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 children's 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.

Postnatal maturation of total cell content and up-regulated surface expression of Mac-1 (CD11b/CD18) in polymorphonuclear leukocytes of human infants.

Markedly deficient expression of membrane-activated complex 1 (Mac-1; CD11b/CD18) by polymorphonuclear neutrophils (PMN) of human neonates compared with adults is well documented. To define postnatal maturation of Mac-1 expression of PMN, lysates of PMN from 21 infants, aged 1-14 months, and concurrent adult controls were assayed by ELISA for total cell content of Mac-1 and LFA-1 (CD11a/CD18), and LFA-1 content was within the normal adult range at all ages tested. Mac-1 content was approximately 50% of adult levels for infants 1-2 months of age and steadily increased to reach normal adult levels by 11-12 months of age. For a separate group of 25 infants, aged 0.5-11 months, measurement of surface expression of Mac-1 and LFA-1 on activated PMN by immunofluorescence flow cytometry yielded results that were similar to those obtained by ELISA.

Atherogenic diet-induced hepatitis is partially dependent on murine TLR4.

Diets high in cholesterol and cholate such as the Paigen diet have been used to study atherogenesis, lithogenesis, and proinflammatory microvascular changes induced by nutritional hypercholesterolemia. Although these diets lead to chronic hepatic inflammation and fibrosis, the early inflammatory changes have been poorly characterized. TLR4, a known receptor for LPS, is also a receptor for a variety of endogenous ligands and has been implicated in atheroma formation. Here, we specifically examined the early inflammatory response of the liver to the atherogenic (ATH) diet and the possible contribution of TLR4. Animals fed the high-cholesterol/cholate diet for 3 weeks developed a significant, predominantly mononuclear leukocyte infiltration in the liver, hepatic steatosis, elevated hepatic expression of MCP-1, RANTES, and MIP-2, and increased serum levels of liver enzymes. In TLR4-deleted animals, there was a 30% attenuation in the serum alanine transaminase levels and a 50% reduction in the leukocyte infiltration with a fourfold reduction in chemokine expression. In contrast, hepatic steatosis did not differ from wild-type controls. TLR2 deletion had no effect on diet-induced hepatitis but increased the amount of steatosis. We conclude that the early inflammatory liver injury but not hepatic lipid loading induced by the ATH diet in mice is mediated in part by TLR4.

The pediatric multiple organ dysfunction syndrome.

OBJECTIVES: To review the epidemiology of pediatric multiple organ dysfunction syndrome (MODS) and summarize current concepts regarding the pathophysiology of shock, organ dysfunction, and nosocomial infections in this population. DATA SOURCE: A MEDLINE-based literature search using the keywords MODS and child, without any restriction to the idiom. MAIN RESULTS: Critically ill children may frequently develop multisystemic manifestations during the course of severe infections, multiple trauma, surgery for congenital heart defects, or transplantations. Descriptive scores to estimate the severity of pediatric MODS have been validated. Young age and chronic health conditions have also been recognized as important contributors to the development of MODS. Unbalanced inflammatory processes and activation of coagulation may lead to the development of capillary leak and acute respiratory distress syndrome. Neuroendocrine and metabolic responses may result in insufficient adaptive immune response and the development of nosocomial infections, which may further threaten host homeostasis. CONCLUSIONS: Over the last 20 yrs, there has been an increasing knowledge on the epidemiology of pediatric MODS and on the physiologic mechanisms involved in the genesis of organ dysfunction. Nevertheless, further studies are needed to more clearly evaluate what is the long-term outcome of pediatric MODS.

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. 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.

Exploring individual opinions of potential evaluators in a 360-degree assessment: four distinct viewpoints of a competent resident.

BACKGROUND: Despite the highly acclaimed psychometric features of a 360-degree assessment in the fields of economics, military, and education, there has been increased interest in developing 360-degree instruments to assess competencies in graduate medical education only in the past recent years. Most of the effort to date, however, has focused on developing instruments and testing their reliability and feasibility. Insufficient attention has gone into issues of construct validity and particularly understanding the underlying constructs on which the instruments are based as well as the phenomena that affect ratings. PURPOSE: In preparation for developing a 360-degree assessment instrument, we explored variations in evaluators' opinion type of a competent resident and offer observation about evaluator's professional background and opinions. METHOD: Evaluators from two residency programs ranked 36 opinion statements, using a relative-ranking model, based on their opinion of a competent resident. By-person factor analysis was used to structure opinion types. RESULTS: Factor analysis of 156 responses identified four factors interpreted as four different opinion types of a competent resident: (a) altruistic, compassionate healer (n = 42 evaluators), (b) scientifically grounded clinician (n = 30), (c) holistic, humanistic clinician (n = 62), and (d) patient-focused, health manager (n = 31). Although 72% of nurses/respiratory therapist evaluators expressed type C, 28% expressed other types just as often. Only 14% of evaluator physicians expressed type D, and the remainders were evenly split among the other types. CONCLUSIONS: Our evaluators in 360-degree system expressed four opinion types of a competent resident. The individual opinion and not professional background influences the characteristics an evaluator values in a competent resident. We propose that these values will have an impact on competency assessment and should be taken into account in a 360-degree assessment.

Innate immunity in critical care.

