JPH0321189B2 - - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to hollow-eye bar oxygenators. Prior art Artificial lungs can be roughly divided into bubble type and membrane type. Membrane type oxygenators, which use a gas exchange membrane, use a gas exchange method that is more physiological than the bubble type, which uses a blood-gas direct contact method. Therefore, the membrane type is recommended because it has various advantages. Conventionally, in order to perform extracorporeal circulation using a membrane oxygenator, a so-called double pump system having a circuit as shown in FIG. 1 is generally used. This double pump system has a first
blood storage tank R ₁ , first blood pump P ₁ , oxygenator 10,
The second blood reservoir R ₂ and the second pump P ₂ are connected in sequence to form a circuit. In such a circuit, the pressure applied to the oxygenator 10 is only its own pressure loss, and the safety of the device is ensured. However, such a double pump system has various drawbacks, such as requiring two pumps, increasing the amount of circuit priming, and making operations complicated. On the other hand, in the double pump system as shown in FIG. ₁ above, _a single pump system as shown in FIG. If used, the above-mentioned drawbacks will be overcome. However, in this case, the internal pressure in the circuit near the outlet of the blood pump P is the sum of the pressure in the blood feeding catheter section and the pressure loss in the oxygenator 10, and the oxygenator 10 is required to have high pressure resistance. Ru. However, conventional stacked or coiled membrane oxygenators using flat membrane gas exchange membranes have low pressure resistance and pose problems in device safety. Furthermore, in the conventional membrane oxygenator, the pressure loss is large and the internal pressure in the circuit becomes extremely high, creating a risk of rupture at each connection part, tube, etc. Furthermore, due to the increase in internal pressure, the thickness of the blood layer increases, resulting in a decrease in performance. By the way, in contrast to membrane oxygenators that use conventional flat membranes, hollow fiber oxygenators have been developed that use porous hollow fibers whose inner wall surfaces are at least hydrophobic as gas exchange membranes. Compared to those using flat membranes, this hollow fiber oxygenator has higher pressure resistance and a larger membrane area per unit volume of the device, and the blood layer is regulated by the inner diameter of the porous hollow fibers. Gas exchange performance is also stable. The present inventors have taken the lead in the practical application of hollow fiber oxygenator lungs, and have repeatedly conducted numerous practical studies. It has been confirmed that some hollow-eye bar oxygenators can be effectively used with a single pump system as described above. In this case, the inner diameter of the porous hollow fibers used in the conventional hollow fiber oxygenator is 200μ or more. This is done in consideration of increased pressure loss and hydrophobic occlusion. On the other hand, if the inner diameter of the hollow fiber is less than 200μ, it is thought that the oxygen addition performance will increase, and in fact, according to the experiments of the present inventors, for example, only the inner diameter of the hollow fiber is different, and the other things are the same. Among the two hollow-eye oxygenators used as conditions, the one with an inner diameter of 190μ is:
Compared to those with an inner diameter of 200μ, the blood flow rate (Q〓 ₃₀ ) that can oxygenate blood with an oxygen saturation of 65% to 95% or more is
Improved by about 10%, and priming volume also increased by 10
For those with an inner diameter of less than 200μ,
It has been confirmed that an artificial lung that is much smaller and has higher performance than conventional ones can be realized. However, such high performance is based only on the assumption that a double pump system is used; if an oxygenator using a hollow fiber with an inner diameter of less than 200μ is used in a single pump system, blood damage, especially hemolysis, will increase. It turned out to be extremely dangerous. Purpose of the Invention The present invention was made in view of the above-mentioned circumstances, and is a single-pump system by improving a small, high-performance hollow fiber oxygenator using porous hollow fibers with an average inner diameter of less than 200μ. However, the main objective is to allow extracorporeal circulation to be carried out safely, especially without the risk of hemolysis occurring. The inventors of the present invention have repeatedly and diligently studied these objectives, and have obtained the following knowledge. First, using an oxygenator using a hollow fiber with an inner diameter of less than 200μ, we created a circuit similar to a single pump system as shown in Figure 2, and changed the blood pump pressure and the oxygenator outlet circuit internal pressure as appropriate. The amount of hemolysis occurring in the oxygenator was evaluated. As a result, the present inventors discovered that when the circuit pressure at the inlet of the oxygenator exceeds 600 mmHg, the amount of hemolysis increases rapidly. It has also been found that the criticality of the internal pressure of the oxygenator inlet circuit always occurs in the same way regardless of the membrane area, hollow fiber inner diameter, blood flow rate, etc. Note that one example of such an experiment is shown in Experimental Example below. By the way, in a single pump system as shown in FIG. 2, the circuit internal pressure at the inlet of the oxygenator 10 is calculated by adding the pressure of the blood feeding catheter section, the pressure loss of the oxygenator 10, and the pressure loss of other tubes, heat exchangers, etc. It becomes something. In this case, the pressure in the blood feeding catheter section is usually set at a maximum of about 400 mmHg or less, and the pressure drop in the tube etc. may be small. Therefore, in order to safely perform single-pump system circulation using a hollow-eye bar type oxygenator, the pressure loss of the oxygenator must be 600mm at the oxygenator inlet critical pressure confirmed as above.
