Katri Typpo

Day 1 multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit.

Objective: 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. Design: Retrospective analysis of a contemporaneously collected clinical PICU database. Setting: Virtual Pediatric Intensive Care Unit Performance System database patient admissions from January 2004 to December 2005 for 35 U.S. children’s hospitals. Patients: 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. Interventions: Analysis: Student’s t test, chi-square test, Mann-Whitney rank sum, Kruskal-Wallis, and linear and logistic regression. Measurements and Main Results: 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. Conclusions: 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.

Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care

BackgroundThe 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.ObjectiveTo 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.MethodsWe 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.ResultsWe 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 Medicines 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.ConclusionsThe 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.

Children with Chronic Illness Return to Their Baseline Functional Status after Organ Dysfunction on the First Day of Admission in the Pediatric Intensive Care Unit

OBJECTIVE To determine chronic illness outcomes after admission with multiple organ dysfunction syndrome (MODS) for patients in the pediatric intensive care unit (PICU). STUDY DESIGN We evaluated consecutive PICU admissions from 35 US childrens hospitals from January 2004-December 2005 in the virtual PICU Performance System database. We excluded hospitals with >10% missing values for MODS variables and patients<1 month or>18 years of age. MODS was identified by laboratory and vital sign values from day of admission with International Pediatric Sepsis Consensus Conference criteria. Chronic illness was identified by secondary diagnoses, classified by modified Delphi method. We evaluated functional outcomes with pediatric overall performance category and pediatric cerebral performance category scores from PICU admission and discharge. RESULTS Of 44 693 admissions, 52.1% had a chronic diagnosis. Chronic diagnoses increased MODS at PICU admission (24.6% vs 12.0%, P<.001) and mortality rates (3.7% vs 1.9%, P<.001). Patients with a chronic diagnosis had similar changes in pediatric overall performance category and pediatric cerebral performance category scores from PICU admission to discharge as previously healthy children. However, outcome in different chronic diagnosis categories was variable. CONCLUSIONS Chronic illness increased MODS incidence at PICU admission and impacted all-cause PICU mortality rates. Although, in aggregate, children who survive return to baseline functional status, this varies by chronic illness category.

Existing data analysis in pediatric critical care research

Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM.

Impact of resident duty hour limits on safety in the intensive care unit: a national survey of pediatric and neonatal intensivists.

Objective: Resident duty-hour regulations potentially shift the workload from resident to attending physicians. We sought to understand how current or future regulatory changes might impact safety in academic pediatric and neonatal intensive care units. Design: Web-based survey. Setting: U.S. academic pediatric and neonatal intensive care units. Subjects: Attending pediatric and neonatal intensivists. Interventions: We evaluated perceptions on four intensive care unit safety-related risk measures potentially affected by current duty-hour regulations: 1) attending physician and resident fatigue; 2) attending physician workload; 3) errors (self-reported rates by attending physicians or perceived resident error rates); and 4) safety culture. We also evaluated perceptions of how these risks would change with further duty-hour restrictions. Measurements and Main Results: We administered our survey between February and April 2010 to 688 eligible physicians, of whom 360 (52.3%) responded. Most believed that resident error rates were unchanged or worse (91.9%) and safety culture was unchanged or worse (84.4%) with current duty-hour regulations. Of respondents, 61.9% believed their own work-hours providing direct patient care increased and 55.8% believed they were more fatigued while providing direct patient care. Most (85.3%) perceived no increase in their own error rates currently, but in the scenario of further reduction in resident duty-hours, over half (53.3%) believed that safety culture would worsen and a significant proportion (40.3%) believed that their own error rates would increase. Conclusions: Pediatric intensivists do not perceive improved patient safety from current resident duty-hour restrictions. Policies to further restrict resident duty-hours should consider unintended consequences of worsening certain aspects of intensive care unit safety.

Clinical characteristics associated with postoperative intestinal epithelial barrier dysfunction in children with congenital heart disease.

