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Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Evaluation of Conventional Nonpulsatile and Novel Pulsatile Extracorporeal Life Support Systems in a Simulated Pediatric Extracorporeal Life Support Model *Shigang Wang, *Alissa Evenson, *Brian J. Chin, †Allen R. Kunselman, and *‡§Akif Ündar *Pediatric Cardiovascular Research Center, Penn State Hershey Children’s Hospital, Penn State Milton S. Hershey Medical Center, Department of Pediatrics, Penn State Hershey College of Medicine; †Department of Public Health Sciences, Penn State Hershey College of Medicine; ‡Department of Surgery, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Hershey, PA; and §Department of Bioengineering, College of Engineering, Pennsylvania State University, University Park, PA, USA
Abstract: The objective of this study is to evaluate two extracorporeal life support (ECLS) circuits and determine the effect of pulsatile flow on pressure drop, flow/pressure waveforms, and hemodynamic energy levels in a pediatric pseudopatient. One ECLS circuit consisted of a Medos Deltastream DP3 diagonal pump and Hilite 2400 LT oxygenator with arterial/venous tubing. The second circuit consisted of a Maquet RotaFlow centrifugal pump and Quadrox-iD Pediatric oxygenator with arterial/venous tubing. A 14Fr Medtronic Bio-Medicus one-piece pediatric arterial cannula was used for both circuits. All trials were conducted at flow rates ranging from 500 to 2800 mL/min using pulsatile or nonpulsatile flow. The post-cannula pressure was maintained at 50 mm Hg. Blood temperature was maintained at 36°C. Real-time pressure and flow data were
recorded using a custom-based data acquisition system. The results showed that the Deltastream DP3 circuit produced surplus hemodynamic energy (SHE) in pulsatile mode at all flow rates, with greater SHE delivery at lower flow rates. Neither circuit produced SHE in nonpulsatile mode. The Deltastream DP3 pump also demonstrated consistently higher total hemodynamic energy at the preoxygenator site in pulsatile mode and a lesser pressure drop across the oxygenator. The Deltastream DP3 pump generated physiological pulsatility without backflow and provided increased hemodynamic energy. This novel ECLS circuit demonstrates suitable in vitro performance and adaptability to a wide range of pediatric patients. Key Words: Extracorporeal life support—Pulsatile flow— Pediatrics—Centrifugal pump—Diagonal pump.
Despite improving extracorporeal life support (ECLS) technology and patient outcomes, the Extracorporeal Life Support Organization’s January 2013 ECLS Registry Report International Summary states that mortality rates are still high (up to 60% in neonatal procedures for cardiac complications), and
there are still significant complications with the use of ECLS, including high rates of mechanical failure, acute renal failure, and hemorrhaging (1). In order to minimize mortality and morbidity, translational research is imperative. New devices should be tested through simulated ECLS to determine their benefits and drawbacks before they are used in clinical practice. The Penn State Hershey Pediatric Cardiovascular Research Center is one of the few centers in the USA to scientifically evaluate new ECLS circuits (2–22). All ECLS circuits currently utilized in the USA for mechanical circulatory support are operated in nonpulsatile mode, including the pediatric ECLS circuit most commonly used at the time of this study, which consists of the Maquet RotaFlow centrifugal pump and Quadrox-iD Pediatric oxygenator
doi:10.1111/aor.12290 Received November 2013; revised December 2013. Address correspondence and reprint requests to Dr. Akif Ündar, Penn State Hershey College of Medicine, Department of Pediatrics—H085, 500 University Drive, P.O. Box 850, Hershey, PA 17033-0850, USA. E-mail: [email protected] Presented in part at the 10th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion in Philadelphia, PA, USA, May 28–31, 2014.
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(Maquet Cardiopulmonary AG, Hirrlingen, Germany). This circuit is currently in use at Penn State Milton S. Hershey Medical Center. However, previous studies have established the benefits of pulsatile flow, including better vital organ microcirculation, decreased need for inotropic support, improved cerebral oxygen saturation, lower gastrointestinal bleeding rates, and shorter hospital stays after acute and chronic mechanical circulatory support (23–27). In addition, pulsatile flow is expected to maintain significantly better perfusion to vital organs during long-term circulatory support (26,28–30). The objective of this study was to determine the differences between these two ECLS circuits and to evaluate pulsatile flow in terms of pressure drops, flow/pressure waveforms, and hemodynamic energy levels in a simulated pediatric ECLS circuit. MATERIALS AND METHODS Experimental setup The experimental Medos ECLS circuit consisted of a Deltastream DP3 diagonal pump (Medos Medizintechnik AG, Stolberg, Germany), a Hilite 2400 LT PMP diffusion membrane oxygenator (Medos), and 100 cm of tubing with a 1/4-in. internal diameter (ID) and a 1/16-in. wall for both arterial and venous lines (Table 1). The experimental Maquet ECLS circuit included a RotaFlow centrifugal pump (Maquet), a Quadrox-iD Pediatric oxygenator, and 100 cm of tubing with a 1/4-in. ID and a 3/32-in. wall for both arterial and venous lines. Both circuits were identical with regard to tubing length between all circuit components. Figure 1 presents the components of the circuit. A 14Fr Medtronic Bio-Medicus one-piece pediatric arterial cannula (Medtronic, Inc., Minneapolis, MN, USA) and an ECMO-TEMP SMS-3000 heater–cooler unit (Seabrook, Inc., Cincinnati, OH, USA) were used for both ECLS circuits.
A 300-mL-capacity soft bag served as a pseudopatient. A Hoffman clamp was placed downstream of the arterial cannula to ensure a constant arterial pressure would be delivered to the pseudopatient during all trials. The circuit was first primed with lactated Ringer’s solution for de-airing, and then packed human red blood cells were added. The hematocrit of the priming solution was 35%. The total priming volume of the circuit was approximately 700 mL. Pulsatile mode setting The Deltastream DP3 pump was evaluated in pulsatile mode at a rotational differential of 1500 revolutions per minute (rpm), a frequency of 90 bpm, and a systolic/diastolic ratio of 50%. Based on our earlier experiments, we selected these settings to provide adequate quality of pulsatility (21,22). With the help of the Maquet HL-20 heart–lung machine console base, the RotaFlow pump could produce pulsatile flow at pulsatile settings of 10% base flow, 90 bpm (pump rate), 20% of the pump head start point, and 80% of the pump head stop point. Experimental design Before the test was conducted, the priming solution was adequately mixed in the circuit. The trials were conducted at flow rates of 500 mL/min, 1000 mL/min, 1500 mL/min, 2000 mL/min, 2400 mL/ min, and 2800 mL/min (this flow rate was only used in the RotaFlow circuit) in pulsatile and nonpulsatile modes at a blood temperature of 36°C. The postcannula pressure was maintained at 50 mm Hg; the venous pressure was kept at 5 mm Hg during all trials. Two Transonic ultrasound flow probes (Transonic Systems, Inc., Ithaca, NY, USA) were placed at a pre-oxygenator site and a pre-cannula site. Five Maxxim disposable pressure transducers (Maxxim Medical, Inc., Ithaca, NY, USA) were placed at
TABLE 1. The components of the experimental circuit
Blood pump Priming volume Revolution speed Maximal flow rate Oxygenator Priming volume Gas exchange surface area Maximal flow rate Hollow fiber material Arterial line tubing Venous line tubing Coating material
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Medos ECLS circuit
Maquet ECLS circuit
Deltastream DP3 diagonal pump 16 mL 0–10 000 rpm 8 L/min Hilite 2400 LT 95 mL 0.65 m2 2400 mL/min Polymethylpentene 1/4″ ID × 1/16″ wall × 100 cm 1/4″ ID × 1/16″ wall × 100 cm Rheoparin
RotaFlow centrifugal pump 32 mL 0–5000 rpm 9.9 L/min Quadrox-iD Pediatric 81 mL 0.8 m2 2800 mL/min Polymethylpentene 1/4″ ID × 3/32″ wall × 100 cm 1/4″ ID × 3/32″ wall × 100 cm Bioline
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FIG. 1. The experimental ECLS circuit.
pre-oxygenator, post-oxygenator, pre-cannula, postcannula, and venous line sites. All flow and pressure sensors were located at identical distances from the respective circuit components in order to provide consistency of data measurements.
second. A 20-s segment of pressure and flow data was recorded at all sites and converted into hemodynamic energy using the equations below. The entire process was repeated six times for each unique combination, yielding a total of 96 trials.
