New Technology
Impact of Pulsatile Flow Settings on Hemodynamic Energy Levels Using the Novel Diagonal Medos DP3 Pump in a Simulated Pediatric Extracorporeal Life Support System
World Journal for Pediatric and Congenital Heart Surgery 2014, Vol. 5(3) 440-448 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135114526760 pch.sagepub.com
Pelumi Adedayo, MS1, Shigang Wang, MD1, ¨ ndar, PhD1,3 Allen R. Kunselman, MD2, and Akif U
Abstract Background: The objective of this study was to evaluate the pump performance of the novel diagonal Medos Deltastream DP3 diagonal pump (MEDOS Medizintechnik AG, , Stolberg, Germany) under nonpulsatile to pulsatile mode with varying differential speed values in a simulated pediatric extracorporeal life support system. Methods: The experimental circuit consisted of a Medos Deltastream DP3 pump head and console, a Medos Hilite 2400 LT hollow fiber membrane oxygenator (MEDOS Medizintechnik AG), a 14F Medtronic DLP arterial cannula (Medtronic Inc, Minnesota), and a 20F Terumo TenderFlow Pediatric venous return cannula (Terumo Corporation, Michigan). Trials were conducted at flow rates ranging from 500 mL/min to 2,000 mL/min (500 mL/min increments) and pulsatile differential speed values ranging from 500 rpm to 2,500 rpm (500 rpm increments) using human blood (hematocrit 35%). The postcannula pressure was maintained constantly at 60 mm Hg. Real-time pressure and flow data were recorded using a custom-made data acquisition system and Labview software. Results: Under all experimental conditions, pulsatile flow (P) generated significantly greater energy equivalent pressure (EEP), surplus hemodynamic energy (SHE), and total hemodynamic energy (THE) than those of nonpulsatile flow (NP). Under NP, SHE was zero. Higher differential speed values generated greater EEP, SHE, and THE values. There was little variation in the oxygenator pressure drop and the cannula pressure drop in P, compared to NP. Conclusions: The novel Medos Deltastream DP3 diagonal pump is able to generate physiological quality of P, without backflow. With increased differential rpm, the pump generated greater EEP, SHE, and THE. Physiological quality of pulsatility may be associated with better microcirculation because of greater EEP, SHE, and THE. Keywords ECMO, infant, pediatrics, perfusion, diagonal pump, pulsatile flow, extracorporeal life support, hemodynamic energy, surplus hemodynamic energy Submitted October 02, 2013; Accepted February 10, 2014.
Introduction Extracorporeal life support (ECLS) can be life saving for pediatric patients with end-stage congenital heart disease, cardiomyopathies, and fulminant myocarditis who have heart failure. It is also applicable to patients awaiting recovery, those with difficulty weaning off from cardiopulmonary bypass (CPB), or those still awaiting transplant.1–4 Applicable pumps include the roller pumps and rotary pumps. Rotary pumps include the axial, diagonal, and centrifugal pumps. A 2010 survey showed that globally, more than 70% of ECLS centers use the newer centrifugal pumps for their pediatric patients.5 The United States lagged behind with only 29% of centers used centrifugal pumps and over 70% still used the older roller pumps.
1 Department of Pediatrics, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA 2 Department of Public Health and Sciences, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA 3 Department of Surgery and Bioengineering, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA
Corresponding Author: ¨ ndar, Department of Pediatrics, Penn State Hershey College of Medicine, Akif U H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850, USA. Email: [email protected]
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Abbreviations and Acronyms CPB ECLS EEP MAP MCS MP NP P SHE THE
cardiopulmonary bypass extracorporeal life support energy equivalent pressure mean arterial pressure mechanical circulatory support mean pressure nonpulsatile flow pulsatile flow surplus hemodynamic energy total hemodynamic energy
Nevertheless, 30% of US centers have changed their pump to newer models in the last 3 years.6 Diagonal pumps are new generation pump, which has the capacity to delivery both pulsatile (P) and nonpulsatile flow (NP) with very small priming volume, which may facilitate its usage for neonates, infants, and adult patients with ECLS.7–9 The authors have already documented that one of the major limitations of P is a lack of precise quantification and definition of pulsatility.10 Pulsatility depends on energy gradient generated by pump rather than pressure or flow waveforms alone. Hence, pulsatile pressure-flow waveforms are quantified in terms of hemodynamic energy levels. Energy equivalent pressure (EEP) is derived from Shepard’s formula using both pressure and flow.11 Energy equivalent pressure can be measured in millimeter of mercury (mm Hg) which allows direct comparison with mean arterial pressure (MAP). Pulsatile flow always yields higher EEP than MAP, and the difference between EEP and MAP is called surplus hemodynamic energy (SHE) or extraenergy generated secondary to pulsatility compared to NP. Regardless of type of ECLS pump (axial, centrifugal, or diagonal), the EEP and MAP values are identical for NP and therefore, SHE or extrahemodynamic energy is ‘‘zero.’’ Research studies have shown more EEP, SHE, and total hemodynamic energy (THE) with P than with NP. Propulsatile flow investigators believe that because of these extra energies, P may maintain better microcirculation and vital organ recovery.12–21 Quantification of pressure-flow waveforms in terms of EEP, SHE, and THE is extremely important to make direct and meaningful comparisons of different perfusion modalities or different forms of pulsatility in patients. Depending on the P settings, new generation diagonal pump produces significantly different hemodynamic energy levels from diminished pulsatility to the physiological quality of pulsatility.7–9 Therefore, translational research in terms of P settings will help clinicians to determine the best possible pressure-flow waveform with the most physiological hemodynamic energy delivery for their patients. Prior to clinical use of any new components of the ECLS circuitry (all might have already approved by the government agencies for clinical use), translational research is a must to determine not only the advantages (if any) of the new components but also to warn the investigators about limitations of the new devices.7–9,22 For instance, all manufacturers for arterial and venous cannulae supply pressure-flow waveforms of any size for
users. All of these waveforms are not applicable to pediatric and adult patients because manufacturers use ‘‘water’’ as a priming solution for cannulae evaluation. Thus, it is necessity to reevaluate all cannulae with different sizes using ‘‘human blood’’ as a priming solution.23,24 We have also documented that simple hemodynamic evaluations of centrifugal blood pumps not only allowed us to select better products but also save significant amount of funds for our institution. We proved that 1 centrifugal pump with 30 times lesser cost had better hemodynamic performance in addition to similar clinical outcomes.25,26 Therefore, translational research is vital not only to find better products but also to minimize the waste of funds. Independent scientific evaluation of any new product using identical clinical setup in a laboratory is a must, not an option. In the United States, the most common myth about pediatric mechanical circulatory support (MCS) systems is that most of the centers (if not all) use only NP for chronic support. It is true that new generation nonpulsatile centrifugal pumps (Rotaflow and CentriMag) are used as a temporary Ventricular Assist Device up to a month, but Berlin Excor is the only device clinically used for pediatric patients for chronic support (up to several months) and this is a ‘‘pulsatile’’ device.27,28 The unique diagonal pump system described in this article is the only available system that can produce both P and NP. Pilot clinical trials have already been conducted with nonpulsatile and pulsatile modes in the Europe.29–31 However, our research group is the only one performing ‘‘scientifically independent’’ studies to evaluate the advantages of the system along with limitations in a laboratory setting.7–9 The objective of this study was to evaluate the pump performance of the Medos Deltastream DP3 pump (MEDOS Medizintechnik AG, Stolberg, Germany) under nonpulsatile to pulsatile mode with varying differential speed values in a simulated pediatric ECLS system.
Materials and Methods Experimental Circuit The experimental circuit (Figure 1) consisted of a Medos Deltastream DP3 pump head and console (MEDOS Medizintechnik AG), a Medos Hilite 2400 LT hollow fiber membrane oxygenator (MEDOS Medizintechnik AG), a 14F Medtronic DLP arterial cannula (Medtronic Inc, Minnesota), a 20F Terumo TenderFlow pediatric venous return cannula (Terumo Corporation, Michigan), and 1/4-in inner diameter 3 feet tubing for both arterial and venous lines. An open soft bag containing 200 mL of blood was used as venous reservoir. A 300 mL capacity soft bag served as a pseudo-patient. A Hoffman clamp was placed downstream of the arterial cannula to keep a given arterial pressure during all trials.
