Larry D. Baer

Laboratory Evaluation of Hemolysis and Systemic Inflammatory Response in Neonatal Nonpulsatile and Pulsatile Extracorporeal Life Support Systems.

The objective of this study was to compare the systemic inflammatory response and hemolytic characteristics of a conventional roller pump (HL20-NP) and an alternative diagonal pump with nonpulsatile (DP3-NP) and pulsatile mode (DP3-P) in simulated neonatal extracorporeal life support (ECLS) systems. The experimental neonatal ECLS circuits consist of a conventional Jostra HL20 roller pump or an alternative Medos DP3 diagonal pump, and Medos Hilite 800 LT hollow-fiber oxygenator with diffusion membrane. Eighteen sterile circuits were primed with freshly donated whole blood and divided into three groups: conventional HL20 with nonpulsatile flow (HL20-NP), DP3 with nonpulsatile flow (DP3-NP), and DP3 with pulsatile flow (DP3-P). All trials were conducted for durations of 12 h at a flow rate of 500 mL/min at 36°C. Simultaneous blood flow and pressure waveforms were recorded. Blood samples were collected to measure plasma-free hemoglobin (PFH), human tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-8, in addition to the routine blood gas, lactate dehydrogenase, and lactic acid levels. HL20-NP group had the highest PFH levels (mean ± standard error of the mean) after a 12-h ECLS run, but the difference among groups did not reach statistical significance (HL20-NP group: 907.6 ± 253.1 mg/L, DP3-NP group: 343.7 ± 163.2 mg/L, and DP3-P group: 407.6 ± 156.6 mg/L, P = 0.06). Although there were similar trends but no statistical differences for the levels of proinflammatory cytokines among the three groups, the HL20-NP group had much greater levels than the other groups (P > 0.05). Pulsatile flow generated higher total hemodynamic energy and surplus hemodynamic energy levels at pre-oxygenator and pre-clamp sites (P < 0.01). Our study demonstrated that the alternative diagonal pump ECLS circuits appeared to have less systemic inflammatory response and hemolysis compared with the conventional roller pump ECLS circuit in simulated neonatal ECLS systems. Pulsatile flow delivered more hemodynamic energy to the pseudo-patient without increased odds of hemolysis compared with the conventional, nonpulsatile roller pump group.

Hemodynamic Evaluation of the Avalon Elite Bi-Caval Dual Lumen Cannulae

In previous studies, we have evaluated the hemodynamic properties of selected oxygenators, pumps (centrifugal and roller), and single lumen cannulae. Because the dual lumen cannulae are widely used in veno-venous extracorporeal life support (ECLS) and are receiving popularity due to their advantages over the single lumen cannulae, we evaluated the flow ranges and pressure drops of three different sizes of Avalon Elite dual lumen cannulae (13Fr, 16Fr, and 19Fr) in a simulated neonatal ECLS circuit primed with human blood. The experimental ECLS circuit was composed of a RotaFlow centrifugal pump, a Capiox BabyRX05 oxygenator, 3 ft of 1/4-in venous and arterial line tubing, an Avalon Elite dual lumen cannula, and a soft reservoir as a pseudo-right atrium. All experiments were conducted at 37°C using an HCU 30 heater-cooling unit and with human blood at a hematocrit of 36%. The blood pressure in the pseudo-right atrium was continuously monitored and maintained at 4-5 mm Hg. For each cannula, pump flow rates and pressures at both the arterial and venous sides were recorded at revolutions per minute (RPMs) from 1750 to 3750 in 250 intervals. For each RPM, six data sets were recorded for a total of 162 data sets. The total volume of the system was 300 mL. The flow range for the 13Fr, 16Fr, and 19Fr cannulae were from 228 to 762 mL/min, 478 to 1254 mL/min, and 635 to 1754 mL/min, respectively. The pressure drops at the arterial side were higher than the venous side at all tested conditions except at 1750 rpm for the 19Fr cannula. The results of this study showed the flow ranges and the pressure drops of three different sized dual lumen cannulae using human blood, which is more applicable in clinical settings compared with evaluations using water.