Data acquisition Five pressure transducers and two flowmeter outputs were connected to a signal-conditioning unit (SC-2345, National Instruments, Austin, TX, USA) and a data acquisition device (NI USB-6521, National Instruments). The digital signals were transferred from the data acquisition device to a computer via a USB port. A customized user interface based on Labview 7.1 software for Windows (National Instruments) recorded real-time data at 1000 samples per
Calculating hemodynamic energy The hemodynamic energy created by different modes was quantified by related mathematical formulas. With the help of Shepard’s formula for energy-equivalent pressure (EEP) (31) and the data for simultaneous blood flow (f) and pressure (p) recorded by the Labview 7.1 software, EEP, surplus hemodynamic energy (SHE), and total hemodynamic energy (THE) were calculated for a time interval (t1 to t2) as follows: Artif Organs, Vol. 39, No. 1, 2015
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EEP ( mm Hg ) = ∫ fpdt t1
SHE ( ergs cm 3 ) = 1332
∫
t2
t1
fdt
× ( EEP − mean arterial pressure) THE ( ergs cm 3 ) = 1332 × EEP The constant 1332 converts pressure from units of mm Hg to dynes per cm2 (1 mm Hg = 1332 dyn/cm2).
TABLE 2. Flow rates and rotational speeds Rotational speed (rpm) Flow rate
Circuit
Nonpulsatile
Pulsatile
500 mL/min
Medos Maquet Medos Maquet Medos Maquet Medos Maquet Medos Maquet Maquet
3500 1656 4500 2085 5350 2505 6350 2945 7150 3260 3630
3450 — 4400 — 5300 — 6300 — 7100 — —
1000 mL/min 1500 mL/min 2000 mL/min
Calculating pressure drops Oxygenator pressure drop (mm Hg) was calculated as pre-oxygenator pressure minus postoxygenator pressure. Arterial cannula pressure drop (mm Hg) was calculated as pre-cannula pressure minus post-cannula pressure. Circuit pressure drop (mm Hg) was calculated as pre-oxygenator pressure minus post-cannula pressure. Statistical analysis ANOVA models were fit to continuous outcomes (e.g., pressure drop) to compare flow rate (500, 1000, 1500, 2000, 2400, or 2800 mL/min), pump (Deltastream DP3 or RotaFlow), and pulsatility mode (nonpulsatile or pulsatile). A linear mixedeffects model was fit to continuous outcomes (mean arterial pressure [MAP], EEP, SHE, and THE) to compare the flow rate, pump, mode, and location (e.g., pre-oxygenator, post-cannula) (32). The linear mixed-effects model is an extension of linear regression that accounts for the within-subject variability inherent in repeated-measures designs. In this study, the repeated factor is the location. For each outcome, P values were adjusted for multiple-comparisons testing using the Tukey–Kramer procedure. All hypothesis tests were two-sided, and all analyses were performed using SAS software, version 9.3 (SAS Institute, Inc., Cary, NC, USA). RESULTS Rotational speed The Deltastream DP3 pump generated consistently higher rotational speed than the RotaFlow pump at identical flow rates in nonpulsatile mode, with the Deltastream DP3 pump rotating an average of 2.15 times faster than the RotaFlow pump (Table 2). Additionally, there was a consistent 50rpm decrease in rotational speed in the Deltastream DP3 pump when it was used in pulsatile mode versus nonpulsatile mode (Table 2). Artif Organs, Vol. 39, No. 1, 2015
2400 mL/min 2800 mL/min*
* The maximal flow rate for the Medos Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate.
Pulsatile flow When we attempted to use the RotaFlow centrifugal pump in pulsatile mode, we noted excessive heat generation at the pump driver and were unable to produce adequate pulsatile flow in excess of 1700 mL/min. The Deltastream DP3 diagonal pump generated adequate pulsatile flow without any excessive heat generation, in addition to adequate nonpulsatile flow, at all flow rates evaluated. Figure 2 shows flow and pressure waveforms at 1500 mL/min for both circuits and both pulsatility modes in the Deltastream DP3 circuit. Hemodynamic energy The Deltastream DP3 circuit in pulsatile mode was capable of producing EEP in excess of MAP at all flow rates and at both the pre-oxygenator and postcannula sites, whereas neither the Deltastream DP3 nor the RotaFlow circuit was able to produce EEP in nonpulsatile mode (Table 3). A decrease in the percentage of EEP generated was seen at both the preoxygenator and post-cannula sites as flow rate increased. The excess EEP produced in pulsatile mode was transferred to the patient as SHE. Lower flow rates produced less SHE at the pre-oxygenator sites but increased SHE at the post-cannula site, demonstrating greater SHE delivery to the pseudopatient at lower flow rates (Fig. 3). The post-cannula SHE decreased with higher flow rates because, for both the oxygenator and cannula, higher flow rates were associated with higher pressure drops (Table 4). THE at the pre-oxygenator site was consistently higher in the Deltastream DP3 circuit in pulsatile mode than in either circuit in nonpulsatile mode. THE delivery to the pseudopatient from the postcannula site remained consistent (Fig. 4).
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FIG. 2. Flow and pressure waveforms at 1500 mL/min in pulsatile (P) and nonpulsatile (NP) mode.
Pressures MAP at the pre-oxygenator site increased as flow rate increased in both circuits and in both pulsatility modes in the Deltastream DP3 circuit. Pulsatile mode produced greater MAP at the pre-oxygenator
site (1 mm Hg at 500 mL/min flow rate to 14.3 mm Hg at 2400 mL/min flow rate) at all flow rates in the Deltastream DP3 circuit when compared with either circuit in nonpulsatile mode (Table 3).
