Search

Background: Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol., Methods: In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia., Results: Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia., Conclusion: Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia., (© 2023. The Author(s).)

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery., Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death., Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P  = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P  = .49)., Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results., (© 2023 The Author(s).)

Background: The PEPaNIC multicenter randomized controlled trial (RCT) has shown that early administration of supplemental parenteral nutrition (early-PN) as compared with withholding PN for 1 week (late-PN) induced long-term internalizing, externalizing and total emotional/behavioral problems in critically ill children, as observed 4 years later. Early-PN was further shown to alter the methylation status of 37 CpG-sites in leukocyte DNA between admission and discharge from the pediatric intensive care unit (PICU). In a preplanned subanalysis of the PEPaNIC trial, we now investigated whether the altered methylation of these CpG-sites could statistically explain the negative impact of early-PN on emotion/behavior documented 4 years after PICU admission., Results: The combination of DNA methylation data and data on behavior 4 years after PICU admission was available for 403 of the 1440 patients (aged 0-17 years at PICU admission) who were included in the PEPaNIC RCT (192 early-PN and 211 late-PN patients). Mediation analyses with use of bootstrapped multivariable non-linear regression analyses adjusted for baseline risk factors revealed that the adverse alterations by early-PN in methylation of the 37 CpG-sites together statistically explained its harmful impact on internalizing, externalizing and total emotional/behavioral problems. When adding the methylation status of the 37 CpG-sites to the models, the explanatory power improved with a 1.710 to 1.851-fold increase, and the impact of the altered methylation status of the CpG-sites explained the impact of the randomization to early-PN versus late-PN., Conclusions: Abnormal DNA methylation induced by the early use of PN in the PICU provides a biological basis for its long-term harmful effect on emotion/behavior of critically ill children 4 years after PICU admission. Trial Registration ClinicalTrials.gov NCT01536275, registered February 17, 2012, https://clinicaltrials.gov/ct2/show/NCT01536275 ., (© 2021. The Author(s).)

Objective: To demonstrate feasibility of a music medicine intervention trial in pediatric intensive care and to obtain information on sedation and analgesia dose variation to plan a larger trial., Material and Methods: Pilot randomized controlled trial (RCT) was conducted at the Stollery Children's Hospital general and cardiac intensive care units (PICU/PCICU). The study included children 1 month to 16 years of age on mechanical ventilation and receiving sedation drugs. Patients were randomized in a 1:1:1 ratio to music, noise cancellation or control. The music group received classical music for 30 min three times/day using headphones. The noise cancellation group received the same intervention but with no music. The control group received usual care., Results: A total of 60 patients were included. Average enrollment rate was 4.8 patients/month, with a consent rate of 69%. Protocol adherence was achieved with patients receiving > 80% of the interventions. Overall mean (SD) daily Sedation Intensity Score was 52.4 (30.3) with a mean (SD) sedation frequency of 9.75 (7.21) PRN doses per day. There was a small but statistically significant decrease in heart rate at the beginning of the music intervention. There were no study related adverse events. Eighty-eight percent of the parents thought the headphones were comfortable; 73% described their child more settled during the intervention., Conclusions: This pilot RCT has demonstrated the feasibility of a music medicine intervention in critically ill children. The study has also provided the necessary information to plan a larger trial.

Background: Stress induced by pain and anxiety is common in pediatric intensive care unit (PICU) patients. Sedation/analgesia in PICU is usually achieved through various analgesics and sedatives. Excessive use of these drugs can put patients at risk for hemodynamic/respiratory instability, prolonged ventilation, withdrawal, delirium, and critical illness polyneuromyopathy.The use of non-pharmacologic interventions has been recommended by sedation guidelines. However, non-pharmacological measures in PICU, including music and noise reduction, have been inadequately studied., Methods: The Music Use for Sedation in Critically ill Children (MUSiCC trial) pilot study is an investigator-initiated, three-arm, randomized controlled trial (RCT) on the use of music for sedation in PICU. The main goal of the study is to demonstrate feasibility of a music trial in PICU and to obtain the necessary information to plan a larger trial. The study compares music versus noise cancelation versus control in sedated and mechanically ventilated children admitted to PICU. In the music group, children receive the music (modified classical music) three times a day for 30 min at a time. Music is delivered with noise cancelation headphones. The noise cancelation group receives the same intervention but with a no music (sham playlist). The control group receives usual care with no specific intervention. Children remain in the study until extubation or a maximum of 7 days. The primary outcomes of the study are feasibility and sedation/analgesia requirements. Secondary outcomes include change in vital signs before and during the intervention, ICU delirium, and adverse effects related to the intervention. The estimated sample size is 20 subjects per group for a total of 60 children., Discussion: Despite being recommended by current guidelines, evidence to support the use of music in PICU is lacking. Music has the potential to reduce sedation requirements and their negative side effects. This pilot RCT will demonstrate feasibility and provide the necessary information to plan a larger trial focusing on the effectiveness of the intervention., Trial Registration: The study was registered at ClinicalTrials.gov (NCT03497559) on April 13, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Background Management of patients with hypoplastic left heart syndrome has benefited from advancements in medical and surgical care. Outcomes have improved, although survival and long-term functional and cognitive deficits remain a concern. Methods and Results This is a cohort study of all consecutive patients with hypoplastic left heart syndrome undergoing surgical palliation at a single center. We aimed to examine demographic and perioperative factors from each surgical stage for their association with survival and neurocognitive outcomes. A total of 117 consecutive patients from 1996 to 2010 underwent surgical palliation. Seventy patients (60%) survived to the Fontan stage and 68 patients (58%) survived to undergo neurocognitive assessment at a mean (SD) age of 56.6 months (6.4 months). Full-scale, performance, and verbal intelligence quotient, as well as visual-motor integration mean (SD) scores were 86.7 (16.1), 86.3 (15.8), 88.8 (17.2), and 83.2 (14.8), respectively. On multivariable analysis, older age at Fontan, sepsis peri-Norwood, lowest arterial partial pressure of oxygen postbidirectional cavopulmonary anastomosis, and presence of neuromotor disability pre-Fontan were strongly associated with lower scores for all intelligence quotient domains. Older age at Fontan and sepsis peri-Norwood remained associated with lower scores for all intelligence quotient domains in a subgroup analysis excluding patients with disability pre-Fontan or with chromosomal abnormalities. Conclusions Older age at Fontan and sepsis are among independent predictors of poor neurocognitive outcomes for patients with hypoplastic left heart syndrome. Further studies are required to identify the appropriate age range for Fontan completion, balancing a lower risk of acute and long-term hemodynamic complications while optimizing long-term neurocognitive outcomes.

Background: The aim of the study was to determine opinions and knowledge regarding the process of obtaining informed consent to participate in observational research in pediatric intensive care., Methods: Survey 1 asked decision makers what model(s) of consent was acceptable for each type of observational research both before and after background information. Survey 2 asked decision makers about the experience of being asked for consent to observational research, and knowledge regarding the consent process both before and after background information., Results: Cooperation rate was 100/117 (85%). The proportion in favor of any of the offered alternatives to signed informed consent for observational research, after receiving all the background information, was 74-80%, lowest for observational prospective research with a minimal risk intervention 37/50 (74%; 95% CI 60-84%). The proportion who agreed they felt overwhelmed by being approached for consent to observational research was 26 (52%; 95% CI 39-65%). Most respondents (from 60 to 74%) felt they understood the concepts regarding observational research; however, after reading background information, most (from 60 to 74%) felt their understanding had improved "a great deal"., Conclusion: Understanding of risk, practical difficulties, consent bias, and Research Ethics Board safeguards was poor. Future study is needed to confirm our finding that most agreed with alternative methods of consent for observational research., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Background: We aimed to determine predictors of, and outcomes after, veno-arterial extracorporeal membrane oxygenation instituted within 48 h after cardiac surgery (early ECMO) in young infants., Methods: Patients ≤ 6 weeks old having cardiac surgery from 2003 to 2012 were enrolled prospectively. Patients cannulated pre-operatively, intra-operatively, or ≥ 48 h post-operatively were excluded. Variables at p  ≤ 0.1 on univariate regression were entered into multiple logistic regression to predict early ECMO. Early-ECMO cases were matched 1:2 for six demographic variables, and death by age 2 years old (determined using conditional logistic regression; presented as odds ratio (OR), 95% confidence interval (CI)) and General Adaptive Composite scores at age 2 years (determined using Wilcoxon rank sum) were compared; p  ≤ 0.05 was considered statistically significant., Results: Of 565 eligible patients over the 10-year period, 20 had early ECMO instituted at a mean (standard deviation) of 12.4 (11.4) h post-operatively, 10 of whom had extracorporeal cardiopulmonary resuscitation. Of early-ECMO patients, 8 (40%) were found to have residual anatomic defects requiring intervention with catheterization ( n  = 1) and/or surgery ( n  = 7). On multiple regression, the post-operative day 1 highest vasoactive-inotrope score (OR 1.02; 95%CI 1.06,1.08; p  < 0.001), highest lactate (OR 1.2; 95%CI 1.06,1.35; p  = 0.003), and lowest base deficit (OR 0.82; 95%CI 0.71,0.94; p  = 0.004), CPB time (OR 1.01; 95%CI 1.00,1.02; p  = 0.002), and single-ventricle anatomy (OR 5.35; 95%CI 1.66,17.31; p  = 0.005) were associated with early ECMO. Outcomes at 2 years old compared between early-ECMO and matched patients were mortality 11/20 (55%) vs 11/40 (28%) (OR 3.22, 95%CI 0.98,10.63; p  = 0.054) and General Adaptive Composite median 65 [interquartile range (IQR) 58, 81.5] in 9 survivors vs 93 [IQR 86.5, 102.5] in 29 survivors ( p  = 0.02)., Conclusions: The identified risk factors for, and outcomes after, having early ECMO may aid decision making in the acute period and confirm that neurodevelopmental follow-up for these children is necessary. The hypothesis that earlier institution of ECMO may improve long-term outcomes requires further study., Competing Interests: The Health Research Ethics Board of the University of Alberta approved this study [Pro00001030]. All parents/guardians signed an informed consent form.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: We aimed to test a novel method of delivery of chloral hydrate (CH) sedation in ventilated critically ill young children., Methods: Children < 12 years old, within 72 hours of admission, who were ventilated, receiving enteral tube-feeds, with intermittent CH ordered were enrolled after signed consent. Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases were compared to historical controls matched for age group and Pediatric Risk of Mortality score (PRISM) category, using Fisher's exact test and the t test. The primary outcome was feasibility, defined as the use of an enteral CH continuous infusion without discontinuation attributable to a pre-specified potential harm., Results: There were 21 patients enrolled, at age 11.4 (12.1) months, with bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD) score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5 (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients, with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8 (IQR 7, 9). Days to titration of adequate sedation (defined as ≤ 3 PRN doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5 (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2 (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p = 0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically significant differences between cases and controls in inotrope scores, signs or treatment of withdrawal, or PICU days., Conclusions: Delivering CH by continuous enteral infusion is feasible, effective, and may be associated with less positive fluid balance. Whether there is a risk of duodenal perforation requires further study.