Diagonal Pump The ‘‘angle of blood path’’ of the inlet and the outlet for a diagonal pump is between 90 and 180 , while the angle of blood path of axial pump is 180 and radial pump (centrifugal) is only 90 . A novel diagonal pump—Medos Deltastream DP3 from
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Figure 1. Experimental circuit setup.
the Medos (Medos Medizintechnik AG) can provide an optional P mode to mimic physiological blood flow for CPB, ECLS, and MCS. Its pump head features a high-tech ceramic bearing and magnetic coupling of forces between the impeller and the driver for longer run times, low-priming volume (16 mL) to minimize hemodilution, and a wide range of flow rates (0-8 L/min) allowing applicability to neonates and adults (Figure 2). Thus far, in Europe, it has been used in clinical venovenous ECLS (up to 109 days) and for MCS (up to 58 days).29–31
Experimental Design The circuit was initially primed with lactated ringer’s solution for de-airing the circuit and then added packed human red blood cells. The hematocrit of the priming solution was 35%. The total priming volume of the circuit was 700 mL. Two transonic
ultrasound flow probes (Transonic Systems, Inc, Ithaca, New York) were placed at the preoxygenator site and precannula site. Five Maxxim disposable pressure transducers (Maxxim Medical, Inc, Ithaca, New York) were placed at preoxygenator, postoxygenator, precannula, postcannula, and venous line sites. Trials were conducted at flow rates ranging from 500 to 2,000 mL/min (500 mL/min increments), with pulsatile and nonpulsatile mode at 36 C. Differential speed values of pulsatile setting ranged from 500 rpm (P500) to 2,500 rpm (P2500; 500 rpm increments). The postcannula pressure was maintained at 60 mm Hg, and the venous line pressure was kept at 10 mm Hg during all trials.
Pulsatile Settings The Medos Deltastream DP3 pump setting for P was at a frequency of 90 beats per minute (bpm), 50% of systole–diastole
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Results Hemodynamic Energy Figure 2. The Medos Deltastream diagonal pump.
ratio, and varying speed differential values at all experimental evaluations.
Data Acquisition All pressure transducers and flowmeter outputs were connected to a signal conditioning unit (SC-2345, National Instruments, Austin, Texas), linked with data acquisition device (National Instruments universal serial bus [USB]-6251, National Instruments), and finally connected to a computer via USB port. A customized user interface based on Labview 7.1 software for Windows (National Instruments) was designed to record realtime data at 1,000 sample per second. A 20-second segment of pressure and flow waveforms was recorded at all sites. The pump test was repeated eight times for each unique combination, yielding a total of 640 trials.
Hemodynamic Energy Calculation With the help of the Shepard’s EEP formula12 and simultaneous blood flow (f) and pressure (p) recorded by Labview software, EEP, SHE, and THE were calculated in an time interval (t1 and t2) as follows. The constant 1,332 converts pressure from units of mm Hg to dynes per cm2 (1 mm Hg ¼ 1,332 dyn/cm2). R t2 R EEP ðmmHgÞ ¼ t1 fpdt t2 fdt t1
SHE (ergs/cm3) ¼ 1,332 (EEP Mean Arterial Pressure) THE (ergs/cm3) ¼ 1,332 EEP
Statistical Analysis Analysis of variance models were fit to the continuous outcomes (eg, %THE, pressure drop) to compare the flow rate
Under NP, SHE is almost zero. In P, SHE appeared and increased with increasing speed differential values. However, SHE decreased with increasing flow rates (Figure 3). At any flow rate, the SHE values were highest at the pre-oxygenator site and lowest at the postcannula site. The THE generated was greater in P compared to NP and increased with greater speed differentials. THE also increased with higher flow rates. At any flow rate, THE values were highest at the preoxygenator site and lowest at the postcannula site (Figure 4). The percentages of THE increase in pulsatile compared to nonpulsatile mode increased with greater differential speed values. However, within any speed differential value, it decreased with higher flow rates (Table 1).
Mean Pressure Versus EEP Pressure waveform at different flow rates were compared in pulsatile and nonpulsatile mode (Figure 5). During NP, the EEP remained the same as the mean pressure (MP). However, in the face of P, the EEP increased up to 21.7% from the MP at the preoxygenator site (Table 2). The EEP also increased with increasing differential speed values. A similar trend is observed at the precannula site.
Oxygenator and Arterial Cannula Pressure Drops Within each flow rate, the oxygenator pressure drop remained relatively constant, even when comparing nonpulsatile to pulsatile values or when comparing increasing speed differential values (Table 3). However, the absolute value of the oxygenator pressure drop increased with higher flow rates, with the highest pressure drop (NP 45.1 + 5.8 mm Hg, P 51.6 + 1.6 mmHg) recorded at a flow rate of 2,000 mL/min. A similar trend is seen with the arterial cannula. The highest pressure drop was recorded at a flow rate of 2,000 mL/mL (NP 56.1 + 0.3, P 62.4.6 + 0.5 mm Hg).
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Figure 3. Surplus hemodynamic energy (SHE) at various flows. *P < .01, nonpulsatile versus pulsatile (P500, P1000, P1500, P2000, and P2500) mode. NP indicates nonpulsatile flow; P, pulsatile flow.
Figure 4. Total hemodynamic energy (THE) at various flow rates. *P < .01, nonpulsatile versus pulsatile (P500, P1000, P1500, P2000, and P2500) mode. NP indicates nonpulsatile flow; P, pulsatile flow. Downloaded from pch.sagepub.com at UNIV OF WESTERN ONTARIO on June 11, 2015
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Table 1. Percentage of Pulsatile THE Increase Compared to Nonpulsatile Flow at Preoxygenator Site Under Various Differential rpms. Percentage of THE Increasea Mode
500 mL/min
NP P500 P1000 P1500 P2000 P2500
– 12.4 + 0.4 25.6 + 1.8b 30.3 + 2.6b 31.8 + 2.5b 29.7 + 2.2b
1,000 mL/min 1,500 mL/min 2,000 mL/min 5.3 19.2 24.0 26.4 26.9
– + 0.3 + 0.4b + 1.4b + 1.3b + 2.0b
2.6 9.7 20.3 23.7 25.7
– + 0.2 + 0.3b + 0.4b + 1.0b + 0.7b
1.2 5.5 11.1 17.9 20.0
– + 0.5 + 0.2b + 0.3b + 0.3b + 0.7b
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; THE, total hemodynamic energy. a Percentage of THE Increase ¼ ([Pulsatile THE Nonpulsatile THE]/ Nonpulsatile THE) 100. b P < .01, pulsatile flow with 500 rpm of differential speed versus pulsatile flow with other differential speeds.
Flow Rates and Revolution Speeds From nonpulsatile to pulsatile mode, the revolutions per minute (rpm) remained the same at lower differential speed values and higher flow rates but increased at higher differential speed values and lower flow rates (Table 4). Under pulsatile mode, at differential speed value of 500 rpm, there was no difference observed in pump flow rate. However, at speed difference values above 500 rpm, pump flow rate increased under pulsatile compared to nonpulsatile mode. The revolution speeds needed to be adjusted to the same as the nonpulsatile rpm in order to keep identical flow rates. When pump was returned to nonpulsatile from pulsatile mode, lower rpms and flow rates are recorded. Figure 5 represents flow waveforms at 1,000 mL/min and 2,000 mL/min of flow rates in pulsatile and nonpulsatile mode. No backflow was observed during all trials of pulsatile mode. All pulsatile data we used were data after revolution speeds of P were adjusted to the same as NP.
