Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction.
Our objective was to evaluate current evidence and to develop consensus ...criteria for gastrointestinal dysfunction in critically ill children.
Electronic searches of PubMed and EMBASE were conducted from January 1992 to January 2020, using medical subject heading terms and text words to define gastrointestinal dysfunction, pediatric critical illness, and outcomes.
Studies were included if they evaluated critically ill children with gastrointestinal dysfunction, performance characteristics of assessment/scoring tools to screen for gastrointestinal dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, case series with sample size ≤10, and non-English language studies with inability to determine eligibility criteria were excluded.
Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment by a task force member.
The systematic review supports the following criteria for severe gastrointestinal dysfunction: 1a) bowel perforation, 1b) pneumatosis intestinalis, or 1c) bowel ischemia, present on plain abdominal radiograph, computed tomography (CT) scan, magnetic resonance imaging (MRI), or gross surgical inspection, or 2) rectal sloughing of gut mucosa.
The validity of the consensus criteria for gastrointestinal dysfunction are limited by the quantity and quality of current evidence.
Understanding the role of gastrointestinal dysfunction in the pathophysiology and outcomes of MODS is important in pediatric critical illness.
Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in ...interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children.
We performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score.
Common variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity.
We provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.
To describe the diagnostic criteria of new and progressive multiple organ dysfunction syndrome and scoring systems that might be used to assess and monitor the severity and progression of multiple ...organ dysfunction syndrome in children presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015).
Literature review, research data, and expert opinion.
Not applicable.
Moderated by an experienced expert from the field, issues relevant to the monitoring of the severity of multiple organ dysfunction syndrome including new and progressive multiple organ dysfunction syndrome and scoring systems were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities.
Summary of presentations and discussion supported and supplemented by relevant literature.
Many sets of diagnostic criteria of multiple organ dysfunction syndrome are presently available. All are useful, but their diagnostic and predictive value can be improved. Several types of diagnostic criteria are candidates to describe the severity and to monitor the progression of cases of multiple organ dysfunction syndrome, which include existing scores of organ dysfunction: Pediatric Logistic Organ Dysfunction, version 2, daily Pediatric Logistic Organ Dysfunction, version 2, organ failure-free days, etc. If a new set of diagnostic criteria of multiple organ dysfunction syndrome is created, its value must be validated. Furthermore, the epidemiology of multiple organ dysfunction syndrome based on these new diagnostic criteria must be compared with the epidemiology found with the preexisting sets of diagnostic criteria. The reliability as well as the added values of additional or new candidate markers of organ dysfunction and multiple organ dysfunction syndrome severity must be studied and compared.
The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved ...clinical outcomes in critically ill children.
Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial.
Thirty-five PICUs.
Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data.
Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time).
Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001).
In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes.
Children with congenital heart disease have loss of intestinal epithelial barrier function, which increases their risk for postoperative sepsis and organ dysfunction. We do not understand how ...postoperative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass might alter intestinal epithelial barrier function. We examined variation in a panel of plasma biomarkers to reflect intestinal epithelial barrier function (cellular and paracellular) after cardiopulmonary bypass and in response to routine ICU care.
Prospective cohort.
University medical center cardiac ICU.
Twenty children aged between newborn and 18 years undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass.
We measured baseline and repeated plasma intestinal fatty acid-binding protein, citrulline, claudin 3, and dual sugar permeability testing to reflect intestinal epithelial integrity, epithelial function, paracellular integrity, and paracellular function, respectively. We measured baseline and repeated plasma proinflammatory (interleukin-6, tumor necrosis factor-α, and interferon-γ) and anti-inflammatory (interleukin-4 and interleukin-10) cytokines, known to modulate intestinal epithelial barrier function in murine models of cardiopulmonary bypass.
