http://prf.sagepub.com /Perfusion http://prf.sagepub.com/content/early/2013/12/06/0267659113509000 The online version of this article can be found at: DOI: 10.1177/0267659113509000 published online 9 January 2014 PerfusionS Bottrell, M Bennett, S Augustin, C Thuys, B Schultz, A Horton and S Horton A comparison study of haemolysis production in three contemporary centrifugal pumps Published by: http://www.sagepublications.com can be found at: PerfusionAdditional services and information for http://prf.sagepub.com/cgi/alerts Email Alerts: http://prf.sagepub.com/subscriptions Subscriptions: http://www.sagepub.com/journalsReprints.nav Reprints:http://www.sagepub.com/journalsPermissions.nav Permissions:What is This? -Jan 9, 2014 OnlineFirst Version of Record >>at BOSTON UNIV on January 13, 2014 prf.sagepub.com Downloaded fromat BOSTON UNIV on January 13, 2014 prf.sagepub.com Downloaded from
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8/20/2019 2014 Bottrell_ Comparison Study of Haemolysis Production in Three Contem...
http://prf.sagepub.com/content/early/2013/12/06/0267659113509000The online version of this article can be found at:
DOI: 10.1177/0267659113509000
published online 9 January 2014Perfusion
S Bottrell, M Bennett, S Augustin, C Thuys, B Schultz, A Horton and S HortonA comparison study of haemolysis production in three contemporary centrifugal pumps
Published by:
http://www.sagepublications.com
can be found at:Perfusion Additional services and information for
Blood trauma has been associated with patients requiring
extracorporeal life support (ECLS), with the type of bloodpump utilised contributing to the degree of haemolysisproduced during support.1 It has been shown that cen-trifugal pumps (CF) possess superior blood handlingcapabilities over periods of days to weeks of support whencompared to roller pump based systems.2 This is one rea-son why CF pumps are gaining wider acceptance in theECLS community. However, there is also variance in thegeneration of haemolysis in different CF pumps that canbe attributed to a number of design factors.
CF pumps may have several key advantages over rollerpumps when considered for short- to medium-term useas a ventricular assist device (VAD) or for extracorporealmembrane oxygenation (ECMO). These advantagesinclude superior blood handling compared to rollerpumps after only 24 hours of use, there is simpler set upand implementation, they are smaller, easier to transportand have improved safety features.2-4
First generation centrifugal pumps were compara-tively larger, produced areas of stasis and contained fric-tion points which adversely affected blood components.With the advent of the current generation of CF pumps,many of these inherent design drawbacks have beenovercome. It is anticipated this will result in continuedimprovements in haemolysis production and patient
management, which is an important consideration when
adopting any new technology.
Methods
To ascertain the red blood cell handling characteristics ofthe three devices, we undertook a bench test similar toour previous study.2
The experimental setup consisted of three pumps: theDeltastream DP3 diagonal rotary pump (MedosMedizintechnik AG, Stolberg. Germany), the Rotaflowshrouded impeller pump (Maquet AG, Hirrlingen,Germany) and the PediVAS magnetically levitated pump
A comparison study of haemolysis production inthree contemporary centrifugal pumps
S Bottrell,1 M Bennett,1 S Augustin,1 C Thuys,1 B Schultz,1
A Horton1 and S Horton1,2
Abstract
One challenge in providing extracorporeal circulation is to supply optimal flow while minimising adverse affects, such ashaemolysis. To determine if the recent generation constrained vortex pumps with their inherent design improvementswould lead to reduced red cell trauma, we undertook a study comparing three devices. Utilizing a simulated short-term ventricular assist circuit primed with whole human blood, we examined changes in plasma free haemoglobin values
over a six-day period. The three pumps investigated were the Maquet Rotaflow, the Levitronix PediVAS and the MedosDeltastream DP3.This study demonstrated that all three pumps produced low levels of haemolysis and are suitable for usein a clinical environment. The Levitronix PediVAS was significantly less haemolytic than either the Rotaflow (p<0.05) or theDP3 (p<0.05). There was no significant difference in plasma free haemoglobin between the Rotaflow and the DP3 (p=0.71).
