Effect of In Vivo Administration of Fibrinogen Concentrate Versus Cryoprecipitate on Ex Vivo Clot Degradation in Neonates Undergoing Cardiac Surgery.

BACKGROUND: Neonates undergoing cardiac surgery require fibrinogen replacement to restore hemostasis after cardiopulmonary bypass (CPB). Cryoprecipitate is often the first-line treatment, but recent studies demonstrate that fibrinogen concentrate (RiaSTAP; CSL Behring) may be acceptable in this population. This investigator-initiated, randomized trial compares cryoprecipitate to fibrinogen concentrate in neonates undergoing cardiac surgery (ClinicalTrials.gov NCT03932240). The primary end point was the percent change in ex vivo clot degradation from baseline at 24 hours after surgery between groups. Secondary outcomes included intraoperative blood transfusions, coagulation factor levels, and adverse events. METHODS: Neonates were randomized to receive cryoprecipitate (control group) or fibrinogen concentrate (study group) as part of a post-CPB transfusion algorithm. Blood samples were drawn at 4 time points: presurgery (T1), after treatment (T2), arrival to the intensive care unit (ICU) (T3), and 24 hours postsurgery (T4). Using the mixed-effect models, we analyzed the percent change in ex vivo clot degradation from a patient's presurgery baseline at each time point. Intraoperative blood product transfusions, coagulation factor levels, perioperative laboratory values, and adverse events were collected. RESULTS: Thirty-six neonates were enrolled (intent to treat [ITT]). Thirteen patients in the control group and seventeen patients in the study group completed the study per protocol (PP). After normalizing to the patient's own baseline (T1), no significant differences were observed in clot degradation at T2 or T3. At T4, patients in the study group had greater degradation when compared to those in the control group (826.5%, 95% confidence interval [CI], 291.1-1361.9 vs -545.9%, 95% CI, -1081.3 to -10.4; P < .001). Study group patients received significantly less median post-CPB transfusions than control group patients (ITT, 27.2 mL/kg [19.0-36.9] vs 41.6 [29.2-52.4]; P = .043; PP 26.7 mL/kg [18.8-32.2] vs 41.2 mL/kg [29.0-51.4]; P < .001). No differences were observed in bleeding or thrombotic events. CONCLUSIONS: Neonates who received fibrinogen concentrate, as compared to cryoprecipitate, have similar perioperative ex vivo clot degradation with faster degradation at 24 hours postsurgery, less post-CPB blood transfusions, and no increased bleeding or thrombotic complications. Our findings suggest that fibrinogen concentrate adequately restores hemostasis and reduces transfusions in neonates after CPB without increased bleeding or thrombosis risk.

Influence of Fibrinogen Concentrate on Neonatal Clot Structure When Administered Ex Vivo After Cardiopulmonary Bypass.

BACKGROUND: Bleeding is a serious complication of cardiopulmonary bypass (CPB) in neonates. Blood product transfusions are often needed to adequately restore hemostasis, but are associated with significant risks. Thus, neonates would benefit from other effective, and safe, hemostatic therapies. The use of fibrinogen concentrate (FC; RiaSTAP, CSL Behring, Marburg, Germany) is growing in popularity, but has not been adequately studied in neonates. Here, we characterize structural and degradation effects on the neonatal fibrin network when FC is added ex vivo to plasma obtained after CPB. METHODS: After approval by the institutional review board and parental consent, blood samples were collected from neonates undergoing cardiac surgery and centrifuged to yield platelet poor plasma. Clots were formed ex vivo from plasma obtained at several time points: (1) baseline, (2) immediately post-CPB, and (3) post-transfusion of cryoprecipitate. In addition, we utilized post-CPB plasma to construct the following conditions: (4) post-CPB +0.5 mg/mL FC, and (5) post-CPB +0.9 mg/mL FC. The resultant fibrin networks were imaged using confocal microscopy to analyze overall structure, fiber density, and alignment. Clots were also analyzed using a microfluidic degradation assay. Fibrinogen content was quantified for all plasma samples. RESULTS: The addition of 0.5 or 0.9 mg/mL FC to post-CPB samples significantly enhanced the median fiber density when compared to untreated post-CPB samples (post-CPB = 0.44 [interquartile range {IQR}: 0.36-0.52], post-CPB +0.5 mg/mL FC = 0.69 [0.56-0.77], post-CPB +0.9 mg/mL FC = 0.87 [0.59-0.96]; P = .01 and P = .006, respectively). The addition of 0.9 mg/mL FC to post-CPB samples resulted in a greater fiber density than that observed after the in vivo transfusion of cryoprecipitate (post-transfusion = 0.54 [0.45-0.77], post-CPB +0.9 mg/mL FC = 0.87 [0.59-0.96]; P = .002). Median fiber alignment did not differ significantly between post-CPB samples and samples treated with FC. Degradation rates were not statistically significant from baseline values with either 0.5 or 0.9 mg/mL FC. In addition, we found a significant correlation between the difference in the baseline and post-CPB fibrinogen concentration with patient age ( P = .033) after controlling for weight. CONCLUSIONS: Our results show that clots formed ex vivo with clinically relevant doses of FC (0.9 mg/mL) display similar structural and degradation characteristics compared to the in vivo transfusion of cryoprecipitate. These findings suggest that FC is effective in restoring structural fibrin clot properties after CPB. Future studies after the administration of FC in vivo are needed to validate this hypothesis.

