve (PV1) are transmitted. ) Is immediately closed (transmission control system g).
[0029]
Pressure relief line (15) connecting the point (15) between the two solenoid valves (SV2 and SV3) of the dialysate feeding circuit (L4) and the point (19) in the closed system of the dialysate drainage line (L5) ( L10) is provided with a pressure relief valve (RV2), which is a flow path through which the pressure is released when the pressure is overloaded due to an unexpected situation. The line also functions as a bypass line during blood filtration.
[0030]
Primary filter washing line connecting the passage side (7) of the ultrafiltration filter (UF1) provided at a point outside the closed system of the dialysate feeding line and the point (21) outside the sealed system of the dialysate drainage line (L7) is provided with a solenoid valve (SV1). When the solenoid valve is closed, the dialysate is totally filtered, and when it is open, the dialysate is completely passed and used for washing the filter (transmission control system f).
[0031]
The dialysate circulation line (L8) ensures a high flow rate circulation in the passage-side compartment of the secondary ultrafiltration filter and suppresses the accumulation of blocking substances and the formation of concentration polarization layers on the membrane surface of the filter, It is possible to maintain the water permeability of the filter, improve the durability, and improve the water quality of the filtrate (endotoxin-free).
[0032]
With the solenoid valves (SV3 and SV4) located in the flow path leading to the diafilter closed and without dialysate being sent to the diafilter, all the dialysate passing through the filter other than the secondary filter filtrate serving as a replacement fluid is relieved of pressure. When it is discharged from the line (L10) into the closed system, blood filtration occurs.
[0033]
The TMP during ultrafiltration is determined from the values of the arterial blood circuit pressure monitor (PG1), venous blood circuit pressure monitor (PG2), and dialysate drainage circuit pressure monitor (PG3). The flow rate adjustment pinch valve (PV1) provided in the filtrate line (L8) is finely adjusted so that the replenishment speed, that is, the filtration speed, is adjusted to a value of 2 and the filtration speed is secondarily feedback controlled by TMP (transmission control) System h).
[0034]
Fluid replacement rate, that is, the filtration rate, with the difference between the flow rate of the dialysate feed pump (P2) monitored by the flow meter (F1) and the flow rate monitored by the flow meter (F2) provided in the dialysate feed line (L4) The flow rate adjustment pinch valve (PV1) provided in the filtrate line (L8) is finely adjusted so that the filtration rate becomes a predetermined arbitrary value, and the feedback control is primarily performed (transmission control system i). ). The reason why the flow rate is not directly measured by installing a flow meter between 12 and 14 of the filtrate circuit (L9) is that the risk of contamination in the flow meter unit cannot be denied. In general, in order to avoid secondary contamination of ultrapure dialysate, the principle is to simplify the inner surface of the flow path smoothly.
[0035]
When the TMP, which is the actual filtration operating pressure, exceeds the specified monitoring value (usually about 300 mmHg) in the metered filtration (filtration rate control) method, the filtration rate is automatically determined (usually post-dilution) It is reduced by 5 to 10 ml / min in the case of a replacement fluid, and about 30 to 60 ml / min in the case of a predilution replacement fluid (transmission control system j).
[0036]
The TMP or the filtration speed as a setting parameter is a function of time, and the removal characteristic is optimally improved by controlling the program to a linear, curved or stepped profile arbitrarily in the time axis direction (transmission control system 1).
[0037]
The solenoid valve (SV3) placed in the dialysate feed line (L4) and the solenoid valve (SV4) placed in the filtrate line (L9) are closed, and the dialysate feed pump monitored by the flow meter (F1) A mechanism for adjusting and controlling the ejection amount so that the flow rate of (P2) is equal to the set filtration rate is provided (transmission control system m), and the total amount ejected by the dialysate liquid pump (P2) is the second limit Blood filtration is performed by permeating through the outer filtration filter (UF2) to be replenished. Further, if the ejection amount of the dialysate liquid delivery pump (P2) is feedback-adjusted so that a predetermined TMP value is obtained, the pressure filtration (TMP control) can be performed.
[0038]
【Example】
Embodiments of the present invention will be described below with reference to the drawings.
(1) Normal pressure (TMP control) hemodiafiltration
It is assumed that blood access, blood / venous side blood circuit, diafilter, dialysate feeding / draining circuit are connected in a typical manner, and the general mechanism is in operation. When the replacement fluid is to be prediluted, the replacement fluid line (L3) is connected between the replacement fluid port (14) of the filtrate line (L9) and the arterial chamber (C1). When the replacement fluid is to be replaced by post-dilution, L3 ′ is connected between the replacement fluid port (14) and the venous chamber (C2) instead of L3. As shown in FIG. 2, the circulating pump (P4) of the dialysate circulation line (L8) is operated to generate positive pressure, and the solenoid valves (SV2) and (SV3) of the dialysate feed line (L4) are opened. The solenoid valve (SV4) of the filtrate line (L9) is closed, and the emergency shut-off pinch valve (PV2) is opened. TMP is obtained from the difference between the average value of the arterial blood circuit pressure monitor (PG1) and the venous blood circuit pressure monitor (PG2) and the dialysate drainage circuit pressure monitor (PG3), and is used as a monitoring parameter. The flow rate is changed by changing the degree of opening and closing of the cross-sectional area of the flow path by the restriction of the flow rate adjusting pinch valve (PV1) to change the fluid replacement speed (that is, the filtration speed), and feedback control is performed so that the measured TMP value becomes equal to the set TMP value ( Transmission control system h). The fluid replacement speed (filtration speed) in a state where the predetermined TMP is reached is provided in the dialysate liquid feed line (L4) from the dialysate liquid feed flow rate (P2 flow rate) monitored by the flow meter (F1). It becomes equal to the value obtained by subtracting the measured value of the flow meter (F2). In the pressure filtration, the replacement fluid rate (filtration rate) varies with time. Therefore, the integrated replacement fluid amount (filtration amount) is obtained by integrating the replacement fluid rate (filtration rate) with time. The filtration speed and integrated filtration amount are displayed on the panel of the device (M).
[0039]
(2) Follow-up (filtration rate control) hemodiafiltration
As in the previous section, the circulating pump (P4) of the dialysate circulation line (L8) is operated to generate positive pressure, and the solenoid valve (SV2) and solenoid valve (SV3) of the dialysate feed line (L4) are opened. The solenoid valve (SV4) of the filtrate line (L9) is closed, and the emergency shut-off pinch valve (PV2) is opened. The difference between the flow rate of the dialysate (P1 flow rate) monitored by the flow meter (F1) and the measured value of the flow meter (F2) provided in the dialysate feed line (L4). This value is monitored, and this value is monitored, and the open / close state of the flow path by the restriction of the flow rate adjustment pinch valve (PV1), that is, the flow rate permeating through the pinch valve is set so as to be equal to the replacement fluid rate (filtration rate) set by the user Perform feedback control (transmission control system i). The filtration speed and integrated filtration amount are displayed on the panel of the device (M).
[0040]
(3) Normal pressure (TMP control) blood filtration
It is assumed that blood access, blood / venous side blood circuit, diafilter, dialysate feeding / draining circuit are connected in a typical manner, and the general mechanism is in operation. When the replacement fluid is to be prediluted, the replacement fluid line (L3) is connected between the replacement fluid port (14) of the filtrate line (L9) and the arterial chamber (C1). When the replacement fluid is to be replaced by post-dilution, L3 ′ is connected between the replacement fluid port (14) and the venous chamber (C2) instead of L3. As shown in FIG. 3, the circulating pump (P4) of the dialysate circulation line (L8) is operated to generate positive pressure, the electromagnetic valve (SV2) of the dialysate feed line (L4) is opened, and the filtrate line (L9). The solenoid valve (SV4) is closed and the emergency shut-off pinch valve (PV2) is opened. Unlike the case of hemodiafiltration, the dialysate is not supplied to the diafilter by closing the solenoid valve (SV3) of the dialysate feed line (L4). TMP is obtained from the difference between the average value of the arterial blood circuit pressure monitor (PG1) and the venous blood circuit pressure monitor (PG2) and the dialysate drainage circuit pressure monitor (PG3), and is used as a monitoring parameter. The flow rate that passes through the pinch valve so that the actual TMP becomes equal to the set TMP by adjusting the open / closed state of the flow path by the throttle of the flow rate adjusting pinch valve (PV1) so as to be a predetermined TMP. Is adjusted (transmission control system h). The fluid replacement speed (filtration speed) in a state where the predetermined TMP is reached is provided in the dialysate liquid feed line (L4) from the dialysate liquid feed flow rate (P1 flow rate) monitored by the flow meter (F1). It becomes equal to the value obtained by subtracting the measured value of the flow meter (F2). Of the dialysate, the flow rate indicated by the flow meter (F2) is bypassed from the pressure relief line (L10) to the dialysate drain line (L5). In the pressure filtration, the replacement fluid rate (filtration rate) varies with time. Therefore, the integrated replacement fluid amount (filtration amount) is obtained by integrating the replacement fluid rate (filtration rate) with time. The filtration speed and integrated filtration amount are displayed on the panel of the device (M).