Comment Our results showed that the hemodynamic profile of pulsatile mode is significantly greater than in nonpulsatile mode. The THE increased with higher speed differentials, at any flow rate. Although THE increased with higher flow rates, the proportion reaching the postcannula site was significantly less compared to the preoxygenator site at higher flow rates. This suggests that maximal benefits of pulsatile mode to the patient will be seen at lower flow rates and lower circuit resistance. The SHE, which is the difference between the mean pressure and EEP, is also higher in pulsatile mode compared to non-pulsatile mode. At any flow rate, SHE values increased with higher differential speed values, suggesting that higher P increased the hemodynamic energy reaching the patient. The percentage of THE increase, as expected, was higher in pulsatile compared to nonpulsatile mode. The value also increased with higher differential speeds but reduced with increasing flow rates. This
implied that P at lower flow rates and higher differential speeds could generate more hemodynamic energy than NP. Energy equivalent pressure was the same as mean pressure under nonpulsatile mode and higher than mean pressure under pulsatile mode. The EEP was also higher at any flow rate and speed differential value combination in pulsatile compared to nonpulsatile mode. This is expected and has been recorded in previous studies.14 However, per the aim of this study, it is interesting to see that EEP increased with increasing speed differential values at all flow rates tested. But the percentages of EEP increase decreased gradually with increased flow rates. The EEP slightly decreased at differential speeds > 1,500 rpm. This suggests, again, that higher differential speed values confer no advantage in pulsatile mode. At any flow rate, the oxygen pressure drop remains constant with increasing speed differential values, whether in pulsatile or nonpulsatile mode. This attributes to the efficiency of the oxygenator used. In addition, P did not have a great effect on the oxygenator pressure drop. At increasing flow rates, however, there was an increase in the oxygenator pressure drop. The above-mentioned trend was replicated in the cannula pressure drop values. Again, it speaks to quality of the cannula used. The common myth of the P is that it creates significantly higher circuit pressures and pressure drops at the same flow and pressure settings. Our results clearly prove this particular oxygenator worked very well at all different flow rates and perfusion modes, and P did not generate any excessive circuit pressures or pressure drops. Our results also showed that when switching from nonpulsatile to pulsatile mode, the rotational speed increased automatically for speed differentials of 1,000 rpm and flow rates less than 2,000 mL/min while the flow rate increased at speed differential values greater than 500 rpm. It seems that it is not advantageous to use a differential value of below 1,000 rpm when trying to maximize the benefits of P on rotational speed. Similarly, flow rates greater than 1,500 mL/min may not be beneficial for generating higher rotational speeds. At 2,000 mL/min, there were no significant changes in the rotational speed (Table 4).
Limitations The same cannulae (14F for arterial and 20F for venous) were used for all trials. In vivo, it would be too big for ECLS at 500 mL/min and hence not an adequate setup for this flow rate. This experiment was performed under in vitro conditions only, using the same resistance setting for all trials. In vivo conditions will present with different resistance in various patients. In the future, then, it would be imperative to translate the results from this study to animal studies. Also, animal studies may make it more appropriate to measure the degree of hemolysis introduced to the patient with increasing differential speed values.
Conclusions To the best of our knowledge, the unique diagonal pump system described in this article is the only available system that
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Figure 5. Flow and pressure waveforms at preoxygenator site under nonpulsatile and pulsatile mode. NP indicates nonpulsatile flow; P, pulsatile flow. Table 2. Mean Pressure and Energy Equivalent Pressure at Preoxygenator and Precannula Sites Under Pulsatile and Nonpulsatile Mode.a Preoxygenator Pressure, mm Hg Mode NP MP EEP P500 MP EEP P1000 MP EEP P1500 MP EEP P2000 MP EEP P2500 MP EEP
Precannula Pressure, mm Hg
500 mL/min
1,000 mL/min
1,500 mL/min
2,000 mL/min
500 mL/min
1,000 mL/min
1,500 mL/min
2,000 mL/min
88.4 + 0.2 88.4 + 0.2 (0.0%)
121.4 + 0.2 121.4 + 0.2 (0.0%)
169.2 + 0.2 169.2 + 0.2 (0.0%)
220.1 + 1.0 220.1 + 1.0 (0.0%)
67.3 + 0.3 67.3 + 0.3 (0.0%)
78.2 + 0.3 78.2 + 0.3 (0.0%)
96.8 + 0.3 96.8 + 0.3 (0.0%)
116.6 + 0.5 116.6 + 0.5 (0.0%)
90.8 + 0.4b 99.3 + 0.4b (9.3%)
122.9 + 0.4 127.8 + 0.4b (3.9%)
170.2 + 0.3 173.6 + 0.2b (2.0%)
220.5 + 0.3 222.7 + 0.2b (1.0%)
69.6 + 0.4 b 75.7 + 0.4b (8.7%)
79.6 + 0.4 82.8 + 0.4b (4.0%)
97.5 + 0.3 99.5 + 0.4b (2.0%)
116.9 + 0.4 118.2 + 0.4 (1.1%)
93.7 + 0.9b 111.0 + 1.8b (18.5%)
129.6 + 0.6b 144.4 + 0.7b (11.7%)
173.8 + 0.5b 185.7 + 0.4b (6.8%)
224.5 + 0.4b 231.9 + 0.4b (3.3%)
72.3 + 0.9b 84.6 + 1.5b (17.1%)
84.8 + 0.5b 94.6 + 0.6b (11.6%)
100.1 + 0.2b 107.0 + 0.2b (6.8%)
119.4 + 0.4b 124.6 + 0.4b (4.4%)
94.7 + 1.4b 115.2 + 2.4b (21.7%)
130.6 + 1.3b 150.5 + 1.8b (15.2%)
181.0 + 0.4b 203.7 + 0.5b (12.5%)
229.9 + 0.7b 244.0 + 0.6b (6.1%)
73.1 + 1.3b 87.8 + 2.1b (20.0%)
85.7 + 1.0b 98.6 + 1.4b (15.0%)
104.9 + 0.2b 117.9 + 0.3b (12.3%)
122.8 + 0.6b 133.2 + 0.6b (8.5%)
95.9 + 1.5b 116.5 + 2.4b (21.4%)
131.9 + 1.3b 153.4 + 1.5b (16.3%)
182.4 + 1.5b 209.3 + 1.6b (14.7%)
237.6 + 0.8b 259.0 + 0.7b (9.0%)
74.2 + 1.3b 88.8 + 2.0b (19.8%)
86.7 + 0.9b 100.6 + 1.1b (16.0%)
106.0 + 0.9b 121.7 + 1.1b (14.8%)
127.6 + 0.6b 143.9 + 0.7b (12.7%)
94.7 + 1.2b 114.5 + 2b (20.9%)
132.2 + 1.5b 53.9 + 2.5b (16.4%)
184.0 + 1.3b 212.0 + 1.4b (15.5%)
239.5 + 1.8b 263.8 + 1.8b (10.2%)
73.1 + 1.1b 87.3 + 1.7b (19.4%)
86.8 + 1.3b 100.9 + 2.0b (16.2%)
107.1 + 0.8b 124.0 + 0.9b (15.8%)
128.8 + 0.9b 147.7 + 0.9b (14.7%)
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; MP, mean pressure; EEP, energy equivalent pressure. a Percentage in parentheses ¼ ([EEP MP]/MP] 100. b P < .01, nonpulsatile (NP) mode versus pulsatile (P500, P1000, P1500, P2000, P2500) mode. Downloaded from pch.sagepub.com at UNIV OF WESTERN ONTARIO on June 11, 2015
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Table 3. Oxygenator Pressure Drop and Arterial Cannula Pressure Drop Under Nonpulsatile and Pulsatile Mode. Oxygenator Pressure Drop, mm Hg Mode
500 mL/min
NP P500 P1000 P1500 P2000 P2500
14.2 + 14.1 + 14.0 + 14.0 + 14.1 + 14.0 +
0.2 0.2 0.2 0.2 0.2 0.2
1,000 mL/min 23.5 23.5 24.1 24.1 24.1 24.0
+ 0.2 + 0.3 + 0.2 + 0.3 + 0.4 + 0.5
1,500 mL/min 33.7 + 33.1 + 33.1 + 34.0 + 35.6 + 40.0 +
5.1 6.9 7.0 7.0 3.6 2.9
Arterial Cannula Pressure Drop, mm Hg 2,000 mL/min 45.1 + 45.4 + 47.5 + 48.8 + 50.0 + 51.6 +
5.8 3.6 3.5 2.9 3.1 1.6
500 mL/min 7.2 + 0.1 7.4 + 0.1 7.6 + 0.1a 7.7 + 0.1a 7.8 + 0.1a 7.7 + 0.1a
1,000 mL/min 18.4 18.8 20.0 20.1 20.3 20.4
+ 0.1 + 0.1 + 0.1a + 0.2a + 0.2a + 0.2a
1,500 mL/min 36.1 + 36.4 + 37.3 + 39.1 + 39.5 + 39.9 +
0.1 0.1 0.1a 0.1a 0.4a 0.4a
2,000 mL/min 56.1 + 56.2 + 57.5 + 59.2 + 61.7 + 62.4 +
0.3 0.1 0.1a 0.2a 0.3a 0.5a
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow. a P < .05, nonpulsatile flow versus pulsatile flow (P500, P1000, P1500, P2000, and P2500).
