Encouraging results of blood conservation in neonatal open-heart surgery.

OBJECTIVE: To report early outcomes of blood conservation in neonatal open-heart surgery. METHODS: Ninety-nine patients undergoing neonatal open-heart surgery during the implementation of a blood conservation program between May 2021 and February 2023 were reviewed. Patients either received traditional blood management (blood prime, n = 43) or received blood conservation strategies (clear prime, n = 56). Baseline characteristics and outcomes were compared between groups. RESULTS: There was no difference in body weight (median, 3.2 kg vs 3.3 kg; P = .83), age at surgery (median, 5 days vs 5 days; P = .37), distribution of The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories categories or duration of cardiopulmonary bypass. Patients in the clear prime group had higher preoperative hematocrit (median, 41% vs 38%; P < .01), shorter postoperative mechanical ventilation time (median, 48 hours vs 92 hours; P = .02) and postoperative intensive care unit length of stay (median, 6 days vs 9 days; P < .01) than patients in the blood prime group. Fourteen patients (25%) in the clear prime group, including 1 Norwood patient, were discharged without any transfusion. Among patients within the clear prime group, hospitalizations without blood exposure were associated with higher preoperative hematocrit (median, 43% vs 40%; P = .02), shorter postoperative mechanical ventilation times (median, 22 hours vs 66 hours; P = .01) and shorter postoperative hospital stays (median, 10 days vs 15 days; P = .02). CONCLUSIONS: Bloodless surgery is possible in a significant proportion of neonates undergoing open-heart surgery, including the Norwood operation, even in the early stages of experience. Early clinical results are favorable but long-term follow-up and continued efforts are warranted to prove safety and reproducibility.

Safety and Efficacy of Extracorporeal Membrane Oxygenation Heating Units.

BACKGROUND: Patient temperature during extracorporeal membrane oxygenation (ECMO) is commonly managed by dedicated heating units (HUs) that are integrated into ECMO circuitry. Currently, no HU has received approval for ECMO by the FDA in the United States. Older FDA-approved HUs have been implicated in life-threatening patient infections and are no longer manufactured or available for use in the United States. METHODS: We performed laboratory tests to evaluate the safety and efficacy of the Micro-Temp and the HTP-1500 HU systems that are potentially suitable for use in ECMO and describe our initial experience with the HTP-1500 HU after being placed in clinical service. RESULTS: Both units demonstrated similar heating efficacy, with the HTP-1500 achieving steady-state temperature approximately 5 h earlier than the Micro-Temp. Microorganisms were detected in the water compartment of all HUs prior to and after performing the manufacturer's recommended cleaning procedure, and after implementation of the HTP-1500 into clinical use we observed a decrease in the rate of bloodstream infection/ECMO days which did not reach statistical significance. CONCLUSION: Based on the results of this analysis and our institutional experience, we believe that integration of the HTP-1500 HU, an easily replaceable HU, into ECMO systems may reduce the risk of bacterial contamination and thus nosocomial infection when the devices are cleaned and maintained according to manufacturer's guidelines.

Right ventricular energy metabolism in a porcine model of acute right ventricular pressure overload after weaning from cardiopulmonary bypass.

Acute right ventricular pressure overload (RVPO) occurs following congenital heart surgery and often results in low cardiac output syndrome. We tested the hypothesis that the RV exhibits limited ability to modify substrate utilization in response to increasing energy requirements during acute RVPO after cardiopulmonary bypass (CPB). We assessed the RV fractional contributions (Fc) of substrates to the citric acid cycle in juvenile pigs exposed to acute RVPO by pulmonary artery banding (PAB) and CPB. Sixteen Yorkshire male pigs (median 38 days old, 12.2 kg of body weight) were randomized to SHAM (Ctrl, n = 5), 2-h CPB (CPB, n = 5) or CPB with PAB (PAB-CPB, n = 6). Carbon-13 (13 C)-labeled lactate, medium-chain, and mixed long-chain fatty acids (MCFA and LCFAs) were infused as metabolic tracers for energy substrates. After weaning from CPB, RV systolic pressure (RVSP) doubled baseline in PAB-CPB while piglets in CPB group maintained normal RVSP. Fc-LCFAs decreased significantly in order PAB-CPB > CPB > Ctrl groups by 13 C-NMR. Fc-lactate and Fc-MCFA were similar among the three groups. Intragroup analysis for PAB-CPB showed that the limited Fc-LCFAs appeared prominently in piglets exposed to high RVSP-to-left ventricular systolic pressure ratio and high RV rate-pressure product, an indicator of myocardial oxygen demand. Acute RVPO after CPB strongly inhibits LCFA oxidation without compensation by lactate oxidation, resulting in energy deficiency as determined by lower (phosphocreatine)/(adenosine triphosphate) in PAB-CPB. Adequate energy supply but also metabolic interventions may be required to circumvent these RV energy metabolic abnormalities during RVPO after CPB.