[0039]
(4) Follow-up (filtration rate control) blood filtration
As in the previous section, the circulating pump (P4) of the dialysate circulation line (L8) is operated to generate positive pressure, the solenoid valve (SV2) of the dialysate feed line (L4) is opened, and the filtrate line (L9 The solenoid valve (SV4) is closed and the emergency shut-off pinch valve (PV2) is opened. Unlike the case of hemodiafiltration, the dialysate is not supplied to the diafilter by closing the solenoid valve (SV3) of the dialysate feed line (L4). The fluid replacement rate (filtration rate) is obtained by the difference between the dialysate feed flow rate (P2 flow rate, the value of the flow meter F1) and the measured value of the flow meter (F2) provided in the dialysate feed line (L4). This value is monitored and feedback control is performed on the degree of opening and closing of the flow rate adjusting pinch valve (PV1) so as to be equal to the replacement fluid speed (filtration speed) set by the user (transmission control system i). Of the dialysate, the flow rate indicated by the flow meter (F2) is bypassed from the pressure relief line (L10) to the dialysate drain line (L5). The filtration speed and integrated filtration amount are displayed on the panel of the device (M). Sub-volume (filtration rate control) As an alternative to blood filtration, adjust the flow rate of the dialysate feed pump (P2) so that it is equal to the fluid replacement rate (filtration rate) set by the user, and the total amount of dialysate sent. Can also be injected into the blood circuit via the filtrate line (L9) and the replacement fluid line (L3 or L3 '). In this case, if the feedback control is performed so that the reading value of the flow meter (F1) is equal to the ejection amount of the dialysate feeding pump (P2), the metering filtration (filtration speed control) becomes accurate (transmission control system m). This method is economically superior in that no dialysate is discarded by bypass.
[0040]
(5) Hemodialysis
It is assumed that the blood access, blood / venous side blood circuit, diafilter, dialysate feeding / draining circuit are connected in a typical manner, and the general mechanism is in an operating state. This method does not require a fluid replacement line. As shown in FIG. 4, the circulation pump (P4) of the dialysate circulation line (L8) is operated, the solenoid valve (SV2) of the dialysate feed line (L4), the solenoid valve (SV4) of the filtrate line (L9), and the pinch. The valves (PV1 and PV2) are opened, the solenoid valve (SV3) of the dialysate feed line (L4) is closed, and the total amount of dialysate ejected by the dialysate feed pump (P2) is outside the secondary limit. The solution is filtered by the filtration filter (UF2) and sent as it is to the blood purifier (D). The hemodialysis method according to the present invention is suitable for the use of a recently developed internal filtration type dialyzer. An internal filtration type dialyzer (dialyzer) increases the pressure loss of the blood flow path or dialysate flow path inside the dialyzer, and intentionally promotes spontaneous filtration and back filtration inside the purifier. It is devised to perform pseudo hemodiafiltration.
[0041]
(6) Cleaning process
Effective cleaning is achieved by practicing at least the following three steps. It is assumed that the dialysate feed pump (P2), the drainage pump (P3), and the like as basic configurations are in an operating state. Short out 17 and 18 of the circuit. (1) At the beginning of the washing process, the solenoid valve (SV2) of the dialysate liquid feed line (L4) is closed and the solenoid valve (SV3) is opened as shown in FIG. L9) Solenoid valve (SV4) is closed, circulation pump (P4) is operated, and secondary ultrafiltration is performed in the flow path of 5 → 9 → 10 → 11 → 13 → 15 → 16 → 22 in the single pass system. The circulation circuit (L8) including the passage side compartment of the filter (UF2) is washed, and the contaminant is quickly discharged out of the system. (2) Next, as a main washing process, two methods can be selected as a method of washing the dialysate circulation line (L8), the secondary ultrafiltration filter and the filtrate line (L9). (A) As shown in FIG. 6, during the washing process, the solenoid valve (SV3) of the dialysate liquid feeding line (L4) and the solenoid valve (SV4) of the filtrate line (L9) are alternately opened and closed to limit the secondary limit. The filtration filter (UF2) is alternately switched between a flow path that passes through and a flow path that completely filters, and the dialysate feed line (L4), dialysate circulation line (L8), filtrate line (L9), and secondary limit The filter (UF2) is completely washed. The solenoid valve (SV2) related to the circulation of the cleaning liquid (the cleaning liquid or the disinfecting liquid flows instead of the dialysate during the cleaning) is opened. Since the passage side of the secondary ultrafiltration filter (UF2) is flushed at a high flow rate, film surface deposits can be removed. The time for switching the two solenoid valves can be arbitrarily set. (B) During the washing process, both the solenoid valve SV3 of the dialysate feed line (L4) and the solenoid valve SV4 of the filtrate line (L9) are opened, and the washing solution is passed through the secondary ultrafiltration filter (UF2). And the two flow paths on the filtration side. The flow rate adjusting pinch valve (PV1) is adjusted so that the specified flow rate flows through the filter passage side. (3) At the end of the cleaning process, the same process as (1) is carried out for a fixed time (optional), and the exudates that have peeled off from the filter membrane surface by the process (2) are quickly removed from the system by a single pass. To discharge.