Table 4. Revolutions Per Minute and Flow Rates With Nonpulsatile and Pulsatile Mode. Revolutions per minute, rpm Mode NP P500 P500 ! rpm P500 ! NP P1000 P1000 ! rpm P1000 ! NP P1500 P1500 ! rpm P1500 ! NP P2000 P2000 ! rpm P2000 ! NP P2500 P2500 ! rpm P2500 ! NP
Flow rates, mL/min
500 mL/min 1,000 mL/min 1,500 mL/min 2,000 mL/min 500 mL/min 3,650 3,650 3,650 3,650 3,750 3,650 3,550 4,000 3,650 3250 4,450 3,650 2,750 4,750 3,650 2,600
4,550 4,550 4,550 4,550 4,550 4,550 4,550 4,750 4,550 4,350 5,050 4,550 3,900 5,350 4,550 3,500
5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,750 5,550 5,250 6,000 5,550 4,950
6,500‘ 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,700 6,500 6,250
519.1 + 518.1 + 517.9 + 519.4 + 542.4 + 518.3 + 493.0 + 592.5 + 518.3 + 426.9 + 662.9 + 523.8 + 341.8 + 720.6 + 519.7 + 322.9 +
2.1 1.8 1.9 1.9 8.0 4.4 6.6 8.7 4.5 8.1 7.6 5.9 8.9 4.9 3.9 3.8
1,000 mL/min 1,007.2 1,005.9 1,006.3 1,007.2 1,022.8 1,022.4 1,007.3 1,081.3 1,018.6 930.9 1,154.5 1,024.1 819.8 1,247.2 1,024.2 686.0
+ 1.1 + 1.8 + 1.9 + 1.1 + 3.6 + 2.7 + 1.0 + 3.8 + 6.9 + 10.9 + 5.1 + 8.0 + 10.4 + 3.8 + 7.1 + 18.0
1,500 mL/min 1,531.3 1,529.3 1,528.8 1,531.4 1,533.9 1,534.6 1,534.4 1,555.1 1,552.8 1,535.2 1,619.6 1,551.6 1,449.4 1,701.9 1,557.0 1,327.5
+ + + + + + + + + + + + + + + +
9.0 7.9 8.9 9.1 3.1 4.0 2.9 2.3 2.7 2.2 2.8 9.4 15.5 5.7 7.0 26.4
2,000 mL/min 2,005.5 2,004.1 2,001.6 2,003.4 2,002.9 2,003.8 2,002.2 2,011.2 2,009.2 2,001.2 2,028.7 2,028.5 2,001.8 2,090.3 2,024.8 1,912.0
+ + + + + + + + + + + + + + + +
5.4 5.4 6.5 6.3 7.9 6.0 6.5 8.0 7.6 6.9 9.6 6.8 7.6 10.3 9.0 6.8
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; RPM, revolutions per minute. P ! rpm, same rpm with nonpulsatile flow; P ! NP, return from pulsatile to nonpulsatile flow.
can produce both physiologic quality pulsatile and conventional NP. It is quite evident that the novel diagonal pump can generate significantly higher EEP, SHE, and THE in pulsatile setting than in nonpulsatile setting. Because of extra energy, physiological quality of pulsatility may maintain better microcirculation and vital organ recovery. Further animal studies focusing on the impact of varying differential speed values on hemolysis may help to determine the optimal P settings for pediatric populations. Acknowledgments Special thanks go to Dr Ju¨rgen O. Bo¨hm, Andreas Spilker, from Medos Medizintechnik AG, Stolberg, Germany, and Ivo Simundic and Dr Georg Matheis from Novalung GmbH, Heilbronn, Germany, for lending the DP3 pump console and sending disposables (oxygenator, pump head, and tubing) for this study.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Penn State Hershey College of Medicine, Depart¨ ). ment of Pediatrics seed funds (AU
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¨ ndar A, Haidet KK, Shenberger J. 6. Reed-Thurtson D, Qiu F, U Pediatric and neonatal extracorporeal life support technology component utilization: are us clinicians implementing new technology? Artif Organs. 2012;36(7): 607-615. ¨ ndar A. Use of a novel diag7. Evenson A, Wang S, Kunselman AR, U onal pump in an in-vitro neonatal pulsatile extracorporeal life support circuit. Artif Organs. 2014;38(1): E1-E9. doi:10.1111/aor.12240. ¨ ndar A. Impact of pulsatile 8. Krawiec C, Wang S, Kunselman AR, U flow on hemodynamic energy in a medos deltastream DP3 pediatric extracorporeal life support system. Artif Organs. 2014;38(1): 19-27. doi:10.1111/aor.12117. ¨ ndar A. In vitro performance analysis 9. Wang S, Kunselman AR, U of novel pulsatile diagonal pump in simulated pediatric mechanical circulatory support system. Artif Organs. 2014;38(1): 64-72. doi:10.1111/aor.12181. ¨ ndar A. Myths and truths of pulsatile and nonpulsatile perfusion 10. U during acute and chronic cardiac support. Artif Organs. 2004; 28(5): 439-443. 11. Shepard R, Simpson D, Sharp J. Energy equivalent pressure. Arch Surg. 1966;93(5): 730-740. 12. 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(1): 208-215. 13. 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(6): 2046-2053. 14. Vasku˚ J, Wotke J, Dobsa´k P, et al. Acute and chronic consequences of non-pulsatile blood flow pattern in long-term total artificial heart experiment. Pathophysiology. 2007;14(2): 87-95. 15. Koning NJ, Vonk AB, van Barneveld LJ, et al. Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics. J Appl Physiol (1985). 2012;112(10): 1727-1734. 16. Agˆirbas¸ li MA, Song J, Lei F, Wang S, et al. Comparative effects of pulsatile and non-pulsatile flow on plasma fibrinolytic balance in pediatric patients undergoing cardiopulmonary bypass. Artif Organs. 2014;38(1): 28-33. doi: 10.1111/aor.12182. 17. Baraki H, Gohrbandt B, Del Bagno B, Haverich A, Boethig D, Kutschka I. Does pulsatile perfusion improve outcome after cardiac surgery? a propensity-matched analysis of 1959 patients. Perfusion. 2012;27(3): 166-174. 18. Rogerson A, Guan Y, Kimatian SJ, et al. Transcranial Doppler ultrasonography: a reliable method of monitoring pulsatile flow during cardiopulmonary bypass in infants and young children. J Thorac Cardiovasc Surg. 2010;139(4): e80-e82. ¨ ndar A. 19. Su XW, Guan Y, Barnes M, Clark JB, Myers JL, U Improved cerebral oxygen saturation and blood flow pulsatility
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with pulsatile perfusion during pediatric cardiopulmonary bypass. Pediatr Res. 2011;70(2): 181-185. Travis AR, Giridharan GA, Pantalos GM, et al. Vascular pulsatility in patients with a pulsatile- or continuous-flow ventricular assist device. J Thorac Cardiovasc Surg. 2007;133(2): 517-524. ¨ ndar A. Evaluation of Akc¸evin A, Alkan-Bozkaya T, Qiu F, U perfusion modes on vital organ recovery and thyroid hormone homeostasis in pediatric patients undergoing cardiopulmonary bypass. Artif Organs. 2010;34(11): 879-884. 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(3): 476-481. doi:10.1177/2150135111402226. ¨ ndar A. HemodyQiu F, Lu CK, Palanzo D, Baer L, Myers JL, U namic evaluation of the Avalon Elite bi-caval lumen cannulae. Artif Org. 2011;35(11): 1048-1051. ¨ ndar A, Myers JL. HemodyQiu F, Clark JB, Kunselman AR, U namic evaluation of arterial and venous cannulae in a simulated neonatal ECLS circuit. Perfusion. 2011:26(4): 276-283. ¨ ndar Guan Y, Su X, McCoach R, Kunselman A, El-Banayosy A, U A. Mechanical performance comparison between rotaflow and centrimag centrifugal pumps in an adult ECLS model. Perfusion. 2010;25(2): 71-76. Palanzo DA, El-Banayosy A, Stephenson E, Brehm C, Kunselman A, Pae WE. Comparison of hemolysis between CentriMag and RotaFlow rotary blood pumps during extracorporeal membrane oxygenation. Artif Organs. 2013;37(9): E162-E166. doi:10.1111/ aor.12158. Fraser CD Jr, Jaquiss RD, Rosenthal DN, et al. Prospective trial of a pediatric ventricular assist device. N Engl J Med. 2012;367(6): 532-541. Almond CS, Morales DL, Blackstone EH, et al. Berlin heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children. Circulation. 2013;127(16): 1702-1711. Schmid C, Philipp A, Hilker M, et al. Venovenous extracorporeal life support for acute lung failure in adults. J Heart Lung Transplant. 2012;31(1): 9-15. Tiedge S and Optenho¨fel J. First uses of a new diagonal pump in extracorporeal support systems for children and infants (German). Kardiotechnik. 2011;20(3): 72-76. 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(5): 828-835. doi:10. 1093/ejcts/ezt427. Fitzmaurice GM, Laird NM, Ware JH. Applied Longitudinal Analysis. Hoboken, NJ: John Wiley & Sons, 2004.
