Publications by authors named "Jill M Cholette"

44 Publications

Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial.

Crit Care Med 2021 Apr;49(4):e369-e380

Department of Pediatrics, Washington University in St. Louis, St. Louis, MO.

Objectives: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children.

Design: Post hoc analysis of a Bayesian phase 2b randomized clinical trial.

Setting: Seven PICUs.

Patients: Children less than 18 years old with newly inserted central venous catheter.

Interventions: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care.

Measurements And Main Results: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count.

Conclusions: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.
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http://dx.doi.org/10.1097/CCM.0000000000004848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979442PMC
April 2021

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

Crit Care Med 2021 03;49(3):e235-e246

Department of Pediatrics, Washington University in St. Louis, St. Louis, MO.

Objectives: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children.

Design: Bayesian phase 2b randomized clinical trial.

Setting: Seven PICUs.

Patients: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding.

Intervention: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm).

Measurements And Main Results: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms.

Conclusions: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.
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http://dx.doi.org/10.1097/CCM.0000000000004784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902342PMC
March 2021

Intraoperative Cortical Asynchrony Predicts Abnormal Postoperative Electroencephalogram.

Ann Thorac Surg 2021 02 6;111(2):645-654. Epub 2020 Jun 6.

Department of Surgery, University of Rochester Medical Center, Rochester, New York.

Background: Postoperative electroencephalograms (EEGs) can identify seizure activity and neurologic dysfunction in high-risk neonates requiring cardiac surgical procedures. Although intraoperative EEG monitoring is uncommon, variations in cerebral blood flow and temperature during antegrade cerebral perfusion (ACP) can manifest as cortical asynchrony during EEG monitoring. We hypothesized that intraoperative EEG cortical asynchrony would identify neonates at risk for abnormal postoperative EEG tracings.

Methods: Neonates requiring ACP for cardiac repair or palliation had continuous baseline, intraoperative, and postoperative hemodynamic and EEG monitoring. Synchronous and asynchronous cortical bursts were quantified during (1) cooling before ACP, (2) ACP, and (3) rewarming. Asynchronous bursts were defined as interhemispheric variations in electrical voltage or frequency. Neonates were divided into 2 groups, those with and without an abnormal postoperative EEG, which was defined as either persistent asynchrony for more than 2 hours or seizure activity on EEG.

Results: Among 40 neonates, 296 asynchronous bursts were noted, most commonly during rewarming. Eight (20%) neonates had an abnormal postoperative EEG (seizure activity, n = 3; persistent asynchrony, n = 5). Baseline demographics and intraoperative hemodynamics were similar between the groups. However, the total number of intraoperative asynchronous bursts was greater in neonates with an abnormal postoperative EEG (17 [11, IQR:24] vs 3 [IQR:1, 7]; P < .001). Multivariate analysis confirmed that the number of asynchronous bursts was independently associated with an abnormal postoperative EEG (odds ratio,1.35; confidence interval,:1.10, 1.65; P = .004).

Conclusions: Neonates with a greater number of intraoperative asynchronous cortical bursts had an abnormal postoperative EEG.
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http://dx.doi.org/10.1016/j.athoracsur.2020.04.090DOI Listing
February 2021

Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients: A Randomized Clinical Trial.

JAMA 2019 12;322(22):2179-2190

Research CHU de Québec-Université Laval Centre, Population Health and Optimal Health Practices and Research Unit, Trauma, Emergency, Critical Care Medicine, Université Laval and Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Faculty of Medicine, Université Laval, Québec City, Québec, Canada.

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.

Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children.

Design, Setting, And Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded.

Interventions: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group.

Main Outcomes And Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death.

Results: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34).

Conclusions And Relevance: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells.

Trial Registration: ClinicalTrials.gov Identifier: NCT01977547.
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http://dx.doi.org/10.1001/jama.2019.17478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081749PMC
December 2019

Bleeding Assessment Scale in Critically Ill Children (BASIC): Physician-Driven Diagnostic Criteria for Bleeding Severity.

Crit Care Med 2019 12;47(12):1766-1772

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Children's Hospital of Richmond at VCU, Richmond, VA.

Objective: Although bleeding frequently occurs in critical illness, no published definition to date describes the severity of bleeding accurately in critically ill children. We sought to develop diagnostic criteria for bleeding severity in critically ill children.

Design: Delphi consensus process of multidisciplinary experts in bleeding/hemostasis in critically ill children, followed by prospective cohort study to test internal validity.

Setting: PICU.

Patients: Children at risk of bleeding in PICUs.

Interventions: None.

Measurements And Main Results: Twenty-four physicians worldwide (10 on a steering committee and 14 on an expert committee) from disciplines related to bleeding participated in development of a definition for clinically relevant bleeding. A provisional definition was created from 35 descriptors of bleeding. Using a modified online Delphi process and conference calls, the final definition resulted after seven rounds of voting. The Bleeding Assessment Scale in Critically Ill Children definition categorizes bleeding into severe, moderate, and minimal, using organ dysfunction, proportional changes in vital signs, anemia, and quantifiable bleeding. The criteria do not include treatments such as red cell transfusion or surgical interventions performed in response to the bleed. The definition was prospectively applied to 40 critically ill children with 46 distinct bleeding episodes. The kappa statistic between the two observers was 0.74 (95% CI, 0.57-0.91) representing substantial inter-rater reliability.

Conclusions: The Bleeding Assessment Scale in Critically Ill Children definition of clinically relevant bleeding severity is the first physician-driven definition applicable for bleeding in critically ill children derived via international expert consensus. The Bleeding Assessment Scale in Critically Ill Children definition includes clear criteria for bleeding severity in critically ill children. We anticipate that it will facilitate clinical communication among pediatric intensivists pertaining to bleeding and serve in the design of future epidemiologic studies if it is validated with patient outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000004025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861687PMC
December 2019

Transfusion medicine: A research agenda for the coming years.

Transfus Apher Sci 2019 Oct 6;58(5):698-700. Epub 2019 Aug 6.

Department of Pathology and Laboratory Medicine (Transfusion Medicine), University of Rochester Medical Center, Rochester, NY, USA; Department of Medicine, Hematology-Oncology Division,Rochester, NY, USA.

The important scientific and clinical advances of the last century in transfusion medicine include methods for avoiding hemolytic transfusion reactions and preventing transmission of viral infectious diseases. The next great clinical advances will require improving the efficacy and safety of transfusions, as well as acknowledgement of the now proven serious complications of transfusion, including nosocomial infection, thrombosis, inflammation and multi-organ failure. Possible strategies include (1) universal leukoreduction to mitigate transfusion immunomodulation effects and improve storage conditions, (2) minimizing transfusion of ABO incompatible antibodies and cellular/soluble antigens, (3) substituting use of safer solutions for normal saline during apheresis, component infusion and washing (4) new techniques to improve the efficacy and safety of blood components, including improved storage solutions/conditions, supernatant removal by washing, and rejuvenation and (5) maximizing the risk to benefit ratio of transfusions by employing more restrictive and physiologic indications for transfusion (including patient blood management) and improving clinical decision making through novel laboratory and bedside tests such as thromboelastography.
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http://dx.doi.org/10.1016/j.transci.2019.08.015DOI Listing
October 2019

Met-Hemoglobin Is a Biomarker for Poor Oxygen Delivery in Infants Following Surgical Palliation.

World J Pediatr Congenit Heart Surg 2019 07 29;10(4):485-491. Epub 2019 May 29.

3 Department of Pediatrics, University of Rochester, Rochester, NY, USA.

Background: Infants with cyanotic congenital heart disease demonstrate wide fluctuations in hemoglobin (Hb), oxygen saturation, and cardiac output following palliation. Methemoglobin (Met-Hb), the product of Hb oxidation, may represent a compensatory mechanism during hypoxia and may be utilized as a biomarker.

Methods: Arterial and venous Met-Hb levels were obtained from infants requiring palliation. The primary outcome was to describe the relationship between Met-Hb and other indices of tissue oxygenation (venous saturation, estimated arteriovenous oxygen difference [Est AV-Diff], and lactate). Secondary outcomes were to determine the impact of elevated Met-Hb levels ≥1.0% and the effect of red blood cell (RBC) transfusion on Met-Hb levels.

Results: Fifty infants and 465 Met-Hb values were studied. Venous Met-Hb levels were significantly higher than arterial levels (venous: 0.84% ± 0.36% vs arterial: 0.45% ± 0.18%; < .001). Venous Met-Hb demonstrated a significant inverse relationship with venous oxygen saturation ( = -0.6; < .001) and Hb ( = -0.3, < .001) and a direct relationship with the Est AV-Diff ( = 0.3, < .001). A total of 129 (29.6%) venous Met-Hb values were elevated (≥1.0%) and were associated with significantly lower Hb and venous saturation levels and higher Est AV-Diff and lactate levels. Methemoglobin levels decreased significantly following 65 RBC transfusions (0.94 ± 0.40 vs 0.77 ± 0.34; < .001). Linear mixed models demonstrated that higher venous Met-Hb levels were associated with lower measures of tissue oxygenation and not related to any preoperative clinical differences.

Conclusion: Methemoglobin may be a clinically useful marker of tissue oxygenation in infants following surgical palliation.
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http://dx.doi.org/10.1177/2150135119852327DOI Listing
July 2019

Total plasma heme concentration increases after red blood cell transfusion and predicts mortality in critically ill medical patients.

Transfusion 2019 06 27;59(6):2007-2015. Epub 2019 Feb 27.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.

Background: Relationships between red blood cell (RBC) transfusion, circulating cell-free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients.

Study Design And Methods: This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion. Cell-free heme was measured in RBC units before transfusion and in the patients' plasma before and after transfusion.

Results: Total plasma heme levels increased in response to transfusion, from a median (interquartile range [IQR]) of 35 (26-76) μmol/L to 47 (35-73) μmol/L (p < 0.001). Posttransfusion total plasma heme was higher in nonsurvivors (54 [35-136] μmol/L) versus survivors (44 [31-65] μmol/L, p = 0.03). Posttransfusion total plasma heme predicted hospital mortality (odds ratio [95% confidence interval] per quartile increase in posttransfusion plasma heme, 1.76 [1.17-2.66]; p = 0.007). Posttransfusion total plasma heme was not correlated with RBC unit storage duration and weakly correlated with RBC unit cell-free heme concentration.

Conclusions: Total plasma heme concentration increases in critically ill patients after RBC transfusion and is independently associated with mortality. This transfusion-associated increase in total plasma heme is not fully explained by RBC unit storage age or cell-free heme content. Additional studies are warranted to define mechanisms of transfusion-related plasma heme accumulation and test prevention strategies.
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http://dx.doi.org/10.1111/trf.15218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548617PMC
June 2019

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

Pediatr Crit Care Med 2018 09;19(9):884-898

Division of Pediatric Critical Care, Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA.

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.
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http://dx.doi.org/10.1097/PCC.0000000000001613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126913PMC
September 2018

Recommendations on RBC Transfusion in Infants and Children With Acquired and Congenital Heart Disease From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Pediatr Crit Care Med 2018 09;19(9S Suppl 1):S137-S148

Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Objectives: To present the recommendations and supporting literature for RBC transfusions in critically ill children with acquired and congenital heart disease developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Design: Consensus conference series of 38 international, multidisciplinary experts in RBC transfusion management of critically ill children.

Methods: Experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations and research priorities for RBC transfusions in critically ill children. The cardiac disease subgroup included three experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases 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.

Results: Twenty-one recommendations were developed and reached agreement. For children with myocardial dysfunction and/or pulmonary hypertension, there is no evidence that transfusion greater than hemoglobin of 10 g/dL is beneficial. For children with uncorrected heart disease, we recommended maintaining hemoglobin greater than 7-9.0 g/dL depending upon their cardiopulmonary reserve. For stable children undergoing biventricular repairs, we recommend not transfusing if the hemoglobin is greater than 7.0 g/dL. For infants undergoing staged palliative procedures with stable hemodynamics, we recommend avoiding transfusions solely based upon hemoglobin, if hemoglobin is greater than 9.0 g/dL. We recommend intraoperative and postoperative blood conservation measures. There are insufficient data supporting shorter storage duration RBCs. The risks and benefits of RBC transfusions in children with cardiac disease requires further study.

Conclusions: We present RBC transfusion management recommendations for the critically ill child with cardiac disease. Clinical recommendations emphasize relevant hemoglobin thresholds, and research recommendations emphasize need for further understanding of physiologic and hemoglobin thresholds and alternatives to RBC transfusion in subpopulations lacking pediatric literature.
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http://dx.doi.org/10.1097/PCC.0000000000001603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126364PMC
September 2018

Recommendations on RBC Transfusion in General Critically Ill Children Based on Hemoglobin and/or Physiologic Thresholds From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Pediatr Crit Care Med 2018 09;19(9S Suppl 1):S98-S113

Division of Pediatric Critical Care, Department of Pediatrics, Sainte-Justine Hospital, Université de Montréal, Montréal, QC, Canada.

Objectives: To present the consensus recommendations and supporting literature for RBC transfusions in general critically ill children from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Design: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.

Methods: The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based recommendations and research priorities regarding RBC transfusions in critically ill children. The subgroup on RBC transfusion in general critically ill children included six experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 30, 2017, using a combination of keywords to define concepts of RBC transfusion and critically ill children. Recommendation consensus was obtained using the Research and Development/UCLA Appropriateness Method. The results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.

Results: Three adjudicators reviewed 4,399 abstracts; 71 papers were read, and 17 were retained. Three papers were added manually. The general Transfusion and Anemia Expertise Initiative subgroup developed, and all Transfusion and Anemia Expertise Initiative members voted on two good practice statements, six recommendations, and 11 research questions; in all instances, agreement was reached (> 80%). The good practice statements suggest a framework for RBC transfusion in PICU patients. The good practice statements and recommendations focus on hemoglobin as a threshold and/or target. The research questions focus on hemoglobin and physiologic thresholds for RBC transfusion, alternatives, and risk/benefit ratio of transfusion.

Conclusions: Transfusion and Anemia Expertise Initiative developed pediatric-specific good practice statements and recommendations regarding RBC transfusion management in the general PICU population, as well as recommendations to guide future research priorities. Clinical recommendations emphasized relevant hemoglobin thresholds, and research recommendations emphasized a need for further understanding of physiologic thresholds, alternatives to RBC transfusion, and hemoglobin thresholds in populations with limited pediatric literature.
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http://dx.doi.org/10.1097/PCC.0000000000001590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125789PMC
September 2018

Decreased Hemolysis and Improved Platelet Function in Blood Components Washed With Plasma-Lyte A Compared to 0.9% Sodium Chloride.

Am J Clin Pathol 2018 Jul;150(2):146-153

Department of Pathology and Laboratory Medicine, Transfusion Medicine Division, Rochester, NY.

Objectives: Washing cellular blood products is accepted to ameliorate repeated severe allergic reactions but is associated with RBC hemolysis and suboptimal platelet function. We compared in vitro hemolysis and platelet function in blood components after washing with Plasma-Lyte A (PL-A) vs normal saline (NS).

Methods: RBC (n = 14) were washed/resuspended in NS or PL-A. Free hemoglobin and heme were determined at 0, 24, 48, and 72 hours. Platelet concentrates (PCs; n = 21) were washed with NS or PL-A and resuspended in same washing solution (n = 13) or ABO-identical plasma (n = 8). Platelet aggregation and spreading were evaluated.

Results: The 24-hour free hemoglobin and heme levels were higher in NS (P < .05). Improved platelet function was observed in PL-A-washed PCs (P < .001).

Discussion: PL-A showed less RBC hemolysis and better platelet function than NS. Whether such differences would occur in vivo is unknown.
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http://dx.doi.org/10.1093/ajcp/aqy036DOI Listing
July 2018

Indications for red cell transfusions in pediatric patients.

Transfus Apher Sci 2018 Jun 10;57(3):342-346. Epub 2018 May 10.

Transfusion Medicine/Blood Bank Division of Pathology and Laboratory Medicine, University of Rochester Medical Center, Strong Memorial and Golisano Children's Hospitals, United States.

Red cell transfusions are amongst the most common therapeutic procedures in seriously ill children, particularly in the inpatient setting. This is despite the fact that there is no evidence base for most clinical settings, with the exception of patients with hemoglobinopathies, particularly thalassemia and sickle cell anemia. Obviously exsanguinating hemorrhage and life threatening anemia are urgent indications for which no other therapeutic approach is currently available. Most transfusions are, however, given prophylactically to prevent the complications of hypoxia or hemodynamic stability, based upon expert opinion and a faith in the oxygen carrying capacity and beneficial hemodynamic properties of transfused red cells. The question confronting current day pediatric practice is to what extent transfused red cells prevent adverse events, other than in thalassemia and sickle cell anemia, as opposed to causing them. Do transfusions of red cells prevent organ failure, stroke, etc. or not? There is epidemiologic evidence in the adult randomized trial literature that liberal red cell transfusion likely causes more such adverse events than it prevents. The relevance of such studies to children, particularly neonates, is uncertain. Randomized trials in critically ill neonates have yielded little to no evidence that liberal red cell transfusion is beneficial, but the data are not definitive. In critically ill older children the data suggest there is no benefit to liberal red cell transfusion, but the indications for red cell transfusion are uncertain. Most practitioners would agree that combining laboratory data such hemoglobin/hematocrit with clinical indications for transfusions (evidence of end organ hypoxia such as tachycardia, shortness of breath, etc.) is the only viable strategy at present, until more definitive randomized trial data are available.
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http://dx.doi.org/10.1016/j.transci.2018.05.017DOI Listing
June 2018

Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.

Transfusion 2018 07 30;58(7):1631-1639. Epub 2018 Mar 30.

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.

Background: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin.

Study Design And Methods: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures. The median free Hb in patients without infection (30 mg/dL; 29 interquartile range [IQR], 24-52 mg/dL) was lower than in those who became infected (39 mg/dL; IQR, 33-88 mg/ 31 dL; p = 0.0046). The median mechanical ventilation requirements were 19 (IQR, 7-72) hours in patients with higher levels of haptoglobin versus 48 (IQR, 18-144) hours in patients with lower levels (p = 0.0047). Transfusion dose, bypass duration, and complexity of surgery were all significantly correlated with Hb levels and haptoglobin levels. Multivariate analyses demonstrated that these variables were independently and significantly associated with outcomes.

Conclusions: Elevated pre- and postoperative levels of free Hb and decreased levels of haptoglobin were associated with adverse clinical outcomes, inflammation, and unfavorable physiologic metrics. Transfusion, RACHS score, and duration of bypass were associated with increased free Hb and decreased haptoglobin. Further investigation of the role of hemolysis and haptoglobin as potential mediators or markers of outcomes is warranted.
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http://dx.doi.org/10.1111/trf.14601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105435PMC
July 2018

0.9% NaCl (Normal Saline) - Perhaps not so normal after all?

Transfus Apher Sci 2018 Feb 21;57(1):127-131. Epub 2018 Feb 21.

Department of Pathology and Laboratory Medicine (Transfusion Medicine), University of Rochester Medical Center, Rochester, NY, USA; Department of Medicine (Hematology-Oncology), University of Rochester Medical Center, Rochester, NY, USA.

Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A. Normal saline is the solution most widely employed in medical and pediatric care, as well as in hematology and transfusion medicine. However, there is growing concern that normal saline is more toxic than balanced, buffered crystalloids such as Plasma-Lyte and Lactated Ringer's. Normal saline is the only solution recommended for red cell washing, administration and salvage in the USA, but Plasma-Lyte A is also FDA approved for these purposes. Lactated Ringer's has been traditionally avoided in these applications due to concerns over clotting, but existing research suggests this is not likely a problem. In animal models and clinical studies in various settings, normal saline can cause metabolic acidosis, vascular and renal function changes, as well as abdominal pain in comparison with balanced crystalloids. The one extant randomized trial suggests that in very small volumes (2 l or less) normal saline is not more toxic than other crystalloids. Recent evidence suggests that normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A and similar solutions during short term storage (24 hours) after washing or intraoperative salvage. There are now abundant data to raise concerns as to whether normal saline is the safest replacement solution in infusion therapy, red cell washing and salvage, apheresis and similar uses. In the USA, Plasma-Lyte A is also FDA approved for use with blood components and is likely a safer solution for these purposes. Its only disadvantage is a higher cost. Additional studies of the safety of normal saline for virtually all current clinical uses are needed. It seems likely that normal saline will eventually be abandoned in favor of safer, more physiologic crystalloid solutions in the coming years.
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http://dx.doi.org/10.1016/j.transci.2018.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899644PMC
February 2018

Modified Repair of Type I and II Truncus Arteriosus Limits Early Right Ventricular Outflow Tract Reoperation.

Semin Thorac Cardiovasc Surg 2018 8;30(2):199-204. Epub 2018 Feb 8.

Department of Surgery, University of Rochester Medical Center, Rochester, New York; Department of Pediatrics, University of Rochester Medical Center, Rochester, New York; Pediatric Cardiac Consortium of Upstate New York. Electronic address:

Repair of truncus arteriosus often requires early right ventricular outflow tract (RVOT) reoperation. Using a modified repair, the branch pulmonary arteries are left in situ, which may avoid earlier RVOT reoperation. We hypothesized that our modified repair for type I and II truncus arteriosus would extend the time to RVOT reoperation. Infants with truncus arteriosus were divided into 2 groups: (1) traditional technique where the branch pulmonary arteries are excised from the truncal root, or (2) modified repair where the branch pulmonary arteries are left in situ and septated from the truncal root. Regardless of the approach, a bioprosthetic conduit or homograft was used to establish right ventricular to pulmonary artery continuity. Follow-up pulmonary artery angiograms were used to assess for branch pulmonary artery stenosis. From 54 infants (modified repair: 33, traditional technique: 21), there were no significant differences in age at repair, gender, or type of truncus arteriosus. With 100% follow-up, use of the modified repair resulted in a lower rate of branch pulmonary artery stenosis, and greater freedom from surgical branch pulmonary arterioplasty. Five- and 10-year freedom from RVOT reoperation (5 years: modified-81.5% vs traditional-30.5%, P = 0.004; 10 years: modified-53.3% vs traditional-30.5%, P = 0.01) favored the modified repair. Cox regression analysis demonstrated that the modified repair was associated with an independently lower risk for RVOT reoperation (hazard ratio: 0.08, confidence interval: 0.01, 0.75, P = 0.02). Thus, maintaining the branch pulmonary artery architecture resulted in greater freedom from RVOT reoperation.
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http://dx.doi.org/10.1053/j.semtcvs.2018.02.003DOI Listing
November 2018

Oxidation Reduction Potential (ORP) is Predictive of Complications Following Pediatric Cardiac Surgery.

