Current Issue of JECT

The premier source of the most current research and information related to extracorporeal technology including Cardiopulmonary Bypass, Extracorporeal Life Support, Mechanical Assist Devices, and Perioperative Blood Management.

Volume 50 / Issue 4 / December 2018 Contents



Impact of Hemolysis on Acute Kidney Injury and Mortality in Children Supported with Cardiac Extracorporeal Membrane OxygenationSantiago Borasino, MD; Yuvraj Kalra, MD; Ashley R. Elam, MD; Lawrence Carlisle O’Meara, CCP, FPP; Joseph G. Timpa, CCP, FPP; Kellen G. Goldberg, MPS, CCP; J. Leslie Collins Gaddis, MD; Jeffrey A. Alten, MD

Abstract: Intravascular hemolysis with elevated plasma-free hemoglobin (PFH) complicates extracorporeal membrane oxygenation (ECMO). In 50 consecutive pediatric cardiac patients requiring ECMO, we sought to describe the relationship between PFH and clinical outcomes; primary outcomes were acute kidney injury (AKI) and prolonged (>14 days) renal replacement therapy (RRT). Median age was 35 days, median weight 3.9 kg, and median ECMO duration 4.2 days. Seventy-eight percent (39/50) weaned off ECMO; survival to discharge was 50% (25/50). Seventy percent (35/50) had AKI on ECMO. Seventy-seven percent (30/39) required RRT post-ECMO; median duration was 5.2 days (0, 14.2). Prolonged RRT was associated with higher daily PFH (67.5 mg/dL [54.1, 102.5] vs. 46.7 mg/dL [40, 72.6], p 5 .025) and higher peak PFH (120 mg/dL [90, 200] vs. 60 mg/dL [40, 135], p 5 .016). After adjusting for ECMO duration and oliguria/elevated creatinine on ECMO day 0, peak PFH >90 mg/dL was associated with prolonged RRT (operating room [OR] 5 18, confidence interval [CI] 1.9–167.8). Patients who died had higher daily PFH (65 mg/dL [51.6, 111.7] vs. 42.5 mg/dL [37.5, 60], p 5 .0040). Adjusting for ECMO duration and blood product administration, daily PFH >53 mg/dL was associated with mortality (OR 4.8, CI 1.01–23.3). Elevated PFH during pediatric cardiac ECMO is associated with prolonged RRT and non-survival to discharge. Initiatives to decrease PFH burden may improve clinical outcomes.

Keywords: hemolysis, acute kidney injury, renal replacement therapy, children, cardiac extracorporeal membrane oxygenation. J Extra Corpor Technol. 2018;50:217–24

Is Conventional Bypass for Coronary Artery Bypass Graft Surgery a Misnomer?
Donald S. Likosky, PhD; Robert A. Baker, PhD, CCP; Richard F. Newland, BSc; Theron A. Paugh, CCP; Timothy A. Dickinson, MS, CCP; David Fitzgerald, MPH, CCP; Joshua B. Goldberg, MD; Nicholas B. Mellas, CCP; Alan F. Merry, MB, ChB; Paul S. Myles, MPH, DSc; Gaetano Paone, MD, MHSA; Kenneth G. Shann, CCP; Jane Ottens, CCP; Timothy W. Willcox, CCP; for The International Consortium for Evidence-Based Perfusion, the PERForm Registry, the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR), and the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative

Abstract: Although recent trials comparing on vs. off-pump revascularization techniques describe cardiopulmonary bypass (CPB) as “conventional,” inadequate description and evaluation of how CPB is managed often exist in the peer-reviewed literature. We identify and subsequently describe regional and center-level differences in the techniques and equipment used for conducting CPB in the setting of coronary artery bypass grafting (CABG) surgery. We accessed prospectively collected data among isolated CABG procedures submitted to either the Australian and New Zealand Collaborative Perfusion Registry (ANZCPR) or Perfusion Measures and outcomes (PERForm) Registry between January 1, 2014, and December 31, 2015. Variation in equipment and management practices reflecting key areas of CPB is described across 47 centers (ANZCPR: 9; PERForm: 38). We report average usage (categorical data) or median values (continuous data) at the center-level, along with the minimum and maximum across centers. Three thousand five hundred sixty-two patients were identified in the ANZCPR and 8,450 in PERForm. Substantial variation in equipment usage and CPB management practices existed (within and across registries). Open venous reservoirs were commonly used across both registries (nearly 100%), as were “all-but-cannula” biopassive surface coatings (>90%), whereas roller pumps were more commonly used in ANZCPR (ANZCPR: 85% vs. PERForm: 64%). ANZCPR participants had 640 mL absolute higher net prime volumes, attributed in part to higher total prime volume (1,462 mL vs. 1,217 mL) and lower adoption of retrograde autologous priming (20% vs. 81%). ANZCPR participants had higher nadir hematocrit on CPB (27 vs. 25). Minimal absolute differences existed in exposure to high arterial outflow temperatures (36.6°C vs. 37.0°C). We report substantial center and registry differences in both the type of equipment used and CPB management strategies. These findings suggest that the term “conventional bypass” may not adequately reflect real-world experiences. Instead of using this term, authors should provide key details of the CPB practices used in their patients.

Keywords: cardiopulmonary bypass (CPB), equipment; registry, collaborative; perfusion. J Extra Corpor Technol. 2018; 50:225–30

Association of Primary Hemodilution and Retrograde Autologous Priming with Transfusion in Cardiac Surgery: Analysis of the Perfusion Case Database of the Japanese Society of ExtraCorporeal Technology in Medicine
Chihiro Saito, MS; Tetsuya Kamei, PhD; Shoji Kubota, CCP(Japan); Kiyoshi Yoshida, CCP (Japan); Makoto Hibiya, PhD; Shuji Hashimoto, PhD 

Abstract: It is important to avoid unnecessary blood cell transfusion. However, the associations of hemodilution and retrograde autologous priming with red blood cell transfusion during and after cardiopulmonary bypass (CPB) in cardiac surgery in Japan are currently unclear. We analyzed these associations using data for 3,090 adults from the Perfusion Case Database of the Japanese Society of Extra-Corporeal Technology in Medicine. Percent hemodilution was calculated by total priming volume and weight. Logistic regression models were used to adjust for covariates including type of surgery, gender, age, hemoglobin concentration before CPB, CPB time, urine volume during CPB, and institution. The percentages of red blood cell transfusions during CPB for patients with <15, 15 to <20, 20 to <25, 25 to <30, and $30% hemodilution were 43.0, 51.5, 68.9, 77.3, and 87.7%, respectively. This increase in line with increasing dilution was significant after adjusting for covariates. The percentage of red blood cell transfusion after CPB also increased slightly between 39.0 and 49.4% with percent hemodilution, but the trend after adjusting for covariates was not significant. Use of retrograde autologous priming was significantly associated with blood cell transfusion during CPB after adjusting for covariates, but was not significantly related to blood cell transfusion after CPB. These results suggest that optimizing the percent hemodilution and use of retrograde autologous priming might reduce the use of red blood cell transfusion during CPB in clinical practice in Japan.

Keywords: hemodilution, blood transfusion, cardiac surgery, cardiopulmonary bypass, extracorporeal circuit. J Extra Corpor Technol. 2018; 50:231–6

An Ethanol-Free Autologous Thrombin System
Andrea M. Matuska, PhD; Marina K. Klimovich, BS; John R. Chapman, PhD