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Impact of Pulsatile Flow Settings on Hemodynamic Energy Levels Using the Novel Diagonal Medos DP3 Pump in a Simulated Pediatric Extracorporeal Life Support System
World Journal for Pediatric and Congenital Heart Surgery 2014, Vol. 5(3) 440-448 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2150135114526760 pch.sagepub.com
Pelumi Adedayo, MS1, Shigang Wang, MD1, ¨ ndar, PhD1,3 Allen R. Kunselman, MD2, and Akif U
Abstract Background: The objective of this study was to evaluate the pump performance of the novel diagonal Medos Deltastream DP3 diagonal pump (MEDOS Medizintechnik AG, , Stolberg, Germany) under nonpulsatile to pulsatile mode with varying differential speed values in a simulated pediatric extracorporeal life support system. Methods: The experimental circuit consisted of a Medos Deltastream DP3 pump head and console, a Medos Hilite 2400 LT hollow fiber membrane oxygenator (MEDOS Medizintechnik AG), a 14F Medtronic DLP arterial cannula (Medtronic Inc, Minnesota), and a 20F Terumo TenderFlow Pediatric venous return cannula (Terumo Corporation, Michigan). Trials were conducted at flow rates ranging from 500 mL/min to 2,000 mL/min (500 mL/min increments) and pulsatile differential speed values ranging from 500 rpm to 2,500 rpm (500 rpm increments) using human blood (hematocrit 35%). The postcannula pressure was maintained constantly at 60 mm Hg. Real-time pressure and flow data were recorded using a custom-made data acquisition system and Labview software. Results: Under all experimental conditions, pulsatile flow (P) generated significantly greater energy equivalent pressure (EEP), surplus hemodynamic energy (SHE), and total hemodynamic energy (THE) than those of nonpulsatile flow (NP). Under NP, SHE was zero. Higher differential speed values generated greater EEP, SHE, and THE values. There was little variation in the oxygenator pressure drop and the cannula pressure drop in P, compared to NP. Conclusions: The novel Medos Deltastream DP3 diagonal pump is able to generate physiological quality of P, without backflow. With increased differential rpm, the pump generated greater EEP, SHE, and THE. Physiological quality of pulsatility may be associated with better microcirculation because of greater EEP, SHE, and THE. Keywords ECMO, infant, pediatrics, perfusion, diagonal pump, pulsatile flow, extracorporeal life support, hemodynamic energy, surplus hemodynamic energy Submitted October 02, 2013; Accepted February 10, 2014.
Introduction Extracorporeal life support (ECLS) can be life saving for pediatric patients with end-stage congenital heart disease, cardiomyopathies, and fulminant myocarditis who have heart failure. It is also applicable to patients awaiting recovery, those with difficulty weaning off from cardiopulmonary bypass (CPB), or those still awaiting transplant.1–4 Applicable pumps include the roller pumps and rotary pumps. Rotary pumps include the axial, diagonal, and centrifugal pumps. A 2010 survey showed that globally, more than 70% of ECLS centers use the newer centrifugal pumps for their pediatric patients.5 The United States lagged behind with only 29% of centers used centrifugal pumps and over 70% still used the older roller pumps.
1 Department of Pediatrics, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA 2 Department of Public Health and Sciences, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA 3 Department of Surgery and Bioengineering, Penn State Hershey Pediatric Cardiovascular Research Center, Penn State Milton S. Hershey Medical Center, Penn State Hershey College of Medicine, Penn State Hershey Children’s Hospital, Hershey, PA, USA
Corresponding Author: ¨ ndar, Department of Pediatrics, Penn State Hershey College of Medicine, Akif U H085, 500 University Drive, PO Box 850, Hershey, PA 17033-0850, USA. Email: [email protected]
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Abbreviations and Acronyms CPB ECLS EEP MAP MCS MP NP P SHE THE
cardiopulmonary bypass extracorporeal life support energy equivalent pressure mean arterial pressure mechanical circulatory support mean pressure nonpulsatile flow pulsatile flow surplus hemodynamic energy total hemodynamic energy
Nevertheless, 30% of US centers have changed their pump to newer models in the last 3 years.6 Diagonal pumps are new generation pump, which has the capacity to delivery both pulsatile (P) and nonpulsatile flow (NP) with very small priming volume, which may facilitate its usage for neonates, infants, and adult patients with ECLS.7–9 The authors have already documented that one of the major limitations of P is a lack of precise quantification and definition of pulsatility.10 Pulsatility depends on energy gradient generated by pump rather than pressure or flow waveforms alone. Hence, pulsatile pressure-flow waveforms are quantified in terms of hemodynamic energy levels. Energy equivalent pressure (EEP) is derived from Shepard’s formula using both pressure and flow.11 Energy equivalent pressure can be measured in millimeter of mercury (mm Hg) which allows direct comparison with mean arterial pressure (MAP). Pulsatile flow always yields higher EEP than MAP, and the difference between EEP and MAP is called surplus hemodynamic energy (SHE) or extraenergy generated secondary to pulsatility compared to NP. Regardless of type of ECLS pump (axial, centrifugal, or diagonal), the EEP and MAP values are identical for NP and therefore, SHE or extrahemodynamic energy is ‘‘zero.’’ Research studies have shown more EEP, SHE, and total hemodynamic energy (THE) with P than with NP. Propulsatile flow investigators believe that because of these extra energies, P may maintain better microcirculation and vital organ recovery.12–21 Quantification of pressure-flow waveforms in terms of EEP, SHE, and THE is extremely important to make direct and meaningful comparisons of different perfusion modalities or different forms of pulsatility in patients. Depending on the P settings, new generation diagonal pump produces significantly different hemodynamic energy levels from diminished pulsatility to the physiological quality of pulsatility.7–9 Therefore, translational research in terms of P settings will help clinicians to determine the best possible pressure-flow waveform with the most physiological hemodynamic energy delivery for their patients. Prior to clinical use of any new components of the ECLS circuitry (all might have already approved by the government agencies for clinical use), translational research is a must to determine not only the advantages (if any) of the new components but also to warn the investigators about limitations of the new devices.7–9,22 For instance, all manufacturers for arterial and venous cannulae supply pressure-flow waveforms of any size for
users. All of these waveforms are not applicable to pediatric and adult patients because manufacturers use ‘‘water’’ as a priming solution for cannulae evaluation. Thus, it is necessity to reevaluate all cannulae with different sizes using ‘‘human blood’’ as a priming solution.23,24 We have also documented that simple hemodynamic evaluations of centrifugal blood pumps not only allowed us to select better products but also save significant amount of funds for our institution. We proved that 1 centrifugal pump with 30 times lesser cost had better hemodynamic performance in addition to similar clinical outcomes.25,26 Therefore, translational research is vital not only to find better products but also to minimize the waste of funds. Independent scientific evaluation of any new product using identical clinical setup in a laboratory is a must, not an option. In the United States, the most common myth about pediatric mechanical circulatory support (MCS) systems is that most of the centers (if not all) use only NP for chronic support. It is true that new generation nonpulsatile centrifugal pumps (Rotaflow and CentriMag) are used as a temporary Ventricular Assist Device up to a month, but Berlin Excor is the only device clinically used for pediatric patients for chronic support (up to several months) and this is a ‘‘pulsatile’’ device.27,28 The unique diagonal pump system described in this article is the only available system that can produce both P and NP. Pilot clinical trials have already been conducted with nonpulsatile and pulsatile modes in the Europe.29–31 However, our research group is the only one performing ‘‘scientifically independent’’ studies to evaluate the advantages of the system along with limitations in a laboratory setting.7–9 The objective of this study was to evaluate the pump performance of the Medos Deltastream DP3 pump (MEDOS Medizintechnik AG, Stolberg, Germany) under nonpulsatile to pulsatile mode with varying differential speed values in a simulated pediatric ECLS system.
Materials and Methods Experimental Circuit The experimental circuit (Figure 1) consisted of a Medos Deltastream DP3 pump head and console (MEDOS Medizintechnik AG), a Medos Hilite 2400 LT hollow fiber membrane oxygenator (MEDOS Medizintechnik AG), a 14F Medtronic DLP arterial cannula (Medtronic Inc, Minnesota), a 20F Terumo TenderFlow pediatric venous return cannula (Terumo Corporation, Michigan), and 1/4-in inner diameter 3 feet tubing for both arterial and venous lines. An open soft bag containing 200 mL of blood was used as venous reservoir. A 300 mL capacity soft bag served as a pseudo-patient. A Hoffman clamp was placed downstream of the arterial cannula to keep a given arterial pressure during all trials.
Diagonal Pump The ‘‘angle of blood path’’ of the inlet and the outlet for a diagonal pump is between 90 and 180 , while the angle of blood path of axial pump is 180 and radial pump (centrifugal) is only 90 . A novel diagonal pump—Medos Deltastream DP3 from
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Figure 1. Experimental circuit setup.
the Medos (Medos Medizintechnik AG) can provide an optional P mode to mimic physiological blood flow for CPB, ECLS, and MCS. Its pump head features a high-tech ceramic bearing and magnetic coupling of forces between the impeller and the driver for longer run times, low-priming volume (16 mL) to minimize hemodilution, and a wide range of flow rates (0-8 L/min) allowing applicability to neonates and adults (Figure 2). Thus far, in Europe, it has been used in clinical venovenous ECLS (up to 109 days) and for MCS (up to 58 days).29–31
Experimental Design The circuit was initially primed with lactated ringer’s solution for de-airing the circuit and then added packed human red blood cells. The hematocrit of the priming solution was 35%. The total priming volume of the circuit was 700 mL. Two transonic
ultrasound flow probes (Transonic Systems, Inc, Ithaca, New York) were placed at the preoxygenator site and precannula site. Five Maxxim disposable pressure transducers (Maxxim Medical, Inc, Ithaca, New York) were placed at preoxygenator, postoxygenator, precannula, postcannula, and venous line sites. Trials were conducted at flow rates ranging from 500 to 2,000 mL/min (500 mL/min increments), with pulsatile and nonpulsatile mode at 36 C. Differential speed values of pulsatile setting ranged from 500 rpm (P500) to 2,500 rpm (P2500; 500 rpm increments). The postcannula pressure was maintained at 60 mm Hg, and the venous line pressure was kept at 10 mm Hg during all trials.
Pulsatile Settings The Medos Deltastream DP3 pump setting for P was at a frequency of 90 beats per minute (bpm), 50% of systole–diastole
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443 (500; 1,000; 1,500; 2,000 mL/min) and mode (nonpulsatile, pulsatile 1,000; pulsatile 1,500; pulsatile 2,000). A linear mixed-effects model was fit to the continuous outcomes (eg, MAP, EEP, SHE, and THE) to compare the flow rate, mode, and location (eg, preoxygenator, postoxygenator, precannula, and postcannula).32 The linear mixed-effects model is an extension of linear regression that accounts for the within-subject variability inherent in repeated measure 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 hypotheses tests were twosided and all analyses were performed using version 9.3 of the SAS System for Windows (SAS Institute Inc, Cary, North Carolina).
Results Hemodynamic Energy Figure 2. The Medos Deltastream diagonal pump.
ratio, and varying speed differential values at all experimental evaluations.
Data Acquisition All pressure transducers and flowmeter outputs were connected to a signal conditioning unit (SC-2345, National Instruments, Austin, Texas), linked with data acquisition device (National Instruments universal serial bus [USB]-6251, National Instruments), and finally connected to a computer via USB port. A customized user interface based on Labview 7.1 software for Windows (National Instruments) was designed to record realtime data at 1,000 sample per second. A 20-second segment of pressure and flow waveforms was recorded at all sites. The pump test was repeated eight times for each unique combination, yielding a total of 640 trials.
Hemodynamic Energy Calculation With the help of the Shepard’s EEP formula12 and simultaneous blood flow (f) and pressure (p) recorded by Labview software, EEP, SHE, and THE were calculated in an time interval (t1 and t2) as follows. The constant 1,332 converts pressure from units of mm Hg to dynes per cm2 (1 mm Hg ¼ 1,332 dyn/cm2). R t2 R EEP ðmmHgÞ ¼ t1 fpdt t2 fdt t1
SHE (ergs/cm3) ¼ 1,332 (EEP Mean Arterial Pressure) THE (ergs/cm3) ¼ 1,332 EEP
Statistical Analysis Analysis of variance models were fit to the continuous outcomes (eg, %THE, pressure drop) to compare the flow rate
Under NP, SHE is almost zero. In P, SHE appeared and increased with increasing speed differential values. However, SHE decreased with increasing flow rates (Figure 3). At any flow rate, the SHE values were highest at the pre-oxygenator site and lowest at the postcannula site. The THE generated was greater in P compared to NP and increased with greater speed differentials. THE also increased with higher flow rates. At any flow rate, THE values were highest at the preoxygenator site and lowest at the postcannula site (Figure 4). The percentages of THE increase in pulsatile compared to nonpulsatile mode increased with greater differential speed values. However, within any speed differential value, it decreased with higher flow rates (Table 1).
Mean Pressure Versus EEP Pressure waveform at different flow rates were compared in pulsatile and nonpulsatile mode (Figure 5). During NP, the EEP remained the same as the mean pressure (MP). However, in the face of P, the EEP increased up to 21.7% from the MP at the preoxygenator site (Table 2). The EEP also increased with increasing differential speed values. A similar trend is observed at the precannula site.
Oxygenator and Arterial Cannula Pressure Drops Within each flow rate, the oxygenator pressure drop remained relatively constant, even when comparing nonpulsatile to pulsatile values or when comparing increasing speed differential values (Table 3). However, the absolute value of the oxygenator pressure drop increased with higher flow rates, with the highest pressure drop (NP 45.1 + 5.8 mm Hg, P 51.6 + 1.6 mmHg) recorded at a flow rate of 2,000 mL/min. A similar trend is seen with the arterial cannula. The highest pressure drop was recorded at a flow rate of 2,000 mL/mL (NP 56.1 + 0.3, P 62.4.6 + 0.5 mm Hg).