[0042]
(7) Program filtration control (see Figs. 7 and 8)
The purpose of the program filtration control is to control the loss of essential proteins such as albumin by reducing the filtration flux for a certain period of time early after the start of treatment, and to reduce the water permeability of the diafilter in the latter half of the treatment. Sometimes the filtration flux is maintained to some extent and the treatment efficiency is maintained.
[0043]
In any of the subordinate (TMP control) type or subordinate (filtration rate control) type, the TMP or the filtration rate is a function of time, and a setting that is linear, curvilinear, or stepped with respect to the time axis can be selected. . Normally, in the pressure filtration, as shown in FIG. 7C, the initial TMP value is set to a low value (50 mmHg or less), the TMP is increased to an S-shaped (sigmoid) curve, and the optimum TMP value (usually 100 to 200 mmHg) is set. The inflection point is set so that the pressure is finally about 300 mmHg (three-point sigmoid method), or a four-point broken line method similar to the sigmoid method as shown in FIG. Alternatively, as shown in FIG. 7B, gradually increase to the optimal TMP (usually 100 to 200 mmHg) linearly over the first 60 minutes, and then gradually reach a pressure of about 300 mmHg with a gentle straight line until the end. It can also be made (three-point broken line method). As shown in FIG. 7A, there is a method of setting a TMP profile with a simple straight line (two-point straight line method), but albumin loss tends to increase. In addition, an arbitrary TMP profile can be constructed by incorporating various functions having TMP as a dependent variable and time as an independent variable.
[0044]
In addition, in the volumetric filtration, as shown in FIGS. 8B and 8C, the initial filtration rate is set to a low value (usually 20 ml / min or less), and the filtration rate is gradually increased over a period of about 5 to 60 minutes. The blood flow is increased to about 80 ml / min in the case of 250 ml / min. Thereafter, a profile that gradually decreases by 10 to 20 ml / min toward the end of the treatment is preferable. After reaching the optimum value as shown in FIG. 8D, it may be gradually decreased after maintaining the optimum filtration rate for a certain time (usually 1 to 3 hours) (four-point broken line method). In the method of FIG. 8A in which the filtration rate is simply reduced linearly, the initial albumin loss tends to increase. In the case of pressure filtration, it is possible to keep the TMP constant during the course of treatment, but in the case of metered volume filtration, the initial filtration rate set to a high value is maintained throughout the entire process due to deterioration of the water permeability due to membrane deterioration and blood concentration. Is difficult. Furthermore, a filtration condition profile combining a metered type and a pressured type is also possible. For example, the filtration rate is set to a low value of 20 ml / min (arbitrary) for 10 minutes from the start of treatment, and thereafter, the filtration rate is gradually increased to an optimal value of 80 ml / min (arbitrary) and kept at a constant value. During this time, the TMP value is monitored, and when the TMP reaches 300 mmHg (arbitrary), it is switched to constant pressure filtration as it is.
[0045]
The table below shows a list of transmission control systems.

[0046]
【The invention's effect】
According to the online hemodiafiltration apparatus according to the present invention, (1) a dialysate replacement solution that does not contain contamination such as endotoxin can be stably supplied. (2) By managing the ultrafiltration filter automatically, the filter is not contaminated, the removal performance is maintained, and the durability is further improved. (3) The safety mechanism prevents blood from flowing back through the replacement fluid system and contaminating the dialysate system. (4) A roller pump is not used for the replacement fluid, and therefore a replacement fluid circuit including an expensive pump segment is not necessary, which is economically advantageous. (5) Since filtration conditions can be optimally programmed as a function of time, the removal performance of large molecular weight uremic toxins is improved while preventing excessive albumin loss.