Objective: 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. Design: Prospective cohort. Setting: University medical center cardiac ICU. Patients: Twenty children aged between newborn and 18 years undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass. Interventions: 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-&agr;, and interferon-&ggr;) and anti-inflammatory (interleukin-4 and interleukin-10) cytokines, known to modulate intestinal epithelial barrier function in murine models of cardiopulmonary bypass. Measurements and Main Results: 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. Conclusions: 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.

DIFFERENTIAL DEVELOPMENT OF CHOLINERGIC-LIKE NEURONS IN THE SUPERIOR OLIVE: A LIGHT MICROSCOPIC STUDY

To better understand the development of cholinergic-like neurons within the superior olivary complex, we investigated the onset and distribution of two well-known markers of cholinergic-like neurons in hamsters: choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). From embryonic day (E) 14 through postnatal day (P) 0, olivary cells immunopositive for ChAT were restricted to the rostral periolivary (RPO) area. Between P0 and P3, ChAT-positive cells are found in progressively more caudal and ventral periolivary locations. Although rostral and ventral periolivary cells exhibited an early onset of ChAT expression, stable numbers were not reached until P4. In contrast, ChAT expression within the lateral superior olive (LSO) is not visible until after P0 and higher numbers of ChAT-positive cells are obtained by P5. The AChE expression lags several days but follows roughly the same pattern of onset as for ChAT. Additionally in rostral and ventral periolivary regions as well as in the LSO, there were fewer AChE-labeled cells than ChAT-labeled cells. The observed temporal relationships in cholinergic-like expression within olivary cells suggest that different cholinergic-like populations may be defined on the basis of the onset of neurotransmitter-related enzymes: RPO cells are first, cells in ventral periolivary regions are second, and cells associated with the LSO are last. The differences observed in the onset of ChAT and AChE expression may reflect differences in the timing of target innervation as well as differences in synaptogenesis.

Monitoring severity of multiple organ dysfunction syndrome: New technologies

Objective: 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). Data Sources: Literature review, research data, and expert opinion. Study Selection: Not applicable. Data Extraction: 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. Data Synthesis: Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions: 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.

Readmission and Late Mortality After Critical Illness in Childhood.

Objectives: Little is known about the ongoing mortality risk and healthcare utilization among U.S. children after discharge from a hospitalization involving ICU care. We sought to understand risks for hospital readmission and trends in mortality during the year following ICU discharge. Design: Retrospective observational cohort study. Setting: This study was performed using administrative claims data from 2006-2013 obtained from the Truven Health Analytics MarketScan Database. Subjects: We included all children in the dataset admitted to a U.S. ICU less than or equal to 18 years old. Interventions: The primary outcome was nonelective readmission in the year following discharge. Risk of rehospitalization was determined using a Cox proportional hazards model. Measurements and Main Results: We identified 109,130 children with at least one ICU admission in the dataset. Over three quarters of the index ICU admissions (78.6%) had an ICU length of stay less than or equal to 3 days, and the overall index hospitalization mortality rate was 1.4%. In multivariate analysis, risk of nonelective readmission for children without cancer was higher with longer index ICU admission length of stay, younger age, and several chronic and acute conditions. By the end of the 1-year observation period, 36.0% of children with an index ICU length of stay greater than or equal to 14 days had been readmitted, compared with only 13.9% of children who had an index ICU length of stay equals to 1 day. Mortality in the year after ICU discharge was low overall (106 deaths per 10,000 person-years of observation) but was high among children with an initial index ICU admission length of stay greater than or equal to 14 days (599 deaths per 10,000 person-years). Conclusions: Readmission after ICU care is common. Further research is needed to investigate the potentially modifiable factors affecting likelihood of readmissions after discharge from the ICU. Although late mortality was relatively uncommon overall, it was 10-fold higher in the year after ICU discharge than in the general U.S. pediatric population.

Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome

Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a “motor” of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness.