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

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial. Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. Design, Setting, and Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded. Interventions: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. Main Outcomes and Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death. Results: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34). Conclusions and Relevance: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells. Trial Registration: ClinicalTrials.gov Identifier: NCT01977547.

Addressing the competency of breaking bad news: What are Canadian general paediatric residency programs currently doing.

OBJECTIVE: To describe how breaking bad news (BBN) is currently taught in Canadian general paediatric residency programs and the confidence level of fourth year paediatric residents (Ped-PGY4) in BBN and managing end-of-life-care (EOLC). METHODS: A prospective, cross-sectional survey of General Paediatric Residency Program Directors (PDs) and Ped-PGY4s was conducted. RESULTS: When learning to BBN, residents state faculty observation (22/23) and interactive workshops (14/23) are the most helpful, while PDs state interactive workshops (9/16) and deliberate practice (5/16) are ideal. Residents identified a knowledge gap and discomfort with providing anticipatory guidance, and symptom management, including prescribing opioids. CONCLUSIONS: In the era of competency-based medical education, there is an opportunity to create a standardized national curriculum addressing universal competencies related to BBN and EOLC.

Parental Presence at the Bedside of Critically Ill Children in a Unit With Unrestricted Visitation.

OBJECTIVES: To determine the percentage of time that critically ill children have a parent at the bedside and to identify extrinsic factors that are associated with percent of time with parental presence at the bedside. DESIGN: Prospective cohort study. SETTING: PICU in a single tertiary care children's hospital. SUBJECTS: Primary two parents of all children admitted to the PICU on 12 preselected days during a 1-year period from 2014 to 2015. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: A total of 111 observations of 108 unique PICU admissions and families were performed. Children had at least one parent present a mean of 58.2% (SD, 34.6%) of the time. Mothers spent more time at the bedside (56.3% [SD, 31.0%]) than fathers (37.3% [SD, 29.5%]) (p = 0.0001). Percent of time with parental presence at the bedside was positively correlated with age (rs = 0.23; p = 0.02) and negatively associated with Pediatric Risk of Mortality III score (rs = -0.26; p = 0.01). Percent of time with parental presence at the bedside was lower for children who were mechanically ventilated (42.8% [SD, 35.5%]) than not (64.5% [SD, 32.2%]) (p = 0.01) and whose parent(s) were single (45.5% [SD, 27.5%]) or cohabitating/common-law (35.7% [SD, 26.4%]) compared with parents who were married (64.2% [SD, 34.2%]) or separated/divorced (68.3% [SD, 28.8%]) (p = 0.02). Percent of time with parental presence at the bedside was higher for children with chronic illnesses (63.4% [SD, 32.9%] vs 50.1% [SD, 35.8%] without; p = 0.04), when there was a bed in the patient room (61.4% [SD, 34.0%] vs 32.5% [SD, 28.3%] without; p = 0.01), and when parents slept in the patient room (90.3% [SD, 11.2%]) compared with their own home (37.6% [SD, 34.4%]) (p < 0.0001). Percent of time with parental presence at the bedside was not correlated with day of PICU stay, number of siblings, previous PICU admission, isolation status, or nursing ratio. CONCLUSIONS: Children had a parent present at the bedside approximately 60% of the time. The parents of younger, sicker children may benefit from supportive interventions during PICU admission. Further research is needed to examine both extrinsic and intrinsic factors affecting parental presence at the bedside.

Autonomic instability in a dehydrated child on guanfacine: Case report and literature review.

An 8-year-old girl on guanfacine extended-release (GXR) for attention-deficit/hyperactivity disorder presented with somnolence, bradycardia and hypotension during a heat wave. No overdose was suspected. She was admitted to the intensive care unit for monitoring and ongoing fluid resuscitation for hypotension. Electrocardiogram showed intermittent atrioventricular dissociation. Upon restarting the drug post-discharge, blood pressures were normal, and follow-up electrocardiograms documented asymptomatic bradycardia but no dissociation. GXR is used as monotherapy or adjunct therapy in the treatment of inattention and hyperactivity in children. No published paediatric or adult study has documented atrioventricular dissociation, bradycardia or hypotension significant enough to warrant hospital admission. This case suggests that GXR can pose a hemodynamic risk to children in the context of elevated environmental temperatures and dehydration. Clinicians should be aware of this potential complication and should counsel patients about signs and symptoms of hypotension, bradycardia, bradypnea and somnolence.

Is Serum Bicarbonate Level Associated With Negative Outcomes in Pediatric Patients?: A Retrospective Cohort Study.