TABLE 3. MAP and EEP at pre-oxygenator and post-cannula sites under pulsatile (P) and nonpulsatile (NP) modes Pre-oxygenator site
Post-cannula site
Flow rate
Circuit
Mode
MAP (mm Hg)
EEP (mm Hg)
MAP (mm Hg)†
EEP (mm Hg)
500 mL/min
Medos
1000 mL/min
Maquet Medos
1500 mL/min
Maquet Medos
2000 mL/min
Maquet Medos
2400 mL/min
Maquet Medos
2800 mL/min‡
Maquet Maquet
NP P NP NP P NP NP P NP NP P NP NP P NP NP
81.1 ± 0.0 82.8 ± 0.2* 81.8 ± 0.0 118.4 ± 0.0 119.0 ± 0.5 113.8 ± 0.0* 155.8 ± 0.0 160.1 ± 0.6* 152.9 ± 0.0 207.4 ± 0.0 211.8 ± 0.5* 202.8 ± 0.0 254.1 ± 0.1 257.0 ± 0.8* 242.7 ± 0.0 294.8 ± 0.1
81.1 ± 0.0 93.8 ± 0.2 (13.3%)* 81.8 ± 0.0 118.4 ± 0.0 130.5 ± 0.5 (9.6%)* 113.8 ± 0.0 155.8 ± 0.0 173.5 ± 0.5 (8.3%)* 152.9 ± 0.0 207.4 ± 0.0 225.7 ± 0.5 (6.6%)* 202.8 ± 0.0 254.1 ± 0.1 270.8 ± 0.8 (5.4%)* 242.7 ± 0.0 294.8 ± 0.1
50.0 ± 0.0 50.6 ± 0.2 50.3 ± 0.0 50.8 ± 0.0 50.3 ± 0.2 50.4 ± 0.0 50.5 ± 0.0 50.7 ± 0.1 50.2 ± 0.0 50.3 ± 0.0 50.4 ± 0.1 50.5 ± 0.0 50.3 ± 0.0 50.4 ± 0.1 50.6 ± 0.0 50.6 ± 0.1
50.0 ± 0.0 57.8 ± 0.2 (14.1%)* 50.3 ± 0.0 50.8 ± 0.0 55.5 ± 0.2 (10.4%)* 50.4 ± 0.0 50.5 ± 0.0 54.8 ± 0.1 (8.1%)* 50.2 ± 0.0 50.3 ± 0.0 53.1 ± 0.1 (5.2%)* 50.5 ± 0.0 50.3 ± 0.0 52.1 ± 0.1 (3.4%)* 50.6 ± 0.0 50.6 ± 0.1
Values in parentheses are EEP percentage increase compared to MAP [((EEP − MAP)/MAP) × 100]. * P < 0.01 versus nonpulsatile mode. † The pseudopatient’s MAP was maintained at 50 mm Hg at the post-cannula site by a Hoffman clamp. ‡ The maximal flow rate for the Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate. Artif Organs, Vol. 39, No. 1, 2015
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FIG. 3. Surplus hemodynamic energy (SHE) at different flow rates and sites in pulsatile (P) and nonpulsatile (NP) mode. *P < 0.001 versus nonpulsatile mode.
In both pulsatility modes in the Deltastream DP3 circuit, the pressure drop was higher across the oxygenator at 500 mL/min; however, at higher flow rates the pressure drop across the cannula was higher (Table 4). The pressure drop across the oxygenator was consistently lower in the Deltastream DP3 circuit at all flow rates in both pulsatile and nonpulsatile mode, ranging from 1.7 mm Hg to 13.2 mm Hg lower in nonpulsatile modes and 1.5 mm Hg to 12.7 mm Hg lower in pulsatile mode (Table 4). However, the pressure drop in the overall circuit was slightly higher in the Deltastream DP3 circuit at all flow rates except for 500 mL/min in nonpulsatile mode. This is accounted for by the fact that the Deltastream DP3 circuit produced higher pressures overall at those same flow rates and pulsatility modes (Table 3).
DISCUSSION We tried to generate pulsatility from a RotaFlow pump on the console base of a Maquet HL-20 heart-lung machine to provide a direct comparison between pulsatile and nonpulsatile modes. Unfortunately, our research found that the RotaFlow circuit produced an error message at 500 mL/min flow rate and could not produce adequate flow rates in excess of 1700 mL/min in pulsatile mode. We also noted excessive heat generation at the pump driver when the RotaFlow pump was used in pulsatile mode. The next-generation Medos ECLS circuit consists of a Deltastream DP3 diagonal pump and a polymethylpentene (PMP) diffusion membrane oxygenator. This novel diagonal pump can sufficiently
TABLE 4. The pressure drops of oxygenators, cannula, and circuit under pulsatile (P) and nonpulsatile (NP) mode Pressure drop (mm Hg) Flow rate
Circuit
Mode
Oxygenator
Cannula
Circuit
500 mL/min
Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Maquet
NP P NP NP P NP NP P NP NP P NP NP P NP NP
7.9 ± 0.0 8.1 ± 0.0 9.6 ± 0.0* 15.9 ± 0.0 15.9 ± 0.0 18.9 ± 0.0* 22.1 ± 0.0 22.5 ± 0.1 28.4 ± 0.0* 29.6 ± 0.0 29.4 ± 0.1 39.4 ± 0.0* 34.7 ± 0.0 34.5 ± 0.1 47.8 ± 0.0* 58.2 ± 0.0
6.2 ± 0.0 (19.9%) 6.7 ± 0.0 (20.8%) 6.5 ± 0.0 (20.6%) 19.8 ± 0.0 (29.3%) 20.5 ± 0.1 (29.8%)# 18.5 ± 0.0 (29.2%) 35.5 ± 0.0 (33.7%) 37.8 ± 0.1 (34.6%)# 35.7 ± 0.0 (34.8%) 58.8 ± 0.0 (37.4%) 61.3 ± 0.2 (38.0%)# 58.7 ± 0.0 (38.6%) 80.0 ± 0.0 (39.3%) 81.7 ± 0.3 (39.5%)# 78.2 ± 0.0 (40.7%) 103.8 ± 0.1 (42.5%)
31.1 ± 0.0 32.2 ± 0.1 31.5 ± 0.0* 67.6 ± 0.0 68.8 ± 0.3 63.4 ± 0.0* 105.3 ± 0.0 109.4 ± 0.4 102.7 ± 0.0* 157.1 ± 0.1 161.3 ± 0.5 152.2 ± 0.0* 203.8 ± 0.1 206.6 ± 0.7 192.1 ± 0.0* 244.2 ± 0.1
1000 mL/min 1500 mL/min 2000 mL/min 2400 mL/min 2800 mL/min†
Values in parentheses = (cannula pressure/circuit pressure drop) × 100. * P < 0.01 versus Medos; # P < 0.01 versus nonpulsatile mode. † The maximal flow rate for the Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate. Artif Organs, Vol. 39, No. 1, 2015
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FIG. 4. Total hemodynamic energy (THE) at different flow rates and sites in pulsatile (P) and nonpulsatile (NP) mode. *P < 0.001 versus nonpulsatile mode.