Current Techniques and Outcomes in Extracorporeal Life Support

For patients with catastrophic cardiac or pulmonary failure, extracorporeal life support (ECLS) often represents the last line of defense against impending and near-certain demise. Recent increases in the application of this technology for adult support have contributed to the continued growth of ECLS utilization in the USA and around the world. With widened application, there is increased clinical demand for this expensive yet potentially life-saving technology. For scientists and clinicians working in the field, there is an obligation to pursue the continued refinement of ECLS technology, all with the goal of improving patient survival and subsequent quality of life. As ECLS becomes more common, providers will be challenged to be judicious in the selection of both the most appropriate patients for ECLS as well as the most appropriate equipment. In this report, we aim to review current ECLS use and outcomes, both nationally and at our center, and to describe our recent and future translational research projects intended to elevate ECLS circuitry.

Successful treatment of peripartum cardiomyopathy with extracorporeal membrane oxygenation

A 24-year-old female developed heart failure within four months of delivering her first child. Echocardiogram revealed a moderately dilated left ventricle with severely reduced systolic function. She continued to decompensate, requiring intubation and inotropic support. When the use of an intra-aortic balloon pump failed to stabilize the patient, the decision was made to place her on ECMO. The circuit consisted of a Quadrox D membrane oxygenator and a CentriMag® centrifugal pump. After 11 days of support, the patient met the weaning criteria and was successfully removed from ECMO. She was discharged one month after her admission. The new technology available allows for ECMO to be considered as an earlier option for the treatment and management of these patients as a bridge to recovery.

Comparison of hollow-fiber membrane oxygenators with different perfusion modes during normothermic and hypothermic CPB in a simulated neonatal model.

Purpose: The objectives of this investigation were (1) to compare two hollow-fiber membrane oxygenators (Capiox Baby RX versus Lilliput 1-D901) in terms of pressure drops and surplus hemodynamic energy (SHE) during normothermic and hypothermic cardiopulmonary bypass (CPB) in a simulated neonatal model; and (2) to evaluate pulsatile and non-pulsatile perfusion modes for each oxygenator in terms of SHE levels. Methods: In a simulated patient, CPB was initiated at a constant pump flow rate of 500 mL/min. The circuit was primed with fresh bovine blood. After 5 min of normothermic CPB, the pseudo-patient was cooled down to 25°C for 10 min followed by 30 min of hypothermic CPB. The pseudo-patient then underwent 10 min of rewarming and 5 min of normothermic CPB. At each experimental site (pre- and post-oxygenator and pre-aortic cannula), SHE was calculated using the following formula {SHE (ergs/cm3) = 1332 [((ffpdt)/(ffdt))-mean arterial pressure]} (f = pump flow and p = pressure). A linear mixed-effects model that accounts for the correlation among repeated measurements was fit to the data to assess differences in SHE between oxygenators, pumps, and sites. Tukey’s multiple comparison procedure was used to adjust p-values for post-hoc pairwise comparisons. Results: The pressure drops in the Capiox group compared to the Lilliput group were significantly lower during hypothermic non-pulsatile (21.3∓0.5 versus 50.7∓0.9 mmHg, p B < 0.001) and pulsatile (22∓0.0 versus 53.3∓0.5 mmHg, p < 0.001) perfusion, respectively. Surplus hemodynamic energy levels were significantly higher in the pulsatile group compared to the non-pulsatile group, with Capiox (1655∓92 versus 10 008∓1370 ergs/cm3, p < 0.001) or Lilliput (1506∓112 versus 7531∓483 ergs/cm3, p < 0.001) oxygenators. During normothermic CPB, both oxygenators had patterns similar to those observed under hypothermic conditions. Conclusions: The Capiox oxygenator had a significantly lower pressure drop in both pulsatile and non-pulsatile perfusion modes. For each oxygenator, the SHE levels were significantly higher in the pulsatile mode.

Translational Research in Pediatric Extracorporeal Life Support Systems and Cardiopulmonary Bypass Procedures: 2011 Update

Over the past 6 years at Penn State Hershey, we have established the pediatric cardiovascular research center with a multidisciplinary research team with the goal to improve the outcomes for children undergoing cardiac surgery with cardiopulmonary bypass (CPB) and extracorporeal life support (ECLS). Due to the variety of commercially available pediatric CPB and ECLS devices, both in vitro and in vivo translational research have been conducted to achieve the optimal choice for our patients. By now, every component being used in our clinical settings in Penn State Hershey has been selected based on the results of our translational research. The objective of this review is to summarize our translational research in Penn State Hershey Pediatric Cardiovascular Research Center and to share the latest results with all the interested centers.

