ASTM F1841-1997(2005) Standard Practice for Assessment of Hemolysis in Continuous Flow Blood Pumps《连续流动血泵里溶血评定的标准操作规程》.pdf

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1、Designation: F 1841 97 (Reapproved 2005)Standard Practice forAssessment of Hemolysis in Continuous Flow BloodPumps1This standard is issued under the fixed designation F 1841; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year

2、 of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.INTRODUCTIONThe goal of blood pump development is to replace or supplement the function of the human heart.As a result, conti

3、nuous flow blood pumps, including roller pumps and centrifugal pumps, arecommonly used in clinical extracorporeal circulation. They are used not only for cardiopulmonarybypass in routine cardiac surgery but also for ventricular assist, percutaneous cardiopulmonarysupport, and extracorporeal membrane

4、 oxygenation.Many investigators have attempted to develop an atraumatic blood pump. Hemolysis is one of themost important parameters of blood trauma induced by blood pumps. However, comparative in vitroevaluation of the reported results of hemolysis are difficult due to the lack of uniformity of the

5、 testmethods employed. Thus, it is necessary to standardize the method of performing in vitro hemolysistests for the evaluation of continuous flow blood pumps.1. Scope1.1 This practice covers a protocol for the assessment of thehemolytic properties of continuous flow blood pumps used inextracorporea

6、l or implantable circulatory assist. An assessmentis made based on the pumps effects on the erythrocytes overa certain period of time. For this assessment, a recirculation testis performed with a pump for 6 h.1.2 The values stated in both inch-pound and SI units are tobe regarded as the standard. Th

7、e SI units given in parenthesesare for information only.1.3 This standard does not purport to address all of thesafety concerns, if any, associated with its use. It is theresponsibility of the user of this standard to establish appro-priate safety and health practices and determine the applica-bilit

8、y of regulatory limitations prior to use.2. Referenced Documents2.1 ASTM Standards:2F 1830 Practice for Selection of Blood for in vitro Evalua-tion of Blood Pumps3. Terminology3.1 Definitions:3.1.1 continuous flow blood pumpa blood pump thatproduces continuous blood flow due to its rotary motion.3.1

9、.2 free plasma hemoglobinthe amount of hemoglobin(iron or heme-containing protein) in plasma.3.1.3 hemolysisdamage to erythrocytes resulting in theliberation of hemoglobin into the plasma.3.1.4 Index of Hemolysis3.1.4.1 normalized index of hemolysisadded grams ofplasma free hemoglobin per 100 l of b

10、lood pumped, correctedfor plasma volume using hematocrit and normalized by flowrate and circulation time.3.1.4.2 normalized milligram index of hemolysis normal-ized index of hemolysis expressed by milligram value of freeplasma hemoglobin.3.1.4.3 modified index of hemolysismass of hemoglobinreleased

11、into plasma normalized by the total amount ofhemoglobin pumped through the loop.4. Formulas4.1 Normalized Index of Hemolysis (N.I.H.) (1,2,3,4)3:N.I.H. g/100l 5DfreeHb 3 V 3100 Ht1003100Q 3 T(1)1This practice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices

12、 and is the direct responsibility of SubcommitteeF04.30 on Cardiovascular Standards.Current edition approved Mar. 1, 2005. Published March 2005. Originallyapproved in 1997. Last previous edition approved in 1997 as F 1841 97.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcon

13、tact ASTM Customer Service at serviceastm.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.3The boldface numbers given in parentheses refer to a list of references at theend of the text.1Copyright ASTM International, 100 Barr H

14、arbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.Dfree Hb = increase of plasma free hemoglobin concentra-tion (g/L) over the sampling time interval,where:V = circuit volume (L),Q = flow rate (L/min),Ht = hematocrit (%), andT = sampling time interval (min).4.2 Normalized Mill

15、igram Index of Hemolysis. (mg.N.I.H.)(2,3,4):2mg.N.I.H.mg/100l 5DfreeHb 3 V 3100 Ht1003100Q 3 T(2)4.3 Modified Index of Hemolysis (M.I.H.):4.3.1 Modified index of hemolysis (M.I.H.) (5,6) that can bewritten with no units or as (milligram of hemoglobin releasedinto plasma/mg of total hemoglobin pumpe

16、d through the loop):M.I.H. 5DfreeHb3 V 3100 Ht1003106Q 3 T 3 Hb(3)where:Hb = total blood hemoglobin concentration at timezero (mg/L), andDfree Hb = increase of plasma free hemoglobin concentra-tion (mg/L) over the sampling time interval.4.3.2 Among these indices, M.I.H. is recommended as anindex to