provide both pulsatile and nonpulsatile flow that can accommodate either pediatric or adult patients. The pumps currently used in the USA are either occlusive roller pumps or nonocclusive centrifugal pumps that may generate backflow. The Deltastream DP3 diagonal pump is unique in its ability to provide nonocclusive, pulsatile flow without backflow. This new ECLS system has already been successfully used in European clinics (33,34) but is not yet approved by the Food and Drug Administration (FDA) in the USA. We were interested in determining any potential benefits or drawbacks that the Deltastream DP3 ECLS circuit might offer in either pulsatile or nonpulsatile mode. Mounting evidence has demonstrated the superiority of pulsatile flow over continuous flow during acute and chronic mechanical support (23–27). However, all ECLS circuits currently used in the USA, including the RotaFlow ECLS circuit used at Penn State Milton S. Hershey Medical Center at the time of the study, can provide only adequate nonpulsatile flow. We conducted this study to compare and contrast the RotaFlow and Deltastream DP3 ECLS systems in pulsatile and nonpulsatile flow to determine if one had significant benefits over the other. The RotaFlow ECLS circuit uses a centrifugal pump and a Quadrox-iD Pediatric oxygenator, the first oxygenator approved by the FDA for long-term mechanical circulatory support use in the USA. The next-generation Deltastream DP3 ECLS circuit contains a diagonal pump and a Hilite 2400 LT PMP diffusion membrane oxygenator. The Deltastream DP3 diagonal pump has numerous improvements, including a low priming volume (16 mL), a wide range of flow rates (0–8 L/min) that can accommodate both adult and pediatric patients, and the option
to provide pulsatile flow. Moreover, the Deltastream MDC console has valuable safety features, including a flow sensor with an integrated bubble detector, backflow detection, zero-flow mode, four pressure sensors, and two temperature sensors. Data collected from comparing these two ECLS systems will enable us to decide which system and which mode of flow will optimize patient outcomes in the future. Our results show that the RotaFlow circuit had a much lower rate of revolution than any setting in the Deltastream DP3 circuit, as the RotaFlow pump has a larger impeller. The pulsatile flow settings selected for the Deltastream DP3 circuit in this current study were based on our previous studies demonstrating that these settings can provide adequate SHE under pulsatile mode (20–22). With our selected pulsatile settings, the Deltastream DP3 circuit generated slightly higher flow rates when switching from nonpulsatile mode to pulsatile mode. To maintain identical flow rates for both modes, rotational speed was adjusted after each trial. The pressure and flow waveforms show that the Deltastream DP3 circuit is capable of producing excellent-quality pulsatility without backflow. Moreover, in pulsatile mode, EEP was consistently higher than MAP in the Deltastream DP3 circuit. Therefore, pulsatile flow was always able to provide SHE to the pseudopatient, even at low flow rates, while generating more THE compared with nonpulsatile mode from both ECLS circuits. The post-cannula SHE decreased with higher flow rates because higher flow rates were associated with higher pressure drops for both the oxygenator and the cannula. The post-cannula THE was roughly the same for all circuits at all flow rates because a uniform post-cannula pressure of 50 mm Hg was maintained by a Hoffman clamp. Artif Organs, Vol. 39, No. 1, 2015
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The results of the present study demonstrate a consistently lower pressure drop across the Hilite 2400 LT PMP diffusion membrane oxygenator than across the Quadrox-iD Pediatric oxygenator at identical flow rates, while the pre-oxygenator MAP and the overall circuit pressure drops were slightly higher in the Deltastream DP3 circuit than in the RotaFlow circuit. Similar findings were reported in our previous study (17). At low flow rates, the oxygenator caused the largest pressure drops; however, at high flow rates, the arterial cannula caused the largest pressure drops. Therefore, in order to select the best ECLS circuit or mode, the circuit must be evaluated as a whole unit, including pump, oxygenator, and cannula, to ensure the best patient outcomes. LIMITATIONS The limitations of this study include using the same arterial cannula for all flow rates in both ECLS circuits and conducting the experiment in an in vitro setting. This may not accurately represent performance in a clinical setting. Additionally, we were not able to test pulsatile flow in the RotaFlow circuit because the centrifugal pump mounted on the HL-20 heart–lung machine could not generate adequate flow rates in our simulated pediatric ECLS circuit, in addition to generating excessive heat at the pump driver. The RotaFlow pump has previously been evaluated in both pulsatile and nonpulsatile modes in adult CPB patients, with the researchers finding significantly lower flow rates in pulsatile mode from the sensors located at the post-oxygenator location, despite the heart–lung machine indicating identical perfusion flow rate in both pulsatile and nonpulsatile modes (35). Further experiments should be conducted to clarify these findings, especially in pediatric patients. CONCLUSIONS The Deltastream DP3 diagonal pump displayed excellent flow/pressure waveforms, demonstrated adequate pulsatile flow without backflow for pediatric patients, and provided higher levels of hemodynamic energy to the pseudo-patients. The Hilite 2400 LT oxygenator had lower pressure drops than the Quadrox-iD Pediatric oxygenator and retained greater hemodynamic energy across the oxygenator. The Deltastream DP3 pediatric extracorporeal life support circuit has demonstrated suitable in vitro performance and adaptability to a wide range of pediatric patients, in addition to its critical ability to generate more physiological pulsatile flow. Artif Organs, Vol. 39, No. 1, 2015
Conflict of Interest: None. REFERENCES 1. Extracorporeal Life Support Organization. Extracorporeal Life Support Registry Report: international summary. Ann Arbor, MI: ELSO, 2013. 2. Haines N, Rycus PT, Zwischenberger JB, Bartlett RH, Ündar A. Extracorporeal Life Support Registry Report 2008: neonatal and pediatric cardiac cases. ASAIO J 2009;55:111–6. 3. Qiu F, Talor J, Zahn J, et al. Translational research in pediatric extracorporeal life support systems and cardiopulmonary bypass procedures: 2011 update. World J Pediatr Congenit Heart Surg 2011;2:476–81. 4. Palanzo D, Qiu F, Baer L, Clark JB, Myers JL, Ündar A. Evolution of the extracorporeal life support circuitry. Artif Organs 2010;34:869–73. 5. Reed-Thurston D, Shenberger J, Qiu F, Ündar A. Neonatal extracorporeal life support: will the newest technology reduce morbidity? Artif Organs 2011;35:989–96. 6. Reed-Thurston D, Qiu F, Ündar A, Kopenhaver-Haidet K, Shenberger J. Pediatric and neonatal extracorporeal life support technology component utilization: are U.S. clinicians implementing new technology? Artif Organs 2012;36:607–15. 7. McCoach R, Weaver B, Carney E, et al. Pediatric extracorporeal life support systems: education and training at Penn State Hershey Children’s Hospital. Artif Organs 2010;34: 1023–6. 8. Vasavada R, Qiu F, Ündar A. Current status of pediatric/ neonatal extracorporeal life support: clinical outcomes, circuit evolution, and translational research. Perfusion 2011;26:294– 301. 9. Ündar A. Facts and myths surrounding pediatric mechanical cardiovascular circulatory support research: a personal perspective. Artif Organs 2012;36:467–9. 10. Ündar A, Wang S. Current devices for pediatric extracorporeal life support and mechanical circulatory support systems in the United States [invited review]. Biomed Mater Eng 2013;23:57–62. 11. Khan S, Vasavada R, Qiu F, Kunselman A, Ündar A. Extracorporeal life support systems: alternative versus conventional circuits. Perfusion 2011;26:191–8. 12. Clark JB, Guan Y, McCoach R, Kunselman AR, Myers JL, Ündar A. An investigational study of minimum rotational pump speed to avoid retrograde flow in three centrifugal pumps in a pediatric extracorporeal life support model. Perfusion 2011;26:185–90. 13. Qiu F, Clark JB, Kunselman AR, Ündar A, Myers JL. Hemodynamic evaluation of arterial and venous cannulae in a simulated neonatal ECLS circuit. Perfusion 2011;26:276–83. 14. Qiu F, Lu CK, Palanzo D, Baer L, Myers JL, Ündar A. Hemodynamic evaluation of the Avalon Elite bi-caval lumen cannulae. Artif Organs 2011;35:1048–51. 15. Qiu F, Uluer MC, Kunselman AR, Clark JB, Myers JL, Ündar A. Impact of tubing length on hemodynamics in a simulated neonatal extracorporeal life support circuit. Artif Organs 2010;34:1003–9. 16. Vasavada R, Khan S, Qiu F, Kunselman A, Ündar A. Impact of oxygenator selection on hemodynamic energy indicators under pulsatile and non-pulsatile flow in a neonatal ECLS model. Artif Organs 2011;35:E101–7. 17. Qiu F, Khan S, Talor J, Kunselman A, Ündar A. Evaluation of two pediatric polymethyl pentene membrane oxygenators with pulsatile and nonpulsatile perfusion. Perfusion 2011;26: 229–37. 18. Haines NM, Wang S, Myers JL, Ündar A. Comparison of two extracorporeal life support systems with pulsatile and nonpulsatile flow. Artif Organs 2009;33:958–66. 19. Durandy Y, Wang S, Ündar A. An original versatile nonocclusive pressure regulated roller blood pump for
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extracorporeal perfusion. Artif Organs 2013;doi: 10.1111/aor. 12192; [Epub ahead of print]. Evenson A, Wang S, Kunselman AR, Ündar A. Use of a novel diagonal pump in an in-vitro neonatal pulsatile extracorporeal life support circuit. Artif Organs 2014;38:E1–9. Wang S, Kunselman AR, Ündar A. Novel pulsatile diagonal pump for pediatric extracorporeal life support system. Artif Organs 2013;37:37–47. Krawiec C, Wang S, Kunselman AR, Ündar A. Impact of pulsatile flow on hemodynamic energy in a Medos Deltastream DP3 pediatric extracorporeal life support system. Artif Organs 2014;38:19–27. O’Neil MP, Fleming JC, Badhwar A, Guo LR. Pulsatile versus nonpulsatile flow during cardiopulmonary bypass: microcirculatory and systemic effects. Ann Thorac Surg 2012;94:2046–53. Akçevin A, Alkan-Bozkaya T, Qiu F, Undar A. Evaluation of perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiopulmonary bypass. Artif Organs 2010;34:879–84. Su XW, Guan Y, Barnes M, Clark JB, Myers JL, Undar A. Improved cerebral oxygen saturation and blood flow pulsatility with pulsatile perfusion during pediatric cardiopulmonary bypass. Pediatr Res 2011;70:181–5. Crow S, John R, Boyle A, et al. Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices. J Thorac Cardiovasc Surg 2009;137:208–15. Baraki H, Gohrbandt B, Del Bagno B, Haverich A, Boethig D, Kutschka I. Does pulsatile perfusion improve outcome
28.