Inhaled nitric oxide reduces injury and microglia activation in porcine hippocampus after deep hypothermic circulatory arrest.

OBJECTIVE: Dysregulation of local nitric oxide (NO) synthetases occurs during ischemia and reperfusion associated with cardiopulmonary bypass, deep hypothermic circulatory arrest (DHCA), and reperfusion. Rapid fluctuations in local NO occurring in neonates and infants probably contribute to inflammation-induced microglial activation and neuronal degeneration after these procedures, eventually impairing neurodevelopment. We evaluated the anti-inflammatory efficacy of inhaled NO (iNO) in a piglet model emulating conditions during pediatric open-heart surgery with DHCA. METHODS: Infant Yorkshire piglets underwent DHCA (18°C) for 30 minutes, followed by reperfusion and rewarming either with or without iNO (20 ppm) in the ventilator at the onset of reperfusion for 3 hours (n = 5 per group, DHCA-iNO and DHCA). Through craniotomy, brains were extracted after perfusion fixation for histology. RESULTS: Plasma NO metabolites were elevated 2.5 times baseline data before DHCA by iNO. Fluoro-Jade C staining identified significantly lower number of degenerating neurons in the hippocampus of the DHCA-iNO group (P = .02) compared with the DHCA group. Morphologic analyses of ionized calcium-binding adapter molecule-1 stained microglia, evaluating cell body and dendritic process geometry with Imaris imaging software, revealed subjectively less microglial activation in the hippocampus of pigs receiving iNO. CONCLUSIONS: Using DHCA for 30 minutes, consistent with clinical exposure, we noted that iNO reduces neuronal degeneration in the hippocampus. In addition, iNO reduces microglial activation in the hippocampus after DHCA. The data suggest that iNO reduces neuronal degeneration by ameliorating inflammation and may be a practical mode of neuroprotection for infants undergoing DHCA.

Shear stress associated with cardiopulmonary bypass induces expression of inflammatory cytokines and necroptosis in monocytes.

Cardiopulmonary bypass (CPB) is required during most cardiac surgeries. CBP drives systemic inflammation and multiorgan dysfunction that is especially severe in neonatal patients. Limited understanding of molecular mechanisms underlying CPB-associated inflammation presents a significant barrier to improve clinical outcomes. To better understand these clinical issues, we performed mRNA sequencing on total circulating leukocytes from neonatal patients undergoing CPB. Our data identify myeloid cells, particularly monocytes, as the major cell type driving transcriptional responses to CPB. Furthermore, IL-8 and TNF-α were inflammatory cytokines robustly upregulated in leukocytes from both patients and piglets exposed to CPB. To delineate the molecular mechanism, we exposed THP-1 human monocytic cells to CPB-like conditions, including artificial surfaces, high shear stress, and cooling/rewarming. Shear stress was found to drive cytokine upregulation via calcium-dependent signaling pathways. We also observed that a subpopulation of THP-1 cells died via TNF-α-mediated necroptosis, which we hypothesize contributes to post-CPB inflammation. Our study identifies a shear stress-modulated molecular mechanism that drives systemic inflammation in pediatric CPB patients. These are also the first data to our knowledge to demonstrate that shear stress causes necroptosis. Finally, we observe that calcium and TNF-α signaling are potentially novel targets to ameliorate post-CPB inflammation.

Development of the Adult ECMO Specialist Certification Examination.

The American Society of Extracorporeal Technology Board of Directors, consistent with the American Society of Extracorporeal Technology's safe patient care improvement mission, charged the International Board of Blood Management to write a knowledge and skill certification examination for healthcare personnel employed as adult extracorporeal membrane oxygenation (ECMO) specialists. Nineteen nationally recognized ECMO subject-matter experts were selected to complete the examination development. A job analysis was performed, yielding a job description and examination plan focused on 16 job categories. Multiple-choice test items were created and validated. Qualified ECMO specialists were identified to complete a pilot examination and both pre- and post-examination surveys. The examination item difficulty and candidate performance were ranked and matched using Rasch methodology. Candidates' examination scores were compared with their profession, training, and experience as ECMO specialists. The 120-item pilot examination form ranked 76 ECMO specialist candidates consistent with their licensure, ECMO training, and clinical experience. Forty-three registered nurses, 28 registered respiratory therapists, four certified clinical perfusionists, and one physician assistant completed the pilot examination process. Rasch statistics revealed examination reliability coefficients of .83 for candidates and .88 for test items. Candidates ranked the appropriateness for examination items consistent with the item content, difficulty, and their personal examination score. The pilot examination pass rate was 80%. The completed examination product scheduled for enrollment in March 2020 includes 100 verified test items with an expected pass rate of 84% at a cut score of 67%. The online certification examination based on a verified job analysis provides an extramural assessment that ranks minimally prepared ECMO specialists' knowledge, skills, and abilities (KSA) consistent with safe ECMO patient care and circuit management. It is anticipated that ECMO facilities and ECMO service providers will incorporate the certification examination as part of their process improvement, safety, and quality assurance plans.