17、express the degree of hemolysis caused by a bloodpump in a recirculating system. N.I.H. was proposed to accountfor the plasma volume based on the hemotocrit. Recentdevelopment of less hemolytic blood pumps has since made itconvenient to use mg. N.I.H. rather than N.I.H. However, boththe N.I.H. and t

18、he mg N.I.H. vary with hematocrit of the blood(6). M.I.H. is the recommended index to express the degree ofhemolysis caused by a blood pump in a recirculating system.The M.I.H. equation corrects for differences in blood hemo-globin concentration and hematocrit directly (5).4.4 Testing BloodBecause t

19、he level of trauma-inducedhemolysis is different based on the source of blood, it isnecessary to identify the source of blood and its respectiveindex of hemolysis. Human, bovine, or porcine blood arerecommended as the primary sources of testing blood (seePractice F 1830). It is preferable that the b

20、lood collected at astandard slaughter house not be used due to the risk of beingcontaminated with fluids other than blood, unless the blood isobtained by controlled venipuncture. Although animal blood isused in the development stage of a pump, it is suggested thatpre-clinical evaluation tests be rep

21、eated with human blood.5. Summary of Practice5.1 BloodThe blood is obtained from human volunteers,cattle or pigs having normal body temperatures, no physicalsigns of disease, including diarrhea or rhinorrhea, and anacceptable range of hemotological profiles. The blood shouldbe collected by vascular

22、puncture using a needle (14G orlarger) and collected into the standard 5002000 mL bagscontaining citrate phospate dextrose adenine (CPDA-1) anti-coagulant solution (See Appendix X2) or heparin sulfate (SeeAppendix X3). The blood from a slaughterhouse can typicallybe used if it is obtained by control

23、led venipuncture.5.2 Test Loop (4) (See Fig. 1)The test loop consists of atotal of 6.6 ft (2 m) of 3/8 in. (9.5 mm) ID polyvinylchloridetubing and a reservoir (typically, 13 by 13 cm) with a samplingport. The primed blood volume is 450 6 45 mL. A screwclamp, that is positioned at the outlet side, is

24、 applied to producethe required conditions for the left heart assist application (5L/min against 100 mm Hg pressure head (that is, with thepressure sampling ports at the same vertical height, thepressure in the outlet line of the pump is 100 mm Hg greaterthan in the inlet line) and for the cardiopul

25、monary bypassapplication (5 L/min against 500 mm Hg pressure head).(Optional testing at 350 or 700 mm Hg is also advisable.) Tomonitor such pressure heads, the pressure monitoring lines areincorporated into the test loop both at the inlet and outlet tubes.An ultrasonic or electromagnetic flow probe

26、is placed at theoutlet side of the pump between the clamp and the reservoir tomonitor the flow rate. A thermistor is connected to the loop,and the blood temperature is measured using a correspondingthermometer.5.3 Pump ConditionsPump flow rate is set at 5 6 0.25L/min at the circulating blood tempera

27、ture of 37 6 1C. Thetotal pressure head is set at 100 6 3 mm Hg for the left heartassist application and 500 6 15 mm Hg for cardiopulmonarybypass application. However, additional testing temperaturescan be chosen from 0 to 42C according to the intended clinicaluse of the pump (for example, cardiopul

28、monary bypass mayinclude cooling and warming during surgery.)5.4 EvaluationThe free plasma hemoglobin is determinedby a clinically approved assay method (see 9.3). The freeplasma hemoglobin is standardized by calculating the M.I.H.6. Significance and Use6.1 The objective of this practice is to stand

29、ardize theevaluation method for detecting the hemolytic effect of acontinuous flow blood pump used in extracorporeal circulationand circulatory assistance.7. Preparation of Hemolysis Test7.1 BloodThe blood is obtained from human volunteershaving normal body temperature, exhibiting no physical signso

30、f disease and having hematological profiles in the normalacceptable range. (Donors are subjected to standard blooddonor screening procedures.) The donor should be fasted for 8h or more to avoid additional hemolysis due to a highconcentration of lipids in the blood. The delay in the collectionof the

31、blood and the hemolysis test should not exceed 48 h ofrefrigerated storage with the blood temperature kept between 2and 8 C or more than2hatambient condition. As analternative source of blood, animal blood can be used, but it isnecessary that the source of blood is identified. The preferredanimal bl

32、ood is bovine and porcine (See Practice F 1830).Since the use of completely fasted animals is impractical, it isrecommended that the animals be subjected to a 12-h fasting.As a quality control measure, any blood having free plasmahemoglobin of more than 20 mg/dL should not be used for thistest. In o

33、rder to standardize the blood trauma testing, the bloodsubjected to the test should have the hematocrit value adjustedto be within the range 30 6 2 % by hemodilution (withphospate buffered saline) or hemoconcentration (via minimalF 1841 97 (2005)2centrifugation). Proper and acceptable ranges of the