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31. 32. 33.
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after cardiac surgery? A propensity-matched analysis of 1959 patients. Perfusion 2012;27:166–74. Travis AR, Giridharan GA, Pantalos GM, et al. Vascular pulsatility in patients with a pulsatile or continuous flow ventricular assist device. J Thorac and Cardiovasc Surg 2007;133: 517–24. Ündar A. Myths and truths of pulsatile and non-pulsatile perfusion during acute and chronic cardiac support [invited editorial]. Artif Organs 2004;28:439–43. Baba A, Dobsak P, Saito I, et al. Microcirculation of the bulbar conjunctiva in the goat implanted with a total artificial heart: effects of pulsatile and nonpulsatile flow. ASAIO J 2004;50:321–7. Shepard RB, Simpson DC, Sharp JF. Energy equivalent pressure. Arch Surg 1966;93:730–40. Fitzmaurice GM, Laird NM, Ware JH. Applied Longitudinal Analysis. Hoboken, NJ: John Wiley & Sons, 2004. Fleck T, Benk C, Klemm R, et al. First serial in vivo results of mechanical circulatory support in children with a new diagonal pump. Eur J Cardiothorac Surg 2013;44:828–35. doi: 10.1093/ ejcts/ezt427; [Epub 2013 Aug 26]. Tiedge S, Optenhöfel J. First uses of a new diagonal pump in extracorporeal support systems for children and infants. Kardiotechnik 2011;20:72–6. In German. Gu YJ, van Oeveren W, Mungroop HE, et al. Clinical effectiveness of centrifugal pump to produce pulsatile flow during cardiopulmonary bypass in patients undergoing cardiac surgery. Artif Organs 2011;35:E18–26.
Artif Organs, Vol. 39, No. 1, 2015
Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Evaluation of Conventional Nonpulsatile and Novel Pulsatile Extracorporeal Life Support Systems in a Simulated Pediatric Extracorporeal Life Support Model *Shigang Wang, *Alissa Evenson, *Brian J. Chin, †Allen R. Kunselman, and *‡§Akif Ündar *Pediatric Cardiovascular Research Center, Penn State Hershey Children’s Hospital, Penn State Milton S. Hershey Medical Center, Department of Pediatrics, Penn State Hershey College of Medicine; †Department of Public Health Sciences, Penn State Hershey College of Medicine; ‡Department of Surgery, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Hershey, PA; and §Department of Bioengineering, College of Engineering, Pennsylvania State University, University Park, PA, USA
Abstract: The objective of this study is to evaluate two extracorporeal life support (ECLS) circuits and determine the effect of pulsatile flow on pressure drop, flow/pressure waveforms, and hemodynamic energy levels in a pediatric pseudopatient. One ECLS circuit consisted of a Medos Deltastream DP3 diagonal pump and Hilite 2400 LT oxygenator with arterial/venous tubing. The second circuit consisted of a Maquet RotaFlow centrifugal pump and Quadrox-iD Pediatric oxygenator with arterial/venous tubing. A 14Fr Medtronic Bio-Medicus one-piece pediatric arterial cannula was used for both circuits. All trials were conducted at flow rates ranging from 500 to 2800 mL/min using pulsatile or nonpulsatile flow. The post-cannula pressure was maintained at 50 mm Hg. Blood temperature was maintained at 36°C. Real-time pressure and flow data were
recorded using a custom-based data acquisition system. The results showed that the Deltastream DP3 circuit produced surplus hemodynamic energy (SHE) in pulsatile mode at all flow rates, with greater SHE delivery at lower flow rates. Neither circuit produced SHE in nonpulsatile mode. The Deltastream DP3 pump also demonstrated consistently higher total hemodynamic energy at the preoxygenator site in pulsatile mode and a lesser pressure drop across the oxygenator. The Deltastream DP3 pump generated physiological pulsatility without backflow and provided increased hemodynamic energy. This novel ECLS circuit demonstrates suitable in vitro performance and adaptability to a wide range of pediatric patients. Key Words: Extracorporeal life support—Pulsatile flow— Pediatrics—Centrifugal pump—Diagonal pump.
Despite improving extracorporeal life support (ECLS) technology and patient outcomes, the Extracorporeal Life Support Organization’s January 2013 ECLS Registry Report International Summary states that mortality rates are still high (up to 60% in neonatal procedures for cardiac complications), and
there are still significant complications with the use of ECLS, including high rates of mechanical failure, acute renal failure, and hemorrhaging (1). In order to minimize mortality and morbidity, translational research is imperative. New devices should be tested through simulated ECLS to determine their benefits and drawbacks before they are used in clinical practice. The Penn State Hershey Pediatric Cardiovascular Research Center is one of the few centers in the USA to scientifically evaluate new ECLS circuits (2–22). All ECLS circuits currently utilized in the USA for mechanical circulatory support are operated in nonpulsatile mode, including the pediatric ECLS circuit most commonly used at the time of this study, which consists of the Maquet RotaFlow centrifugal pump and Quadrox-iD Pediatric oxygenator
doi:10.1111/aor.12290 Received November 2013; revised December 2013. Address correspondence and reprint requests to Dr. Akif Ündar, Penn State Hershey College of Medicine, Department of Pediatrics—H085, 500 University Drive, P.O. Box 850, Hershey, PA 17033-0850, USA. E-mail: [email protected] Presented in part at the 10th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion in Philadelphia, PA, USA, May 28–31, 2014.