Use of Factor VIIa and Anti-inhibitor Coagulant Complex in Pediatric Cardiac Surgery Patients.

OBJECTIVES: Postoperative bleeding is a common cause of morbidity and mortality in cardiac patients who undergo cardiopulmonary bypass (CPB). Pediatric patients are especially at risk for adverse effects of surgery and CPB on the coagulation system. This can result in bleeding, transfusions, and poor outcomes. Excessive bleeding unresponsive to blood products can warrant the off-label use of recombinant activated clotting factor VIIa (rFVIIa) and/or anti-inhibitor coagulant complex (FEIBA). Several studies have shown the utility in these agents off-label in patients who have undergone cardiac bypass surgery with acute bleeding episodes that are refractory to blood products. However, data regarding use of these agents in pediatrics are sparse. The purpose of this study is to report the use of rFVIIa and FEIBA in pediatric cardiac surgery patients in our institution. METHODS: This was a retrospective chart review of pediatric cardiothoracic surgery patients who received rFVIIa or FEIBA at Children's Healthcare of Atlanta during the study period. RESULTS: Thirty-three patients received rFVIIa and 9 patients received FEIBA either intraoperatively or postoperatively for bleeding related to the cardiac procedure. Approximately 13% of rFVIIa patients and 55% of FEIBA patients required repeat doses. There were decreases for all blood products administered after rFVIIa and FEIBA were given. However, the doses used did not correlate with either positive or negative outcomes. Seventeen percent (n = 7) of rFVIIa patients experienced a thrombus and 22% (n = 2) of FEIBA patients experienced a thrombus. CONCLUSIONS: Both rFVIIa and FEIBA reduced blood product usage in pediatric patients following cardiac procedures.

Fibrinogen Concentrate as an Alternative to Cryoprecipitate in a Postcardiopulmonary Transfusion Algorithm in Infants Undergoing Cardiac Surgery: A Prospective Randomized Controlled Trial.

BACKGROUND: Infants undergoing cardiac surgery are at risk for bleeding and massive transfusion due to an immature coagulation system, complex surgeries, and cardiopulmonary bypass (CPB) effects. Hemodilution from CPB promotes an acquired hypofibrinogenemia that results in impaired fibrin formation, inadequate clot formation, and increased bleeding. In North America, the current standard of care to supplement fibrinogen is cryoprecipitate. An alternative option is the off-label use of fibrinogen concentrate (FC; RiaSTAP; CSL Behring, Marburg, Germany), a purified fibrinogen. Because perioperative allogenic transfusions are associated with increased morbidity and mortality, we sought to determine whether FC would be an acceptable alternative to cryoprecipitate in a post-CPB transfusion algorithm in infants undergoing open-heart surgery. METHODS: We randomized 60 infants (<12 months) undergoing nonemergent cardiac surgery with CPB at 2 tertiary care children's hospitals to receive either cryoprecipitate or FC in a post-CPB transfusion algorithm. Infants underwent a stratified randomization based on institution and surgical complexity. The primary outcome was the difference in number of intraoperative allogenic blood product transfusions. Secondary outcomes included 24-hour chest tube output (CTO), mechanical ventilation time, adverse events (AEs), intensive care unit (ICU) length of stay (LOS), hospital LOS, postoperative thrombosis, and death within 30 days of surgery. The primary analysis followed the intent-to-treat (ITT) principle and was performed using linear regression adjusted for institution and complexity of surgery. A per-protocol (PP) analysis was also performed. RESULTS: Between June 2016 and January 2018, we enrolled 60 patients with complete data available for 25 patients who received cryoprecipitate and 29 patients who received FC. Patients in the cryoprecipitate group (median age: 4 months [2-6 months]) received 5.5 (4.0-7.0) allogeneic blood units in the ITT analysis and 6.0 units (5.0-7.0 units) in the PP analysis. Patients in the FC group (median age: 4 months [2-5]) received 4 units (3.0-5.0 units) in the ITT analysis and 4.0 units (3.0-5.0 units) in the PP analysis. In the adjusted ITT analysis, the FC group received 1.79 units (95% confidence interval [CI], 0.64-2.93; P = .003) less than the cryoprecipitate group. In the adjusted PP analysis, the FC group received 2.67 units (95% CI, 1.75-3.59; P < .001) less than the cryoprecipitate group. There were no significant differences in secondary outcomes or AEs. CONCLUSIONS: Our findings suggest that FC may be considered as an alternative to cryoprecipitate for the treatment of hypofibrinogenemia in infants with bleeding after CPB. Although we found no significant differences between secondary outcomes or AEs, further studies are needed to assess safety.

The Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Cardiac Anesthesia Database Collaboration.

Multi-institutional databases and registries have proliferated over the last decade in all specialties of medicine. They may be especially helpful in low-frequency/high-acuity fields such as pediatric and congenital heart diseases. The Society of Thoracic Surgeon's Congenital Heart Surgery Database (STSCHSD) is the largest single data set for the congenital heart disease population and includes contemporaneous data from over 120 programs in the United States (and several outside of the United States), capturing greater than 98% of the congenital cardiac surgical procedures in the United States. In 2010, the Congenital Cardiac Anesthesia Society partnered with the STSCHSD to incorporate anesthesia-related elements into the data set. Voluntary site participation in the anesthesia data has grown steadily. Currently, over 60 sites performing more than 60% of cardiac bypass procedures in the STSCHSD are submitting anesthesia data annually into the STSCHSD. Anesthesia data include perioperative medication usage, modalities for hemodynamic and neurologic monitoring, blood product, antifibrinolytic and procoagulant use, and anesthesia-related adverse events. This special article provides a descriptive summary of relevant findings to date, reflecting the wide variety in anesthesia practice patterns present among institutions and illustrates the functionality of a multisite registry in pediatric cardiac anesthesia which can be utilized both locally and nationally.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Current use of factor concentrates in pediatric cardiac anesthesia.

Excessive bleeding following pediatric cardiopulmonary bypass is associated with increased morbidity and mortality, both from the effects of hemorrhage and the therapies employed to achieve hemostasis. Neonates and infants are especially at risk because their coagulation systems are immature, surgeries are often complex, and cardiopulmonary bypass technologies are inappropriately matched to patient size and physiology. Consequently, these young children receive substantial amounts of adult-derived blood products to restore adequate hemostasis. Adult and pediatric data demonstrate associations between blood product transfusions and adverse patient outcomes. Thus, efforts to limit bleeding after pediatric cardiopulmonary bypass and minimize allogeneic blood product exposure are warranted. The off-label use of factor concentrates, such as fibrinogen concentrate, recombinant activated factor VII, and prothrombin complex concentrates, is increasing as these hemostatic agents appear to offer several advantages over conventional blood products. However, recognizing that these agents have the potential for both benefit and harm, well-designed studies are needed to enhance our knowledge and to determine the optimal use of these agents. In this review, our primary objective was to examine the evidence regarding the use of factor concentrates to treat bleeding after pediatric CPB and identify where further research is required. PubMed, MEDLINE/OVID, The Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched to identify existing studies.