OBJECTIVES: Early identification of children at risk for adverse outcomes is important. Serum bicarbonate is easily collected and widely available. We described the relationship between bicarbonate and adverse outcomes in children presenting to the emergency department (ED). METHODS: We conducted a retrospective cohort study of children aged 0 to 17 years from January 1, 2007, to December 31, 2011, who had a serum bicarbonate measured in the ED. Primary outcome was the predictive ability of bicarbonate for the individual components of the composite outcome that included at least one of the following: intensive care unit admission, assisted ventilation, inotropic support, cardiopulmonary resuscitation, or death. Secondary outcome was the relationship between bicarbonate level of greater and less than 13 mEq/L and the composite outcome. RESULTS: We reviewed 16,989 charts, of which 432 had an adverse outcome. Receiver operating characteristic curve analysis showed that a bicarbonate level of less than 18.5 mEq/L predicted inotropic support with an area under the curve of 0.69 (95% confidence interval [CI], 0.60-0.77; P < 0.001) and death with an area under the curve of 0.75 (CI, 0.66-0.85; P < 0.001). Significantly more patients with bicarbonate level of less than 13 mEq/L had at least 1 adverse outcome compared with those with bicarbonate level of greater than 13 mEq/L (4.4% vs 2.5%, P = 0.001), odds ratio 1.96 (95% CI, 1.3-2.97). CONCLUSIONS: Among children presenting to the ED, bicarbonate level of 18.5 mEq/L had fair specificity in predicting inotropic support and death. Negative outcomes are significantly associated with bicarbonate level of less than 13 mEq/L. Bicarbonate should routinely be measured in children at risk of clinical deterioration.

Perceived potentially inappropriate treatment in the PICU: frequency, contributing factors and the distress it triggers.

Background: Potentially inappropriate treatment in critically ill adults is associated with healthcare provider distress and burnout. Knowledge regarding perceived potentially inappropriate treatment amongst pediatric healthcare providers is limited. Objectives: Determine the frequency and factors associated with potentially inappropriate treatment in critically ill children as perceived by providers, and describe the factors that providers report contribute to the distress they experience when providing treatment perceived as potentially inappropriate. Methods: Prospective observational mixed-methods study in a single tertiary level PICU conducted between March 2 and September 14, 2018. Patients 0-17 years inclusive with: (1) ≥1 organ system dysfunction (2) moderate to severe mental and physical disabilities, or (3) baseline dependence on medical technology were enrolled if they remained admitted to the PICU for ≥48 h, and were not medically fit for transfer/discharge. The frequency of perceived potentially inappropriate treatment was stratified into three groups based on degree of consensus (1, 2 or 3 providers) regarding the appropriateness of ongoing active treatment per enrolled patient. Distress was self-reported using a 100-point scale. Results: Of 374 patients admitted during the study, 133 satisfied the inclusion-exclusion criteria. Eighteen patients (unanimous - 3 patients, 2 providers - 7 patients; single provider - 8 patients) were perceived as receiving potentially inappropriate treatment; unanimous consensus was associated with 100% mortality on 3-month follow up post PICU discharge. Fifty-three percent of providers experienced distress secondary to providing treatment perceived as potentially inappropriate. Qualitative thematic analysis revealed five themes regarding factors associated with provider distress: (1) suffering including a sense of causing harm, (2) conflict, (3) quality of life, (4) resource utilization, and (5) uncertainty. Conclusions: While treatment perceived as potentially inappropriate was infrequent, provider distress was commonly observed. By identifying specific factor(s) contributing to perceived potentially inappropriate treatment and any associated provider distress, organizations can design, implement and assess targeted interventions.

A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

ABSTRACT: This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.

A Pilot Cross-Discipline Evidence-Based Palliative Care Curriculum for Postgraduate Medical Trainees.

INTRODUCTION: It is widely recognized that physicians of all backgrounds benefit from having a general palliative care skill set to optimally manage their patients at the end of life. However, strategies to teach palliative care skills to trainees outside palliative medicine vary widely. In this report, we provide an evidence-based and cross-disciplinary palliative care framework applicable to a spectrum of specialty training environments and intended for nonpalliative care trainees. INNOVATION: We developed and implemented a concise, multimodal, and evidence-based pilot palliative care curriculum focused on essential general palliative care skills required by physicians providing patient care along the continuum of life across specializations. A needs assessment (local research, literature review, and consensus expert opinion) in combination with learner characteristics (Kolb Learning Style Inventory, Palliative Medicine Comfort and Confidence Survey, and knowledge pretest) informed the development of a curricular outline. The first iteration of the curriculum was formulated and delivered. Extensive evaluation, reassessment, and feedback led to a second iteration, which is presented here. OUTCOMES: Although the context will differ according to specialization, there are essential palliative care skills required of most specialist physicians. General palliative themes identified for focus include symptom management, communication, psychosocial aspects of care, care coordination and access, and myths and pitfalls in palliative care. COMMENT: Specialty trainees' value embedded training in essential themes in palliative care within the context of their training program. The process and results of this project, including the provision of a framework, may be applied to postgraduate training programs in various specialties.