Pediatr Cardiol 2018 Feb 31;39(2):299-306. Epub 2017 Oct 31.

Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.

Oxidation reduction potential (ORP) or Redox is the ratio of activity between oxidizers and reducers. Oxidative stress (OS) can cause cellular injury and death, and is important in the regulation of immune response to injury or disease. In the present study, we investigated changes in the redox system as a function of cardiopulmonary bypass (CPB) in pediatric patients. 664 plasma samples were collected from 162 pediatric patients having cardiac surgery of various CPB times. Lower ORP values at 12 h post-CPB were associated with poor survival rate (mean ± SD 167 ± 20 vs. 138 ± 19, p = 0.005) and higher rate of thrombotic complications (153 ± 21 vs. 168 ± 20, p < 0.008). Similarly, patients who developed infections had lower ORP values at 6 h (149 ± 19 vs. 160 ± 22, p = 0.02) and 12 h (156 ± 17 vs. 168 ± 21, p = 0.004) post-CPB. Patients that developed any post-operative complication also had lower 6 h (149 ± 17 vs. 161 ± 23, p = 0.002) and 12 h (157 ± 18 vs. 170 ± 21, p = 0.0007) post-CPB ORP values. Free hemoglobin and IL-6, IL-10, and CRP were not associated with ORP levels. However, higher haptoglobin levels preoperatively were protective against decreases in ORP. Decreased ORP is a marker for poor outcome and predictive of post-operative thrombosis, infection, and other complications in critically ill pediatric cardiac surgery patients. These results suggest that redox imbalance and OS may contribute to the risk of complications and poor outcome in pediatric CBP patients. Haptoglobin may be a marker for increased resilience to OS in this population.
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http://dx.doi.org/10.1007/s00246-017-1755-xDOI Listing
February 2018

Patient Blood Management in Pediatric Cardiac Surgery: A Review.

Anesth Analg 2018 10;127(4):1002-1016

Division of Pediatric Critical Care, Children's Hospital of Illinois At OSF St Frances, University of Illinois at Peoria, Peoria, Illinois.

Efforts to reduce blood product transfusions and adopt blood conservation strategies for infants and children undergoing cardiac surgical procedures are ongoing. Children typically receive red blood cell and coagulant blood products perioperatively for many reasons, including developmental alterations of their hemostatic system, and hemodilution and hypothermia with cardiopulmonary bypass that incites inflammation and coagulopathy and requires systemic anticoagulation. The complexity of their surgical procedures, complex cardiopulmonary interactions, and risk for inadequate oxygen delivery and postoperative bleeding further contribute to blood product utilization in this vulnerable population. Despite these challenges, safe conservative blood management practices spanning the pre-, intra-, and postoperative periods are being developed and are associated with reduced blood product transfusions. This review summarizes the available evidence regarding anemia management and blood transfusion practices in the perioperative care of these critically ill children. The evidence suggests that adoption of a comprehensive blood management approach decreases blood transfusions, but the impact on clinical outcomes is less well studied and represents an area that deserves further investigation.
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http://dx.doi.org/10.1213/ANE.0000000000002504DOI Listing
October 2018

Transfer of Neonates with Critical Congenital Heart Disease Within a Regionalized Network.

Pediatr Cardiol 2017 Oct 15;38(7):1350-1358. Epub 2017 Jul 15.

Pediatric Cardiac Consortium of Upstate New York, New York, USA.

Regionalization of pediatric cardiac surgical care varies between and within states. In most geographic regions, at least some neonates with critical heart disease are transferred from their birth hospital to a different hospital for surgery. The impact of neonatal transfer for surgery, particularly over a considerable distance (>10 miles), has been largely unexplored. We sought to examine the impact of transferring neonates for cardiac surgery. We queried the New York State Cardiac Surgery database (2005-2014) from a single institution to identify neonates born within the cardiac surgery center and those transferred for surgery. Outcomes were compared between groups, with subgroup analysis of neonates with single ventricle anatomy. 113 surgical neonates were born at the cardiac surgery center, and 268 were transferred to the cardiac surgery center. Median transfer distance was 91 (IQR 73, 94) miles. Age at operation and the need for preoperative ventilation were significantly lower in neonates born at the cardiac surgery center. In addition, single ventricle anatomy was more prevalent among those born at the cardiac surgery center (48.7 vs. 31.3%; p = 0.001). However, postoperative outcomes were the same-30-day survival was similar across groups (birth: 89% vs. transfer: 90%; p = 0.7), and for those with single ventricle palliation (birth: 81% vs. transfer: 81%; p = 0.9). Within our regionalized network, we found no difference in 30-day survival between neonates either born or transferred to a cardiac surgery center, which supports the use of a regionalized network of hospitals to the care of children with congenital heart disease.
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http://dx.doi.org/10.1007/s00246-017-1668-8DOI Listing
October 2017

Management of Platelet Disorders and Platelet Transfusions in ICU Patients.

Transfus Med Rev 2017 10 4;31(4):252-257. Epub 2017 May 4.

Pulmonary and Critical Care, Department of Medicine, Strong Memorial Hospital and Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY.

Thrombocytopenia or receipt of antiplatelet drugs, with or without bleeding, is a common indication for platelet transfusions in the ICU. However, there is almost no evidence base for these practices other than expert opinion. Also common is use of platelet transfusions prior to invasive procedures or surgery in patients with thrombocytopenia. Likewise, there is no high-quality evidence that such practices are efficacious or safe. Recently, it has become clear that, whether causal or not, patients receiving prophylactic platelet transfusions experience high rates of nosocomial infection, thrombosis, organ failure, and mortality, which increase the urgency and need for randomized trials to assess these practices. Investigational methods of improving the safety and efficacy of platelet transfusions include use of alternate strategies such as antifibrinolytics; use of ABO-identical, leukoreduced, and washed platelet transfusions; and improved storage solutions.
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http://dx.doi.org/10.1016/j.tmrv.2017.04.002DOI Listing
October 2017

Continuous Cardiopulmonary Bypass During the Repair of Total Anomalous Pulmonary Venous Return.