It turns out that it has to be less than 200mmHg, which is calculated by subtracting this 400mmHg from Hg. In other words, with a single pump system, the pressure loss of the oxygenator is
If it exceeds 200 mmHg, there is a risk that the amount of hemolysis will increase rapidly. Now, the pressure drop in an oxygenator depends on the dimensions of the hollow fiber. As a result of various studies on the relationship between hollow fiber dimensions and pressure loss, the present inventors determined that the average inner diameter of the hollow fiber is d, its average total length is L, and the effective length used as a gas exchange membrane, that is, from the total length to both ends. When the length after subtracting the partition wall thickness is l, the pressure loss is
It was found that it is proportional to d ⁴ /(L×l). On the other hand, pressure loss also depends on blood flow rate and blood viscosity. Therefore, blood viscosity of about 0.25 poise (for example, hematocrit value Ht 35%,
When we measured the pressure loss of various oxygenators with different hollow fiber dimensions using blood at a temperature of 37°C and a blood flow rate of Q〓 ₃₀ , which is among the highest under normal conditions, we found that the pressure loss was less than 200 mmHg. To get d ⁴ /
It has been found that (L/l) must be greater than or equal to 4.3×10 ⁻¹⁰ cm ² . The present invention has been made based on this new discovery. That is, the present invention uses porous hollow fibers having at least a hydrophobic inner wall surface as a gas exchange membrane, bundles a plurality of the porous hollow fibers, and embeds both ends of the porous hollow fibers in a partition wall to open the porous fibers. In a hollow fiber oxygenator in which the blood flow path is inside the hollow fibers, the average inner diameter of the porous hollow fibers is 100μ or more.
It is less than 200μ, and when this average inner diameter is d (cm), its average total length is L (cm), and the average effective length obtained by subtracting the partition wall thickness at both ends from the total length is l (cm), d ⁴ / The hollow fiber oxygenator is characterized by having the relationship (L×l)≧4.3×10 ⁻¹⁰ cm ² and being used in a circuit using one blood pump. In this case, a plurality of hollow fibers are bundled, both ends of which are opened, and both ends are embedded within a pair of partition walls to form an oxygenator. Therefore, the effective length is the length in which both ends are embedded in the partition wall, that is, the thickness of the partition wall is subtracted from the total length. Note that the average inner diameter of the porous hollow fibers used in the hollow fiber oxygenator previously announced by the present inventors is ^200μ or more;
There is also one in which (L×l) is set to 4.7×10 ⁻¹⁰ cm ² . However, such condition settings were not determined based on suitability for a single pump system, and the present invention, which was made based on the inventors' new discoveries detailed above, is based on such published facts. Therefore, it cannot be inferred. Specific Configuration of the Invention The specific configuration of the present invention will be described in detail below. In the present invention, the porous hollow fiber used as a gas exchange membrane is hydrophobic at least on its inner wall surface, that is, its blood contact surface, and the contact angle of the inner wall surface with water is 90° or more. For this reason, porous hollow fibers include polyolefin resins such as polypropylene and polyethylene, fluorine resins,
It may be made of hydrophobic resin such as silicone resin, or it may be made of other materials, and at least the inner wall surface thereof may be treated with silicone oil, reactive silicone resin, etc. to make it hydrophobic. . Among these, the porous hollow fibers are preferably formed from polyolefin resin, particularly polypropylene. A porous hollow fiber made of such a material has a large number of micropores that communicate with the hollow inner wall and outer wall. There is no particular limit to the average pore diameter of micropores, but when observed with an electron microscope, it is generally 200
It is preferably ~2000 Å. Note that when the micropore has an elliptical shape, the pore diameter may be the geometric average of the short diameter and the long diameter, and the average may be determined. Further, there is no particular restriction on the average porosity of the hollow fibers, but it is generally preferably about 30 to 80%. Furthermore, the average wall thickness of the hollow fiber is generally approximately