The effect of cardiopulmonary bypass prime volume on the need for blood transfusion after pediatric cardiac surgery.

OBJECTIVE: There is increasing awareness that erythrocyte transfusions after pediatric cardiac surgery have deleterious effects. Despite reports of decreased transfusion requirements associated with smaller cardiopulmonary bypass circuits, the relationship between circuit prime volume and need for transfusion has not been systematically examined. METHODS: Pediatric patients at our institution who underwent cardiopulmonary bypass between January 2005 and December 2010 were reviewed. Demographics, intraoperative data, and transfusion of packed red blood cells were retrospectively recorded. Cardiopulmonary bypass prime volume was indexed by patient body surface area. Logistic regression analysis was used to correlate these variables with need for transfusion. RESULTS: In the perioperative period, 1912 patients received transfusions and 266 did not. In univariate analysis, indexed prime volume was a significant predictor of transfusion (odds ratio, 1.007; P < .001). Other significant variables in univariate analysis included age, surgeon, Risk Adjustment for Congenital Heart Surgery 1 (RACHS-1) category, preoperative hemoglobin, total bypass time, aortic crossclamp time, use and duration of deep hypothermic circulatory arrest, lowest body core temperature, and cardiopulmonary bypass flow rate. Previous cardiac surgery was not a significant predictor. In multivariable analysis controlling for RACHS-1 category, surgeon, minimal core body temperature, and preoperative hemoglobin, indexed prime volume remained an independent predictor of transfusion (odds ratio, 1.006; 95% confidence interval, 1.005-1.007, P < .001). CONCLUSIONS: Perioperative need for transfusion in pediatric cardiac surgical patients is independently related to the prime volume of the cardiopulmonary bypass circuit. It therefore seems prudent to minimize circuit prime volumes to avoid unnecessary use of blood products.

A decade of pediatric mechanical circulatory support before and after cardiac transplantation.

OBJECTIVES: We reviewed the use of pediatric mechanical circulatory support before and after transplantation to examinine current results and future strategies. METHODS: All patients listed for transplantation from January 2000 to December 2010 who required either extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD) support before ("intention to transplant") or after transplantation were included. Indications for mechanical assistance, age, weight, duration of support, complications while on support, causes of death, and overall actuarial survival were recorded. RESULTS: Thirty-seven patients were received VADs; 32 (86.5%) survived to transplantation. Postoperative hemorrhagic or thrombotic complications affected all of those under 15 kg. One patient in the survivor cohort demonstrated focal neurologic findings. Three (8.1%) had panel reactive antibody levels of 10% or more while on device support; all received transplants. ECMO as an intention to bridge to transplantation was used in 28 patients; 7 died, 7 were weaned, and 14 were bridged to transplantation. Nineteen patients required ECMO after transplantation; 3 additional patients had percutaneous VAD support for late rejection. There was a significant (P = .02) difference in survival after listing for transplantation among those supported with ECMO, with VAD, and those not supported with a device. No difference in posttransplant survival was demonstrated between those patients supported with either ECMO or VAD before transplant compared with all others not bridged to transplantation. CONCLUSIONS: Both VAD and ECMO support are highly effective means of bridging patients to transplantation and supporting patients after transplanatation. Ideally, the availability of smaller devices for children will have a favorable impact on the morbidity related to anticoagulation in the smallest patients.

Rationale and use of perfusion variables in the 2010 update of the society of thoracic surgeons congenital heart surgery database.

Patients undergoing congenital heart surgery are at risk of morbidity and mortality. The reasons underlying this risk are complex. To identify opportunities to reduce adverse sequelae, the cardiovascular perfusion community was invited to amend existing perfusion-related fields as well as add new ones to the current version of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD). The International Consortium for Evidence-Based Perfusion (ICEBP) was invited by the STS-CHSD Task Force to identify and resolve ambiguities related to definitions among the 3 current perfusion-related fields as well as to propose new variables (and definitions) for inclusion in the 2010 update of the STS-CHSD. The ICEBP used teleconferences, wiki-based communication software, and e-mail to discuss current definitions and create new fields with definitions. The ICEBP created modified definitions to existing fields related to cardiovascular perfusion and also developed and defined new fields that focus on (1) techniques of circulatory arrest and cerebral perfusion, (2) strategies of myocardial protection, and (3) techniques to minimize hemodilution and allogeneic blood transfusions. Three fields in the STS-CHSD related to perfusion were redefined, and 23 new variables and definitions were selected for inclusion. Identifying and defining fields specific to the practice of perfusion are requisite for assessing and subsequently improving the care provided to patients undergoing congenital heart surgery. The article describes the methods and justification for adjudicating extant and new perfusion-related fields added to the 2010 update of the STS-CHSD.