[0047]
In the present invention, contamination of the water-based flow path in the online hemodiafiltration device (M) does not occur. In any process, there is no stagnation in the circuit from the filtrate side (12) of the secondary ultrafiltration filter to the replacement fluid port (14) that actually extracts the replacement fluid, leading to bacterial growth and thus an increase in endotoxin levels. In addition, it eliminates the need to place complicated structures on the inner surface of the flow path, and a pinch valve that presses the tube from the outside is adopted for the valve, so that bacterial contamination and inorganic deposits do not occur in the flow path. It has been devised.
[0048]
In practicing treatment with the on-line hemodiafiltration apparatus according to the present invention, it is preferable that clean dialysis fluid satisfying certain water quality standards (Journal of Japanese Dialysis Medicine 31: 1107-1109, 1998) is supplied to the apparatus. However, this apparatus also has a high dialysate purification capability. First, the dialysate supplied to the apparatus is supplied only to the permeated water of the primary ultrafiltration filter installed outside the closed system. Also, intermittent accumulation of the solute blocked on the membrane surface can be prevented by flushing the compartment on the passing side of the primary ultrafiltration filter at high speed intermittently, and the solute blocking performance and water permeability of the filter can be maintained over a long period of time. Can do. Next, partial filtration is further performed with a secondary ultrafiltration filter in a closed system, and a filtrate having an endotoxin concentration of 0 is stably injected into the blood circuit as a replacement fluid. Since the flow-through compartment of the secondary filter always ensures a high flow rate, it prevents the accumulation of solutes blocked on the membrane surface more than the primary filter, and maintains the solute blocking performance and water permeability of the filter for a long time. Expect the effect. Maintaining the performance of the filter for a long time also leads to cost reduction.
[0049]
The on-line hemodiafiltration apparatus according to the present invention does not use a roller pump for driving the replacement fluid, which is essential in the conventional on-line hemodiafiltration apparatus, and therefore does not require a pump segment in the replacement fluid line. Economical benefits are increased by eliminating the need for expensive roller pumps and fluid replacement lines, and feedback control makes it possible to set conditions for filtration (fluid replacement) with higher accuracy than conventional online hemodiafiltration devices. Yes. In the present invention, as a measure against blood contamination, the pressure of the filtrate part of the dialysate water system circuit is always set higher than the blood circuit pressure, and a blood leakage sensor for detecting blood backflow is prepared in case of an unexpected situation. L3 or L3 ′) or a filtrate line (L9) is attached, and in conjunction with this, by holding a safety mechanism that double shuts off the filtrate line (L9) from the replacement fluid line (L3 or L3 ′), the blood circuit Thus, the blood does not flow back through the replacement fluid line (L3 or L3 ′) and reaches the filtrate portion of the dialysate water system circuit to cause blood contamination.
[0050]
In an online hemodiafiltration device that uses a conventional roller pump to set the fluid replacement rate (filtration rate), the TMP changes over time due to membrane deterioration of the diafilter over time and reduced water permeability due to an increase in blood hematocrit accompanying water removal. The on-line hemodiafiltration apparatus according to the present invention overcomes the drawbacks of large fluctuations by program pressure control or program filtration speed control, and the dialysis worker frequently monitors and resets the filtration conditions. It became unnecessary. In particular, the program pressure control can cope with an unexpected decrease in blood flow by instantaneously reducing the filtration rate.
[0051]
In the online hemodiafiltration apparatus according to the present invention, the filtration conditions at the initial stage of treatment are set to a low level by program pressure control or program filtration speed control, and the filtration conditions are gradually increased to a high level over time (high filtration speed or high TMP). By shifting to, a large amount of albumin loss in the initial treatment can be suppressed. As a result, it is possible to use a membrane having a large pore size that could not be used because the albumin loss is excessive in the conventional hemodiafiltration device, and further to remove large molecule uremic toxins such as β2 microglobulin and α1 microglobin. Can be increased. In addition, taking into account the membrane degradation in the latter half of the treatment, it is possible to program the profile of filtration conditions such as gradually increasing TMP in a stepwise or stepwise manner and gradually decreasing the filtration rate. It contributes to optimally improving the removal efficiency of such large molecule uremic toxins.
[0052]
With the online hemodiafiltration method according to the present invention, not only maintenance treatment for patients with chronic renal failure, but also treatment for patients with acute renal failure and multiple organ failure who are extremely poor in hemodynamics and who are difficult to perform normal hemodialysis Can be done.