An ex vivo circuit, which closely represented our clin-ical circuit setup used for VAD, was constructed for eachof the three devices. The three circuits (Figure 1) con-sisted of a standardised, custom-made ¼ inch tubing set
(Lovell Surgical, Melbourne, Victoria, Australia).The circuits were initially primed with 240 ml ofPlasmalyte 148 (Baxter Healthcare, Old Toongabbie, NSW,Australia) and 33 ml of albumin 20% (CSL Ltd, Parkville,Victoria, Australia) then recirculated for 10 minutes, asper our normal practice for priming ECLS circuits.
One fresh unit of citrated whole human bank blood,mean volume 516 ml (range 510-519 ml) and a meanage of 4 days (range 3-6 days), was mixed with 1g of cef-tazodime and 15 mmol of sodium bicarbonate. Excessclear prime was removed from the experimental circuitsand 170 ml of the blood mixture was added to give atotal circuit prime volume of 280 ml and a final mean
haemoglobin (Hb) of 100 g/L. After circulating, bloodchemistry analysis was performed to confirm similaritybetween circuits at the initiation of the study period andany residual air in the circuit was removed to minimisethe blood-air interface.
Trial conditions were established using the Rotaflowas the reference pump, as this is our current clinicaldevice. These conditions consisted of a sub-atmosphericpreload pressure (-15 to -20 mmHg), an afterload pres-
sure (130-140 mmHg) and a flow rate of 700 ml/min.The parameters were determined from our patient VADdatabase which showed the average flow was 720 ml/min, the preload pressure was -14 mmHg and the after-load pressure was 130 mmHg. The preload pressure wasachieved by adjusting the height of the reservoir bag rela-tive to the pump head of each circuit and the afterloadpressure was attained by the use of a variable-occlusionclamp placed on the pump outlet tubing. The individualpump revolutions were maintained at 2320 revolutionsper minute (rpm) for the Rotaflow, 4900 rpm for the DP3and 3200 rpm for the PediVAS system for the duration of
the study. Each of the circuits was recalibrated for pres-sure and flow on a daily basis at the time of blood sam-pling by adjusting the height of the bag and the variable-occlusion clamp. Flow for all pumps was deter-mined using a Sono TT Ultrasonic flow monitor (EmtecMedical Technology, Munich, Germany). The tempera-ture for the study circuits was maintained at a room tem-perature of 22 degrees Celsius.
Pressure was measured using two medical laboratorymanometers PM-9100HA (Lut-ron Electronic EnterpriseCo. Ltd, Taipei, Taiwan) with an accuracy of ± 2%.
Once the study parameters were met for flow and inletand outlet pressures, an initial blood sample was takenfrom each circuit to establish the baseline plasma freehaemoglobin (Plasma Hb) levels and then, at the sametime daily, for six days. A total of five benchtop studygroups were completed. Each study group had three cir-
cuits running concurrently. Samples were taken at a
point five centimetres from the pump head outlet. Prior
to the blood sample being taken, 1 ml of blood was taken
and discarded and then 0.5 ml of blood was taken pas-sively into a 2 ml syringe. The blood samples were gentlysyringed into a 0.5 ml EDTA blood tube with immediateanalysis after being received by the Royal Children’sHospital (RCH) biochemistry laboratory and performed
Table 1. Characteristics of centrifugal pumps used in the study.
on the VITROS® 5600 Integrated System (Ortho ClinicalDiagnostics, High Wycombe, Bucks, UK). The VITROS®5600 utilizes the measurement principle of opticalabsorbance. Absorbances in the range of 400 – 800 nmare automatically read and recorded for each sample andthen multi-variant analysis of the spectral data provides
estimates of haemolysis.The haemolysis index is then calculated according to:
H = (dA/d ) * (aH)
where H = Haemolysis index dA/d = Derivative absorbance vector aH = Haemolysis coefficient vector (522 – 750 nm) * = Vector dot product (sum of the products of
each vector row)
A limitation of this study was the adjustment of the
afterload pressure by placing variable-occlusion clampson the tubing. It has been noted that this method ofobtaining resistance may, in itself, cause increased turbu-lence and result in greater haemolysis, but this techniquewas chosen as we were able to produce a reliable after-load pressure and any contribution to haemolysis shouldbe consistent across all three circuits.