Background: The accuracy of arterial lines (AL) using the flush test or stopcock test has not been described in children, nor has the difference between invasive arterial blood pressure (IABP) versus non-invasive cuff (NIBP) blood pressure., Methods: After ethics approval and consent, we performed the flush test and stopcock test on AL (to determine over damping, under damping, and optimal damping), and determined the difference (NIBP-IABP) in systolic, diastolic, and mean blood pressure (ΔSBP, ΔDBP, and ΔMAP). The primary outcome was incidence (95 % CI) of optimally damped AL. Predictors of ΔBP (effect size (95 % CI)) were determined using multiple linear regression., Results: There were 147 AL tests in 100 enrolled patients with mean age 44.7 (SD 56) months, weight 16.8 (SD 18.3) kg, male 59 %, postoperative-cardiovascular 52 %, peripheral-AL 78 %, inotropes 29 %, vasodilators 15 %, and ventilated 73 %. The flush test performed in 66 patients (45 %) showed optimal damping in 30 (46 %; 95 % CI 34, 57 %), over damping in 25 (38 %) and under damping in 11 patients (17 %). The stopcock test was over-damped in 128/146 patients (88 %), with the same damping as the flush test in 24/64 (38 %). In optimally damped (flush test) AL, ΔSBP, ΔDBP, and ΔMAP were 0.8 (SD 12.2), -5.2 (SD 8.7), and -4.9 (7.6) respectively. A second set of AL tests was done 2 h later on the same day in 62 patients; AL damping often changed (10/28 flush tests) and ΔBPs correlated poorly (r = 0.31-0.55). Predictors (effect size) of ΔDBP were vasodilator infusion (15.6 (2.9 to 28.3); p = 0.016) and optimal damping (-7.2 (-12.2 to 2.2); p = 0.005); and of ΔMAP were vasodilator infusion (10.0 (-0.3 to 20.4); p = 0.057) and optimal damping (-4.0 (-8 to 0.1); p = 0.058). There were no independent predictors of damping category (n = 66 flush tests)., Conclusions: Optimally damped AL occur in half of critically ill children, and this is not predictable. There is much variability in ∆BP between NIBP and the gold standard IABP, and this varies even in the same patient on the same day, and is not easily predictable. In critically ill children, NIBP may not be accurate enough to guide management, and more attention to ensuring the AL is optimally damped is needed.