Longitudinal Echocardiographic Evaluation of an Unusual Presentation of X-Linked Myxomatous Valvular Dystrophy Caused by Filamin A Mutation.

Polyvalvar myxomatous valve degeneration is a clinical pathology rarely encountered during cardiac anesthesia, but, when present, most commonly occurs in the context of a connective tissue disorder. Filamin A mutations have begun to be recognized as a source of progressive myxomatous mitral and tricuspid valve degeneration. These lesions can be diagnosed by echo, but their clinical presentation can be equivocal. We present a patient with significant echocardiographic findings of mitral and tricuspid valvar regurgitation, aortic dilatation, and intraoperative findings of aortic ectasia. In our case, a detailed family history led to a preoperative echocardiogram revealing myxomatous mitral and tricuspid valve degeneration with significant regurgitation and aortic dilatation. Genetic evaluation led to the diagnosis of a Filamin A mutation. Pre- and postrepair echocardiographic assessments of valvar function played a key role in the management of this patient. Continued surveillance of his aortic dilation and evaluation of postrepair valve function warrants close follow-up with a high likelihood for further surgical intervention.

Fibrin Network Changes in Neonates after Cardiopulmonary Bypass.

BACKGROUND: Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of "fetal" fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of "fetal" fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB). METHODS: Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy. RESULTS: Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen. CONCLUSIONS: The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion.

Computational simulation and comparison of prothrombin complex concentrate dosing schemes for warfarin reversal in cardiac surgery.

BACKGROUND: Prothrombin complex concentrate (PCC) is increasingly used for acute warfarin reversal. We hypothesized that computational modeling of thrombin generation (TG) could be used to optimize the timing and dose of PCC during hemodilution induced by cardiopulmonary bypass (CPB). METHODS: Thrombin generation patterns were modeled in anticoagulated patients (n = 59) using a published computational model. Four dosing schemes were evaluated including single full dose (median, 41.2 IU/kg) of PCC before or after CPB, ½-dose before and after CPB, or 1/3-dose before CPB plus 2/3-dose after CPB. Hemodilution was modeled as 40 or 60 % dilution of factors from baseline. The lag time (s) of TG, and peak thrombin level (nM) were evaluated. RESULTS: Prolonged lag time, and reduced peak TG were due to low vitamin K-dependent (VKD) factors, and pre-CPB PCC dose-dependently restored TG to near-normal or normal range. After 40 % dilution, TG parameters were similar among 4 regimens at the end of therapy. The recovery of VKD factors was less when PCC was given before CPB after 60 % dilution, but TG parameters were considered hemostatically effective (>200 nM) with any regimen. Withholding the full dose of PCC until post-CPB resulted in severely depressed TG peak (median, 47 nM) after 60 % dilution, and some supra-normal TG peaks after treatment. CONCLUSIONS: Pre-CPB administration of full or divided doses of PCC prevents extremely low TG peak during surgery, and maintains hemostatic TG peaks in both 40 and 60 % hemodilution models. Although PCC's hemostatic activity appears to be highest using the full dose after CPB, hypercoagulability may develop in some cases.

Excessive postoperative bleeding and outcomes in neonates undergoing cardiopulmonary bypass.