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(Maquet Cardiopulmonary AG, Hirrlingen, Germany). This circuit is currently in use at Penn State Milton S. Hershey Medical Center. However, previous studies have established the benefits of pulsatile flow, including better vital organ microcirculation, decreased need for inotropic support, improved cerebral oxygen saturation, lower gastrointestinal bleeding rates, and shorter hospital stays after acute and chronic mechanical circulatory support (23–27). In addition, pulsatile flow is expected to maintain significantly better perfusion to vital organs during long-term circulatory support (26,28–30). The objective of this study was to determine the differences between these two ECLS circuits and to evaluate pulsatile flow in terms of pressure drops, flow/pressure waveforms, and hemodynamic energy levels in a simulated pediatric ECLS circuit. MATERIALS AND METHODS Experimental setup The experimental Medos ECLS circuit consisted of a Deltastream DP3 diagonal pump (Medos Medizintechnik AG, Stolberg, Germany), a Hilite 2400 LT PMP diffusion membrane oxygenator (Medos), and 100 cm of tubing with a 1/4-in. internal diameter (ID) and a 1/16-in. wall for both arterial and venous lines (Table 1). The experimental Maquet ECLS circuit included a RotaFlow centrifugal pump (Maquet), a Quadrox-iD Pediatric oxygenator, and 100 cm of tubing with a 1/4-in. ID and a 3/32-in. wall for both arterial and venous lines. Both circuits were identical with regard to tubing length between all circuit components. Figure 1 presents the components of the circuit. A 14Fr Medtronic Bio-Medicus one-piece pediatric arterial cannula (Medtronic, Inc., Minneapolis, MN, USA) and an ECMO-TEMP SMS-3000 heater–cooler unit (Seabrook, Inc., Cincinnati, OH, USA) were used for both ECLS circuits.
A 300-mL-capacity soft bag served as a pseudopatient. A Hoffman clamp was placed downstream of the arterial cannula to ensure a constant arterial pressure would be delivered to the pseudopatient during all trials. The circuit was first primed with lactated Ringer’s solution for de-airing, and then packed human red blood cells were added. The hematocrit of the priming solution was 35%. The total priming volume of the circuit was approximately 700 mL. Pulsatile mode setting The Deltastream DP3 pump was evaluated in pulsatile mode at a rotational differential of 1500 revolutions per minute (rpm), a frequency of 90 bpm, and a systolic/diastolic ratio of 50%. Based on our earlier experiments, we selected these settings to provide adequate quality of pulsatility (21,22). With the help of the Maquet HL-20 heart–lung machine console base, the RotaFlow pump could produce pulsatile flow at pulsatile settings of 10% base flow, 90 bpm (pump rate), 20% of the pump head start point, and 80% of the pump head stop point. Experimental design Before the test was conducted, the priming solution was adequately mixed in the circuit. The trials were conducted at flow rates of 500 mL/min, 1000 mL/min, 1500 mL/min, 2000 mL/min, 2400 mL/ min, and 2800 mL/min (this flow rate was only used in the RotaFlow circuit) in pulsatile and nonpulsatile modes at a blood temperature of 36°C. The postcannula pressure was maintained at 50 mm Hg; the venous pressure was kept at 5 mm Hg during all trials. Two Transonic ultrasound flow probes (Transonic Systems, Inc., Ithaca, NY, USA) were placed at a pre-oxygenator site and a pre-cannula site. Five Maxxim disposable pressure transducers (Maxxim Medical, Inc., Ithaca, NY, USA) were placed at
TABLE 1. The components of the experimental circuit
Blood pump Priming volume Revolution speed Maximal flow rate Oxygenator Priming volume Gas exchange surface area Maximal flow rate Hollow fiber material Arterial line tubing Venous line tubing Coating material
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Medos ECLS circuit
Maquet ECLS circuit
Deltastream DP3 diagonal pump 16 mL 0–10 000 rpm 8 L/min Hilite 2400 LT 95 mL 0.65 m2 2400 mL/min Polymethylpentene 1/4″ ID × 1/16″ wall × 100 cm 1/4″ ID × 1/16″ wall × 100 cm Rheoparin
RotaFlow centrifugal pump 32 mL 0–5000 rpm 9.9 L/min Quadrox-iD Pediatric 81 mL 0.8 m2 2800 mL/min Polymethylpentene 1/4″ ID × 3/32″ wall × 100 cm 1/4″ ID × 3/32″ wall × 100 cm Bioline
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FIG. 1. The experimental ECLS circuit.
pre-oxygenator, post-oxygenator, pre-cannula, postcannula, and venous line sites. All flow and pressure sensors were located at identical distances from the respective circuit components in order to provide consistency of data measurements.
second. A 20-s segment of pressure and flow data was recorded at all sites and converted into hemodynamic energy using the equations below. The entire process was repeated six times for each unique combination, yielding a total of 96 trials.
Data acquisition Five pressure transducers and two flowmeter outputs were connected to a signal-conditioning unit (SC-2345, National Instruments, Austin, TX, USA) and a data acquisition device (NI USB-6521, National Instruments). The digital signals were transferred from the data acquisition device to a computer via a USB port. A customized user interface based on Labview 7.1 software for Windows (National Instruments) recorded real-time data at 1000 samples per
Calculating hemodynamic energy The hemodynamic energy created by different modes was quantified by related mathematical formulas. With the help of Shepard’s formula for energy-equivalent pressure (EEP) (31) and the data for simultaneous blood flow (f) and pressure (p) recorded by the Labview 7.1 software, EEP, surplus hemodynamic energy (SHE), and total hemodynamic energy (THE) were calculated for a time interval (t1 to t2) as follows: Artif Organs, Vol. 39, No. 1, 2015
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EEP ( mm Hg ) = ∫ fpdt t1
SHE ( ergs cm 3 ) = 1332
∫
t2
t1
fdt
× ( EEP − mean arterial pressure) THE ( ergs cm 3 ) = 1332 × EEP The constant 1332 converts pressure from units of mm Hg to dynes per cm2 (1 mm Hg = 1332 dyn/cm2).
TABLE 2. Flow rates and rotational speeds Rotational speed (rpm) Flow rate
Circuit
Nonpulsatile
Pulsatile
500 mL/min
Medos Maquet Medos Maquet Medos Maquet Medos Maquet Medos Maquet Maquet
3500 1656 4500 2085 5350 2505 6350 2945 7150 3260 3630
3450 — 4400 — 5300 — 6300 — 7100 — —
1000 mL/min 1500 mL/min 2000 mL/min
Calculating pressure drops Oxygenator pressure drop (mm Hg) was calculated as pre-oxygenator pressure minus postoxygenator pressure. Arterial cannula pressure drop (mm Hg) was calculated as pre-cannula pressure minus post-cannula pressure. Circuit pressure drop (mm Hg) was calculated as pre-oxygenator pressure minus post-cannula pressure. Statistical analysis ANOVA models were fit to continuous outcomes (e.g., pressure drop) to compare flow rate (500, 1000, 1500, 2000, 2400, or 2800 mL/min), pump (Deltastream DP3 or RotaFlow), and pulsatility mode (nonpulsatile or pulsatile). A linear mixedeffects model was fit to continuous outcomes (mean arterial pressure [MAP], EEP, SHE, and THE) to compare the flow rate, pump, mode, and location (e.g., pre-oxygenator, post-cannula) (32). The linear mixed-effects model is an extension of linear regression that accounts for the within-subject variability inherent in repeated-measures designs. In this study, the repeated factor is the location. For each outcome, P values were adjusted for multiple-comparisons testing using the Tukey–Kramer procedure. All hypothesis tests were two-sided, and all analyses were performed using SAS software, version 9.3 (SAS Institute, Inc., Cary, NC, USA). RESULTS Rotational speed The Deltastream DP3 pump generated consistently higher rotational speed than the RotaFlow pump at identical flow rates in nonpulsatile mode, with the Deltastream DP3 pump rotating an average of 2.15 times faster than the RotaFlow pump (Table 2). Additionally, there was a consistent 50rpm decrease in rotational speed in the Deltastream DP3 pump when it was used in pulsatile mode versus nonpulsatile mode (Table 2). Artif Organs, Vol. 39, No. 1, 2015
2400 mL/min 2800 mL/min*
* The maximal flow rate for the Medos Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate.
