ASTM F1841-97(2017) Standard Practice for Assessment of Hemolysis in Continuous Flow Blood Pumps.pdf

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1、Designation: F1841 97 (Reapproved 2017)Standard Practice forAssessment of Hemolysis in Continuous Flow BloodPumps1This standard is issued under the fixed designation F1841; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the year o

2、f last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () 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, continuo

3、us 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 ox

4、ygenation.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 te

5、stmethods 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 inextracorporeal o

6、r 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 either SI units or inch-pound unitsare to be regarded separately as s

7、tandard. The values stated ineach system may not be exact equivalents; therefore, eachsystem shall be used independently of the other. Combiningvalues from the two systems may result in non-conformancewith the standard.1.3 This standard does not purport to address all of thesafety concerns, if any,

8、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-bility of regulatory limitations prior to use.1.4 This international standard was developed in accor-dance with internationally recognized pri

9、nciples on standard-ization established in the Decision on Principles for theDevelopment of International Standards, Guides and Recom-mendations issued by the World Trade Organization TechnicalBarriers to Trade (TBT) Committee.2. Referenced Documents2.1 ASTM Standards:2F1830 Practice for Selection o

10、f Blood for in vitro Evaluationof Blood Pumps3. Terminology3.1 Definitions:3.1.1 continuous flow blood pumpa blood pump thatproduces continuous blood flow due to its rotary motion.3.1.2 free plasma hemoglobinthe amount of hemoglobin(iron or heme-containing protein) in plasma.3.1.3 hemolysisdamage to

11、 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 blood pumped, correctedfor plasma volume using hematocrit and normalized by flowrate and circulation time.3.1.4.2 norm

12、alized milligram index of hemolysisnormalized index of hemolysis expressed by milligram valueof free plasma hemoglobin.1This practice is under the jurisdiction ofASTM Committee F04 on Medical andSurgical Materials and Devices and is the direct responsibility of SubcommitteeF04.30 onCardiovascular St

13、andards.Current edition approved Sept. 1, 2017. Published September 2017. Originallyapproved in 1997. Last previous edition approved in 2013 as F1841 97 (2013).DOI: 10.1520/F1841-97R17.2For referenced ASTM standards, visit the ASTM website, www.astm.org, orcontact ASTM Customer Service at serviceast

14、m.org. For Annual Book of ASTMStandards volume information, refer to the standards Document Summary page onthe ASTM website.Copyright ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United StatesThis international standard was developed in accordance with in

15、ternationally recognized principles on standardization established in the Decision on Principles for theDevelopment of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.13.1.4.3 modified index of hemolysismass of he

16、moglobinreleased 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 5 freeHb 3V 3100 2 Ht1003100Q 3T(1)free Hb = increase of plasma free hemoglobin concentra-tion (g/L) over the sampling ti

17、me interval,where:V = circuit volume (L),Q = flow rate (L/min),Ht = hematocrit (%), andT = sampling time interval (min).4.2 Normalized Milligram Index of Hemolysis. (mg.N.I.H.)(2, 3, 4):2mg.N.I.H.mg/100l 5 freeHb 3V 3100 2 Ht1003100Q 3T(2)4.3 Modified Index of Hemolysis (M.I.H.):4.3.1 Modified index

18、 of hemolysis (M.I.H.) (5, 6) that canbe written with no units or as (milligram of hemoglobinreleased into plasma/mg of total hemoglobin pumped throughthe loop):M.I.H. 5 freeHb 3V 3100 2 Ht1003106Q 3T 3Hb(3)where:Hb = total blood hemoglobin concentration at timezero (mg/L), andfree Hb = increase of

19、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 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. Re

20、centdevelopment 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 the 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 s

21、ystem.The M.I.H. equation corrects for differences in blood hemo-globin concentration and hematocrit directly (5).4.4 Testing BloodBecause the level of trauma-inducedhemolysis is different based on the source of blood, it isnecessary to identify the source of blood and its respectiveindex of hemolys