BACKGROUND: Neonates undergoing cardiac surgery are especially prone to the hemostatic alterations of cardiopulmonary bypass (CPB) and are at high risk for post-CPB bleeding. An immature coagulation system, significant hemodilution from the CPB prime, long CPB times at low temperatures, and extensive suture lines increase neonates' susceptibility to bleeding after CPB. In this study, we examined the relationship between excessive bleeding in neonates after CPB and major postoperative adverse events. METHODS: We retrospectively reviewed the medical records of 169 neonates who underwent complex congenital heart surgery with CPB between January 1, 2010, and December 31, 2011. Perioperative data were collected and analyzed with specific focus on post-CPB bleeding as measured by 24-hour postoperative chest tube output (CTO), post-CPB transfusion requirements, and major postoperative adverse events, including renal dysfunction, dialysis, thrombosis, extracorporeal membrane oxygenation (ECMO), and in-hospital mortality. We used Spearman correlation to determine correlations between multiple perioperative variables and 24-hour CTO and postoperative blood product requirements. Also, we used logistic regression analysis to determine the association between excessive bleeding (defined as 24-hour CTO >75th percentile) and major postoperative adverse events. RESULTS: Significant correlations were found between 24-hour CTO and postoperative blood product transfusion with weight, Risk Adjustment for Congenital Heart Surgery (RACHS-1) score, CPB time, and lowest temperature. Logistic regression found that excessive bleeding after CPB was an independent predictor of postoperative dialysis (relative risk [RR] 12.0; confidence interval, 1.50-54.69; P = 0.02) and ECMO (RR 9.95; confidence interval, 3.07-28.47; P = 0.0008). RACHS-1 score was a significant predictor of in-hospital mortality (P = 0.03). CONCLUSIONS: Excessive postoperative bleeding in neonates after CPB is independently associated with increased adverse events, specifically the need for postoperative dialysis and ECMO support. Our findings in neonates are congruent with other recent research that also has found increasing transfusion requirements after pediatric CPB to be independently associated with an increase in major postoperative adverse events. Our results may aid clinicians in anticipating potential adverse events after neonatal bypass and in allocating the resources necessary to manage these events.

Early postoperative bleeding is independently associated with increased surgical mortality in infants after cardiopulmonary bypass.

OBJECTIVE: Infants undergoing cardiac surgery often have postoperative bleeding contributing to the occurrence of adverse events. A quantitative evaluation of postoperative bleeding has not been well described. METHODS: We identified 1071 infants who had undergone cardiopulmonary bypass from August 1, 2008 to December 31, 2011. The volume of postoperative bleeding and its effect on mortality were reviewed. RESULTS: Postoperative bleeding during the first 12 hours postoperatively was stratified by quartiles. Bleeding was significantly associated with increased mortality (odds ratio [OR], 1.15; 95% confidence interval [CI] 1.10-1.21; P < .001). Other risk factors significantly associated with mortality included greater Risk Adjustment for Congenital Heart Surgery score (OR, 1.5; 95% CI, 1.22-1.85; P < .001), single ventricle anatomy (OR, 3.09; 95% CI, 1.68-5.67; P < .001), younger age (OR, 0.99; 95% CI, 0.98-0.99; P < .001), and longer perfusion time (OR, 1.01; 95% CI, 1.01-1.02; P < .001). Subjects with greater bleeding volumes experienced a longer postoperative mechanical ventilation and intensive care unit stay. The overall hospital mortality was 4.1%. On multivariate analysis, adjusting for age, single ventricle anatomy, Risk Adjustment for Congenital Heart Surgery score, and perfusion time, an increasing bleeding volume was independently associated with increased mortality. Packed red blood cell transfusion was independently associated with an increased duration of mechanical ventilation (P = .01) and intensive care unit length of stay (P = .003). CONCLUSIONS: Early postoperative hemorrhage was independently associated with an increased mortality in infants after cardiac surgery. The longer interval from surgery to death suggests that other factors, aside from the bleeding itself, including the transfusion volume, might contribute to mortality. Initiatives to limit postoperative bleeding and to critically appraise packed red blood cell transfusion practices are warranted.

In-hospital shunt occlusion in infants undergoing a modified blalock-taussig shunt.