Pulsatile flow When we attempted to use the RotaFlow centrifugal pump in pulsatile mode, we noted excessive heat generation at the pump driver and were unable to produce adequate pulsatile flow in excess of 1700 mL/min. The Deltastream DP3 diagonal pump generated adequate pulsatile flow without any excessive heat generation, in addition to adequate nonpulsatile flow, at all flow rates evaluated. Figure 2 shows flow and pressure waveforms at 1500 mL/min for both circuits and both pulsatility modes in the Deltastream DP3 circuit. Hemodynamic energy The Deltastream DP3 circuit in pulsatile mode was capable of producing EEP in excess of MAP at all flow rates and at both the pre-oxygenator and postcannula sites, whereas neither the Deltastream DP3 nor the RotaFlow circuit was able to produce EEP in nonpulsatile mode (Table 3). A decrease in the percentage of EEP generated was seen at both the preoxygenator and post-cannula sites as flow rate increased. The excess EEP produced in pulsatile mode was transferred to the patient as SHE. Lower flow rates produced less SHE at the pre-oxygenator sites but increased SHE at the post-cannula site, demonstrating greater SHE delivery to the pseudopatient at lower flow rates (Fig. 3). The post-cannula SHE decreased with higher flow rates because, for both the oxygenator and cannula, higher flow rates were associated with higher pressure drops (Table 4). THE at the pre-oxygenator site was consistently higher in the Deltastream DP3 circuit in pulsatile mode than in either circuit in nonpulsatile mode. THE delivery to the pseudopatient from the postcannula site remained consistent (Fig. 4).
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FIG. 2. Flow and pressure waveforms at 1500 mL/min in pulsatile (P) and nonpulsatile (NP) mode.
Pressures MAP at the pre-oxygenator site increased as flow rate increased in both circuits and in both pulsatility modes in the Deltastream DP3 circuit. Pulsatile mode produced greater MAP at the pre-oxygenator
site (1 mm Hg at 500 mL/min flow rate to 14.3 mm Hg at 2400 mL/min flow rate) at all flow rates in the Deltastream DP3 circuit when compared with either circuit in nonpulsatile mode (Table 3).
TABLE 3. MAP and EEP at pre-oxygenator and post-cannula sites under pulsatile (P) and nonpulsatile (NP) modes Pre-oxygenator site
Post-cannula site
Flow rate
Circuit
Mode
MAP (mm Hg)
EEP (mm Hg)
MAP (mm Hg)†
EEP (mm Hg)
500 mL/min
Medos
1000 mL/min
Maquet Medos
1500 mL/min
Maquet Medos
2000 mL/min
Maquet Medos
2400 mL/min
Maquet Medos
2800 mL/min‡
Maquet Maquet
NP P NP NP P NP NP P NP NP P NP NP P NP NP
81.1 ± 0.0 82.8 ± 0.2* 81.8 ± 0.0 118.4 ± 0.0 119.0 ± 0.5 113.8 ± 0.0* 155.8 ± 0.0 160.1 ± 0.6* 152.9 ± 0.0 207.4 ± 0.0 211.8 ± 0.5* 202.8 ± 0.0 254.1 ± 0.1 257.0 ± 0.8* 242.7 ± 0.0 294.8 ± 0.1
81.1 ± 0.0 93.8 ± 0.2 (13.3%)* 81.8 ± 0.0 118.4 ± 0.0 130.5 ± 0.5 (9.6%)* 113.8 ± 0.0 155.8 ± 0.0 173.5 ± 0.5 (8.3%)* 152.9 ± 0.0 207.4 ± 0.0 225.7 ± 0.5 (6.6%)* 202.8 ± 0.0 254.1 ± 0.1 270.8 ± 0.8 (5.4%)* 242.7 ± 0.0 294.8 ± 0.1
50.0 ± 0.0 50.6 ± 0.2 50.3 ± 0.0 50.8 ± 0.0 50.3 ± 0.2 50.4 ± 0.0 50.5 ± 0.0 50.7 ± 0.1 50.2 ± 0.0 50.3 ± 0.0 50.4 ± 0.1 50.5 ± 0.0 50.3 ± 0.0 50.4 ± 0.1 50.6 ± 0.0 50.6 ± 0.1
50.0 ± 0.0 57.8 ± 0.2 (14.1%)* 50.3 ± 0.0 50.8 ± 0.0 55.5 ± 0.2 (10.4%)* 50.4 ± 0.0 50.5 ± 0.0 54.8 ± 0.1 (8.1%)* 50.2 ± 0.0 50.3 ± 0.0 53.1 ± 0.1 (5.2%)* 50.5 ± 0.0 50.3 ± 0.0 52.1 ± 0.1 (3.4%)* 50.6 ± 0.0 50.6 ± 0.1
Values in parentheses are EEP percentage increase compared to MAP [((EEP − MAP)/MAP) × 100]. * P < 0.01 versus nonpulsatile mode. † The pseudopatient’s MAP was maintained at 50 mm Hg at the post-cannula site by a Hoffman clamp. ‡ The maximal flow rate for the Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate. Artif Organs, Vol. 39, No. 1, 2015
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FIG. 3. Surplus hemodynamic energy (SHE) at different flow rates and sites in pulsatile (P) and nonpulsatile (NP) mode. *P < 0.001 versus nonpulsatile mode.
In both pulsatility modes in the Deltastream DP3 circuit, the pressure drop was higher across the oxygenator at 500 mL/min; however, at higher flow rates the pressure drop across the cannula was higher (Table 4). The pressure drop across the oxygenator was consistently lower in the Deltastream DP3 circuit at all flow rates in both pulsatile and nonpulsatile mode, ranging from 1.7 mm Hg to 13.2 mm Hg lower in nonpulsatile modes and 1.5 mm Hg to 12.7 mm Hg lower in pulsatile mode (Table 4). However, the pressure drop in the overall circuit was slightly higher in the Deltastream DP3 circuit at all flow rates except for 500 mL/min in nonpulsatile mode. This is accounted for by the fact that the Deltastream DP3 circuit produced higher pressures overall at those same flow rates and pulsatility modes (Table 3).
