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Abstract: Open-heart surgery with cardiopulmonary bypass often leads to complications including pain, systemic inflammation, and organ damage. Traditionally managed with opioids, these pain relief methods bring potential long-term risks, prompting the exploration of alternative treatments. The legalization of cannabis in various regions has reignited interest in cannabinoids, such as cannabidiol, known for their anti-inflammatory, analgesic, and neuroprotective properties. Historical and ongoing research acknowledges the endocannabinoid system's crucial role in managing physiological processes, suggesting that cannabinoids could offer therapeutic benefits in postsurgical recovery. Specifically, cannabidiol has shown promise in managing pain, moderating immune responses, and mitigating ischemia/reperfusion injury, underscoring its potential in postoperative care. However, the translation of these findings into clinical practice faces challenges, highlighting the need for extensive research to establish effective, safe cannabinoid-based therapies for patients undergoing open-heart surgery. This narrative review advocates for a balanced approach, considering both the therapeutic potential of cannabinoids and the complexities of their integration into clinical settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Society of Critical Care Medicine (SCCM) Reviewer Academy seeks to train and establish a community of trusted, reliable, and skilled peer reviewers with diverse backgrounds and interests to promote high-quality reviews for each of the SCCM journals. Goals of the Academy include building accessible resources to highlight qualities of excellent manuscript reviews; educating and mentoring a diverse group of healthcare professionals; and establishing and upholding standards for insightful and informative reviews. This manuscript will map the mission of the Reviewer Academy with a succinct summary of the importance of peer review, process of reviewing a manuscript, and the expected ethical standards of reviewers. We will equip readers to target concise, thoughtful feedback as peer reviewers, advance their understanding of the editorial process and inspire readers to integrate medical journalism into diverse professional careers., Competing Interests: Dr. Alexander has received funding from the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development (R13HD104432), Food and Drug Administration (FP01029501), US Department of Defense (W81XWH2210301), and unrestricted grants from the Extracorporeal Life Support Organization (ELSO). Her institution received funding from Novartis (end-point adjudication committee PANORAMA-HF) and she serves as the ELSO Treasurer of the Board of Directors. Dr. Barreto received funding from Wolters-Kluwer. Dr. Morrow’s institution received funding from the Society of Critical Care Medicine (SCCM) for her role as Senior Associate Editor for Pediatric Critical Care Medicine, the National Research Foundation of Southern Africa, and EuroQual; she received funding from the Brazilian Physiotherapy Association. Dr. Mayer’s institution received funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (no. K23-AR079583); he received support for article research from the NIH. Dr. Lane-Fall’s institution receives funding from NIH (R01HL153735, P30AG059302, UM1HL088957, U01OD033246, R01HD105446, R01HD109229), Agency for Healthcare Research and Quality (K12HS026372), Patient-Centered Outcomes Research Institute (21106), and the American Heart Association (962544). She serves as the Vice President of the Anesthesia Patient Safety Foundation and is on the Board of Directors of the Foundation for Anesthesia Education and Research. Dr. Kudchadkar has received funding from NIH/NICHD (R01HD103811) and NIH/NIDDK (R01DK132348). Dr. Rech has received research funding from Spero Pharmaceuticals. Ms. Napolitano receives funding from NIH (1R44HD105552, 1R21HD103927-01A1, 1R01HD106996) and FDA (5P50FD006427) and also has research/consulting relationships with Drager, Philips/Respironics, Timpel, Actuated Medical, and Vero-Biotech. Dr. Sorce disclosed that she is an SCCM Executive Board Member. Dr. Tasker is the Editor-in-Chief for Pediatric Critical Care Medicine. Dr. Buchman is Editor-in-Chief for Critical Care Medicine. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

A multidisciplinary team is needed to optimally care for infants with congenital heart disease (CHD). Different compositions of teams trained in cardiology, critical care, cardiothoracic surgery, anesthesia, and neonatology have been identified as being primarily responsible for perioperative care of this high-risk population in dedicated cardiac intensive care units (CICUs). Although the specific role of cardiac intensivists has become more well defined over the past two decades, the responsibilities of neonatologists remain highly variable in the CICU with neonatologists providing care along with a unique spectrum of primary, shared, or consultative care. The neonatologist can function as the primary physician and assume all or share responsibility with the cardiac intensivists for the management of infants with CHD. A neonatologist can provide care as a secondary consultant physician in a supportive role for the primary CICU team. Additionally, neonates with CHD can be mixed with older children in a CICU, cohorted in a dedicated space within the CICU or placed in a stand-alone infant CICU without older children. Although variations exist between centers on which model of care is deployed and the location within a CICU, characterization of current practice patterns represents the initial step required to determine optimal best practices to improve the quality of care for neonates with cardiac disease. In this manuscript, we present four models utilized in the United States in which the neonatologist provides neonatal-cardiac-focused care in a dedicated CICU. We also outline the different permutations of location where neonates can be cared for in dedicated pediatric/infant CICUs.