[Brief description of the drawings]
FIG. 1 is a basic configuration diagram of the present invention.
FIG. 2 is a diagram of one embodiment of hemodiafiltration practice according to the present invention.
FIG. 3 is a diagram of one embodiment of blood filtration practice according to the present invention.
FIG. 4 is a diagram of one embodiment of hemodialysis practice according to the present invention.
FIG. 5 shows an example of a cleaning process in the present invention.
FIG. 6 shows an example of a cleaning process in the present invention.
FIG. 7 shows an example of a time profile of programmed pressure (TMP control) filtration according to the present invention.
FIG. 8 shows an example of a time-dependent profile of programmed metering (filtration rate control) filtration according to the present invention.
[Explanation of symbols]
B, B 'blood leak sensor
C1 Arterial chamber
C2 vein chamber
D Blood Purifier (Diafilter)
F1 flow meter (after dialysate pump)
F2 flow meter (after joining the dialysate circulation line to the dialysate feed line)
L1 Arterial blood circuit (1-2)
L2 Venous blood circuit (3-4)
L3 predilution fluid line (14-C1)
L3 'post-dilution replacement fluid line (14-C2)
L4 dialysate feeding line (5-6-8-9-13-15-16-17)
L5 dialysate drainage line (18-19-20-21-22)
L6 water removal line (20-23)
L7 Primary filter washing line (7-21)
L8 dialysate circulation line (9-10 ~ 11-13-9)
L9 filtrate line (12-14-16)
L10 Pressure relief line (15-19)
M Online hemodiafiltration machine
P1 blood pump
P2 dialysate pump
P3 Dialysate drainage pump
P4 dialysate circulation pump
P5 water removal pump
PG1 Arterial blood circuit pressure monitor
PG2 Venous blood circuit pressure monitor
PG3 Dialysate drainage circuit pressure monitor
PV1 Flow control pinch valve
PV2 emergency shut-off pinch valve
RV1 pressure relief valve (dialysate circulation line (L8))
RV2 pressure relief valve (pressure relief line (L10))
SV1 solenoid valve (primary filter cleaning line)
SV2 solenoid valve (dialysate feeding line)
SV3 Solenoid valve (dialysis fluid feed line)
SV4 solenoid valve (filtrate line)
UF1 ultrafiltration filter (endotoxin removal filter)
UF2 ultrafiltration filter (endotoxin removal filter)
UV check valve (filtrate line (L9))
1 Connection point between the arterial puncture needle and the arterial blood circuit (L1)
2 Connection point between arterial blood circuit (L1) and blood purifier (D)
Connection point of 3 blood purifier (D) and venous blood circuit (L2)
4 Connection point between venous blood circuit (L2) and venous puncture needle
5 Dialysate supply point to dialysate monitoring device
6 Connection point between filter load part of dialysate feeding circuit (L4) and inlet part of ultrafiltration filter (UF1)
7 Ultrafiltration filter (UF1) passage outlet and primary filter cleaning line (L7) connection point
8 Connection point of ultrafiltration filter (UF1) filtrate side and dialysate feed line (L4)
9 Branch point from dialysate feeding line (L4) of dialysate circulation circuit (L7)
10 Connection point between filter load part of dialysate circulation circuit (L8) and inlet part of ultrafiltration filter (UF2)
11 Connection point between ultrafiltration filter (UF2) passage outlet and dialysate circulation circuit (L8)
12 Connection point of ultrafiltration filter (UF2) filtrate side and filtrate line (L9)
13 Return point of dialysate circulation circuit (L8) to dialysate feed line (L4)
14 Replacement port (connection point of filtrate line (L9) and replacement line (L3 or L3 '))
15 Branch point from dialysate liquid supply line (L4) of pressure relief line (L10)
16 Reflux point of filtrate line (L9) drain line to dialysate feed line (L4)
17 Connection point between dialysate feeding line (L5) and blood purifier (D)
18 Connection point between blood purifier and dialysate drainage line (L5)
19 Junction point of pressure relief line (L10) to dialysate drainage line (L5)
20 Branch point from dialysate drainage line (L5) of drainage line (L6)
21 Connection point of dialysate drainage line (L5) of primary filter washing line (L7) to outside of closed system
22 Dialysate drainage line (L5) end
23 Water removal line (L6) end

Claims (19)

A blood purification device for purifying waste accumulated in blood in a pathological state by membrane separation,
In order to have the ability to supply dialysate, which is a large amount of electrolyte solution,
(A) Blood roller type for circulating the blood purifier as a flow path for the blood pump and the blood of the arterial and venous blood circuit,
( B ) a liquid feeding line for feeding dialysate into the blood purifier,
( C ) a drainage line for draining dialysate in which waste products are dissolved by material exchange with blood;
( D ) a closed system that keeps the flow rates of the liquid feed line and the drain line equal ;
( E ) a pressure monitor provided near the blood purifier in the venous chamber, arterial chamber and dialysate drainage line;
( F ) A dewatering line having a dewatering pump for removing extra body fluid accumulated in the body from the blood by ultrafiltration at an accurate and constant rate, and a drainage line outside the system, and a configuration characteristic of the present invention As