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Figure 3. Surplus hemodynamic energy (SHE) at various flows. *P < .01, nonpulsatile versus pulsatile (P500, P1000, P1500, P2000, and P2500) mode. NP indicates nonpulsatile flow; P, pulsatile flow.
Figure 4. Total hemodynamic energy (THE) at various flow rates. *P < .01, nonpulsatile versus pulsatile (P500, P1000, P1500, P2000, and P2500) mode. NP indicates nonpulsatile flow; P, pulsatile flow. Downloaded from pch.sagepub.com at UNIV OF WESTERN ONTARIO on June 11, 2015
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Table 1. Percentage of Pulsatile THE Increase Compared to Nonpulsatile Flow at Preoxygenator Site Under Various Differential rpms. Percentage of THE Increasea Mode
500 mL/min
NP P500 P1000 P1500 P2000 P2500
– 12.4 + 0.4 25.6 + 1.8b 30.3 + 2.6b 31.8 + 2.5b 29.7 + 2.2b
1,000 mL/min 1,500 mL/min 2,000 mL/min 5.3 19.2 24.0 26.4 26.9
– + 0.3 + 0.4b + 1.4b + 1.3b + 2.0b
2.6 9.7 20.3 23.7 25.7
– + 0.2 + 0.3b + 0.4b + 1.0b + 0.7b
1.2 5.5 11.1 17.9 20.0
– + 0.5 + 0.2b + 0.3b + 0.3b + 0.7b
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; THE, total hemodynamic energy. a Percentage of THE Increase ¼ ([Pulsatile THE Nonpulsatile THE]/ Nonpulsatile THE) 100. b P < .01, pulsatile flow with 500 rpm of differential speed versus pulsatile flow with other differential speeds.
Flow Rates and Revolution Speeds From nonpulsatile to pulsatile mode, the revolutions per minute (rpm) remained the same at lower differential speed values and higher flow rates but increased at higher differential speed values and lower flow rates (Table 4). Under pulsatile mode, at differential speed value of 500 rpm, there was no difference observed in pump flow rate. However, at speed difference values above 500 rpm, pump flow rate increased under pulsatile compared to nonpulsatile mode. The revolution speeds needed to be adjusted to the same as the nonpulsatile rpm in order to keep identical flow rates. When pump was returned to nonpulsatile from pulsatile mode, lower rpms and flow rates are recorded. Figure 5 represents flow waveforms at 1,000 mL/min and 2,000 mL/min of flow rates in pulsatile and nonpulsatile mode. No backflow was observed during all trials of pulsatile mode. All pulsatile data we used were data after revolution speeds of P were adjusted to the same as NP.
Comment Our results showed that the hemodynamic profile of pulsatile mode is significantly greater than in nonpulsatile mode. The THE increased with higher speed differentials, at any flow rate. Although THE increased with higher flow rates, the proportion reaching the postcannula site was significantly less compared to the preoxygenator site at higher flow rates. This suggests that maximal benefits of pulsatile mode to the patient will be seen at lower flow rates and lower circuit resistance. The SHE, which is the difference between the mean pressure and EEP, is also higher in pulsatile mode compared to non-pulsatile mode. At any flow rate, SHE values increased with higher differential speed values, suggesting that higher P increased the hemodynamic energy reaching the patient. The percentage of THE increase, as expected, was higher in pulsatile compared to nonpulsatile mode. The value also increased with higher differential speeds but reduced with increasing flow rates. This
implied that P at lower flow rates and higher differential speeds could generate more hemodynamic energy than NP. Energy equivalent pressure was the same as mean pressure under nonpulsatile mode and higher than mean pressure under pulsatile mode. The EEP was also higher at any flow rate and speed differential value combination in pulsatile compared to nonpulsatile mode. This is expected and has been recorded in previous studies.14 However, per the aim of this study, it is interesting to see that EEP increased with increasing speed differential values at all flow rates tested. But the percentages of EEP increase decreased gradually with increased flow rates. The EEP slightly decreased at differential speeds > 1,500 rpm. This suggests, again, that higher differential speed values confer no advantage in pulsatile mode. At any flow rate, the oxygen pressure drop remains constant with increasing speed differential values, whether in pulsatile or nonpulsatile mode. This attributes to the efficiency of the oxygenator used. In addition, P did not have a great effect on the oxygenator pressure drop. At increasing flow rates, however, there was an increase in the oxygenator pressure drop. The above-mentioned trend was replicated in the cannula pressure drop values. Again, it speaks to quality of the cannula used. The common myth of the P is that it creates significantly higher circuit pressures and pressure drops at the same flow and pressure settings. Our results clearly prove this particular oxygenator worked very well at all different flow rates and perfusion modes, and P did not generate any excessive circuit pressures or pressure drops. Our results also showed that when switching from nonpulsatile to pulsatile mode, the rotational speed increased automatically for speed differentials of 1,000 rpm and flow rates less than 2,000 mL/min while the flow rate increased at speed differential values greater than 500 rpm. It seems that it is not advantageous to use a differential value of below 1,000 rpm when trying to maximize the benefits of P on rotational speed. Similarly, flow rates greater than 1,500 mL/min may not be beneficial for generating higher rotational speeds. At 2,000 mL/min, there were no significant changes in the rotational speed (Table 4).
Limitations The same cannulae (14F for arterial and 20F for venous) were used for all trials. In vivo, it would be too big for ECLS at 500 mL/min and hence not an adequate setup for this flow rate. This experiment was performed under in vitro conditions only, using the same resistance setting for all trials. In vivo conditions will present with different resistance in various patients. In the future, then, it would be imperative to translate the results from this study to animal studies. Also, animal studies may make it more appropriate to measure the degree of hemolysis introduced to the patient with increasing differential speed values.
