Ketorolac Dosing and Outcomes in Neonates Following Congenital Heart Surgery: A Retrospective Analysis.

BACKGROUND: Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as ketorolac, has increased. Published data on use in neonates are limited. OBJECTIVES: To describe ketorolac dosing and safety and efficacy outcomes in the first 48 hours postcardiac surgery in neonates. DESIGN: We performed a single-center retrospective cohort study of neonates (ages < 28 d) who received ketorolac following cardiac surgery from November 2020 to July 2023 (inclusive). The primary safety outcome was a clinically significant decline in renal function, as defined by the composite of an increase in serum creatinine by greater than or equal to 0.3 mg/dL from baseline within 96 hours of ketorolac initiation and urine output less than or equal to 0.5 mL/kg/hr for 6 hours. The secondary safety outcome was clinically significant bleeding, defined as the composite of major bleeding by the International Society on Thrombosis and Hemostasis pediatric criteria and severe/fatal bleeding by the criteria of Nellis et al (2019). Efficacy was measured by opioid utilization based on a standardized pain score-driven analgesia protocol. INTERVENTIONS: Ketorolac was administered at 0.5 mg/kg every 6 hours as per an institutional clinical management algorithm. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients met the eligibility criteria. The median ketorolac dose was 0.5 mg/kg/dose, and median (interquartile range [IQR]) duration of therapy was 48 hours (6-48 hr). No patients experienced a significant decline in renal function, and there were no clinically significant bleeding events. The median (IQR) IV morphine milligram equivalents (MMEs)/kg/d of opioid administration was 0.2 MME/kg/d (0.1-0.25 MME/kg/d) at the time of ketorolac initiation and 0.1 MME/kg/d (0.1-0.2 MME/kg/d) at 48 hours post-ketorolac initiation. CONCLUSIONS: If validated prospectively, these findings suggest that a ketorolac regimen of 0.5 mg/kg/dose every 6 hours in neonates postcardiac surgery may be safe with regard to renal function and bleeding risk. Additional randomized studies would be needed to determine efficacy with regard to opioid-sparing capacity.

Pediatric Extracorporeal Membrane Oxygenation Anticoagulation and Monitoring: Where We Were and Where Are We Now?

Extracorporeal membrane oxygenation (ECMO) support in neonates and pediatric patients has continued to advance. In addition to technologic progress, there is a growing interest in the anticoagulation agents and laboratory monitoring strategies used in children requiring ECMO support. This review summarizes current available evidence and provides guidance for clinicians regarding anticoagulation agents and monitoring.

Ketorolac in neonates and infants following congenital heart surgery: a retrospective review.

INTRODUCTION: Pain management is essential in the immediate post-surgical period. We sought to describe the ketorolac dose regimen in neonates and infants following cardiac surgery. Secondary outcomes included renal dysfunction, bleeding, and pain management. METHODS: We performed a single-centre retrospective cohort study of neonates and infants (aged < 12 months) who received ketorolac following cardiac surgery, from November 2020 through November 2021 (inclusive). Ketorolac was administered at 0.5 mg/kg every 6 hours. Safety was defined by absence of a clinically significant decline in renal function (i.e., increase in serum creatinine [SCr] by ≥ 0.3 mg/dL from baseline within 48 hours and/or urine output ≤ 0.5 mL/kg/hour for 6 hours) and absence of clinically significant bleeding defined as major by International Society on Thrombosis and Hemostasis paediatric criteria or Severe/Fatal Bleeding Events by Nellis et al. Efficacy measures included pain scores and opioid utilisation. RESULTS: Fifty-five patients met eligibility criteria. The median (range) dose and duration of ketorolac administration was 0.5 mg/kg/dose for 48 (6-90) hours. Among all patients, there was not a statistically significant difference observed in median SCr within 48 hours of baseline (p > .9). There were no major or severe bleeding events. The median (range) opioid requirements (morphine intravenous equivalents per kg per day) at 48 hours post-ketorolac initiation was 0.1 (0-0.8) mg/kg/day. CONCLUSIONS: If validated prospectively, these findings suggest that a ketorolac regimen 0.5 mg/kg/dose every 6 hours in neonates and infants post-cardiac surgery may be safe with regard to renal function and bleeding risk, and effective regarding opioid-sparing capacity.

Annexin A2 Loss After Cardiopulmonary Bypass and Development of Acute Postoperative Respiratory Dysfunction in Children.