Abstract: Thrombin is a coagulation protein of central importance to hemostasis and wound healing that can be sourced from human blood, bovine blood, and engineered cell lines. Only autologous thrombin lacks the risks of transmitting emergent pathogens or eliciting an immunogenic response. Previous commercial autologous thrombin devices require the use of high concentrations of ethanol to achieve thrombin stability, introducing cytotoxicity risks. A new point of care device for preparing an ethanol-free autologous thrombin serum was investigated. The ethanol-free autologous serum (AS) was prepared using the Thrombinator System (Arthrex, Inc., Naples, FL). A total of 120 devices were tested with the blood of 30 healthy donors to determine the reliability and flexibility of the procedure. AS was prepared from both whole blood (WB) and platelet-poor plasma (PPP). Study endpoints were thrombin activity determined using a coagulation analyzer and formation of cohesive bone graft composites objectively measured using a durometer. The average thrombin activity produced by this system from 24 donors was 20.6 6 2.7 IU/mL for WB and 13.4 6 3.8 IU/mL for PPP which correlated to clot times of 3.9 and 5.9 seconds, respectively. The device tolerated use of varying volumes of blood to prepare AS. In addition, the system was able to generate four successive and comparable AS productions. When combined with platelet-rich plasma and bone graft material, cohesive scaffolds were always formed. A new device and method for preparing single donor, ethanol-free, AS with thrombin activity was demonstrated.

Keywords: thrombin, autologous, blood-coagulation, platelet rich plasma, fibrin, device. J Extra Corpor Technol. 2018;50:237–43

Potential Deleterious Interactions between Certain Chemical Compounds and a Thermoplastic Polyurethane Heat Exchanger Membrane Oxygenator
Brian C. Forsberg, MPH, CCP, FPP; William M. Novick, MS, MD; Cynthia Cervantes, MHSA, CCP; Jorge Lopez, PhD; Marcelo Cardarelli, MD, MPH

Abstract: Extracorporeal membrane oxygenation (ECMO) has become a powerful tool in the race to reverse failure to rescue events. Rapid implementation set the stage for the advent of the 30-day wet-priming storage as a standard practice. A recent alert regarding methylene blue (MB) unidirectional leach from patient’s circulation through the oxygenator thermoplastic polyurethane (TPU) heat-exchanger membrane into the heater–cooler unit (HCU) water bath led us to believe that despite reassurances, the reverse process might be possible. To that effect, we performed a pilot in vitro experiment. We tested three adult ECMO sets (Adult Quadrox iD Oxygenator, Getinge, Doral, FL) probing for the transfer of MB between the water bath of a Sarns Dual Heater Cooler (Terumo Corporation, Ann Arbor, MI) and the circuit stored wet-primed for 30 days. In each test, 1,500 mg of reconstituted MB (HiMedia, Mumbai, India) were added to the 7.5 L of water in the HCU, circulated for 6 hours on which the water lines were disconnected and the setup was stored for 30 days. The primed circuit was tested for MB transfer at days 0, 13, and 30 by means of optical density (OD) at 665 nm and 26.5°C. Transference of MB from the HCU water bath into the ECMO circuit could be detected as early as day 13 after setup, achieving significant values by day 30 (median OD .019 (.014–.021). Expected OD if no diffusion present: 0. The complete separation of water interfaces between the patient’s circuit and the HCU water bath may prove to be more dogma than fact when certain chemical substances are used in conjunction with TPU membrane oxygenators. Whether the transfer of substances is due to chemical processes or molecular weight needs further evaluation. Meanwhile, the use of chemicals for the cleaning of the HCU should be mindful of potential noxious effects.

Keywords: CPB, equipment, extracorporeal membrane oxygenation (ECMO). J Extra Corpor Technol. 2018;50:244–7


Unplanned Autotransplantation for Complex Multi-Valve Replacement in a Super Morbid Obese Female: The Challenge of Intraoperative Decision Making
Charles McDonald, PhD, CCP, FANZCP; Daniel Dallimore, BHB, MB ChB, FANZCA; Mathew Oates, MBBS; Kiran Shekar, MBBS, FCICM, FCCCM, PhD; Bruce Thomson, BMedSci, MBBS, FRACS (CTh)

Abstract: Cardiac autotransplantation is a rare technique typically reserved for the treatment of malignant tumors of the left atrium and left ventricle. Even when well planned, it conveys a high risk to the patient. This report discusses the intraoperative progression to an unplanned autotransplant for mitral valve repair while considering some decision making processes that cardiac surgeons make.