DISCUSSION We tried to generate pulsatility from a RotaFlow pump on the console base of a Maquet HL-20 heart-lung machine to provide a direct comparison between pulsatile and nonpulsatile modes. Unfortunately, our research found that the RotaFlow circuit produced an error message at 500 mL/min flow rate and could not produce adequate flow rates in excess of 1700 mL/min in pulsatile mode. We also noted excessive heat generation at the pump driver when the RotaFlow pump was used in pulsatile mode. The next-generation Medos ECLS circuit consists of a Deltastream DP3 diagonal pump and a polymethylpentene (PMP) diffusion membrane oxygenator. This novel diagonal pump can sufficiently
TABLE 4. The pressure drops of oxygenators, cannula, and circuit under pulsatile (P) and nonpulsatile (NP) mode Pressure drop (mm Hg) Flow rate
Circuit
Mode
Oxygenator
Cannula
Circuit
500 mL/min
Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Medos Medos Maquet Maquet
NP P NP NP P NP NP P NP NP P NP NP P NP NP
7.9 ± 0.0 8.1 ± 0.0 9.6 ± 0.0* 15.9 ± 0.0 15.9 ± 0.0 18.9 ± 0.0* 22.1 ± 0.0 22.5 ± 0.1 28.4 ± 0.0* 29.6 ± 0.0 29.4 ± 0.1 39.4 ± 0.0* 34.7 ± 0.0 34.5 ± 0.1 47.8 ± 0.0* 58.2 ± 0.0
6.2 ± 0.0 (19.9%) 6.7 ± 0.0 (20.8%) 6.5 ± 0.0 (20.6%) 19.8 ± 0.0 (29.3%) 20.5 ± 0.1 (29.8%)# 18.5 ± 0.0 (29.2%) 35.5 ± 0.0 (33.7%) 37.8 ± 0.1 (34.6%)# 35.7 ± 0.0 (34.8%) 58.8 ± 0.0 (37.4%) 61.3 ± 0.2 (38.0%)# 58.7 ± 0.0 (38.6%) 80.0 ± 0.0 (39.3%) 81.7 ± 0.3 (39.5%)# 78.2 ± 0.0 (40.7%) 103.8 ± 0.1 (42.5%)
31.1 ± 0.0 32.2 ± 0.1 31.5 ± 0.0* 67.6 ± 0.0 68.8 ± 0.3 63.4 ± 0.0* 105.3 ± 0.0 109.4 ± 0.4 102.7 ± 0.0* 157.1 ± 0.1 161.3 ± 0.5 152.2 ± 0.0* 203.8 ± 0.1 206.6 ± 0.7 192.1 ± 0.0* 244.2 ± 0.1
1000 mL/min 1500 mL/min 2000 mL/min 2400 mL/min 2800 mL/min†
Values in parentheses = (cannula pressure/circuit pressure drop) × 100. * P < 0.01 versus Medos; # P < 0.01 versus nonpulsatile mode. † The maximal flow rate for the Hilite 2400 LT oxygenator is 2400 mL/min; we did not exceed the recommended flow rate. Artif Organs, Vol. 39, No. 1, 2015
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FIG. 4. Total hemodynamic energy (THE) at different flow rates and sites in pulsatile (P) and nonpulsatile (NP) mode. *P < 0.001 versus nonpulsatile mode.
provide both pulsatile and nonpulsatile flow that can accommodate either pediatric or adult patients. The pumps currently used in the USA are either occlusive roller pumps or nonocclusive centrifugal pumps that may generate backflow. The Deltastream DP3 diagonal pump is unique in its ability to provide nonocclusive, pulsatile flow without backflow. This new ECLS system has already been successfully used in European clinics (33,34) but is not yet approved by the Food and Drug Administration (FDA) in the USA. We were interested in determining any potential benefits or drawbacks that the Deltastream DP3 ECLS circuit might offer in either pulsatile or nonpulsatile mode. Mounting evidence has demonstrated the superiority of pulsatile flow over continuous flow during acute and chronic mechanical support (23–27). However, all ECLS circuits currently used in the USA, including the RotaFlow ECLS circuit used at Penn State Milton S. Hershey Medical Center at the time of the study, can provide only adequate nonpulsatile flow. We conducted this study to compare and contrast the RotaFlow and Deltastream DP3 ECLS systems in pulsatile and nonpulsatile flow to determine if one had significant benefits over the other. The RotaFlow ECLS circuit uses a centrifugal pump and a Quadrox-iD Pediatric oxygenator, the first oxygenator approved by the FDA for long-term mechanical circulatory support use in the USA. The next-generation Deltastream DP3 ECLS circuit contains a diagonal pump and a Hilite 2400 LT PMP diffusion membrane oxygenator. The Deltastream DP3 diagonal pump has numerous improvements, including a low priming volume (16 mL), a wide range of flow rates (0–8 L/min) that can accommodate both adult and pediatric patients, and the option
to provide pulsatile flow. Moreover, the Deltastream MDC console has valuable safety features, including a flow sensor with an integrated bubble detector, backflow detection, zero-flow mode, four pressure sensors, and two temperature sensors. Data collected from comparing these two ECLS systems will enable us to decide which system and which mode of flow will optimize patient outcomes in the future. Our results show that the RotaFlow circuit had a much lower rate of revolution than any setting in the Deltastream DP3 circuit, as the RotaFlow pump has a larger impeller. The pulsatile flow settings selected for the Deltastream DP3 circuit in this current study were based on our previous studies demonstrating that these settings can provide adequate SHE under pulsatile mode (20–22). With our selected pulsatile settings, the Deltastream DP3 circuit generated slightly higher flow rates when switching from nonpulsatile mode to pulsatile mode. To maintain identical flow rates for both modes, rotational speed was adjusted after each trial. The pressure and flow waveforms show that the Deltastream DP3 circuit is capable of producing excellent-quality pulsatility without backflow. Moreover, in pulsatile mode, EEP was consistently higher than MAP in the Deltastream DP3 circuit. Therefore, pulsatile flow was always able to provide SHE to the pseudopatient, even at low flow rates, while generating more THE compared with nonpulsatile mode from both ECLS circuits. The post-cannula SHE decreased with higher flow rates because higher flow rates were associated with higher pressure drops for both the oxygenator and the cannula. The post-cannula THE was roughly the same for all circuits at all flow rates because a uniform post-cannula pressure of 50 mm Hg was maintained by a Hoffman clamp. Artif Organs, Vol. 39, No. 1, 2015
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The results of the present study demonstrate a consistently lower pressure drop across the Hilite 2400 LT PMP diffusion membrane oxygenator than across the Quadrox-iD Pediatric oxygenator at identical flow rates, while the pre-oxygenator MAP and the overall circuit pressure drops were slightly higher in the Deltastream DP3 circuit than in the RotaFlow circuit. Similar findings were reported in our previous study (17). At low flow rates, the oxygenator caused the largest pressure drops; however, at high flow rates, the arterial cannula caused the largest pressure drops. Therefore, in order to select the best ECLS circuit or mode, the circuit must be evaluated as a whole unit, including pump, oxygenator, and cannula, to ensure the best patient outcomes. LIMITATIONS The limitations of this study include using the same arterial cannula for all flow rates in both ECLS circuits and conducting the experiment in an in vitro setting. This may not accurately represent performance in a clinical setting. Additionally, we were not able to test pulsatile flow in the RotaFlow circuit because the centrifugal pump mounted on the HL-20 heart–lung machine could not generate adequate flow rates in our simulated pediatric ECLS circuit, in addition to generating excessive heat at the pump driver. The RotaFlow pump has previously been evaluated in both pulsatile and nonpulsatile modes in adult CPB patients, with the researchers finding significantly lower flow rates in pulsatile mode from the sensors located at the post-oxygenator location, despite the heart–lung machine indicating identical perfusion flow rate in both pulsatile and nonpulsatile modes (35). Further experiments should be conducted to clarify these findings, especially in pediatric patients. CONCLUSIONS The Deltastream DP3 diagonal pump displayed excellent flow/pressure waveforms, demonstrated adequate pulsatile flow without backflow for pediatric patients, and provided higher levels of hemodynamic energy to the pseudo-patients. The Hilite 2400 LT oxygenator had lower pressure drops than the Quadrox-iD Pediatric oxygenator and retained greater hemodynamic energy across the oxygenator. The Deltastream DP3 pediatric extracorporeal life support circuit has demonstrated suitable in vitro performance and adaptability to a wide range of pediatric patients, in addition to its critical ability to generate more physiological pulsatile flow. Artif Organs, Vol. 39, No. 1, 2015
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