The thickness may be approximately 10 to 50μ. In contrast, the average inner diameter d of the hollow fibers is less than 200μ. However, if d becomes too small, hollow fiber clogging may occur, so d is preferably 100μ or more. Also, if d is larger than 190μ,
Compared to 200μ, the oxygen addition ability and the above Q〓 ₃₀ do not increase much, and the priming volume does not decrease much either. For this reason, d is preferably 100 to 190μ. Under these assumptions, the above d ⁴ /(L×l) is
Must be at least 4.3 x 10 ^-10 cm ² . As mentioned above, with this value as the critical value, if it is less than 4.3 × 10 ^-10 cm ² , the pressure drop at Q〓 ₃₀ will be greater than 200 mmHg,
With a single pump system under normal procedure conditions, the amount of hemolysis increases rapidly. In this case, L is obtained by averaging the total length of the porous hollow fibers used, and l is calculated from the total length of each hollow fiber,
It is calculated by subtracting the partition wall thicknesses at both ends, which will be described later, and then averaging them. The hollow fiber oxygenator of the present invention is made by bundling a plurality of such porous hollow fibers, and embedding the fibers at both ends into a polymer partition wall to open the fibers. The inside of each porous hollow fiber is used as a blood flow path, and gas exchange is performed through the minute pores in the thick part. In this case, there is no particular restriction on the number of hollow fibers used, and regardless of the number of hollow fibers used, d ⁴ /
If (L×l) is the same, the same pressure loss is given. However, since the membrane area changes depending on the number of tubes used, Q = ₃₀ and priming volume change, it is common to use around 4000 to 80000 tubes. A partition wall that embeds a plurality of such porous hollow fibers at both ends thereof and supports them in a predetermined housing is formed of a high molecular weight polymer. The polymer may be formed from polyurethane resin, which is known as a potting material. Then, by subtracting the thickness of the partition walls at both ends from the total length, the above-mentioned effective length l is determined. A specific example of a hollow fiber oxygenator configured in this manner is shown in FIG. As shown in the figure, the oxygenator 1 has a housing 2. This housing 2 is constructed by attaching mounting covers 22 and 23 to both ends of a cylindrical body 21, for example. Inside this housing 2, a plurality of porous hollow fibers 3, . . . are arranged substantially in parallel. On the other hand, both ends of the porous hollow fibers 3, . . In this case, the substantial filling rate of the hollow fibers 3, . . . in the partition walls 41, 45 may be approximately 20 to 60%. Further, the thickness of the partition walls 41 and 45 may be approximately 0.5 to 5 cm. In the example shown in FIG. 3, the partition walls 41 and 45 are formed by centrifugal casting;
Its inner wall surface is concave. In such a case,
The average effective length l is calculated from the average total length L by dividing the average partition wall thickness in the substantial convergence part of the hollow fiber into both partition walls 4
You can find it by subtracting 1.45. Such a partition simultaneously forms a closed gas chamber 5 within the housing 2 . The mounting covers 22 and 23 are provided with a gas inlet and an outlet 61 and 65, respectively, and an air flow path is formed in the gas chamber 5. The cylindrical body 21 is extended so as to face the gas inlet and outlet 61, 65, and ribs 251, 255 are formed to prevent short-circuiting of the blown gas. On the other hand, the outer end surfaces of the partition walls 41, 45 are covered by head covers 71, 75, respectively, and the head covers 71, 75 are provided with blood inlets and outlets 81, 85. In addition, in the oxygenator 1 shown in FIG. 3, a constricted portion 215 is formed in the cylindrical body 21 of the housing 2, and the filling rate of the hollow fibers 3 becomes sparse toward the end. . Although it is not necessarily necessary to adopt such a structure, it increases the CO ₂ removal ability. Specific Effects of the Invention The hollow fiber oxygenator of the present invention, which has been described in detail above, introduces blood from the blood inlet 81, allows the blood to pass through the porous hollow fibers, and allows the blood to pass through the blood outlet 81.