Conclusions To the best of our knowledge, the unique diagonal pump system described in this article is the only available system that
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Figure 5. Flow and pressure waveforms at preoxygenator site under nonpulsatile and pulsatile mode. NP indicates nonpulsatile flow; P, pulsatile flow. Table 2. Mean Pressure and Energy Equivalent Pressure at Preoxygenator and Precannula Sites Under Pulsatile and Nonpulsatile Mode.a Preoxygenator Pressure, mm Hg Mode NP MP EEP P500 MP EEP P1000 MP EEP P1500 MP EEP P2000 MP EEP P2500 MP EEP
Precannula Pressure, mm Hg
500 mL/min
1,000 mL/min
1,500 mL/min
2,000 mL/min
500 mL/min
1,000 mL/min
1,500 mL/min
2,000 mL/min
88.4 + 0.2 88.4 + 0.2 (0.0%)
121.4 + 0.2 121.4 + 0.2 (0.0%)
169.2 + 0.2 169.2 + 0.2 (0.0%)
220.1 + 1.0 220.1 + 1.0 (0.0%)
67.3 + 0.3 67.3 + 0.3 (0.0%)
78.2 + 0.3 78.2 + 0.3 (0.0%)
96.8 + 0.3 96.8 + 0.3 (0.0%)
116.6 + 0.5 116.6 + 0.5 (0.0%)
90.8 + 0.4b 99.3 + 0.4b (9.3%)
122.9 + 0.4 127.8 + 0.4b (3.9%)
170.2 + 0.3 173.6 + 0.2b (2.0%)
220.5 + 0.3 222.7 + 0.2b (1.0%)
69.6 + 0.4 b 75.7 + 0.4b (8.7%)
79.6 + 0.4 82.8 + 0.4b (4.0%)
97.5 + 0.3 99.5 + 0.4b (2.0%)
116.9 + 0.4 118.2 + 0.4 (1.1%)
93.7 + 0.9b 111.0 + 1.8b (18.5%)
129.6 + 0.6b 144.4 + 0.7b (11.7%)
173.8 + 0.5b 185.7 + 0.4b (6.8%)
224.5 + 0.4b 231.9 + 0.4b (3.3%)
72.3 + 0.9b 84.6 + 1.5b (17.1%)
84.8 + 0.5b 94.6 + 0.6b (11.6%)
100.1 + 0.2b 107.0 + 0.2b (6.8%)
119.4 + 0.4b 124.6 + 0.4b (4.4%)
94.7 + 1.4b 115.2 + 2.4b (21.7%)
130.6 + 1.3b 150.5 + 1.8b (15.2%)
181.0 + 0.4b 203.7 + 0.5b (12.5%)
229.9 + 0.7b 244.0 + 0.6b (6.1%)
73.1 + 1.3b 87.8 + 2.1b (20.0%)
85.7 + 1.0b 98.6 + 1.4b (15.0%)
104.9 + 0.2b 117.9 + 0.3b (12.3%)
122.8 + 0.6b 133.2 + 0.6b (8.5%)
95.9 + 1.5b 116.5 + 2.4b (21.4%)
131.9 + 1.3b 153.4 + 1.5b (16.3%)
182.4 + 1.5b 209.3 + 1.6b (14.7%)
237.6 + 0.8b 259.0 + 0.7b (9.0%)
74.2 + 1.3b 88.8 + 2.0b (19.8%)
86.7 + 0.9b 100.6 + 1.1b (16.0%)
106.0 + 0.9b 121.7 + 1.1b (14.8%)
127.6 + 0.6b 143.9 + 0.7b (12.7%)
94.7 + 1.2b 114.5 + 2b (20.9%)
132.2 + 1.5b 53.9 + 2.5b (16.4%)
184.0 + 1.3b 212.0 + 1.4b (15.5%)
239.5 + 1.8b 263.8 + 1.8b (10.2%)
73.1 + 1.1b 87.3 + 1.7b (19.4%)
86.8 + 1.3b 100.9 + 2.0b (16.2%)
107.1 + 0.8b 124.0 + 0.9b (15.8%)
128.8 + 0.9b 147.7 + 0.9b (14.7%)
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; MP, mean pressure; EEP, energy equivalent pressure. a Percentage in parentheses ¼ ([EEP MP]/MP] 100. b P < .01, nonpulsatile (NP) mode versus pulsatile (P500, P1000, P1500, P2000, P2500) mode. Downloaded from pch.sagepub.com at UNIV OF WESTERN ONTARIO on June 11, 2015
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Table 3. Oxygenator Pressure Drop and Arterial Cannula Pressure Drop Under Nonpulsatile and Pulsatile Mode. Oxygenator Pressure Drop, mm Hg Mode
500 mL/min
NP P500 P1000 P1500 P2000 P2500
14.2 + 14.1 + 14.0 + 14.0 + 14.1 + 14.0 +
0.2 0.2 0.2 0.2 0.2 0.2
1,000 mL/min 23.5 23.5 24.1 24.1 24.1 24.0
+ 0.2 + 0.3 + 0.2 + 0.3 + 0.4 + 0.5
1,500 mL/min 33.7 + 33.1 + 33.1 + 34.0 + 35.6 + 40.0 +
5.1 6.9 7.0 7.0 3.6 2.9
Arterial Cannula Pressure Drop, mm Hg 2,000 mL/min 45.1 + 45.4 + 47.5 + 48.8 + 50.0 + 51.6 +
5.8 3.6 3.5 2.9 3.1 1.6
500 mL/min 7.2 + 0.1 7.4 + 0.1 7.6 + 0.1a 7.7 + 0.1a 7.8 + 0.1a 7.7 + 0.1a
1,000 mL/min 18.4 18.8 20.0 20.1 20.3 20.4
+ 0.1 + 0.1 + 0.1a + 0.2a + 0.2a + 0.2a
1,500 mL/min 36.1 + 36.4 + 37.3 + 39.1 + 39.5 + 39.9 +
0.1 0.1 0.1a 0.1a 0.4a 0.4a
2,000 mL/min 56.1 + 56.2 + 57.5 + 59.2 + 61.7 + 62.4 +
0.3 0.1 0.1a 0.2a 0.3a 0.5a
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow. a P < .05, nonpulsatile flow versus pulsatile flow (P500, P1000, P1500, P2000, and P2500).
Table 4. Revolutions Per Minute and Flow Rates With Nonpulsatile and Pulsatile Mode. Revolutions per minute, rpm Mode NP P500 P500 ! rpm P500 ! NP P1000 P1000 ! rpm P1000 ! NP P1500 P1500 ! rpm P1500 ! NP P2000 P2000 ! rpm P2000 ! NP P2500 P2500 ! rpm P2500 ! NP
Flow rates, mL/min
500 mL/min 1,000 mL/min 1,500 mL/min 2,000 mL/min 500 mL/min 3,650 3,650 3,650 3,650 3,750 3,650 3,550 4,000 3,650 3250 4,450 3,650 2,750 4,750 3,650 2,600
4,550 4,550 4,550 4,550 4,550 4,550 4,550 4,750 4,550 4,350 5,050 4,550 3,900 5,350 4,550 3,500
5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,550 5,750 5,550 5,250 6,000 5,550 4,950
6,500‘ 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,500 6,700 6,500 6,250
519.1 + 518.1 + 517.9 + 519.4 + 542.4 + 518.3 + 493.0 + 592.5 + 518.3 + 426.9 + 662.9 + 523.8 + 341.8 + 720.6 + 519.7 + 322.9 +
2.1 1.8 1.9 1.9 8.0 4.4 6.6 8.7 4.5 8.1 7.6 5.9 8.9 4.9 3.9 3.8
1,000 mL/min 1,007.2 1,005.9 1,006.3 1,007.2 1,022.8 1,022.4 1,007.3 1,081.3 1,018.6 930.9 1,154.5 1,024.1 819.8 1,247.2 1,024.2 686.0
+ 1.1 + 1.8 + 1.9 + 1.1 + 3.6 + 2.7 + 1.0 + 3.8 + 6.9 + 10.9 + 5.1 + 8.0 + 10.4 + 3.8 + 7.1 + 18.0
1,500 mL/min 1,531.3 1,529.3 1,528.8 1,531.4 1,533.9 1,534.6 1,534.4 1,555.1 1,552.8 1,535.2 1,619.6 1,551.6 1,449.4 1,701.9 1,557.0 1,327.5
+ + + + + + + + + + + + + + + +
9.0 7.9 8.9 9.1 3.1 4.0 2.9 2.3 2.7 2.2 2.8 9.4 15.5 5.7 7.0 26.4
2,000 mL/min 2,005.5 2,004.1 2,001.6 2,003.4 2,002.9 2,003.8 2,002.2 2,011.2 2,009.2 2,001.2 2,028.7 2,028.5 2,001.8 2,090.3 2,024.8 1,912.0
+ + + + + + + + + + + + + + + +
5.4 5.4 6.5 6.3 7.9 6.0 6.5 8.0 7.6 6.9 9.6 6.8 7.6 10.3 9.0 6.8
Abbreviations: NP, nonpulsatile flow; P, pulsatile flow; RPM, revolutions per minute. P ! rpm, same rpm with nonpulsatile flow; P ! NP, return from pulsatile to nonpulsatile flow.
can produce both physiologic quality pulsatile and conventional NP. It is quite evident that the novel diagonal pump can generate significantly higher EEP, SHE, and THE in pulsatile setting than in nonpulsatile setting. Because of extra energy, physiological quality of pulsatility may maintain better microcirculation and vital organ recovery. Further animal studies focusing on the impact of varying differential speed values on hemolysis may help to determine the optimal P settings for pediatric populations. Acknowledgments Special thanks go to Dr Ju¨rgen O. Bo¨hm, Andreas Spilker, from Medos Medizintechnik AG, Stolberg, Germany, and Ivo Simundic and Dr Georg Matheis from Novalung GmbH, Heilbronn, Germany, for lending the DP3 pump console and sending disposables (oxygenator, pump head, and tubing) for this study.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Penn State Hershey College of Medicine, Depart¨ ). ment of Pediatrics seed funds (AU
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