( G ) a primary filter washing line connected in a form of bypassing from the passage side of the primary ultrafiltration filter provided outside the closed system to the dialysate drainage line outside the closed system;
( H ) a dialysate circulation line that keeps the secondary ultrafiltration filter in the dialysate feed line locally at a positive pressure of a certain pressure or higher and maintains a high circulation flow rate;
( I ) A filtrate line that extracts a dialysate filtrate for replacement fluid from a secondary ultrafiltration filter, and has a replacement fluid port in the middle and joins the liquid feeding line;
( J ) a pressure relief line which is a bypass line connecting the dialysate circulation line and the dialysate feed line connected to the dialysate discharge line;
( K ) a replacement fluid line for connecting the filtrate line and the blood circuit to guide the secondary ultrafiltration filter to the blood circuit;
(L) at least has a blood leak Sensor provided the blood circuit merging the vicinity of the replacement fluid line,
Complement Ekikai path stagnation without clean replacement was stable supply system, complex and expensive replacement fluid circuit unnecessary, the replacement fluid circuit safety mechanism such as reverse blood flow does not occur with a roller pump or pump segment for fluid replacement A labor-saving high-performance online hemodiafiltration device that can set conditions by a program in any combination of pre-dilution and post-dilution for hemodiafiltration and blood filtration by pressure control filtration or speed control filtration mode.   In the dialysate feeding circuit, before and after the dialysate circulation line, that is, one place between the dialysate feed pump and the branch point from the dialysate feed line of the dialysate recirculation line, and another place. Is equipped with a flow meter that has the function of outputting measured values at two points between the point where the dialysate recirculation line joins the dialysate feed line again and the point where the filtrate line joins the dialysate feed line The online hemodiafiltration apparatus according to claim 1. The dialysate circulation circuit, a dialysate circulation pump is a water pump, pressure relief valve to be opened at a constant pressure or, and has a solenoid valve for opening and closing by electric signals, high-speed flow coercive the dialysate circulation circuit sag with online hemodiafiltration device according to claim 1 or 2 positive pressure of constant pressure or is held in flow-through side of the primary ultrafiltration filter between the dialysate circulation pump and pressure relief valve. Characterized in that said adjusting freely the fully closed to the filtrate line the cross-sectional area of the flow path from the fully open provided capable flow adjustment Pinchibaru blanking can arbitrarily set the replacement fluid velocity passing through the pinch valve The online hemodiafiltration apparatus according to any one of claims 1 to 3 . Replacement fluid line or immediately downstream of the flow rate adjusting pinch valve in the filtrate line, claims 1 to 4, blocking the flow path from the fully open immediately to fully closed is provided emergency cut-off pinch valve and check valve capable, The online hemodiafiltration apparatus according to any one of the above. The on-line blood according to any one of claims 1 to 5, wherein a blood leakage sensor for detecting blood mixed in the replacement fluid with high sensitivity is provided in the vicinity of the junction with the artery side blood circuit or the vein side blood circuit of the replacement fluid line. Diafiltration device. From a point between the dialysate recirculation line and the dialysis fluid feed line of the joining portion and another electromagnetic valve provided at a position on the downstream point to the bypass soot Ru pressure of the dialysis fluid discharge within the closed system of lines The online hemodiafiltration apparatus according to any one of claims 1 to 6, wherein a pressure relief valve is provided in the relief line. A solenoid valve was installed in the primary filter washing line that connects the passage side nozzle of the primary ultrafiltration filter provided at a point outside the sealed system of the dialysate feeding line and the point outside the sealed system of the dialysate drainage line. The online hemodiafiltration apparatus according to any one of claims 1 to 7 . The permeability析液circulation line, the flow path and becomes part of the flow-through side compartment of the secondary ultrafilter maintaining high positive pressure than the blood circuit pressure, blood is prevented from flowing back the replacement fluid line and the filtrate line The online hemodiafiltration apparatus according to any one of claims 1 to 8 . The permeability析液circulation line, high flow circulation, i.e. high online hemodiafiltration device according to any one of claims 1 to 9 is possible to ensure a shear rate flow-through side compartment of the secondary filter. With the two solenoid valves located in the dialysate feeding line and the filtrate line, which are the channels through which the dialysate is supplied to the blood purifier, closed, the dialysate is