Methadone for Analgesia in Children with Life-Limiting Illness: Experience from a Tertiary Children's Health Service.

Methadone has the potential to assist in the management of pain in children with life-limiting illness, but its use is limited by its complex pharmacokinetic profile and limited research on its use in children. This is a retrospective review of the use of methadone as an analgesic in 16 children with life-limiting illness. Efficacy, dosing and side effect profile were analysed. Fifteen (94%) patients had improvements in their analgesia with minimal observed adverse effects. Patients were either rapidly converted from a prior opioid in one change or received methadone as an adjunct medication. Conversions were calculated using ratios frequently in the range of 10:1 to 20:1 from the oral morphine equivalent total daily dose (MEDD). Adjunct initial dosing was a low dose trial, often beginning with 1 mg at night. Only two patients required a dose adjustment due to side effects attributed to methadone. This was despite the cohort having significant underlying illnesses, extensive concurrent medications, and high methadone dosing where needed. Analysis of dosing and ratios indicates that an individualised approach is required. Based on this and on the infrequency of methadone use in this population, specialist assistance with dosing is recommended. Further research, including prospective and pharmacokinetic studies, is recommended.

B-type natriuretic peptide in pediatrics.

OBJECTIVES: There has been growing interest in the use of serum B-type natriuretic peptide (BNP) and the N-terminal segment of its pro-hormone (NT-proBNP) as biomarkers for cardiac disease. The aim of this review is to summarize the current state of knowledge regarding BNP and NT-proBNP measurement in the pediatric population. DESIGN AND METHODS: A computerized literature search on the National Library of Medicine was done and all articles including BNP and pediatrics were selected and discussed. RESULTS: The data from several studies suggest that the measurement of BNP may be useful in diagnosing and managing pediatric heart failure, congenital heart disease, cardiac transplantation and patients on chemotherapy. There are difficulties in establishing appropriate reference ranges in children. CONCLUSION: There is insufficient evidence for the routine use of BNP or NT-proBNP. Further research to clearly define the clinical utility in the pediatric age group is eagerly anticipated.

Pediatric palliative care in Canada in 2012: a cross-sectional descriptive study.

BACKGROUND: Pediatric palliative care focuses on comprehensive symptom management and enhancing quality of life for children with life-threatening conditions and their families. Our aim was to describe Canadian programs that provided specialized pediatric palliative care in 2012 and the children who received it and to estimate the proportion of children who might benefit that received specialized care. METHODS: A cross-sectional descriptive design was used. Specialized pediatric palliative care programs were included in the study if they offered multidisciplinary consulting pediatric palliative care services to a wide range of children and served all populations of children with life-threatening illness regardless of diagnosis. Investigators in programs that had taken part in a prior study were invited to participate. New programs that met the inclusion criteria were identified through snowball sampling within pediatric palliative care networks. Program data were obtained via surveys with coinvestigators, and health record reviews were used to obtain information about the children who received care through the programs. RESULTS: All 13 programs identified, including 3 with a free-standing hospice, agreed to take part in the study. Of the 1401 children who received care, 508 (36.2%) were under 1 year of age, and 504 (36.0%) had a congenital illness or condition originating in the perinatal period. Of the 431 children who died in 2012, 105 (24.4%) died in a critical care setting. Programs with a hospice provided care to 517 children (36.9%). Children in this group tended to be older, more often had a neurologic illness and received care for a longer time than those who received care from programs without a hospice. Overall, 18.6% (95% confidence interval 17.1%-20.3%) of deceased children who might have benefitted from specialized pediatric palliative care based on diagnosis received such care, with 110 (25.2%) receiving care for less than 8 days. INTERPRETATION: Program growth and changes in patients' demographic and clinical characteristics indicate improved reach of programs. However, barriers remain that prevent most children with life-threatening conditions from receiving specialized pediatric palliative care services.