34、physi-ological blood parameters should be maintained prior to andduring testing (for example, pH, base excess, glucose concen-tration).7.2 Test Loop (See Fig. 1)The closed test loop contains atotal of 6.6 ft (2 m) of 3/8 in. (9.5 mm) ID polyvinylchloridetubing, a reservoir with a sampling port, an u

35、ltrasonic orelectromagnetic flow probe and its corresponding flowmeter, athermistor and its corresponding thermometer, and a bloodpump. The loop should be filled with phosphate buffered salinethat is recirculated for approximately 10 to 20 min to rinse andwet all of the blood-contacting surfaces. Th

36、e phosphate buff-ered saline is drained completely from the loop prior to fillingit with blood. After being washed with phosphate bufferedsaline, the circuit is primed with 450 6 45 mL of fresh bloodinto the reservoir bag. Air collected in the reservoir should beeliminated and no air interface left

37、in the reservoir. A screwclamp, that is applied to produce the required condition ofpressure head, is positioned at the outlet side of the pump. Thepressure monitoring lines are incorporated into the test loopboth at the inlet and outlet tubes. An ultrasonic or electromag-netic flow probe is placed

38、at the outlet side of the pumpbetween the screw clamp and the reservoir to monitor the flowrate.7.3 Pump ConditionsThe flow meter should be calibratedusing blood at the proper hematocrit and temperature. Thepump revolution rate is adjusted to provide 5 6 0.25 L/minflow rate as determined by the in-l

39、ine flow meter, and allexperiments are conducted at a 37 6 1C environment that isachieved through submerging portions of the loop into a waterbath. However, additional tests conducted in temperaturesranging from 0 to 42C can be performed according to theintended clinical use of the pump. Since all t

40、est runs are of a6-h duration, sterility is generally considered not necessary.FIG. 1 Test LoopF 1841 97 (2005)37.4 EvaluationsBlood samples of 1 to 2 mL (preferably 1mL) are drawn from the reservoir before pumping and at everyhour of pumping. It would be preferable to withdraw at leasttwo blood sam

41、ples at each sample time. At each sampling, thefirst sample of 1 mL should be discarded because it maycontain blood that was stagnant in the sampling port. Thesecond sampling of 1 mL should be used for measurement ofplasma free hemoglobin. If the saline is drained completelyfrom the test loop prior

42、to testing, the initial total bloodhemoglobin concentration, plasma hemoglobin concentration,and hematocrit can be determined from the pre-pumpingcontrol blood. Preferably, these time zero measurements areobtained from blood that has circulated through the loop forapproximately 5 min to ensure compl

43、ete mixing and dilution.7.5 Static Blood ControlsThe control blood is kept in ablood bag at the same temperature environment as that of thetesting blood. For sampling, the sampling procedures as thosefor testing blood are required (see 8.5).8. Procedure8.1 Figure 1 describes a standard closed loop f

44、or hemolysistesting, that consists of the blood pump subjected to the test, areservoir with a sampling port, inlet and outlet tubings with apressure monitoring port at each segment of the tubing,pressure transducers or a differencial pressure manometer, athermistor, and a flow probe. A screw clamp i

45、s also included inthis figure.8.2 The blood warmed to 37C (or other appropriate tem-perature) should be infused by gravity into the test loopthrough a sampling port of the blood bag.8.3 After the test loop is operated for approximately 5 minand air bubbles are eliminated from the test loop through t

46、hesampling port, the first blood sample is taken as the pre-pumping control.8.4 The blood pump is started and adjusted at the flow rateof 5 6 0.25 L/min.8.5 The test duration recommended is 6 h, and one bloodsample is taken before pumping, and six blood samples aretaken at every hour of the test. Th

47、is recommended samplingschedule provides a sufficient number of test samples forstatistical evaluation. The free plasma hemoglobin is deter-mined by a clinically accepted assay method. To ensure propersamplings, gentle massaging of the reservoir and discarding 1mL of the blood from the sampling port

48、s are recommendedprior to blood sampling.8.6 For general testing, the circulating blood temperatureshould be maintained at 37 6 1C during the entire testduration, although testing at other appropriate use temperaturesmay be necessary.9. Report9.1 At first, the results should be reported as the timed

49、ependent hemolysis data displayed graphically for each of thefive test devices and static blood controls. The regressioncoefficient of these device plasma hemoglobin plots should begreater than 0.95. Then, the report should be given in the formof an index of hemolysis which is defined as milligram ofplasma free hemoglobin per 100 L blood pumped (mg N.I.H.)and as an M.I.H. value.9.2 At least five such tests should be conducted to confirmthe reproducibility of the tests. The individual index ofhemolysis values (both mg N.I.H. and M.I.H.) should berepor