The primary objective of this study was to determine whether expression of the multifunctional and adherens junction-regulating protein, annexin A2 (A2), is altered following cardiopulmonary bypass (CPB). A secondary objective was to determine whether depletion of A2 is associated with post-CPB organ dysfunction in children. DESIGN: In a prospective, observational study conducted over a 1-year period in children undergoing cardiac surgery requiring CPB, we analyzed A2 expression in peripheral blood mononuclear cells at different time points. We then assessed the relationship of A2 expression with organ function at each time point in the early postoperative period. SETTING: Twenty-three-bed mixed PICU in a tertiary academic center. PARTICIPANTS: Patients 1 month to 18 years old undergoing cardiac surgery requiring CPB. MEAN OUTCOME MEASUREMENTS AND RESULTS: We analyzed A2 expression in 22 enrolled subjects (n = 9, 1-23 mo old; n = 13, 2-18 yr old) and found a proteolysis-mediated decline in intact A2 immediately after bypass (p = 0.0009), reaching a median of 4% of baseline at 6 hours after bypass (p < 0.0001), and recovery by postoperative day 1. The degree of A2 depletion immediately after bypass in 1-23-month-olds correlated strongly with the extent of organ dysfunction, as measured by PICU admission Vasoactive-Ventilation-Renal (p = 0.004) and PEdiatric Logistic Organ Dysfunction-2 (p = 0.039) scores on postoperative day 1. A2 depletion immediately after bypass also correlated with more protracted requirement for both respiratory support (p = 0.007) and invasive ventilation (p = 0.013) in the 1-23-month-olds. CONCLUSIONS AND RELEVANCE: The degree of depletion of A2 following CPB correlates with more severe organ dysfunction, especially acute respiratory compromise in children under 2 years. These findings suggest that loss of A2 may contribute to pulmonary microvascular leak in young children following CPB.

Development of consensus recommendations for the management of post-operative chylothorax in paediatric CHD.

OBJECTIVE: A standardised multi-site approach to manage paediatric post-operative chylothorax does not exist and leads to unnecessary practice variation. The Chylothorax Work Group utilised the Pediatric Critical Care Consortium infrastructure to address this gap. METHODS: Over 60 multi-disciplinary providers representing 22 centres convened virtually as a quality initiative to develop an algorithm to manage paediatric post-operative chylothorax. Agreement was objectively quantified for each recommendation in the algorithm by utilising an anonymous survey. "Consensus" was defined as ≥ 80% of responses as "agree" or "strongly agree" to a recommendation. In order to determine if the algorithm recommendations would be correctly interpreted in the clinical environment, we developed ex vivo simulations and surveyed patients who developed the algorithm and patients who did not. RESULTS: The algorithm is intended for all children (<18 years of age) within 30 days of cardiac surgery. It contains rationale for 11 central chylothorax management recommendations; diagnostic criteria and evaluation, trial of fat-modified diet, stratification by volume of daily output, timing of first-line medical therapy for "low" and "high" volume patients, and timing and duration of fat-modified diet. All recommendations achieved "consensus" (agreement >80%) by the workgroup (range 81-100%). Ex vivo simulations demonstrated good understanding by developers (range 94-100%) and non-developers (73%-100%). CONCLUSIONS: The quality improvement effort represents the first multi-site algorithm for the management of paediatric post-operative chylothorax. The algorithm includes transparent and objective measures of agreement and understanding. Agreement to the algorithm recommendations was >80%, and overall understanding was 94%.

The Use of Hemostatic Blood Products in Children Following Cardiopulmonary Bypass and Associated Outcomes.

To describe the use of hemostatic transfusions in children following cardiac surgery with cardiopulmonary bypass and the association of hemostatic transfusions postoperatively with clinical outcomes. DESIGN: A retrospective cohort study. SETTING: PICU of a tertiary care center from 2011 to 2017. PATIENTS: Children 0-18 years old undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred twenty children underwent cardiac surgery with cardiopulmonary bypass. The median (interquartile range) age was 0.8 years (0.3-5 yr) and 243 (58%) were male. The majority of cases were classified as Risk Adjustment for Congenital Heart Surgery 2 (223, 54%) or Risk Adjustment for Congenital Heart Surgery 3 (124, 30%). Twenty-four percent of children (102/420) received at least one hemostatic transfusion with the most common first product being platelet transfusions (47/102), followed by plasma (44/102), and cryoprecipitate (11/102). The children who received hemostatic transfusions were younger (p = 0.006), had lower body weights (p = 0.004), less likely to be their initial operation with cardiopulmonary bypass (p = 0.003), underwent more complex surgeries (p = 0.001) with longer bypass runs (p < 0.001), and had more use of hypothermic circulatory arrest (p = 0.014). The receipt of hemostatic blood products postoperatively was independently associated with more days of mechanical ventilation (p < 0.001) and longer PICU lengths of stay (p = 0.001) but not with time receiving vasoactive mediations (p = 0.113) or nosocomial infections (p = 0.299). CONCLUSIONS: Nearly one-quarter of children undergoing cardiac repair with cardiopulmonary bypass receive hemostatic transfusions postoperatively. These blood products are independently associated with worse clinical outcomes. Larger studies should be performed to determine the hemostatic efficacy of these products, as well as to clarify associated morbidities, in order to inform proper blood management.

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

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.