At the same time, oxygen, air, etc. are blown through the gas inlet 61, the gas chamber 5, and the gas outlet 65 for use. At this time, oxygen is added to the blood and removed from the blood through the micropores of the porous hollow fiber.
CO ₂ removal is performed. In this case, the hollow-eye bar type oxygenator of the present invention regulates the relationship between d, L, and l as described above, so that the conditions of Ht 35% and 37°C provide blood viscosity that is among the highest under normal procedures. Below,
The pressure drop is less than 200 mmHg at a blood flow rate of Q = ₃₀ , and the risk of hemolysis is extremely low in normal single pump system extracorporeal circulation.
Moreover, since the internal pressure of the circuit can be kept below 600 mmHg at the inlet of the oxygenator, there is no risk of rupture of various connections or tubes. As a result,
Extracorporeal circulation can be performed safely with a single pump system such as the one described above. In addition, since d is less than 200μ, the oxygenation capacity is high and _Q〓30 can be increased, and the priming volume is also small, reducing the burden on the patient and eliminating the need for blood transfusion during circulation. As a result, the hollow fiber oxygenator of the present invention is extremely useful for use in open heart surgery or extracorporeal circulation in a single pump system such as auxiliary circulation. The present inventors conducted various experiments to confirm the effects of the present invention. An example is shown below. Experimental Example 1 Polypropylene porous hollow fibers having an average inner diameter d190μ and an average wall thickness 25μ were prepared. The average porosity of this porous hollow fiber was 50%, and the average pore diameter was 700 Å as measured using an electron microscope. Next, using multiple porous hollow fibers, a membrane area of 1.0 m ² was created with an average effective length of 14 cm and an average total length of 17 cm.
A hollow-eye bar type artificial lung as shown in Fig. 3 was fabricated. In this case, d ⁴ /(L×l) is
It is 5.5× ^{10-10 cm2} . Note that the partition walls 41.45 were formed from polyurethane resin. Next, using this oxygenator 1, as shown in _{FIG .}
fresh heparinized bovine blood with a hemacritt value of 35% and a plasma free hemoglobin level of 25 mg/dl.
was circulated for 3 hours at a blood flow rate of 1/min at a temperature of 37°C. In addition, a control circuit was prepared without connecting the artificial lung 1, and circulation was performed under the same conditions. In such a circulation, the tube on the outlet side of the oxygenator 1 and the inlet side of the blood storage tank _R2 is narrowed with a clamp, and the circuit internal pressure P at the inlet of the oxygenator is set as shown in Table 1 below. Instead, it went through five types of circulation. After 3 hours of circulation, measure the amount of plasma-free hemoglobin (mg/dl-plasma) in the blood, subtract the amount of plasma-free hemoglobin measured in the control circuit from this, and calculate the amount of plasma-free hemoglobin Hb ^* excluding hemolysis caused by the pump and circuit. was calculated. The results are shown in Table 1 below. From the results in Table 1, in a circuit based on a single pump system, the internal pressure P of the inlet circuit of the oxygenator is 600 mm.
It can be seen that when Hg is exceeded, the amount of hemolysis increases rapidly.

[Table] In this way, the pressure inside the circuit at the inlet of the oxygenator is
The criticality that hemolysis rapidly increases when the temperature exceeds 600 mmHg is reproduced in exactly the same way in various oxygenators with different hollow fiber d, l, L and membrane area, and by various changes in blood flow rate. was also reproduced in exactly the same way. Therefore, as described above, it can be seen that in a single pump system, the pressure loss of the hollow fiber oxygenator must be 200 mmHg or less, which is calculated by subtracting the maximum pressure of 400 mmHg in the blood feeding catheter section from the critical pressure of 600 mmHg. Experimental Example 2 4 with an average inner diameter d as shown in Table 2 below
A porous hollow fiber made of polypropylene was prepared.