World J Pediatr Congenit Heart Surg 2016 11;7(6):750-752

Pediatric Cardiac Consortium of Upstate New York, NY, USA

Circulatory arrest (CA) is traditionally utilized during the repair of total anomalous pulmonary venous return (TAPVR). Since 2005, we have exclusively repaired all types of TAPVR using continuous cardiopulmonary bypass. We present our technique using continuous cardiopulmonary bypass throughout the duration of the repair, by temporarily occluding the vertical vein and placing a pump sucker within the pulmonary venous confluence. This technique has been used on 29 consecutive patients and resulted in limited morbidity and absence of pulmonary vein stenosis from most recent follow-up.
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http://dx.doi.org/10.1177/2150135116663699DOI Listing
November 2016

Transfusion-related immunomodulation: review of the literature and implications for pediatric critical illness.

Transfusion 2017 01 2;57(1):195-206. Epub 2016 Oct 2.

Blood Systems Research Institute.

Transfusion-related immunomodulation (TRIM) in the intensive care unit (ICU) is difficult to define and likely represents a complicated set of physiologic responses to transfusion, including both proinflammatory and immunosuppressive effects. Similarly, the immunologic response to critical illness in both adults and children is highly complex and is characterized by both acute inflammation and acquired immune suppression. How transfusion may contribute to or perpetuate these phenotypes in the ICU is poorly understood, despite the fact that transfusion is common in critically ill patients. Both hyperinflammation and severe immune suppression are associated with poor outcomes from critical illness, underscoring the need to understand potential immunologic consequences of blood product transfusion. In this review we outline the dynamic immunologic response to critical illness, provide clinical evidence in support of immunomodulatory effects of blood product transfusion, review preclinical and translational studies to date of TRIM, and provide insight into future research directions.
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http://dx.doi.org/10.1111/trf.13855DOI Listing
January 2017

Left Main Coronary Artery Atresia in an Infant With Inclusion-Cell Disease.

World J Pediatr Congenit Heart Surg 2018 03 12;9(2):246-250. Epub 2016 Sep 12.

1 Division of Pediatric Cardiology, Department of Pediatrics, University of Rochester Medical Center, Golisano Children's Hospital, Rochester, NY, USA.

A 2-month-old male with dysmorphic facies, neonatal thrombocytopenia, left congenital cataract, and long bone abnormalities became hypotensive with ST depression on induction of anesthesia for congenital cataract repair. Echocardiogram demonstrated decreased left ventricular function (ejection fraction 46%), mild mitral valve regurgitation (MR), and regional wall motion abnormalities. The left coronary artery could not be visualized. Subsequent cardiac catheterization confirmed atresia of the left main coronary artery. The patient underwent cardiac surgery with coronary artery bypass grafting of the left internal mammary artery to the left anterior descending coronary artery. His postoperative course was uncomplicated, his ventricular function normalized, and he was discharged home. Over the next few months, he developed progressive, severe MR refractory to medical management. Repeat cardiac catheterization revealed stenosis of the right proximal coronary artery, raising concern for progressive coronary involvement. In addition to dysmorphic features and failure to thrive, there were profound developmental delays and a finding of vacuolated lymphocytes on blood smear, which led to a diagnosis of mucolipidosis II (Inclusion [I]-cell disease). The patient was referred for mitral valve replacement, which was successful; however, ongoing respiratory issues attributed to the progression of I-cell disease led to a prolonged hospitalization with placement of a tracheostomy. Reports of coronary anomalies in patients with I-cell disease are rare. An association between mucopolysaccharidosis syndromes and coronary artery abnormalities has been established and is supported by this case report, highlighting the importance of considering the potential for coronary artery involvement with I-cell disease and other similar storage diseases.
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http://dx.doi.org/10.1177/2150135116664701DOI Listing
March 2018

Cuffed endotracheal tubes in neonates and infants undergoing cardiac surgery are not associated with airway complications.

J Clin Anesth 2016 Sep 4;33:422-7. Epub 2016 Jun 4.

Departments of Pediatrics, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642, USA. Electronic address:

Study Objective: To determine the incidence of postoperative airway complications in infants <5kg in weight undergoing cardiac surgery intubated with Microcuff (Kimberley-Clark, Roswell, GA) endotracheal tubes (ETTs).

Design: Retrospective review of infants weighing <5.0 kg with congenital heart disease (CHD) presenting for cardiac surgery.

Setting: Single-center, tertiary pediatric cardiac critical care unit at a university hospital.

Patients: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013.

Intervention: Intubation with Microcuff (Kimberley-Clark) ETTs.

Study Design: Retrospective review of infants weighing <5.0 kg with CHD presenting for cardiac surgery to a single-center tertiary care university hospital.

Measurements: Perioperative data were collected. Primary outcome was development of tracheal stenosis and/or reintubation for stridor. Stridor was defined as mild (≤2 doses of racemic epinephrine), moderate (>2 doses of racemic epinephrine), or severe (requiring reintubation). Secondary outcomes were variables possibly contributing to postextubation stridor. Infants with a tracheostomy, airway anomalies, and death prior to initial extubation were excluded. Logistic regression analysis was performed to evaluate the association between clinical risk factors and the incidence of postextubation stridor.

Results: A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013; 12 subjects were excluded for death prior to initial extubation. No infant developed tracheal stenosis. The incidence of any stridor was 20.9% (95% confidence interval, 15.8%-27.1%) with severe stridor in 2 cases (1%). Age at surgery, weight, duration of intubation, dexamethasone use, and ETT size were not significantly associated with postextubation stridor. Presence of a comorbidity was significantly associated with stridor (P=.01).