not sent to the blood purifier and the secondary limit is exceeded. the dialysate flow through the filtration filter is discharged by short circuit in a closed system from the total in pressure relief line, online hemodiafiltration according to any one of claims 1 to 10, which enables the practice of hemofiltration apparatus. The solenoid valve of the primary filter cleaning line, and an open state in conjunction with the dialysate receiving chamber waiting time in hemodiafiltration apparatus employing the system that Karidasu dialysate maintaining a closed system by the chamber method, primary The on-line hemodiafiltration apparatus according to any one of claims 1 to 11 , further comprising a transmission control system f that is a primary ultrafiltration filter cleaning mechanism that intermittently flushes the passage side of the ultrafiltration filter. By blood leak sensor mounted on the replacement fluid line in conjunction with the signal detected backflow of blood, blocking the pinch valve of filtration fluid line or Oyo pinch valve mounted on the replacement fluid line beauty filtration fluid line instantaneously, blood The on-line hemodiafiltration according to any one of claims 1 to 12 , further comprising a transmission control system g which is a fluid replacement circuit leakage blocking mechanism for safety to prevent the water from flowing back into the filtrate line and causing contamination. apparatus. From the difference between the average value of the arterial blood circuit pressure monitor and the venous blood circuit pressure monitor and the measured value of the dialysate drainage circuit pressure monitor , the transmembrane pressure in the blood purifier is the operating pressure during ultrafiltration. obtaining the TMP is the difference, in order to obtain the replacement fluid rate or the filtration rate such that any value TMP is defined, and a feedback control by TMP value aperture state of the flow rate adjusting pinch valve provided in the filtration liquid line , online hemodiafiltration device according to any one of claims 1 to 13 having a transmission control system h is a pressure control filtration mechanism for adjusting the replacement fluid flux through the pinch valve. Flow rate and dialysate recirculation line again dialysis the dialysate feeding pump, which is monitored by a flow meter located between the branch point from the dialysate feed line between the permeable析液feeding pump dialysate recirculation line The difference in flow rate monitored by a flow meter located between the point where it joins the liquid feed line and the point where the filtrate line joins the dialysate liquid feed line is regarded as the replacement fluid rate, that is, the filtration rate. any one of claims 1 to 14, having any of the speed control filtration mechanism in which transmission control system which the aperture state of the flow rate adjusting pinch valve provided in the filtration liquid line so that the value for the feedback control by the filtration rate i which is The online hemodiafiltration apparatus according to item 1 . In the operation of the speed control filtration system, the actual when the filtration operation is pressure TMP exceeds a specific monitoring values are automatically automatic filtration rate reduction mechanism to reduce only the velocity defined filtration velocity transfer The online hemodiafiltration device according to any one of claims 1 to 15, further comprising a control system j . Automatic pressure control filtration that automatically switches to constant pressure filtration control so that TMP, which is the monitored value, is automatically maintained when the TMP, which is the actual filtration operating pressure, exceeds a specific monitored value in the speed controlled filtration operation. The online hemodiafiltration apparatus according to any one of claims 1 to 16 , further comprising a transmission control system k which is a transition mechanism. TMP as a configuration parameter in the pressure control filtration, or as a function of the filtration rate of the Oite setting parameter time speed control filtration, any straight line in the time axis direction, the program filtration programmable control curve or stepped profile The online hemodiafiltration apparatus according to any one of claims 1 to 17 , further comprising a transmission control system l that is a setting mechanism. In hemofiltration mode, located between the branch point from the dialysate feed line between the permeable析液liquid feed pump so that the flow rate of the dialysate feeding pump is equal to the set filtration speed dialysate recirculation line It has a transmission control system m that is a blood filtration and feeding control mechanism that is feedback-controlled by the measured value of the flow meter. At the same time, the solenoid valve placed in the dialysate feeding line and the solenoid valve placed in the filtrate line are closed. The on-line hemodiafiltration apparatus according to any one of claims 1 to 18, wherein blood filtration can be carried out by replenishing the entire amount ejected by the dialysate feeding pump through the secondary ultrafiltration filter. .

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