Complications relating to perfusion and extracorporeal circulation associated with the treatment of patients with congenital cardiac disease: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease.

The International Consortium for Evidence-Based Perfusion (www.bestpracticeperfusion.org) is a collaborative partnership of societies of perfusionists, professional medical societies, and interested clinicians, whose aim is to promote the continuous improvement of the delivery of care and outcomes for patients undergoing extracorporeal circulation. Despite the many advances made throughout the history of cardiopulmonary bypass, significant variation in practice and potential for complication remains. To help address this issue, the International Consortium for Evidence-Based Perfusion has joined the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease to develop a list of complications in congenital cardiac surgery related to extracorporeal circulation conducted via cardiopulmonary bypass, extracorporeal membrane oxygenation, or mechanical circulatory support devices, which include ventricular assist devices and intra-aortic balloon pumps. Understanding and defining the complications that may occur related to extracorporeal circulation in congenital patients is requisite for assessing and subsequently improving the care provided to the patients we serve. The aim of this manuscript is to identify and define the myriad of complications directly related to the extracorporeal circulation of congenital patients.

Therapeutic plasma exchange performed in parallel with extra corporeal membrane oxygenation for antibody mediated rejection after heart transplantation.

We report on the feasibility, safety, and efficacy of performing therapeutic plasmapheresis (TPE) in parallel with extracorporeal membrane oxygenation (ECMO) to alleviate antibody mediated rejection (AMR) after heart transplantation. Two pediatric and one adult patient presented with severe congestive heart failure and respiratory distress after heart transplantation and required ECMO support. TPE was initiated to treat AMR while patients remained on ECMO. Each patient received three to five procedures either every day or every other day. One equivalent total plasma volume (TPV) was processed for each procedure (patient TPV + ECMO extracorporeal TPV). A total of 13 TPE procedures were performed with 12 procedures completed without complications or adverse events; one procedure was terminated before completion because of cardiac arrhythmia. Anti-HLA antibody titers decreased after TPE in all three patients. Ventricular function improved and ECMO was discontinued in 2 of 3 patients. Performing large volume TPE with a processed volume up to 2.5 times the patient's TPV is well tolerated in both pediatric (< or = 10 kg) and adult patients. TPE in parallel with ECMO is feasible, safe, and may be measurably effective at reducing anti-HLA antibodies and should be considered as part of the treatment for patients with early AMR after heart transplantation.

180 ml and less: cardiopulmonary bypass techniques to minimize hemodilution for neonates and small infants.

OBJECTIVE: To determine the efficacy of decreasing cardiopulmonary bypass (CPB) prime volume for neonates and small infants by using low prime oxygenators, small diameter polyvinyl chloride (PVC) tubing and removing the arterial line filter (ALF) in an effort to reduce intraoperative exposure to multiple units of packed red blood cells (PRBC). METHODS: Two retrospective database studies comparing neonatal CPB prime volume were undertaken: Study 1--A CPB circuit consisting of a 1/8 inch arterial line, a 3/16 inch venous line and a low prime oxygenator with 172 ml total circuit prime (n=74) was compared to a circuit with a 3/16 inch arterial line, a 1/4 inch venous line and a higher prime oxygenator with a 350 ml total circuit prime (n=74). Study 2--The 172 ml circuit (n=389) was compared to a circuit that included an ALF and had a total circuit prime volume of 218 ml (n=389). RESULTS: Study 1--of the 74 neonates and small infants whose CPB prime volume was 350 ml, 19 were exposed to two or more intraoperative exogenous PRBC units while only 3 neonates and small infants in the 172 ml prime group (n=74) received two or more units (p = 0.0002). Study 2--of the 389 neonates and small infants where an ALF was used (prime volume 218 ml), 54 were exposed to two or more exogenous PRBC units while only 36 of the 389 patients where an ALF was not used (prime volume 172 ml) received two or more units of intraoperative PRBCs (p = 0.0436). CONCLUSION: Decreasing the neonatal and small infant extracorporeal circuit prime volume by as little as 46 ml resulted in significantly fewer multiple exposures to exogenous PRBC units.