BACKGROUND: The clinical variables leading to postoperative thrombotic occlusion of a modified Blalock-Taussig shunt (mBTS) remain elusive. In this investigation, we assess several perioperative variables to determine associations with postoperative in-hospital shunt occlusion. METHODS: We retrospectively reviewed the medical records of infants receiving a mBTS as a first operation between March 1, 2005, and December 31, 2011. Numerous perioperative variables were collected, focusing on those that would increase resistance to blood flow through the shunt or alter coagulation. RESULTS: In all, 207 neonates fit our criteria. In-hospital shunt occlusion occurred in 14 patients (6.8%); 3 patients (21.4%) subsequently died during their hospitalization. Pulmonary atresia/ventricular septal defect with or without major aortopulmonary collateral arteries was the most common diagnosis associated with shunt occlusion (57.1%). Of the collected perioperative variables, pulmonary artery size was significantly associated with shunt occlusion (p = 0.03). Preoperative coagulation values were significantly reduced in those patients who experienced shunt occlusion. Additionally, the immediate postoperative activated partial thromboplastin time was significantly reduced in the occlusion group although values remained well above normal as all infants were treated postoperatively with a heparin infusion. CONCLUSIONS: We found that a patient's anatomy (pulmonary atresia/ventricular septal defect with or without major aortopulmonary collateral arteries) and the size of the pulmonary artery being shunted had a significant impact in predicting postoperative in-hospital shunt occlusion. These results emphasize that technical skills and a low resistance to blood flow are necessary for successful shunt function. Although some perioperative coagulation values were significantly reduced in infants who were destined to experience shunt occlusion, they would be difficult to detect clinically.

Development and implementation of a new data registry in congenital cardiac anesthesia.

A new multisite registry for congenital cardiac anesthesia patients has now been incorporated into The Society of Thoracic Surgeons Congenital Heart Surgery Database. This new registry, "The Joint Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Congenital Cardiac Anesthesia Database," is part of the Congenital Cardiac Anesthesia Society's commitment to patient care and research on outcomes improvement. This report will review the planning and funding of the initial start-up as well as the data elements being used in the registry. Patients in the registry include not only cardiac surgical patients but also those with congenital heart disease undergoing procedures in locations other than the operating room, including in the cardiac catheterization laboratory, intensive care unit, general operating room, and radiology suite. Initial results from the first data harvests are reported, including site participation, patient population submitted, and adverse outcomes observed. These initial results validate the concept and serve as a benchmark for further development and implementation of the registry. Because of the relative infrequency of anesthesia-related events in this low-volume procedure, a multisite data harvest is the most reasonable approach to capture a sufficient number of patient encounters in a timely manner to support outcomes analysis, quality assessment, and quality improvement.

Review of the off-label use of recombinant activated factor VII in pediatric cardiac surgery patients.

In recent years the off-label use of recombinant activated factor VII (rFVIIa) has markedly increased, particularly in pediatric cardiac surgery patients, and practitioners differ widely in their usage of the drug. In 2009, the Congenital Cardiac Anesthesia Society (CCAS) assembled a task force to review the literature on rFVIIa administration to pediatric cardiac surgery patients. The goal of the CCAS Task Force was to assess current practices and make recommendations about rFVIIa therapy to enhance quality of care, improve patient outcomes, reduce costs, and develop future research. In this review we summarized the important topics on current administration of rFVIIa to pediatric cardiac surgery patients including indications for use, efficacy, safety, dosing, and monitoring. All pediatric and pertinent adult literature regarding the administration of rFVIIa to cardiac surgical patients and published since 2000 were selected and studied. Of the 40 pediatric publications reviewed for this report, only 1 was a prospective randomized controlled trial thus making determinations of efficacy difficult. There is no substantive evidence to support the efficacy of rFVIIa as prophylactic or routine therapy during pediatric cardiac surgery. It may prove reasonable as rescue therapy because current observational evidence suggests that potential benefits of rFVIIa for this indication might outweigh the risks. Rescue therapy is appropriate for bleeding that is massive, potentially life-threatening, and refractory to conventional therapy. Nevertheless, extreme caution is advised when considering the administration of rFVIIa to patients who are at risk for thromboembolic complications because rates for clinical and subclinical thrombosis secondary to rFVIIa therapy are unknown at this time. This review is designed to aid practitioners in deciding when and how to administer rFVIIa to pediatric cardiac surgery patients; it is not intended to determine standard-of-care or practice guidelines. There are insufficient data to make evidence-based recommendations. Randomized controlled trials are needed to assess the efficacy of rFVIIa as prophylactic, routine, or rescue therapy and to determine the drug's safety profile particularly with regard to thrombosis. The CCAS rFVIIa Task Force will continue to monitor the literature, gather data, and make updates as more information becomes available.

Benefits and risks of red blood cell transfusion in pediatric patients undergoing cardiac surgery.

