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hemorrhage volume , duration of low output syndrome , and duration of ICU stay [ 11 – 14 ]; in contrast , high COP causes hypervolemia , which can exert adverse effects on hemodynamics . In addition , hypertonic colloidal osmotic fluids have been implicated as a risk factor for acute kidney injury [ 15 – 17 ]. However , a small to moderate volume of colloid poses little risk of adverse events , and COP monitoring may not be mandatory . However , this alone is insufficient grounds to overlook the importance of COP measurement . Stricter control of perioperative COP may further improve postoperative courses .
At present , because COP measurements are difficult to obtain , they are rarely taken . Colloid osmometers are required to measure COP , but they are expensive and not widely used . One possible substitute method is the calculation of COP from the albumin concentration [ 18 ]. However , the disadvantages of this method are low accuracy , an error rate of about 10 %, and a considerable time requirement [ 19 ]; moreover , synthetic colloids , such as hydroxyethyl starch , are not reflected in the calculation . Therefore , there is currently no established COP monitoring method suitable for use during cardiopulmonary bypass .
In this study , we devised a simple method for measuring COP during cardiopulmonary bypass . The ultrafiltration membrane used during cardiopulmonary bypass has a semipermeable membrane structure . Hence , our proposal is to directly and easily measure COP using ultrafiltration membranes . Accordingly , a test circuit was devised , and its usefulness was examined by comparing COP values measured using the ultrafiltration membrane method with those obtained through the colloid osmometer method .
Materials and methods Ethical approval
This study does not involve human and / or animal subjects ; therefore , ethical approval was not required .
COP measurement principle
COP is equivalent to the hydrostatic pressure resulting from the differing concentrations of substances unable to pass across a semipermeable membrane between solutions . Only the concentration difference of the substances unable to cross the semipermeable membrane has an effect , not the vessel size or the relative amounts of solution . An ultrafiltration membrane is a container in which a semipermeable membrane separates blood on one side from the filtrate on the other side . Under normal usage of an ultrafiltration membrane , the inside of the hollow fiber is filled with blood , whereas the outside of the hollow fiber ( the filtrate side ) is filled with crystalloid ( filtrate ) exuded from blood by ultrafiltration . COP is measured with the inside and outside of the membrane filled with blood and filtrate , respectively ; aligning the levels of both fluids to eliminate any hydrostatic pressure difference ; and then measuring the static hydrostatic pressure difference that occurs at standby time . Standby time was defined as the time spent waiting for the solvent to be transferred by COP with the blood pump stopped and
Table 1 . Membrane catalog values used in experiment .
Product name BIOCUBE Hemoconcentrator BHC-110
Membrane material Polyethersulfone Membrane area 1.1 [ m 2 ] UFR * 50 < [ mL / mmHg / h ] Inulin SC ** 0.95 < Albumin SC < 0.05
UFR measurement conditions : JIS T3250 5.6.3 *
SC measurement conditions : JIS T3250 5.6.2 **
Blood flow rate = 300 mL / min
* UFR : ultrafiltration rate , ** SC : sieving coefficient .
with the blood circuit and filtrate circuit exposed to the atmosphere . The principle underlying this method of measurement is the same as that of a colloid osmometer ( Osmomat 050 ; Phoenix Science , Inc ., Tokyo , Japan ).
Test circuit and measurement method
The test circuit was a closed circuit mainly consisting of an ultrafiltration membrane ( BIOCUBE Hemoconcentrator BHC- 110 ; NIPRO Co , Ltd ., Osaka , Japan ) ( Table 1 ) andamedical soft bag connected by a vinyl chloride tube . The test circuit included ( 1 ) a roller pump for circulation , ( 2 ) a sampling port , ( 3 ) a three-way stopcock for switching the blood circuit , ( 4 ) an atmospheric release circuit within the blood circuit ( inner diameter : 3.3 mm ), ( 5 ) a filtrate circuit ( inner diameter : 6 mm ), and ( 6 ) a clamp . The atmospheric release circuits in the blood and filtrate circuits were fixed so they were perpendicular to each other ( Figure 1 ). After the roller pump occlusion was adjusted and reflux was confirmed to be absent , the circuit was primed with physiological saline solution and then calcium-chelated bovine blood ( Osaka Nanko Zoki Co ., Ltd ., Osaka , Japan ) was added to prepare the test liquid .
In preparation for taking a measurement , the filtrate level was set at the height of the three-way stopcock for blood circuit switching and the filtration circuit was closed . The atmospheric release circuit of the blood circuit must be emptied , which was done by switching the three-way stopcock in the blood circuit ( Figure 2b , # 3 ) and returning the blood into the blood circuit via gravity . The blood circuit was cycled for more than 5 min in this state ( Figure 2a ).
At the time of the measurement , the roller pump was stopped , the three-way stopcock was switched , and the blood circuit was switched to an open-air circuit . The clamp of the filtrate circuit was then opened to expose the circuit to the atmosphere . When both circuits are exposed to the atmosphere and then stopped , the solvent migrates in accordance with the difference in osmolality . The time spent waiting for solvent migration to equilibrate was 3 min ( standby time ). After the standby time had passed , the water level difference between the two circuits was measured ( Figure 2b ). The water level difference was measured in centimeters : a 1 cm difference was considered equivalent to a 1 cmH 2 O hydrostatic pressure difference , which was further converted to mmHg by considering 1 cmH 2 O equivalent