Statistical Analysis
A one-way analysis of variance (ANOVA) on natural logtransformed data was used on the plasma-free haemo-globin measurements (Stata Quest 12.1, StataCorporation, College Station, TX, USA). The Mann-Whitney U-test was then used to determine at what daya difference between the non-transformed data of the DP3, Rotaflow and PediVAS pumps occurred. A probability value less than 0.05 was considered significant.
Results
Plasma Hb values for the control sample were deductedfrom the daily results of the three pump groups. The geo-metric mean for plasma Hb values was then plotted againstthe sample day (Figure 2). It was observed that there was atrend for the DP3 and Rotaflow to become more haemo-lytic than the PediVAS pump after two days, with levelscontinuing to rise over the course of the trial. For the com-parison between the DP3 and Rotaflow pumps only,ANOVA calculations on log transformed data showed nostatistical difference between the two groups (p=0.71).
Discussion
Haemolysis remains a reliable marker for pump-inducedblood cell trauma. In this study, it was found that the
Levitronix PediVAS was the least haemolytic of the three
devices bench tested (p<0.05). There was a differencenoted in plasma Hb levels from day two onwards in theLevitronix PediVAS when compared to the Medos DP3(p<0.05) and the Maquet Rotaflow pumps (p<0.05).When comparing the plasma Hb levels of the Rotaflowand DP3, there was no significant difference (p=0.71).We analysed the effect of three different devices on thered blood cells, however, this may not translate to thehandling characteristics on the other formed elementscontained within blood, e.g., platelets and white cells.5 We also note that a statistical difference shown may nottranslate into a meaningful clinical difference as there are variable physiological mechanisms that clear plasma free
Hb.6The excellent blood handling characteristics of the
PediVAS pump were expected from the growing body ofevidence in the recent literature.7-13 This pump isdesigned such that the revolution of the rotor occurswith less friction and wear. This is controlled by themotor and results in a stable, entirely levitated impeller(Figure 3). There are no seals in the device and, com-bined with the suspended impeller, heat generation isgreatly reduced. The lower heat generation results in lessthermal damage to blood components, causing less hae-molysis and a reduced risk of thrombus generation.4,14,15
However, it is also the most expensive of the three devicestested in this study.The Rotaflow pump has been used by our unit clini-
cally for the last 13 years for short-term VAD and ECMO(up to 8 weeks duration). It is a well-engineered, safe andreliable device that has provided excellent service to ourpatient population. The Rotaflow has some significantdesign advantages compared to first generation pumpsthat have meant lower levels of pump-induced haemoly-sis and wear, with the clinical benefit of improved circuitlongevity. Inside this pump, the rotor is suspended anddriven by a radial magnetic field that stabilizes the impel-ler and allows it to be spun on a single blood-flushed
Figure 2. Natural Log of plasma free Hb vs. days.
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pivot bearing, as seen in Figure 3. This, in turn, avoidsstagnant zones and reduces areas of high shear and tur-bulence, giving it a favourable hydraulic efficiency.18
The Deltastream diagonal pump has undergone gen-erational change from an integrated motor and impellerto a DP2 pump head with separated motor and pumphead to the latest development, the DP3 pump.20 TheMedos DP3 is a diagonal/hybrid rotary pump thatemploys a ceramic bearing, magnetic coupling with sep-arate pump head and a prime volume of 16 ml.21
It has been hypothesised by Haneya et al. that thedesign of the previous (DP2) diagonal pump may haveled to higher levels of blood trauma.21 This, to some
extent, may be due to the higher rpm required to achievea set flow, causing increased shear stress from the bear-ing. With the newer generation DP3 (Figure 5), this pur-ported issue has been rectified by removing the metalshaft and sealing ring. The power from the motor isimparted via a magnetic coupling to the impeller, mini-mising friction. Our results confirm that the DP3 is atleast as good as the Rotaflow in handling red blood cells.
Rotary pumps can be classified into either centrifugalor axial pumps. Centrifugal pumps produce higher pres-sures, but use lower rpm to achieve this. The impellerblades of centrifugal pumps use the conservation of
angular motion to push the blood off the blades to theoutlet of the pump. Moazami et al. describe this by stat-ing, “its rotating element acts as a spinning disk withblades that can be viewed as a ‘thrower’, meaning that thefluid is captured and thrown tangentially out off theblade tip to the outlet”.23
The axial pumps operate at higher rpm to provideadequate outlet pressures to achieve flow. The DP3 pumpis a hybrid of these technologies, with faster rpm, butshorter transit time, allowing for a proposed beneficialhandling of formed elements within blood (Figure 6).
There are many aspects of the pump design processthat can affect the rates of haemolysis and thrombosis.The predominant cause of extensive haemolysis in CFblood pumps is thought to be caused by the amount ofshear stress applied and the time of exposure to thatshear stress.25,26 The importance of pump design plays amajor role in this process.
The thickness of the blades, the pitch of the blades, thenumber of blades and the distance from the housing ofthe pump all have an effect on the hydrodynamic andhaemolytic performance of the centrifugal pump.27-29 The importance of minimising stagnant areas in thepump and reducing shear stress and friction on theformed elements will have an impact on the rate of hae-molysis.30 Another critical design element is the methodof support for the rotor. Of the three pump heads that webench tested, one was totally magnetically suspended(Levitronix PediVAS) and the other two (Rotaflow &Deltastream) utilized a small pivot bearing. The mag-netic levitation of the rotor allows for the removal of the
mechanical contact point between the rotor and thehousing. Therefore, frictional resistance is kept to a min-imum, resulting in greater longevity of the device andreduced haemolysis, which was supported in our study.The mechanical pivot bearing offers the advantage oflower production costs and greater stability over the sixdirections of motion for the rotor. However, the addi-tional risk of friction-related heat generation and wearreduces the longevity of the pump by being a potentialsite for fibrin/clot formation.
When considering a blood pump for clinical use,other design factors to consider include:
1. Safety and reliability 2. Operator interface3. Portability 4. Cost5. Multiple modes, e.g., pulsatile flow 6. Data retention
The successful incorporation of these factors is impor-tant in the design process as the technology must beintuitively used by staff from different specialties in anintensive care setting.
Figure 3. Cutaway and schematic of the Levitronix PediVAS pumpand drive motor (Images courtesy of Thoratec Corporation).16,17
Figure 4. Rotaflow centrifugal pump. The pump is designed toexploit the potential of the radial magnetic drive, eliminating acentral shaft and seal by using a blood flushed bearing. 19
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In this ex vivo circuit study, based on plasma free haemo-globin, the PediVAS pump was the least haemolytic overthe six days of the trial. There was divergence of plasmafree haemoglobin at day two when compared to the DP3and Rotaflow. The DP3 and Rotaflow were not signifi-cantly different in their generation of haemolysis over thesix days. The DP3 also has several design features whichmay be considered advantageous. These include a lowprime volume, user friendly software interface, portability
and the ability for pulsatile flow. Based on these featuresand the DP3’s haemolysis profile, the pump warrants fur-ther investigation in our clinical setting.
Acknowledgements
The authors would like to thank the following for their
contributions:
Australian Red Cross Blood Service.Medos Cardiopulmonary Solutions.Lovell Surgical Supplies, Melbourne, Australia.Department of Biochemistry, Royal Children’s Hospital,Melbourne, Australia.N. Stenning and Co. Pty LtdMaquet Getinge Group.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Funding
This research received no specific grant from any fundingagency in the public, commercial or not-for-profit sectors.
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