Benefits of pulsatile flow in pediatric cardiopulmonary bypass procedures: from conception to conduction

This review on the benefits of pulsatile flow includes not only experimental and clinical data, but also attempts to further illuminate the major factors as to why this debate has continued during the past 55 years. Every single component of the cardiopulmonary bypass (CPB) circuitry is equally important for generating adequate quality of pulsatility, not only the pump. Therefore, translational research is a necessity to select the best components for the circuit. Generation of pulsatile flow depends on an energy gradient; precise quantification in terms of hemodynamic energy levels is, therefore, a necessity, not an option. Comparisons between perfusion modes should be done after these basic steps have been taken. We have also included experimental and clinical data for direct comparisons between the perfusion modes. In addition, we included several suggestions for future clinical trials for other interested investigators.

Impact of the 2013/2014 influenza season on extracorporeal membrane oxygenation programs in the United States.

When looking back at the 2013–2014 influenza season, our impressions were that it seemed busier in terms of patients requiring extracorporeal membrane oxygenation (ECMO) than the 2012–2013 season. More patients were placed on veno-venous ECMO for respiratory failure, and the early to middle-aged adults (18–64 years) seemed to be hit the hardest. We decided to compare the data for both seasons to see if our impressions were real. Even though the Centers for Disease Control and Prevention (CDC) considers September through the end of April as the influenza season, we compared from the beginning of November through March, because that is when our activity levels changed. At our institution, we employ centrifugal pumps for our pediatric and adult ECMO circuits. The circuit is comprised of a Bioline-coated Quadrox-D membrane oxygenator (MAQUET Cardiopulmonary AG, Hirrlingen, Germany), centrifugal pump (CentriMag, Levitronix LLC, Waltham, MA, USA; Rotaflow, MAQUET Cardiopulmonary AG; or CARDIOHELP System, MAQUET Cardiopulmonary AG), and coated 1/4′′ or 3/8′′ PVC tubing (Fig. 1). The circuit was primed with 250 or 450 mL of Plasmalyte A depending on the size of the circuit.

The new role of the perfusionist in adult extracorporeal life support

Adult and pediatric extracorporeal life support (ECLS) has been transformed by the European1 and Australian 2 experiences with a reduction of the circuit to its most basic form (Figure 1). Many factors have converged at this point in time to allow us to offer this support. The availability in the U.S.A. of an advanced oxygenator (QuadroxD) (Maquet Inc., Bridgewater, NJ), long-term centrifugal pumps and circuit coatings offers us the means to provide ECLS. The other equally important factor is the intensivist trained in extracorporeal therapies. Once the intensive care unit registered nurse (ICU RN) is trained to safely and effectively manage both the patient and ECLS circuit, this support may be offered. The perfusionist is in an unique position to educate and mentor the ICU RN in ECLS. There is, perhaps, no one in a better position to explain this equipment and its uses in an interdisciplinary-oriented pediatric and adult ECLS program than a perfusionist.

Air-Handling Capabilities of Blood Cardioplegia Delivery Systems in a Simulated Pediatric Model

Blood cardioplegia delivery systems are employed in most pediatric open heart cases to arrest the heart and keep it preserved during aortic cross-clamping. They are also used as part of a modified ultrafiltration system at the end of cardiopulmonary bypass. We evaluated and compared the air-handling capabilities of different types of blood cardioplegia delivery devices. A simple circuit incorporating a cardiotomy reservoir, a roller pump, a cardioplegia test system, and two emboli detection and classification sensors were used to investigate the air-handling capabilities of the following cardioplegia delivery systems: GISH Vision, Maquet Plegiox, Medtronic Trillium MYOtherm XP, Sorin Group BCD Vanguard, Sorin Group CSC14, and Terumo Sarns Conducer and Bubble Trap. The 0.25-in. circuit was primed with 400mL of Lactated Ringers. Outdated packed red blood cells were added to obtain a hematocrit of 24-28%. System pressure was maintained at 50mmHg. Air (0.1, 0.3, 0.5mL) was injected at a speed of 0.1mL/s into the circuit just after the pump head. Gaseous microemboli (GME) were measured prior to the cardioplegia system and after the device to evaluate the air-handling characteristics. The tests were run at 100, 200, and 400mL/min blood flow for both 4 and 37°C. There were no significant differences among the groups when comparing precardioplegia delivery system GME, thus demonstrating that all devices received the same amount of injected air. When comparing the groups for postcardioplegia delivery system GME, significant differences were noted especially at the 400mL/min blood flow rate. These results suggest that for the devices compared in this study, the Maquet Plegiox and the Medtronic Trillium MYOtherm XP eliminated GME the best.