Keywords: mitral valve surgery, transplantation, cardiac surgery. J Extra Corpor Technol. 2018;50:248–51

Role of Methadone in Extracorporeal Membrane Oxygenation: Two Case Reports
Erik Dong, DO; Robert Fellin, PharmD; Danny Ramzy, MD, PhD; Joshua S. Chung, MD; Francisco A. Arabia, MD; Alice Chan, RN, MSN, CNS, CCRN; David Ng, MD; Nicola D’Attellis, MD; Michael Nurok, MBChB, PhD

Abstract: Extracorporeal membrane oxygenation (ECMO) affects pharmacokinetics/dynamics of drugs in unpredictable ways. Anecdotally, ECMO patients require high doses of opioids and sedatives, leading to concerns of tolerance. Methadone is a long-acting synthetic opioid with antagonist properties at the n-methyl-d-aspartate (NMDA) receptor. It has been shown to improve spontaneous breathing trials and weaning from mechanical ventilation; however, there is no literature describing its use in ECMO. We describe two patients from the cardiac surgery intensive care unit at Cedars Sinai (Los Angeles, CA) on ECMO for over 30 days maintained on methadone.

Keywords: extracorporeal membrane oxygenation, methadone, analgesics, sedation, critical care. J Extra Corpor Technol. 2018;50:252–5

How to Manage Thrombocytopenia with ECLS: A Proposal of Clinical Reasoning Tools
Adrien Koeltz, MD;  Nicolas Gendron, PharmD, PhD;  Nadine Ajzenberg, MD, PhD; Dan Longrois, MD, PhD

Abstract: Extracorporeal life support (ECLS) is increasingly used as a rescue therapy in patients with refractory cardiac/respiratory failure for temporary support or bridge to decision-making in both adult and pediatric patients. Complications such as bleeding and thrombosis remain major causes of morbidity and mortality in patients treated with ECLS. Hemostatic complications related to ECLS are multifactorial in patients with multiple organ dysfunctions and are incompletely characterized. Persisting thrombocytopenia and/or platelet dysfunction is the most frequent one. Herein, we report the case of a patient who developed severe thrombocytopenia after 5 days of ECLS associated with thrombi deposition in the circuit and oxygenator. After ECLS circuit and membrane change, we observed an increase and normalization in platelet count in 3 days. We propose a case-based reasoning to manage thrombocytopenia with ECLS.

Keywords: extracorporeal life support, thrombocytopenia, throm


The Safe Addition of Nitric Oxide into the Sweep Gas of the Extracorporeal Circuit during Cardiopulmonary Bypass and Extracorporeal Life Support
Martin Bennett, BAppSc CCP; Clarke Thuys, BAppSc CCP; Simon Augustin, BAppSc, CCP; Brad Schultz, BN, CCP; Steve Bottrell, BN, CCP; Alison Horton, CCP; Andrzej Bednarz, DipBiomed Elec; Steve Horton, PhD, CCP

Abstract: Low cardiac output syndrome and the systemic inflammatory response are consequences of the cardiac surgical perioperative course. The mechanisms responsible are multifactorial, but recent studies have shown that nitric oxide (NO) may be a key component in mitigating some of these processes. Following on from literature reports detailing the use of inhaled NO added to the gas phase of the extracorporeal circuit, we set about developing a technique to perform this addition safely and efficiently. In the setting of cardiopulmonary bypass, the technique was validated in a randomized prospective trial looking at 198 children. The benefits observed in this trial then stimulated the incorporation of NO into all extracorporeal life support (ECLS) circuits. This required additional hardware modifications all of which were able to be performed safely. Initial results from the first series of ECLS patients using NO also appear promising.

Keywords: cardiopulmonary bypass, inflammatory response, SIRS, low cardiac output syndrome, LCOS, nitric oxide, ECLS, ECMO. J Extra Corpor Technol. 2018;50:260–4



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