22、is. Human, bovine, or porcine blood arerecommended as the primary sources of testing blood (seePractice F1830). It is preferable that the blood collected at astandard slaughter house not be used due to the risk of beingcontaminated with fluids other than blood, unless the blood isobtained by control

23、led venipuncture. Although animal blood isused in the development stage of a pump, it is suggested thatpre-clinical evaluation tests be repeated with human blood.5. Summary of Practice5.1 BloodThe blood is obtained from human volunteers,cattle or pigs having normal body temperatures, no physicalsign

24、s of disease, including diarrhea or rhinorrhea, and anacceptable range of hemotological profiles. The blood shouldbe collected by vascular puncture using a needle (14G orlarger) and collected into the standard 5002000 mL bagscontaining citrate phospate dextrose adenine (CPDA-1) anti-coagulant soluti

25、on (See Appendix X2) or heparin sulfate (SeeAppendix X3). The blood from a slaughterhouse can typicallybe used if it is obtained by controlled 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 (typic

26、ally, 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 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

27、 the same vertical height, thepressure in the outlet line of the pump is 100 mm Hg greaterthan in the inlet line) and for the cardiopulmonary 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 press

28、ure monitoring lines areincorporated into the test loop both at the inlet and outlet tubes.An ultrasonic or electromagnetic flow probe 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

29、is measured using a correspondingthermometer.5.3 Pump ConditionsPump flow rate is set at 5 6 0.25L/min at the circulating blood temperature 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. Howeve

30、r, additional testing temperaturescan be chosen from 0 to 42C according to the intended clinicaluse of the pump (for example, cardiopulmonary bypass mayinclude cooling and warming during surgery.)5.4 EvaluationThe free plasma hemoglobin is determinedby a clinically approved assay method (see 9.3). T

31、he freeplasma hemoglobin is standardized by calculating the M.I.H.6. Significance and Use6.1 The objective of this practice is to standardize theevaluation method for detecting the hemolytic effect of acontinuous flow blood pump used in extracorporeal circulationand circulatory assistance.7. Prepara

32、tion of Hemolysis Test7.1 BloodThe blood is obtained from human volunteershaving normal body temperature, exhibiting no physical signsof disease and having hematological profiles in the normalacceptable range. (Donors are subjected to standard blooddonor screening procedures.) The donor should be fa

33、sted for 83The boldface numbers given in parentheses refer to a list of references at theend of the text.F1841 97 (2017)2h or more to avoid additional hemolysis due to a highconcentration of lipids in the blood. The delay in the collectionof the blood and the hemolysis test should not exceed 48 h of

34、refrigerated 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 blood is bovine and porcine (See Practice F1830). Sincet

35、he 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 order to standardize the blood trauma testing, the blood

36、subjected to the test should have the hematocrit value adjustedto be within the range 30 6 2 % by hemodilution (withphospate buffered saline) or hemoconcentration (via minimalcentrifugation). Proper and acceptable ranges of the physi-ological blood parameters should be maintained prior to andduring

37、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 ultrasonic orelectromagnetic flow probe and its corresponding flowmeter, athe

38、rmistor 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. The phosphate buff-ered saline is drained completely from the loop prior to fi

39、llingit 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 in the reservoir. A screwFIG. 1 Test LoopF1841 97 (2017)3clamp, that is appl

40、ied 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 at the outlet side of the pumpbetween the sc

41、rew 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-line flow meter, and allexperiments are condu

42、cted 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 test runs are of a6-h duration, sterility is

43、generally considered not necessary.7.4 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 samples at each sample time. At each sampling, thefirst sample of 1 mL should be

44、 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 to testing, the initial total bloodhemoglobin concentration, plasma hemoglobi

45、n 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 complete mixing and dilution.7.5 Static Blood ControlsThe control blood is kept in

46、 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 for hemolysistesting, that consists of the blood pump subjected to the test, a

47、reservoir 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 is also included inthis figure.8.2 The blood warmed to 37C (or other appropria

48、te 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 thesampling port, the first blood sample is taken as the pre-pumping control.8

49、.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. This 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 ports are recom