All patients had abnormal baseline intestinal fatty acid-binding protein concentrations (mean, 3,815.5 pg/mL; normal, 41-336 pg/mL). Cytokine response to cardiopulmonary bypass was associated with early, but not late, changes in plasma concentrations of intestinal fatty acid-binding protein 2 and citrulline. Variation in biomarker concentrations over time was associated with aspects of ICU care indicating greater severity of illness: claudin 3, intestinal fatty acid-binding protein 2, and dual sugar permeability test ratio were associated with symptoms of feeding intolerance (p < 0.05), whereas intestinal fatty acid-binding protein was positively associated with vasoactive-inotrope score (p = 0.04). Citrulline was associated with larger arteriovenous oxygen saturation difference (p = 0.04) and had a complex relationship with vasoactive-inotrope score.
Children undergoing cardiopulmonary bypass for repair or palliation of congenital heart disease are at risk for intestinal injury and often present with evidence for loss of intestinal epithelial integrity preoperatively. Greater severity of illness requiring increased cardiopulmonary support rather than the inflammatory response to cardiopulmonary bypass seems to mediate late postoperative intestinal epithelial barrier function.
The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement ...of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.
To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.
We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.
We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.
The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
OBJECTIVES:The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in ...pediatric severe sepsis.
DESIGN:Secondary analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient characteristics, ICU interventions, and outcomes were compared across nutrition status categories (expressed as age- and sex-adjusted body mass index z scores using World Health Organization standards). Multivariable regression models were developed to determine adjusted differences in all-cause ICU mortality and ICU length of stay by nutrition status.
SETTING:One-hundred twenty-eight PICUs across 26 countries.
PATIENTS:Children less than 18 years with severe sepsis enrolled in the Sepsis Prevalence, Outcomes, and Therapies study (n = 567).
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Nutrition status data were available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia (20%), South Africa (17%), and South America (10%), with severe overnutrition seen in Australia/New Zealand (17%) and North America (14%). Severe undernutrition was independently associated with all-cause ICU mortality (adjusted odds ratio, 3.0; 95% CI, 1.2–7.7; p = 0.02), whereas severe overnutrition in survivors was independently associated with longer ICU length of stay (1.6 d; p = 0.01).
CONCLUSIONS:There is considerable variation in nutrition status for children with severe sepsis treated across this selected network of PICUs from different geographic regions. Severe undernutrition was independently associated with higher all-cause ICU mortality in children with severe sepsis. Severe overnutrition was independently associated with greater ICU length of stay in childhood survivors of severe sepsis.
Background Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are ...less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 range, 10.4–17.4 versus 10.0 range, 5.4–14.8 years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.
The epidemiology and outcomes of multiple organ dysfunction syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ ...failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of pediatric intensive care unit (PICU) patients based on consensus definitions of organ failure.
Retrospective analysis of a contemporaneously collected clinical PICU database.
Virtual Pediatric Intensive Care Unit Performance System database patient admissions from January 2004 to December 2005 for 35 U.S. children's hospitals.
: We evaluated 63,285 consecutive PICU admissions from January 2004 to December 2005 in the Virtual Pediatric Intensive Care Unit Performance System database. We excluded patients younger than 1 month or older than 18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference criteria with day 1 laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge.
Student's t test, chi-square test, Mann-Whitney rank sum, Kruskal-Wallis, and linear and logistic regression.
We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% vs. 1.2%, p < .001), longer PICU length of stay (3.6 vs. 1.3 days, p < .001), and larger change from baseline Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores at time of PICU discharge (p < .001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p < .001) compared with other age groups.
Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day 1 of intensive care unit admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day 1. Infants are disproportionally affected by MODS.
To describe new technologies (biomarkers and tests) used to assess and monitor the severity and progression of multiple organ dysfunction syndrome in children as discussed as part of the Eunice ...Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015).
Literature review, research data, and expert opinion.
Not applicable.
Moderated by an experienced expert from the field, investigators developing and assessing new technologies to improve the care and understanding of critical illness presented their research and the relevant literature.
Summary of presentations and discussion supported and supplemented by relevant literature.
There are many innovative tools and techniques with the potential application for the assessment and monitoring of severity of multiple organ dysfunction syndrome. If the reliability and added value of these candidate technologies can be established, they hold promise to enhance the understanding, monitoring, and perhaps, treatment of multiple organ dysfunction syndrome in children.
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