Monitoring the hemodynamic state of patients is a hallmark of any intensive care environment. However, no single monitoring strategy can provide all the necessary data to paint the entire picture of the state of a patient; each monitor has strengths and weaknesses, advantages, and limitations. We review the currently available hemodynamic monitors used in pediatric critical care units using a clinical scenario. This provides the reader with a construct to understand the progression from basic to more advanced monitoring modalities and how they serve to inform the practitioner at the bedside., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: To compare the clinical, laboratory, and hemodynamic parameters during hospitalization for patients with multisystem inflammatory syndrome in children (MIS-C), across the Original/Alpha and the Delta variants of severe acute respiratory syndrome coronavirus 2 infection., Design: Retrospective cohort study., Setting: Single-center quaternary children's hospital., Patients: Children with MIS-C admitted from May 2020 to February 2021(Original and Alpha variant cohort) and August 2021 to November 2021 (Delta variant cohort)., Measurements and Main Results: Continuous vital sign measurements, laboratory results, medications data, and hospital outcomes from all subjects were evaluated. Of the 134 patients (102 with Original/Alpha and 32 with Delta), median age was 9 years, 75 (56%) were male, and 61 (46%) were Hispanics. The cohort with Original/Alpha variant had more males (61% vs 41%; p = 0.036) and more respiratory/musculoskeletal symptoms on presentation compared with the Delta variant ( p < 0.05). More patients in the Original/Alpha variant cohort received mechanical ventilation (16 vs 0; p = 0.009). Median hospital length of stay (LOS) was 7 days, and ICU LOS was 3 days for the entire cohort. ICU LOS was shorter in cohort with the Delta variant compared with the Original/Alpha variant (4 vs 2 d; p = 0.001). Only one patient had cardiac arrest, two needed extracorporeal membrane oxygenation, and two needed left ventricular assist device (Impella, Danvers, MA), all in the Original/Alpha variant cohort; no mortality occurred in the entire cohort. MIS-C cohort associated with the Delta variant had lower INR, prothrombin time, WBCs, sodium, phosphorus, and potassium median values ( p < 0.05) during hospitalization compared with the Original/Alpha variants. Hemodynamic assessment showed significant tachycardia in the Original/Alpha variants cohort compared with the Delta variant cohort ( p < 0.05)., Interventions: None., Conclusions: Patients with MIS-C associated with the Delta variants had lower severity during hospitalization compared with the Original/Alpha variant. Analysis of distinct trends in clinical and laboratory parameters with future variants of concerns will allow for potential modification of treatment protocol., Competing Interests: Dr. Jain’s institution received funding from the National Institute for Child Health and Human Development (1R61HD105593). Drs. Jain, Annapragada, Muscal, Vogel, and Rusin received support for article research from the National Institutes of Health (NIH). Dr. Annapragada’s institution received funding from the NIH (R61HD105593); he received funding from Alzeca and Sensulin; he disclosed that he is the inventor on numerous patents that are either licensed to or assigned to his employer, past employers, or other entities. Drs. Muscal and Vogel disclosed the off-label product use of Anakinra. Dr. Vogel’s institution received funding from the NIH; she disclosed the off-label product use of IV immunoglobulin for multisystem inflammatory syndrome in children. Dr. Rusin received funding from Medical Informatics Corp; he disclosed that he is the cofounder and Chief Technology Officer of Medical Informatics, and he disclosed that his wife is the cofounder and Chief Executive Officer of Medical Informatics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Opioids are used to manage pain, comfort, maintain devices, and decrease oxygen consumption around Norwood palliation (NP), but in high dose and prolonged exposure, they increase risk of tolerance and iatrogenic withdrawal syndrome (IAWS). Variability in practice for IAWS prevention potentially increases opioid dose and duration. We hypothesize that protocolized weaning with morphine (MOR) versus nonprotocolized methadone (MTD) is associated with reduction in opioid exposure., Design: A before-versus-after study of outcomes of patients weaned with protocolized MOR versus nonprotocolized MTD including subset analysis for those patients with complications postoperatively. Primary endpoints include daily, wean phase, and total morphine milligram equivalent (MMEq) dose, duration, and, secondarily, length of stay (LOS)., Setting: Quaternary-care pediatric cardiac ICU., Patients: Neonates undergoing single-ventricle palliation., Interventions: Introduction of IAWS prevention protocol., Measurements and Main Results: Analysis included 54 patients who underwent the NP in 2017-2018 including the subset analysis of 34 who had a complicated postoperative course. The total and wean phase opioid doses for the MTD group were significantly higher than that for the MOR group: 258 versus 22 and 115 versus 6 MMEq/kg; p < 0.001. Duration of opioid exposure was 63 days in the MTD group and 12 days in MOR group (p < 0.001). Subanalysis of the complicated subset also identifies higher total and wean dose for MTD group (293 vs 41 and 116 vs 7 MMEq/kg; p < 0.001) with a longer duration (65 vs 22 days; p = 0.001). Within the subset, LOS was 55% longer in the MTD group than that in the MOR group (150 vs 67 d; p = 0.01) and not different in the uncomplicated group., Conclusions: After complex NP, a protocolized opioid weaning using MOR versus MTD is associated with 65% shorter opioid duration, 10-fold decreased dose, and shortened LOS., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