The average wall thickness of each of these four types of porous hollow fibers was 25 μm, the average porosity was 50%, and the average pore diameter was 700 Å by electron microscopy. Using these four types of porous hollow fibers, in the same manner as in Experimental Example 1, the average effective length l and average total length L as shown in Table 2 below were changed, and the number of fibers used was changed as specified, and both were 1.0. A total of 16 types of hollow fiber oxygenator lungs 1 as shown in FIG. 3 were fabricated, each having a membrane area of M ² . In Table 2 below, d ⁴ /(l×L) and priming amount (ml) for each oxygenator are also listed. Next, using each of these 16 types of artificial lungs 1,
As shown in FIG. 5, a circuit was prepared by sequentially connecting a venous blood preparation lung D, a blood storage tank R, a pump P, a heat exchanger HE, and an artificial lung 1. The venous blood preparation lung D was filled with fresh heparinized bovine blood containing 35% Ht and 12 g/dl Hb. In addition, in the venous blood preparation lung D,
By blowing a mixed gas of CO ₂ , O ₂ , and N ₂ , S _V O ₂ 65±2
%, make 50mmHg venous blood with P _V CO ₂ and heat exchanger
The blood temperature was brought to 37°C by HE and the blood was circulated. Further, the gas blown into the gas chamber 5 of the artificial lung 1 was 100% O ₂ gas, and the flow rate was 1/min. In the circulation of each oxygenator 1, the blood flow rate is changed and the oxygen saturation at the outlet of the oxygenator 1 is measured.
Q〓 ₃₀ of each oxygenator 1 was calculated by point interpolation. For each oxygenator lung 1, such measurements were performed three times, and the average Q〓 ₃₀ from each measurement is shown in Table 2 below.
Next, at the blood flow rate of Q〓 ₃₀ thus obtained, the circuit internal pressures at the inlet and outlet of the artificial lung 1 were measured, and from the difference therebetween, the pressure loss ΔP at Q〓 ₃₀ was calculated. The results are shown in Table 2 below. From the results shown in Table 2, d ⁴ /(L×l) is
It can be seen that the pressure drop in the oxygenator is less than 200 mmHg only when it is more than 4.3 × 10 ^-10 cm ² . In addition, when d is 210μ, the pressure loss is 200mm.
It can be seen that even though it may become Hg, the priming volume is large and Q〓 ₃₀ is small with the same membrane area. Additionally, when we made oxygenators with different membrane areas and performed the same measurements as above, we found that Q〓 ₃₀ between oxygenators with the same d, L, and l but with different numbers used. It was confirmed that is proportional to the membrane area, that is, the number of membranes used, and ΔP at Q〓 ₃₀ is almost unchanged.

[Table] Yes.

[Brief explanation of the drawing]

Figure 1 is a schematic diagram for explaining a conventional double pump system for extracorporeal circulation using an oxygenator, and Figure 2 is a schematic diagram for explaining a single pump system for extracorporeal circulation using an oxygenator. be. FIG. 3 is a front view showing an example of the hollow-eye bar type oxygenator of the present invention, with half thereof shown in cross section. FIG. 4 is a schematic diagram for testing the relationship between the internal pressure of the oxygenator inlet circuit and the amount of hemolysis in Experimental Example 1, and _FIG . FIG. 2 is a schematic diagram for explaining a circuit for measurement. 10... Oxygenator, 1... Hollow-eye bar type oxygenator, 2... Housing, 3... Porous hollow fiber,
41, 45... Bulkhead.

Claims (1)

[Scope of Claims] 1. Porous hollow fibers having at least a hydrophobic inner wall surface are used as the gas exchange membrane, a plurality of the porous hollow fibers are bundled, and both ends of the porous hollow fibers are buried in a partition wall and opened, and the porous hollow fibers are In a hollow fiber oxygenator having a blood flow path inside the porous hollow fibers, the average inner diameter of the porous hollow fibers is 100 μ or more and less than 200 μ, this average inner diameter is d (cm), and the average total length is L (cm). , when the average effective length obtained by subtracting the partition wall thickness at both ends from the total length is l (cm), there is a relationship of d ⁴ / (L × l) ≧ 4.3 ^{× 10 -10} cm ² , and one transport unit A hollow eye bar type artificial lung characterized by use in a circuit using a blood pump. 2. The hollow-eye bar type artificial lung according to claim 1, wherein d is 100 to 190μ. 3. The hollow fiber oxygenator according to claim 1 or 2, wherein the porous hollow fibers are made of polyolefin resin.