Introduction: Early administration of antibiotics for sepsis, and of fluid boluses and vasoactive agents for septic shock, is recommended. Evidence for this in children is limited., Methods: The Alberta Sepsis Network prospectively enrolled eligible children admitted to the Pediatric Intensive Care Unit (PICU) with sepsis from 04/2012-10/2014. Demographics, severity of illness, and outcomes variables were prospectively entered into the ASN database after deferred consent. Timing of interventions were determined by retrospective chart review using a study manual and case-report-form. We aimed to determine the association of intervention timing and outcome in children with sepsis. Univariate (t-test and Fisher's Exact) and multiple linear regression statistics evaluated predictors of outcomes of PICU length of stay (LOS) and ventilation days., Results: Seventy-nine children, age median 60 (IQR 22-133) months, 40 (51%) female, 39 (49%) with severe underlying co-morbidity, 44 (56%) with septic shock, and median PRISM-III 10.5 [IQR 6.0-17.0] were enrolled. Most patients presented in an ED: 36 (46%) at an outlying hospital ED, and 21 (27%) at the Children's Hospital ED. Most infections were pneumonia with/without empyema (42, 53%), meningitis (11, 14%), or bacteremia (10, 13%). The time from presentation to acceptable antibiotic administration was a median of 115.0 [IQR 59.0-323.0] minutes; 20 (25%) of patients received their antibiotics in the first hour from presentation. Independent predictors of PICU LOS were PRISM-III, and severe underlying co-morbidity, but not time to antibiotics. In the septic shock subgroup, the volume of fluid boluses given in the first 2 hours was independently associated with longer PICU LOS (effect size 0.22 days; 95% CI 0.5, 0.38; per ml/kg). Independent predictors of ventilator days were PRISM-III score and severe underlying co-morbidity. In the septic shock subgroup, volume of fluid boluses in the first 2 hours was independently associated with more ventilator days (effect size 0.09 days; 95% CI 0.02, 0.15; per ml/kg)., Conclusion: Higher volume of early fluid boluses in children with sepsis and septic shock was independently associated with longer PICU LOS and ventilator days. More study on the benefits and harms of fluid bolus therapy in children are needed.

Purpose of Review: Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease., Sources of Information: The literature search was conducted using PubMed and Google Scholar., Findings: Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD., Implications: There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to invest time, thought and money to fill existing knowledge gaps to improve health outcomes in this population. This review should serve as an impetus for generation of follow-up guidelines of kidney health evaluation in patients with congenital heart disease.

Objective: To determine the health-related quality of life at 4 years of age in children who had undergone cardiac surgery for congenital heart disease in early infancy., Methods: A prospective cohort study of infants undergoing cardiac surgery at 6 weeks of age or younger from July 2000 to June 2005 at the Stollery Children's Hospital. The quality of life was assessed using the Pediatric Quality of Life Inventory, version 4.0, generic core scales, and compared with normative values for the same age. The association between the perioperative variables and health-related quality of life was explored., Results: A total of 242 infants underwent complex heart surgery during the study period. Of the 166 eligible survivors, 130 were included. No significant differences were present between the children with single ventricle versus biventricular repairs, except for lower physical health summary scores in the single ventricle patients (P = .007). Compared with the normative data, the children with biventricular repair had lower total Pediatric Quality of Life Inventory, version 4.0, scores (P = .001) and psychosocial health summary scores (P < .001). The children with single ventricle repair also had lower physical health summary scores (P = .003). Older age at surgery and markers of postoperative low cardiac output syndrome were associated with worse health-related quality of life, and greater socioeconomic status was associated with better quality of life., Conclusions: At 4 years of age, health-related quality of life was significantly lower in children who had undergone surgery for congenital heart disease in early infancy. An association was found between age at surgery and postoperative low cardiac output and socioeconomic status and quality of life., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Many believe that the ethical problems of donation after cardiocirculatory death (DCD) have been "worked out" and that it is unclear why DCD should be resisted. In this paper we will argue that DCD donors may not yet be dead, and therefore that organ donation during DCD may violate the dead donor rule. We first present a description of the process of DCD and the standard ethical rationale for the practice. We then present our concerns with DCD, including the following: irreversibility of absent circulation has not occurred and the many attempts to claim it has have all failed; conflicts of interest at all steps in the DCD process, including the decision to withdraw life support before DCD, are simply unavoidable; potentially harmful premortem interventions to preserve organ utility are not justifiable, even with the help of the principle of double effect; claims that DCD conforms with the intent of the law and current accepted medical standards are misleading and inaccurate; and consensus statements by respected medical groups do not change these arguments due to their low quality including being plagued by conflict of interest. Moreover, some arguments in favor of DCD, while likely true, are "straw-man arguments," such as the great benefit of organ donation. The truth is that honesty and trustworthiness require that we face these problems instead of avoiding them. We believe that DCD is not ethically allowable because it abandons the dead donor rule, has unavoidable conflicts of interests, and implements premortem interventions which can hasten death. These important points have not been, but need to be fully disclosed to the public and incorporated into fully informed consent. These are tall orders, and require open public debate. Until this debate occurs, we call for a moratorium on the practice of DCD.