Conclusions: Microcuff ETTs in infants <5.0 kg in weight undergoing cardiac surgery are associated with a low incidence of severe postextubation stridor. Because cuffed ETTs allow for improved control of ventilation/oxygenation and decreased risk of aspiration, they should be considered for use in this high-risk population. Larger studies are needed to confirm these results.
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http://dx.doi.org/10.1016/j.jclinane.2016.04.038DOI Listing
September 2016

Outcomes Using a Conservative Versus Liberal Red Blood Cell Transfusion Strategy in Infants Requiring Cardiac Operation.

Ann Thorac Surg 2017 Jan 3;103(1):206-214. Epub 2016 Aug 3.

Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, New York.

Background: The optimal hemoglobin for infants after cardiac operation is unknown. Red blood cells (RBCs) are commonly transfused to maintain high hemoglobin concentrations in the absence of a clinical indication. We hypothesized that infants can be managed with a postoperative conservative RBC transfusion strategy, resulting in lower daily hemoglobin concentrations, without evidence of impaired oxygen delivery (ie, lactate, arteriovenous oxygen difference [avOdiff]), or adverse clinical outcomes.

Methods: Infants weighing 10 kg or less undergoing biventricular repair or palliative (nonseptated) operation were randomly assigned to either a postoperative conservative or liberal transfusion strategy. Conservative group strategy was RBC transfusion for a hemoglobin less than 7.0 g/dL for biventricular repairs or less than 9.0 g/dL for palliative procedures plus a clinical indication. Liberal group strategy was RBC transfusion for hemoglobin less than 9.5 g/dL for biventricular repairs or less than 12 g/dL for palliative procedures regardless of clinical indication.

Results: After the operation of 162 infants (82 conservative [53 biventricular, 29 palliative], 80 liberal [52 biventricular, 28 palliative]), including 12 Norwood procedures (6 conservative, 6 liberal), daily hemoglobin concentrations were significantly lower within the conservative group than the liberal group by postoperative day 1 and remained lower for more than 10 days. The percentage of patients requiring a RBC transfusion, number of transfusions, and volume of transfusions were all significantly lower within the conservative group. Despite lower hemoglobin concentrations within the conservative group, lactate, avOdiff, and clinical outcomes were similar.

Conclusions: Infants undergoing cardiac operation can be managed with a conservative RBC transfusion strategy. Clinical indications should help guide the decision for RBC transfusion even in this uniquely vulnerable population. Larger multicenter trials are needed to confirm these results, and focus on the highest risk patients would be of great interest.
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http://dx.doi.org/10.1016/j.athoracsur.2016.05.049DOI Listing
January 2017

Use of a Dacron Annular Sparing Versus Limited Transannular Patch With Nominal Pulmonary Annular Expansion in Infants With Tetralogy of Fallot.

Ann Thorac Surg 2017 Jan 29;103(1):186-192. Epub 2016 Jul 29.

Pediatric Cardiac Consortium of Upstate New York, Rochester, New York; University of Rochester Medical Center, Strong Memorial Hospital, Rochester, New York. Electronic address:

Background: Repair of tetralogy of Fallot (ToF) using a transannular patch can result in severe pulmonary insufficiency (PI) and subsequent right ventricular (RV) dilation. Use of a Dacron (Maquet Cardiovascular LLC, Wayne, NJ) limited transannular patch with nominal pulmonary annular expansion (LTAP) attempts to limit PI. We sought to evaluate the degree of PI and RV dilation resulting from a LTAP or annular sparing (AS) approach.

Methods: Infants less than 1 year of age undergoing ToF repair between 2000 and 2010 were divided into 2 groups: LTAP and AS RV outflow tract patch. Echocardiograms were used to determine RV dimensions and corresponding Z-values.

Results: From 94 infants, 48 required a LTAP and 46 required an AS patch. The preoperative pulmonary valve annulus Z-value was significantly smaller in the LTAP versus AS group (-2.7 ± 1.4 versus -0.9 ± 1.5; p < 0.001). Mean follow-up was obtained at 7.9 ± 3.4 years. Ten-year freedom from severe pulmonary insufficiency was 78.5% versus 93.2% (p = 0.3) in the LTAP and AS groups, respectively. There was no significant difference in the diameter of the RV base Z-value between groups (LTAP: 0.9 ± 0.8 versus AS: 0.0 ± 2.3; p = 0.1). Further, the freedom from reoperation at 10 years was also not significantly different between the LTAP and AS groups (95.6% versus 91.8%; p = 0.5).

Conclusions: When required, a LTAP results in a similar change in RV chamber size and rate of reoperation at an intermediate-term follow-up.
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http://dx.doi.org/10.1016/j.athoracsur.2016.05.056DOI Listing
January 2017

Neurodevelopmental outcomes after neonatal cardiac surgery: Role of cortical isoelectric activity.

J Thorac Cardiovasc Surg 2016 Apr 27;151(4):1137-42. Epub 2015 Oct 27.

Department of Surgery, University of Rochester Medical Center, Rochester, NY.

Objectives: Neonates with congenital heart disease are at risk for impaired neurodevelopment after cardiac surgery. We hypothesized that intraoperative EEG activity may provide insight into future neurodevelopmental outcomes.

Methods: Neonates requiring surgery had continuous intraoperative EEG and hemodynamic monitoring. The level of EEG suppression was classified as either: slow and continuous; moderate burst suppression; severe burst suppression; or isoelectric (no brain activity for >3 minutes). Follow-up neurodevelopmental outcomes were assessed using the Vineland Adaptive Behavior Scale II (Vineland-II).