The purpose of this study is to assess the effect of calcium bolus in response to a hypotensive episode by assessing high-fidelity hemodynamic data obtained from children with single-ventricle physiology with parallel circulation. Single-center, retrospective analysis of hemodynamic data after calcium bolus administrations within the first 2 weeks post-surgery. Time intervals were the baseline (- 60 to - 10 min); the hypotensive episode (- 10 to 0 min); time point zero at the bolus administration; and the response (0 to 60 min). The main responses assessed were the peak increase in mean blood pressure (mBP), duration of the response after the bolus, and markers of oximetric effects. These analyses included 128 boluses in 63 patients. Of the total boluses analyzed, 80% increased the mBP by 5 mmHg or higher with the effect lasting at least 10 min, whereas 10% of the boluses analyzed increased the mBP by 20 mmHg or higher with the effect lasting at least 50 min. The boluses induced a significant increase in arterial oxygen saturation and an upward trend in pulmonary-to-systemic flow ratio, without increasing renal or cerebral oxygen extraction ratios. Calcium chloride boluses are an effective rescue medication for hypotensive episodes in children with parallel circulation. They lead to an improvement in mBP, as well as an increase in pulmonary-to-systemic blood flow ratio. More importantly, these boluses do not compromise systemic oxygen delivery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Cardiovascular dysfunction is associated with poor outcomes in critically ill children., Objective: We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children., Data Sources: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest., Study Selection: Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded., Data Extraction: Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member., Results: Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition., Limitations: All included studies were observational and many were retrospective., Conclusions: The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: Corticosteroids suppress the inflammatory response to cardiopulmonary bypass in children undergoing cardiac surgery. What is less clear is the impact of corticosteroids on the postoperative course., Methods: A systematic review and meta-analysis was made of prospective randomized blinded placebo-controlled trials of pediatric patients who received corticosteroids or saline placebo before surgery was performed. Ten studies met inclusion criteria for a total of 768 patients. In a prespecified subgroup analysis, studies that either were limited to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery congenital heart surgery mortality categories 1 and 2 or excluded neonates were eliminated and a secondary analysis was conducted, which consisted of seven studies and 555 patients., Results: Corticosteroids were associated with a significant improvement in fluid balance at 24 and 36 hours after surgery, with a mean difference of -15.2 mL/kg (95% confidence interval, 25.3 to -5.1 mL/kg; P < .01) and -5.7 mL/kg (95% confidence interval, -9.8 to -1.6 mL/kg; P < .01), respectively. Corticosteroids had no impact on the incidence of infection or mortality. With the secondary analysis, corticosteroids were associated with a trend toward significance in shortening the duration of mechanical ventilation (mean difference -0.7 days; 95% confidence interval, -1.7 to 0.1; P = .08)., Conclusions: Corticosteroids were found to have a favorable impact on postoperative fluid balance and may be associated with shortening the duration of mechanical ventilation. Although corticosteroids had no impact on mortality, they may be beneficial particularly for neonates and patients undergoing highly complex surgery., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The transfusion of stored RBCs decreases nitric oxide bioavailability, which may have an adverse effect on vascular function. We assessed the effects of RBC transfusion on coronary vascular function by evaluating the relationship between myocardial oxygen delivery and demand as evidenced by ST segment variability., Design: Retrospective case-control study., Setting: Nine-hundred seventy-three-bed pediatric hospital with a 54-bed cardiovascular ICU., Patients: Seventy-three neonates with hypoplastic left heart syndrome following the Norwood procedure, 38 with a Blalock-Taussig shunt and 35 with a right ventricle to pulmonary artery shunt., Interventions: RBC transfusion., Materials and Main Results: High-frequency physiologic data were captured 30 minutes prior to the initiation of (baseline) and during the 120 minutes of the transfusion. A rate pressure product was calculated for each subject and used as an indicator of myocardial oxygen demand. Electrocardiogram leads (aVL, V1, II) were used to construct a 3D ST segment vector to assess ST segment variability and functioned as a surrogate indicator of myocardial ischemia. One-hundred thirty-eight transfusions occurred in the Blalock-Taussig shunt group and 139 in the right ventricle to pulmonary artery shunt group. There was no significant change in the rate pressure product for either group; however, ST segment variability progressively increased for the entire cohort during the transfusion, becoming statistically significant by the end of the transfusion. Upon subgroup analysis, this finding was noted with statistical significance in the Blalock-Taussig shunt group and trending toward significance in the right ventricle to pulmonary artery shunt group., Conclusions: We found a significant increase in the ST segment variability and evidence of myocardial ischemia temporally associated with RBC transfusions in neonates following the Norwood procedure, specifically among those in the Blalock-Taussig shunt group, which may impact immediate and long-term outcomes., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Different types of diuretics have been used to minimize fluid overload after resuscitation. This meta-analysis determined the effects of xanthine derivatives on creatinine, creatinine clearance, and urine output. Studies included data from pediatric patients, whoused theophylline or aminophylline, and included pre- and postxanthine data for at least one of the outcomes of interest. A total of 13 studies with 198 patients were included in the pooled analyses. The study recorded data prior, and a mean of 36 hours after xanthine administration. This meta-analysis demonstrates that xanthine derivatives in critically ill children, using a dose of approximately5 mg/kg, lead to a statistically significant increase in creatinine clearance and urine output without significantly altering serum creatinine. Xanthine derivatives may be beneficial for fluid management in critically ill children. Further studies are warranted assessing the association with additional clinical outcomes., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Background: Acute decompensated heart failure (ADHF) is a highly morbid condition among adults. Little is known about outcomes in children with ADHF. We analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF., Methods: Cardiac intensive care unit (CICU) patients ≤18 years of age meeting Pediatric Cardiac Critical Care Consortium criteria for ADHF were included. ADHF was defined as systolic or diastolic dysfunction requiring continuous vasoactive or diuretic infusion, respiratory support, or mechanical circulatory support. Demographics, diagnosis, therapies, complications, and mortality are described for the cohort. Predictors of CICU mortality were identified using logistic regression., Results: Among 26 294 consecutive admissions (23 centers), 1494 (6%) met criteria for analysis. Median age was 0.93 years (interquartile range, 0.1-9.3 years). Patients with congenital heart disease (CHD) comprised 57% of the cohort. Common therapies included the following: vasoactive infusions (88%), central venous catheters (86%), mechanical ventilation (59%), and high flow nasal cannula (46%). Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%). Median length of CICU stay was 7.9 days (interquartile range, 3-18 days) and the CICU readmission rate was 22%. Overall, CICU mortality was 15% although higher for patients with CHD versus non-CHD (19% versus 11%; P <0.001). Independent risk factors associated with CICU mortality included age <30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation, and cardiac arrest., Conclusions: ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with CHD. Opportunities exist to determine best practices around appropriate use of mechanical support, cardiac arrest prevention, and optimal heart transplantation candidacy to improve outcomes for these patients.