Early identification of impending cardiac arrest in neonates and infants in the cardiovascular ICU: a statistical modelling approach using physiologic monitoring data.

OBJECTIVE: To develop a physiological data-driven model for early identification of impending cardiac arrest in neonates and infants with cardiac disease hospitalised in the cardiovascular ICU. METHODS: We performed a single-institution retrospective cohort study (11 January 2013-16 September 2015) of patients ≤1 year old with cardiac disease who were hospitalised in the cardiovascular ICU at a tertiary care children's hospital. Demographics and diagnostic codes of cardiac arrest were obtained via the electronic health record. Diagnosis of cardiac arrest was validated by expert clinician review. Minute-to-minute physiological monitoring data were recorded via bedside monitors. A generalized linear model was used to compute a minute by minute risk score. Training and test data sets both included data from patients who did and did not develop cardiac arrest. An optimal risk-score threshold was derived based on the model's discriminatory capacity for impending arrest versus non-arrest. Model performance measures included sensitivity, specificity, accuracy, likelihood ratios, and post-test probability of arrest. RESULTS: The final model consisting of multiple clinical parameters was able to identify impending cardiac arrest at least 2 hours prior to the event with an overall accuracy of 75% (sensitivity = 61%, specificity = 80%) and observed an increase in probability of detection of cardiac arrest from a pre-test probability of 9.6% to a post-test probability of 21.2%. CONCLUSIONS: Our findings demonstrate that a predictive model using physiologic monitoring data in neonates and infants with cardiac disease hospitalised in the paediatric cardiovascular ICU can identify impending cardiac arrest on average 17 hours prior to arrest.

Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation.

BACKGROUND: Paediatric hospital-associated venous thromboembolism is a leading quality and safety concern at children's hospitals. OBJECTIVE: The aim of this study was to determine risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. METHODS: We conducted a retrospective, case-control study of children admitted to the cardiovascular intensive care unit at Johns Hopkins All Children's Hospital (St. Petersburg, Florida, United States of America) from 2006 to 2013. Hospital-associated venous thromboembolism cases were identified based on ICD-9 discharge codes and validated using radiological record review. We randomly selected two contemporaneous cardiovascular intensive care unit controls without hospital-associated venous thromboembolism for each hospital-associated venous thromboembolism case, and limited the study population to patients who had undergone cardiothoracic surgery or therapeutic cardiac catheterisation. Odds ratios and 95% confidence intervals for associations between putative risk factors and hospital-associated venous thromboembolism were determined using univariate and multivariate logistic regression. RESULTS: Among 2718 admissions to the cardiovascular intensive care unit during the study period, 65 met the criteria for hospital-associated venous thromboembolism (occurrence rate, 2%). Restriction to cases and controls having undergone the procedures of interest yielded a final study population of 57 hospital-associated venous thromboembolism cases and 76 controls. In a multiple logistic regression model, major infection (odds ratio=5.77, 95% confidence interval=1.06-31.4), age ⩽1 year (odds ratio=6.75, 95% confidence interval=1.13-160), and central venous catheterisation (odds ratio=7.36, 95% confidence interval=1.13-47.8) were found to be statistically significant independent risk factors for hospital-associated venous thromboembolism in these children. Patients with all three factors had a markedly increased post-test probability of having hospital-associated venous thromboembolism. CONCLUSION: Major infection, infancy, and central venous catheterisation are independent risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or cardiac catheter-based intervention, which, in combination, define a high-risk group for hospital-associated venous thromboembolism.

Cardiac extracorporeal life support: state of the art in 2007.

Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease.A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation.As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile "Berlin Heart" ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support "urgently" rather than "emergently", before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability.

Caudal anesthesia in pediatric cardiac surgery: does it affect outcome?

OBJECTIVE: The purpose of this study was to examine the influence of caudal anesthesia on outcomes (pediatric intensive care unit [PICU] length of stay, hospital length of stay, ventilatory time, early extubation rate) in pediatric patients undergoing congenital heart disease repair requiring cardiopulmonary bypass (CPB). DESIGN: Retrospective. SETTING: University teaching hospital. PARTICIPANTS: Pediatric patients undergoing surgery to treat congenital heart disease between 1999 and 2002. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Thirty-four patients with atrial septal defect (ASD), 37 with ventricular septal defect, and 46 with tetralogy of Fallot (TOF) were included in the analysis. No differences were found in preoperative and intraoperative data between caudal and noncaudal group for each disorder. There was no difference between caudal and noncaudal groups in PICU and hospital stay. A statistically significant difference was found in the postoperative ventilatory time in patients with ASD and TOF between caudal and noncaudal groups. The early extubation rate was higher in the TOF caudal group compared with the noncaudal group. CONCLUSIONS: This retrospective study demonstrated that postinduction placement of caudal anesthesia does not affect PICU or hospital length of stay. A well-controlled prospective study is needed to confirm these findings.