Results: Twenty-one neonates requiring cardiac surgery developed a slow and continuous EEG pattern after general anesthesia. Ten neonates (48%) maintained continuous brain electrical activity with moderate burst suppression as the maximum level of EEG suppression. Eleven neonates (52%) developed severe burst suppression that progressed into an isoelectric state during the deep hypothermic period required for circulatory arrest. However, the duration of this state was significantly longer than circulatory arrest times (111.1 ± 50 vs 22.3 ± 17 minutes; P < .001). At a mean follow-up at 5.6 ± 1.0 years, compared with neonates with continuous brain electrical activity, neonates who developed an isoelectric state had lower Vineland-II scores in communication. There was an inverse relationship between composite Vineland-II scores and duration of isoelectric activity (R = -0.75, P = .01). Of neonates who experienced an isoelectric state, durations of >90 minutes were associated with the lowest Vineland-II scores (125.0 ± 2.6 vs 81.1 ± 12.7; P < .01).

Conclusions: The duration of cortical isoelectric states seems related to neurodevelopmental outcomes. Strategies using continuous EEG monitoring to minimize isoelectric states may be useful during complex congenital heart surgery.
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http://dx.doi.org/10.1016/j.jtcvs.2015.10.065DOI Listing
April 2016

Distal Transverse Arch to Left Carotid Artery Ratio Helps to Identify Infants With Aortic Arch Hypoplasia.

Ann Thorac Surg 2015 Sep 23;100(3):1004-11; discussion 1011-2. Epub 2015 Jul 23.

Pediatric Cardiac Consortium of Upstate New York, Rochester, New York; University of Rochester Medical Center, Strong Memorial Hospital, Rochester, New York.

Background: Aortic coarctation (CoA) with concomitant aortic arch hypoplasia (AAH) is associated with an increased risk of hypertension after surgical repair. The differentiation of CoA with or without AAH may be critical to delineate the ideal surgical approach that best ameliorates postoperative hypertension. Since 2000, we have defined CoA with AAH when the diameter of the distal transverse aortic arch is equal to or less than the diameter of the left carotid artery. We hypothesized that, based on our definition, aortic tissue from infants having CoA with AAH would demonstrate distinct genetic expression patterns as compared with infants having CoA alone.

Methods: From 6 infants (AAH, 3; CoA, 3), an Affymetrix 1.0 genome array identified genes in the coarctation/arch region that were differentially expressed between infants having CoA with AAH versus CoA alone. Reverse transcription polymerase chain reaction validated genetic differences from a cohort of 21 infants (CoA with AAH, 10; CoA, 11). To evaluate the clinical outcomes based on our definition of CoA with AAH, we reviewed infants repaired using this algorithm from 2000 to 2010.

Results: Microarray data demonstrated genes differentially expressed between groups. Reverse transcription polymerase chain reaction confirmed that CoA with AAH was associated with an increased expression of genes involved in cardiac and vascular development and growth, including hepsin, fibroblast growth factor-18, and T-box 2. The clinical outcomes of 79 infants (AAH, 26; CoA, 53) demonstrated that 90.1% were free of hypertension at 13 years when managed with this surgical strategy.

Conclusions: These findings provide evidence that the ratio of the diameter of the distal transverse arch to the left carotid artery may be helpful to identify CoA with AAH and, when used to delineate the surgical approach, may minimize hypertension.
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http://dx.doi.org/10.1016/j.athoracsur.2015.04.107DOI Listing
September 2015

Pharmacokinetics of ε-Aminocaproic Acid in Neonates Undergoing Cardiac Surgery with Cardiopulmonary Bypass.

Anesthesiology 2015 May;122(5):1002-9

From the Departments of Anesthesiology (M.P.E., D.M.S.), Surgery (G.M.A., R.E.A.), Pediatrics (J.M.C.), and Neurology, Center for Human Experimental Therapeutics (C.V.), University of Rochester School of Medicine and Dentistry, Rochester, New York; and Department of Anaesthesiology, University of Auckland, Auckland, New Zealand (B.A.).

Background: Antifibrinolytic medications such as ε-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. The authors sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population.

Methods: Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70-kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/l).

Results: Pharmacokinetics were described using a two-compartment model plus an additional compartment for the cardiopulmonary bypass pump. First-order elimination was described with a clearance of 5.07 l/h × (WT/70). Simulation showed a dosing regimen with a loading dose of 40 mg/kg and an infusion of 30 mg · kg · h, with a pump prime concentration of 100 mg/l maintained plasma concentrations above 50 mg/l in 90% of neonates during cardiopulmonary bypass surgery.

Conclusions: EACA clearance, expressed using allometry, is reduced in neonates compared with older children and adults. Loading dose and infusion dose are approximately half those required in children and adults.
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http://dx.doi.org/10.1097/ALN.0000000000000616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882606PMC
May 2015

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

Pediatr Crit Care Med 2015 Mar;16(3):227-35

1Department of Pediatrics, University of Rochester, Rochester, NY. 2Department of Medicine, University of Rochester, Rochester, NY. 3Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY. 4Congenital Cardiac Surgery, University of Rochester, Rochester, NY. 5Department of Environmental Medicine, University of Rochester, Rochester, NY. 6Department of Anesthesiology, University of Rochester, Rochester, NY.

Objectives: Infants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown.

Interventions: One hundred and twenty-eight consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed versus standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1-2 units on the day of surgery was performed.

Measurements And Main Results: Mortality was low (4.9%) with no association between RBC storage duration and survival. The postoperative infection rate was significantly higher in children receiving the oldest blood (25-38 d) compared with those receiving the freshest RBCs (7-15 d) (34% vs 7%; p = 0.004). Subgroup analysis of subjects receiving only 1-2 RBC transfusions on the day of surgery (n = 74) also demonstrates a greater prevalence of infections in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage; 1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage; p = 0.01). In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of postoperative infection. Washing the oldest RBCs (> 27 d) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs.

Discussion: Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single-donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on postoperative infection rate in pediatric cardiac surgery are warranted.
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http://dx.doi.org/10.1097/PCC.0000000000000320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351137PMC
March 2015