Thyroid hormone modifies metabolic, immune and cardiovascular functions and has been administered perioperatively to treat a relative reduction of thyroid function in children following cardiopulmonary bypass (CPB) for correction of congenital heart disease. However, it remains unclear whether its use is associated with improved outcomes. We performed a meta-analysis of studies that evaluated the impact of thyroid hormone supplementation on clinical outcomes in children undergoing repair of congenital heart disease using CPB. A systematic review of published trials was conducted to identify studies of children randomized to thyroid hormone supplementation or placebo undergoing congenital heart surgery. A meta-analysis was then conducted to determine the clinical impact of thyroid hormone replacement on cardiac function and postoperative characteristics. The following outcomes were included for the study: duration of mechanical ventilation, duration of intensive care unit (ICU) stay, duration of postoperative hospital stay, inotrope score, cardiac index at 24 hours postoperatively, and inpatient mortality. A total of 9 studies with 711 patients were included in the analyses. All included studies were prospective and patients were randomized to either thyroid hormone or placebo. There was wide variation in thyroid hormone dosing, ranging from 0.4 μg/kg up to 5 μg/kg over a 24-hour period, and duration of therapy, ranging from a single dose after cessation of CPB to continued thyroid hormone for the duration of the ICU stay. There was a significant difference in the mean inotrope score between the 2 groups of -1.249 (95% confidence interval -1.570 to -0.929, P < 0.001), with the inotrope score being significantly lower in the thyroid group. There was no difference in duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, cardiac index, and mortality between groups. In this meta-analysis, routine thyroid hormone replacement with approximately 1-5 μg/kg administered over 24 hours does not significantly alter the postoperative course in children following CPB. However, given a clinically small but significant difference in respect to lower inotrope score and shorter duration of ICU and hospital stays with higher thyroid replacement additional studies are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons., Study Design: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized., Results: Results were similar across the two seasons. Among infants with community-acquired RSVH ( N  = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge., Conclusion: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV., Competing Interests: E.J.A., J.P.D., E.A.F.S., L.R.K., M.L.F., P.S.P., C.M.E., R.C.W., L.I.W., R.Y., P.A.C., J.B.D., and N.H. are independent investigators who have received research support from AstraZeneca/MedImmune. J.P.D., E.A.F.S., L.R.K., and M.L.F. also received travel support from AstraZeneca/MedImmune to present the results of this or other research studies at scientific meetings. J.P.D., M.L.F., and P.S.P. have served on the speakers’ bureau for AstraZeneca/MedImmune. E.J.A., E.A.F.S., and J.P.D. have served as consultants to AbbVie; P.A.C. has received research support from AbbVie. S.J.M. is an independent statistical consultant to AstraZeneca. K.K.M. and C.S.A. are employees of AstraZeneca and hold stock. V.R.K. and C.P.R. were employees of AstraZeneca at the time this research was conducted. C.P.R. is a current employee of Sobi Inc., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Central venous catheter (CVC) use is common in the management of critically ill children, especially those with congenital heart disease. CVCs are known to augment the risk of deep vein thrombosis (DVT), but data on CVC-associated DVTs in the pediatric cardiac intensive care unit (CICU) are limited. In this study, we aim to identify the incidence of and risk factors for CVC-related DVT in this high-risk population, as its complications are highly morbid., Materials and Methods: The PC4 database and a radiologic imaging database were retrospectively reviewed for the demographics and outcomes of patients admitted to the Texas Children's Hospital CICU requiring CVC placement, as well as the incidence of DVT and its complications., Results: Between January 2017 and December 2017, 1215 central lines were placed over 851 admissions. DVT was diagnosed in 8% of admissions with a CVC, 29% of which demonstrated thrombus in the inferior vena cava. The risk factors significantly associated with DVT included the presence of >1 line, higher total line hours, longer intubation times, and extended CICU stay. A diagnosis of low cardiac output syndrome, sepsis, central line-associated bloodstream infection, and cardiac catheterization were also significant risk factors. Interestingly, cardiac surgery with cardiopulmonary bypass appeared to be protective of clot development. DVT was a highly significant risk factor for mortality in these patients., Conclusions: CVC-related DVTs in critically ill children with congenital heart disease are associated with higher risks of morbidity and mortality, highlighting the need for well-designed studies to determine the best preventative and treatment strategies and to establish guidelines for appropriate monitoring and follow-up of these patients., (Published by Elsevier Inc.)

Objectives: Adequate postoperative pain management is crucial in pediatric patients undergoing cardiac surgery because pain can lead to devastating short- and long-term consequences. This review discusses the limitations of current postoperative pain assessment and management in children after cardiac surgery, the obstacles to providing optimal treatment, and concepts to consider that may overcome these barriers., Data Source: MEDLINE and PubMed., Conclusions: Effective pain management in infants and young children undergoing cardiac surgery continues to evolve with innovative methods of both assessment and therapy using newer drugs or novel routes of administration. Artificial intelligence- and machine learning-based pain assessment and patient-tailored management in both pain measurement and prevention are already being integrated into the routine of current practice.

Objectives: Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data., Design: Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration., Setting: Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017., Patients: All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded., Interventions: None., Measurements and Main Results: Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure -15% from baseline and relative hypotension defined -10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2-62 mo) with a dose of 12.5 mg/kg (interquartile range, 10-15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension., Conclusions: In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.

Objectives: Children with medical cardiac disease experience poorer survival to hospital discharge after cardiopulmonary arrest compared with children with surgical cardiac disease. Limited literature exists describing epidemiology and factors associated with mortality in this heterogeneous population. We aim to evaluate the clinical characteristics and outcomes after cardiopulmonary arrest in medical cardiac patients., Design: We performed a retrospective review of pediatric cardiac patients who underwent cardiopulmonary resuscitation in a tertiary care cardiac ICU. Surgical cardiac patients underwent cardiac surgery immediately prior to ICU admission. Nonsurgical cardiac patients were divided into two groups based on the presence of congenital heart disease: congenital heart disease medical or noncongenital heart disease medical. Clinical and outcome variables were collected. Primary outcome was survival to hospital discharge., Settings: Texas Children's Hospital cardiac ICU., Patients: Patients admitted to Texas Children's Hospital cardiac ICU between January 2011 and December 2016., Interventions: None., Measurements and Main Results: Of 150 cardiopulmonary arrest events reviewed, 90 index events were included (46 surgical, 26 congenital heart disease medical, and 18 noncongenital heart disease medical). There was no difference in primary outcome among the three groups. The absence of an epinephrine infusion precardiopulmonary arrest was associated with increased odds of survival in the congenital heart disease medical group (p = 0.03). Noncongenital heart disease medical patients experienced pulseless ventricular tachycardia/ventricular fibrillation more frequently than congenital heart disease medical patients (p = 0.02). Congenital heart disease medical patients had trends toward longer cardiac arrest durations, higher prevalence of neurologic sequelae postcardiopulmonary arrest, and higher mortality when extracorporeal support at cardiopulmonary resuscitation was employed., Conclusions: Although trends in first documented rhythm, neurologic sequelae, and inotropic support prior to cardiopulmonary arrest were noted between groups, no significant differences in survival after cardiac arrest were seen. Larger scale studies are needed to better describe factors associated with cardiopulmonary arrest as well as survival in heterogeneous medical cardiac populations.

Objective: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing., Methods: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC 0-24 :MIC (minimum inhibitory concentration) ratio of >400., Results: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC 0-24 :MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L., Conclusions: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy., Competing Interests: Disclosure The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis.

A surge in cortisol levels is seen after surgery with cardiopulmonary bypass (CPB). Based on evidence of attenuation of the cortisol response to repeated stress in other settings, we hypothesized that the magnitude of cortisol increase in children after a second exposure to CPB would be reduced. Serial cortisol levels were measured at three time points after each CPB: immediately (day 0), on the first morning (day 1), and second morning (day 2). Forty-six children underwent two surgeries with CPB during the study period. The mean age (standard deviation) at first and second surgery was 3.5 (6.3) months and 10.4 (9.9) months, respectively. Cortisol levels at the first surgery were 109 (105) µg/dl, 29 (62) µg/dl, and 17 (12) µg/dl on day 0, 1, and 2, respectively; similarly at second surgery, it was 61 (57) µg/dl on day 0 to 20 (16) µg/dl and 11 (10) µg/dl on day 1 and 2, respectively. After log-transformation and adjusting for time interval between surgeries, cortisol levels at the second surgery were lower by 42% on day 0 (p = 0.02), and 46% lower on day 2 (p = 0.02). A second exposure to CPB in children with congenital heart disease is associated with an attenuated cortisol release.

Cardiac arrest occurs at a higher rate in children with heart disease than in healthy children. Pediatric basic life support and advanced life support guidelines focus on delivering high-quality resuscitation in children with normal hearts. The complexity and variability in pediatric heart disease pose unique challenges during resuscitation. A writing group appointed by the American Heart Association reviewed the literature addressing resuscitation in children with heart disease. MEDLINE and Google Scholar databases were searched from 1966 to 2015, cross-referencing pediatric heart disease with pertinent resuscitation search terms. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. The recommendations in this statement concur with the critical components of the 2015 American Heart Association pediatric basic life support and pediatric advanced life support guidelines and are meant to serve as a resuscitation supplement. This statement is meant for caregivers of children with heart disease in the prehospital and in-hospital settings. Understanding the anatomy and physiology of the high-risk pediatric cardiac population will promote early recognition and treatment of decompensation to prevent cardiac arrest, increase survival from cardiac arrest by providing high-quality resuscitations, and improve outcomes with postresuscitation care., (© 2018 American Heart Association, Inc.)

Introduction: The REGAL (RSV Evidence - A Geographical Archive of the Literature) series has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This seventh and final publication covers the past, present and future approaches to the prevention and treatment of RSV infection among infants and children., Methods: A systematic review was undertaken of publications between January 1, 1995 and December 31, 2017 across PubMed, Embase and The Cochrane Library. Studies reporting data on the effectiveness and tolerability of prophylactic and therapeutic agents for RSV infection were included. Study quality and strength of evidence (SOE) were graded using recognized criteria. A further nonsystematic search of the published literature and Clinicaltrials.gov on antiviral therapies and RSV vaccines currently in development was also undertaken., Results: The systematic review identified 1441 studies of which 161 were included. Management of RSV remains centered around prophylaxis with the monoclonal antibody palivizumab, which has proven effective in reducing RSV hospitalization (RSVH) in preterm infants < 36 weeks' gestational age (72% reduction), children with bronchopulmonary dysplasia (65% reduction), and infants with hemodynamically significant congenital heart disease (53% reduction) (high SOE). Palivizumab has also shown to be effective in reducing recurrent wheezing following RSVH (high SOE). Treatment of RSV with ribavirin has conflicting success (moderate SOE). Antibodies with increased potency and extended half-life are currently entering phase 3 trials. There are approximately 15 RSV vaccines in clinical development targeting the infant directly or indirectly via the mother., Conclusion: Palivizumab remains the only product licensed for RSV prophylaxis, and only available for high-risk infants. For the general population, there are several promising vaccines and monoclonal antibodies in various stages of clinical development, with the aim to significantly reduce the global healthcare impact of this common viral infection., Funding: AbbVie.

Objective: We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes., Design: Observational cohort study including existing and newly enrolled participants., Setting: Multiple PICUs., Patients: Children with septic shock., Interventions: None., Measurements and Main Results: We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype A by day 3. Assignment to endotype A on day 1 was associated with increased odds of mortality. This risk was modified by the subsequent day 3 endotype assignment. Corticosteroids were associated with increased risk of mortality among subjects who persisted as endotype A., Conclusions: A substantial proportion of children with septic shock transition endotypes during the acute phase of illness. The risk of poor outcome and the response to corticosteroids change with changes in endotype assignment. Patients persisting as endotype A are at highest risk of poor outcomes.

Introduction Maternal obesity is associated with an increased risk for adverse perinatal outcomes. Obesity is also associated with a chronic inflammatory state and metabolic derangements that affect the newborn. The additional use of cardiopulmonary bypass during the neonatal period could impact the systemic inflammatory response in the immediate postoperative period that manifests as cardiac depression and multi-organ dysfunction. This study aimed to determine the association of maternal obesity and excessive weight gain during pregnancy with the immediate postoperative morbidity of neonatal patients undergoing cardiopulmonary bypass., Methods: A retrospective review of neonates who underwent cardiopulmonary bypass within the first 30 days of life at our institution between 2011 and 2013 was conducted. Postoperative variables investigated included the duration of length of mechanical ventilation, length of stay in the ICU, peak vasoactive inotrope scores, and peak lactate level. Maternal obesity was defined as 1st trimester body mass index ⩾30 kg/m2. Excessive weight gain was defined as ⩾12 kg gained during pregnancy. In order to determine the association between maternal obesity or excessive weight gain and postoperative variables, we used multiple linear regression, adjusting for birth weight and risk adjustment for congenital heart surgery score., Results: Records from 58 mother-baby dyads were examined. After controlling for birth weight and risk adjustment for congenital heart surgery score, there were no significant associations between maternal obesity and excessive weight gain during pregnancy versus all postoperative outcomes measured., Conclusion: Despite the known negative impact of maternal obesity on perinatal outcomes, we were unable to find associations between maternal obesity and excessive weight gain during pregnancy versus postoperative outcomes.

Introduction Haemodynamically unstable patients can experience potentially hazardous changes in vital signs related to the exchange of depleted syringes of epinephrine to full syringes. The purpose was to determine the measured effects of epinephrine syringe exchanges on the magnitude, duration, and frequency of haemodynamic disturbances in the hour after an exchange event (study) relative to the hours before (control). Materials and methods Beat-to-beat vital signs recorded every 2 seconds from bedside monitors for patients admitted to the paediatric cardiovascular ICU of Texas Children's Hospital were collected between 1 January, 2013 and 30 June, 2015. Epinephrine syringe exchanges without dose/flow change were obtained from electronic records. Time, magnitude, and duration of changes in systolic blood pressure and heart rate were characterised using Matlab. Significant haemodynamic events were identified and compared with control data., Results: In all, 1042 syringe exchange events were found and 850 (81.6%) had uncorrupted data for analysis. A total of 744 (87.5%) exchanges had at least 1 associated haemodynamic perturbation including 2958 systolic blood pressure and 1747 heart-rate changes. Heart-rate perturbations occurred 37% before exchange and 63% after exchange, and 37% of systolic blood pressure perturbations happened before syringe exchange, whereas 63% occurred after syringe exchange with significant differences found in systolic blood pressure frequency (p<0.001), duration (p<0.001), and amplitude (p<0.001) compared with control data., Conclusions: This novel data collection and signal processing analysis showed a significant increase in frequency, duration, and magnitude of systolic blood pressure perturbations surrounding epinephrine syringe exchange events.

Objective: Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock., Design: Retrospective analysis of a pediatric septic shock database., Setting: Twenty-nine PICUs in the United States., Patients: Eight hundred ninety children 10 years and younger with septic shock., Interventions: None., Measurements and Main Results: We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Complicated course was defined as mortality by 28 days or persistence of greater than or equal to two organ failures at day 7 of septic shock. Secondarily, we conducted a stratified analysis using a biomarker-based mortality risk stratification tool. There were 226 patients (25%) with a complicated course and 93 mortalities (10%). Seventy patients had a minimum chloride greater than or equal to 110 mmol/L, 179 had a mean chloride greater than or equal to 110 mmol/L, and 514 had a maximum chloride greater than or equal to 110 mmol/L. A minimum chloride greater than or equal to 110 mmol/L was associated with increased odds of complicated course (odds ratio, 1.9; 95% CI, 1.1-3.2; p = 0.023) and mortality (odds ratio, 3.7; 95% CI, 2.0-6.8; p < 0.001). A mean chloride greater than or equal to 110 mmol/L was also associated with increased odds of mortality (odds ratio, 2.1; 95% CI, 1.3-3.5; p = 0.002). The secondary analysis yielded similar results., Conclusion: Hyperchloremia is independently associated with poor outcomes among children with septic shock.