As the number of neonates and young infants undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) increases, red blood cell (RBC) transfusion will continue to be an integral part of the practice of pediatric cardiac anesthesiology. The decision of when to transfuse RBCs to these patients is complex and influenced by multiple factors such as size, presence of cyanotic heart disease, complexity of the surgical procedure, and the hemostatic alterations induced by CPB. The known benefits of RBC transfusion include an increase in the oxygen-carrying capacity of blood, improved tissue oxygenation, and improved hemostasis. Unfortunately, there is no minimum hemoglobin level that serves as a transfusion trigger for all pediatric patients undergoing cardiac surgery. Physiologic signs such as tachycardia, hypotension, low mixed venous oxygen saturation and increased oxygen extraction ratios can provide objective evidence of the need to augment a given hemoglobin level. Nevertheless, the benefits of RBC transfusion must be balanced against its risks and, in recent years, RBC transfusion has been subjected to intense scrutiny. The adverse consequences of RBC transfusion include the transmission of infectious diseases and immune-mediated and nonimmune-mediated complications. Advances in donor selection, infectious disease testing of donated blood, use of leukocyte reduction and irradiation of blood in defined situations have improved the safety of the blood supply in terms of infection transmission. However, a growing number of prospective randomized clinical trials are finding an association between RBC transfusion and an increased risk of morbidity and mortality even with the use of leuko-reduced blood. Thus, it is becoming increasingly important that the decision to transfuse RBCs be made with a thorough understanding of the benefit-to-risk ratio. This review addresses the benefits and risks of RBC transfusion, pertinent data acquired in the setting of congenital cardiac surgery and techniques designed to minimize the need for RBC transfusion.

Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass.

BACKGROUND: Monitoring heparin concentration along with the activated clotting time (ACT) may provide a more accurate guide for the administration of heparin to infants during cardiopulmonary bypass (CPB). However, standard laboratory assays of heparin concentration (antifactor Xa heparin concentration) require plasma instead of whole blood, and results are not immediately available to clinicians. Alternatively, measurements of whole blood heparin concentration may be performed at the bedside using an automated protamine titration device, the Hepcon instrument (Hepcon Hemostasis Management System Plus; Medtronics, Minneapolis, MN). The purpose of this investigation was to compare ACT measurements from 3 commercially available instruments and bedside measurements of whole blood heparin concentration using the Hepcon instrument with laboratory measurements of antifactor Xa plasma heparin concentration in infants younger than 6 months of age undergoing CPB. METHODS: Forty-four pediatric patients younger than 6 months of age scheduled for elective cardiac surgery requiring CPB were enrolled in this prospective study. Blood samples were drawn 3 minutes after the initial heparin bolus and immediately before the termination of CPB to obtain measurements of heparin anticoagulation. Kaolin-activated ACTs were performed with the Hemochron (International Technidyne Corporation, Edison, NJ), Hepcon, and i-STAT (i-STAT Corporation, East Windsor, NJ) instruments. Whole blood heparin concentration was measured using the Hepcon instrument. Plasma heparin concentration was measured using an antifactor Xa chromogenic substrate assay. RESULTS: Immediately after the initial heparin bolus, none of the ACT values correlated with plasma heparin concentration. When measured immediately before the termination of CPB, only the i-STAT ACT showed a moderate correlation. Conversely, bedside measurements of whole blood heparin concentration showed satisfactory agreement with laboratory measurements of plasma heparin concentration at both time points (concordance correlation coefficients 0.30 and 0.67, respectively). There is a bias in that antifactor Xa-measured plasma heparin concentration tends to be higher than Hepcon-measured whole blood heparin concentration. CONCLUSIONS: In infants younger than 6 months old undergoing CPB, caution is warranted when using ACT values as the sole indication of adequate heparin anticoagulation. In general, ACT prolongation correlates poorly with plasma heparin concentration. Only i-STAT ACT values showed a moderate correlation when measured immediately before the termination of CPB. Alternatively, bedside measurements of whole blood heparin concentration measured by the Hepcon instrument agreed well with antifactor Xa laboratory measurements. Our data support the clinical utility of bedside measurements of heparin concentration to provide timely, convenient, and accurate measurements of heparin concentration in these infants.