Objectives: Although clinical and pharmacologic guidelines exist for the practice of cardiopulmonary resuscitation in children (Pediatric Advanced Life Support), the practice of extracorporeal cardiopulmonary resuscitation in pediatric cardiac patients remains without universally accepted standards. We aim to explore variation in extracorporeal cardiopulmonary resuscitation procedures by surveying clinicians who care for this high-risk patient population., Design: A 28-item cross-sectional survey was distributed via a web-based platform to clinicians focusing on cardiopulmonary resuscitation practices and extracorporeal membrane oxygenation team dynamics immediately prior to extracorporeal membrane oxygenation cannulation., Settings: Pediatric hospitals providing extracorporeal mechanical support services to patients with congenital and/or acquired heart disease., Subjects: Critical care/cardiology specialist physicians, cardiothoracic surgeons, advanced practice nurse practitioners, respiratory therapists, and extracorporeal membrane oxygenation specialists., Interventions: None., Measurements and Main Results: Survey web links were distributed over a 2-month period with critical care and/or cardiology physicians comprising the majority of respondents (75%). Nearly all respondents practice at academic/teaching institutions (97%), 89% were from U.S./Canadian institutions and 56% reported less than 10 years of clinical experience. During extracorporeal cardiopulmonary resuscitation, a majority of respondents reported adherence to guideline recommendations for epinephrine bolus dosing (64%). Conversely, 19% reported using only one to three epinephrine bolus doses regardless of extracorporeal cardiopulmonary resuscitation duration. Inotropic support is held after extracorporeal membrane oxygenation cannulation "most of the time" by 58% of respondents and 94% report using afterload reducing/antihypertensive agents "some" to "most of the time" after achieving full extracorporeal membrane oxygenation support. Interruptions in chest compressions are common during active cannulation according to 77% of respondents., Conclusions: The results of this survey identify wide variability in resuscitative practices during extracorporeal cardiopulmonary resuscitation in the pediatric cardiac population. The deviations from established Pediatric Advanced Life Support CPR guidelines support a call for further inquiry into the pharmacologic and logistical care surrounding extracorporeal cardiopulmonary resuscitation.

Background: Few data are available regarding the use of metolazone in infants in cardiac intensive care. Researchers need to carry out further evaluation to characterise the effects of this treatment in this population., Methods: This is a descriptive, retrospective study carried out in patients less than a year old. These infants had received metolazone over a 2-year period in the paediatric cardiac intensive care unit at our institution. The primary goal was to measure the change in urine output from 24 hours before the start of metolazone therapy to 24 hours after. Patient demographic variables, laboratory data, and fluid-balance data were analysed., Results: The study identified 97 infants with a mean age of 0.32±0.25 years. Their mean weight was 4.9±1.5 kg, and 58% of the participants were male. An overall 63% of them had undergone cardiovascular surgery. The baseline estimated creatinine clearance was 93±37 ml/minute/1.73 m2. Initially, the participants had received a metolazone dose of 0.27±0.10 mg/kg/day, the maximum dose being 0.43 mg/kg/day. They had also received other diuretics during metolazone initiation, such as furosemide (87.6%), spironolactone (58.8%), acetazolamide (11.3%), bumetanide (7.2%), and ethacrynic acid (1%). The median change in urine output after metolazone was 0.9 ml/kg/hour (interquartile range 0.15-1.9). The study categorised a total of 66 patients (68.0%) as responders. Multivariable analysis identified acetazolamide use (p=0.002) and increased fluid input in the 24 hours after metolazone initiation (p0.05)., Conclusions: Metolazone increased urine output in a select group of patients. Efficacy can be maximised by strategic selection of patients.

Objective: We evaluated the use of nesiritide in children with critical CHD, pulmonary congestion, and inadequate urine output despite undergoing conventional diuretic therapy., Design: We conducted a retrospective analysis of 11 patients with critical CHD, comprising 18 infusions, each of which occurred during separate hospitalisations. Haemodynamic parameters were assessed, and the stage of acute kidney injury was determined before and throughout the duration of therapy using a standardised definition of acute kidney injury - The Kidney Disease: Improving Global Outcomes criteria. Patients Children with critical CHD, pulmonary congestion, and inadequate urinary output despite undergoing diuretic therapy were included. Measurements and main results The use of nesiritide was associated with a significant decrease in the maximum and minimum heart rate values and with a trend towards a significant decrease in maximum systolic blood pressure and maximum and minimum central venous pressures. Urine output increased but was not significant. Serum creatinine levels decreased significantly during the course of therapy (-0.26 mg/dl [-0.50, 0.0], p=0.02), and the number of patients who experienced a decrease in the stage of acute kidney injury of 2 or more - where a change in the stage of acute kidney disease of 2 or more was possible, that is, baseline stage >1 - was highly significant (five of 12 patients, 42%, p<0.001)., Conclusions: Nesiritide had a favourable impact on haemodynamics, and its use was not associated with deterioration of renal function in patients with critical CHD.

Background: Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings., Methods: An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology., Results: Palivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1-2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions., Conclusion: Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.

Introduction: REGAL (RSV Evidence-a Geographical Archive of the Literature) has provided a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This review covers the risk and burden of RSV infection in children with underlying medical conditions or chronic diseases (excluding prematurity and congenital heart disease)., Methods: A systematic review of publications between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials.gov was supplemented by papers identified by the authors through March 2017. Studies reporting data for hospital visits/admissions for RSV infection as well as studies reporting RSV-associated morbidity and mortality were included. Study quality and strength of evidence (SOE) were graded., Results: A total of 2703 studies were identified and 58 were included. Down syndrome, irrespective of prematurity and congenital heart disease (moderate SOE), immunocompromised children (low SOE), cystic fibrosis (low SOE), and neurologic conditions (low SOE) were associated with a significantly increased risk of RSV hospitalization. A number of other congenital malformations and chronic conditions were also associated with severe RSV disease (low SOE). In general, pre-existing disease was also a predisposing factor for RSV-related mortality (low SOE)., Conclusion: Severe RSV infection in infants and young children with underlying medical conditions or chronic diseases poses a significant health burden. Further studies are needed to fully quantify the epidemiology, burden and outcomes in these populations, in particular RSV-attributable mortality.

Rationale: We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered., Objectives: To determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock., Methods: We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77)., Measurements and Main Results: Variable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE., Conclusions: PERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.

What Is Known: Spironolactone is used in paediatric patients with heart disease, yet few data are available regarding the impact on potassium supplementation., Objective: We sought to determine the effect of spironolactone on potassium supplementation in paediatric cardiac intensive care patients., Methods: A retrospective, propensity matched cohort study was designed. Patients were included in the study if they received furosemide therapy in the cardiac intensive care unit at our institution. Patients who received spironolactone were matched to patients who did not receive spironolactone. Data collection included patient demographics, diuretic data, potassium monitoring, and total milliequivalents of potassium administered during the cardiac intensive care unit stay., Results and Discussion: A total of 448 patients met study criteria median age 0.43 (IQR 0.06-3.52) years, 58.9% male. Intensive care unit length of stay was 7 (IQR 3-17) days, cardiovascular surgery occurred in 90.4%. Patients had a mean 4.6±2.6 potassium concentrations assessed per day (29.5%±19.4%<3.5 mmol/L, and 2.9%±6.5%>5.5 mmol/L). Patients received a median of 5.1 mEq/kg (0-323.4 mEq/kg) of potassium. Spironolactone (n=224) was administered for 2 days (IQR 1-4) at mean dose of 0.64±0.54 mg kg -1  d -1 . Median total mEq/kg of potassium administered did not differ between groups (4.6 mEq/kg (IQR 0.66-16.8) vs 6.5 mEq/kg (IQR 1.3-18.3 mEq/kg), P=.13). Potassium laboratory values did not differ in hypokalemia (27.8%±19.1% vs 31.2%±19.5%, P=.06) or hyperkalemia (2.8%±5.4% vs 3.2%±7.5%, P=.49) between groups., What Is New: Spironolactone supplementation did not reduce the need for potassium supplementation in paediatric cardiac intensive care patients., Conclusion: The routine use of spironolactone in the paediatric cardiac intensive care population may not be more efficacious than potassium supplementation for maintenance of serum potassium concentrations., (© 2017 John Wiley & Sons Ltd.)

Background: Sequential nephron blockade using intravenous chlorothiazide is often used to enhance urine output in patients with inadequate response to loop diuretics. A few data exist to support this practice in critically ill infants., Methods: We included 100 consecutive patients <1 year of age who were administered intravenous chlorothiazide while receiving furosemide therapy in the cardiac ICU in our study. The primary end point was change in urine output 24 hours after chlorothiazide administration, and patients were considered to be responders if an increase in urine output of 0.5 ml/kg/hour was documented. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected. Multivariable regression analyses were performed to determine variables significant for increase in urine output after chlorothiazide administration., Results: The study population was 48% male, with a mean weight of 4.9±1.8 kg, and 69% had undergone previous cardiovascular surgery. Intravenous chlorothiazide was initiated at 89 days (interquartile range 20-127 days) of life at a dose of 4.6±2.7 mg/kg/day (maximum 12 mg/kg/day). Baseline estimated creatinine clearance was 83±42 ml/minute/1.73 m2. Furosemide dose before chlorothiazide administration was 2.8±1.4 mg/kg/day and 3.3±1.5 mg/kg/day after administration. A total of 43% of patients were categorised as responders, and increase in furosemide dose was the only variable significant for increase in urine output on multivariable analysis (p<0.05). No graphical trends were noted for change in urine output and dose of chlorothiazide., Conclusions: Sequential nephron blockade with intravenous chlorothiazide was not consistently associated with improved urine output in critically ill infants.

Introduction: The REGAL (RSV Evidence-a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. The objective of this fifth publication was to determine the long-term respiratory morbidity associated with RSV lower respiratory tract infection (RSV LRTI) in early life., Methods: A systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015. This was supplemented by inclusion of papers published whilst drafting the manuscript. Studies reporting data on the incidence and long-term wheezing and asthma following RSV LRTI in early life were included. Study quality and strength of evidence (SOE) were graded using recognized criteria., Results: A total of 2337 studies were identified of which 74 were included. Prospective, epidemiologic studies consistently demonstrated that RSV LRTI is a significant risk factor for on-going respiratory morbidity characterized by transient early wheezing and recurrent wheezing and asthma within the first decade of life and possibly into adolescence and adulthood (high SOE). RSV LRTI was also associated with impaired lung function in these children (high SOE). Respiratory morbidity has been shown to result in reduced quality of life and increased healthcare resource use (moderate SOE). The mechanisms through which RSV contributes to wheezing/asthma development are not fully understood, but appear to relate to the viral injury, preexisting abnormal lung function and/or other factors that predispose to wheezing/asthma, including genetic susceptibility, altered immunology, eosinophilia, and associated risk factors such as exposure to environmental tobacco smoke (high SOE)., Conclusion: There is growing evidence that RSV LRTI in early childhood is associated with long-term wheezing and asthma and impaired lung function. Future research should aim to fully elucidate the pathophysiological mechanisms through which RSV causes recurrent wheezing/asthma.