Innate and adaptive immunity are required for effective control of infection. Numerous breakthroughs have been achieved in the last 15 years with regard to the functioning of the innate immune system. This article focuses on new paradigms of microorganism recognition, discusses recently described (or rediscovered) cytokines that provide further insight into the development of sepsis, and reviews both pro- and anti-inflammatory pathways for control of infection. Finally, it discusses what has and has not worked with regard to controlling inflammatory pathways in septic patients.

Considering the use of induced hypothermia in a pediatric patient with traumatic brain injury: a critical appraisal of two meta-analyses.

OBJECTIVE: To review whether induced hypothermia after traumatic brain injury affects morbidity and mortality based on the results of two meta-analyses. DESIGN: Critical appraisals of McIntyre et al: Prolonged therapeutic hypothermia after traumatic brain injury in adults: A systematic review. JAMA 2003; 289:2992-2999, and Henderson et al: Hypothermia in the management of traumatic brain injury: A systematic review and meta-analysis. Intensive Care Med 2003; 29:1637-1644. FINDINGS: Both meta-analyses included trials of adult patients with severe traumatic brain injury randomized to induced hypothermia or normothermia and evaluated risk of death and poor neurologic outcomes. McIntyre et al. found the overall relative risk of mortality with induced hypothermia to be 0.81 (95% confidence interval 0.69-0.96). By designing a priori analyses, these authors also found that the relative risk of death was reduced in patients cooled for >48 hrs, and the risk of poor neurologic outcome was reduced with all durations of cooling, cooling to 32-33 degrees C, and rewarming in <24 hrs. In contrast, Henderson et al. found that induced hypothermia did not change the odds of death after traumatic brain injury (odds ratio 0.81; 95% confidence interval 0.59-1.13) and that normothermic controls had an odds ratio of 0.42 (95% confidence interval 0.25-0.70) for developing intercurrent pneumonia. Both analyses found trials to be heterogeneous with respect to neurologic outcome. CONCLUSIONS: The discrepancies in the results of these contemporaneous meta-analyses may stem, in part, from differences in their trial selection strategies as well as from sources of trial heterogeneity. Nevertheless, McIntyre et al. uncovered the equivalent of a dose-dependent reduction in the risk of death with induced hypothermia, supporting further study of this neuroprotective strategy. Although these meta-analyses included trials containing adult patients, a phase II trial of induced hypothermia in pediatric traumatic brain injury has established its feasibility and safety in infants and children. As in adult patients, induced hypothermia for traumatic brain injury in children can be considered an optional therapy for refractory intracranial hypertension but should not be regarded as standard of care.

Critical appraisal of Perez et al: Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury.

OBJECTIVE: To review the findings and discuss the implications of jugular venous bulb oxygenation monitoring in children with severe traumatic brain injury. DESIGN: A critical appraisal of Perez et al, Jugular venous oxygen saturation or arteriovenous difference of lactate content and outcome in children with severe traumatic brain injury. FINDINGS: Two episodes of jugular venous bulb desaturation and abnormal values of arteriovenous difference in lactate content are associated with poor neurologic outcome in children with severe traumatic brain injury-risk ratio 6.6 (95% confidence interval, 1.5-29.7) and risk ratio 17.6 (95% confidence interval, 2.5-122.5), respectively. This confirms the findings of previously reported adult studies. CONCLUSIONS: This study is the first to demonstrate that jugular venous monitoring may aid in predicting the neurologic outcome of children with severe traumatic brain injury. More studies need to be performed (particularly on safety) before adopting jugular venous bulb oxygenation monitoring as a prediction tool or, ultimately, as a therapeutic intervention to help manage and improve outcome for children with severe traumatic brain injury.

Improving care for children with sickle cell disease/acute chest syndrome.

BACKGROUND: Acute chest syndrome (ACS) is a leading cause of hospitalization and death of children with sickle cell disease (SCD). An evidence-based ACS/SCD guideline was established to standardize care throughout the institution in February 2008. However, by the summer of 2009 use of the guideline was inconsistent, and did not seem to have an impact on length of stay. As a result, an implementation program was developed. OBJECTIVE: This quality-improvement project evaluated the influence of the development and implementation of a clinical practice guideline for children with SCD with ACS or at risk for ACS on clinical outcomes. METHODS: Clinical outcomes of 139 patients with SCD were evaluated before and after the development of the implementation program. Outcomes included average length of stay, number of exchange transfusions, average cost per SCD admission, and documentation of the clinical respiratory score and pulmonary interventions. RESULTS: Average length of stay decreased from 5.8 days before implementation of the guideline to 4.1 days after implementation (P = .033). No patients required an exchange transfusion. Average cost per SCD admission decreased from $30 359 before guideline implementation to $22 368. Documentation of the clinical respiratory score increased from 31.0% before implementation to 75.5%, which is an improvement of 44.5% (P < .001). Documentation of incentive spirometry and positive expiratory pressure increased from 23.3% before implementation to 50.4%, which is an improvement of 27.1% (P < .001). CONCLUSIONS: Implementation of a guideline for children with SCD with ACS or at risk for ACS improved outcomes for patients with SCD.

Mechanisms of decreased leukocyte localization in the developing host.

Delays in leukocyte localization likely contribute to diminished host defense in neonates. Understanding the processes that may be affected has been hampered by the lack of suitable developmental models. Using intravital microscopy, we directly examine leukocyte recruitment in a rabbit pup model. In response to intraperitoneal interleukin (IL)-1beta, there were one-third as many leukocytes that arrested in pup mesenteric vessels and emigrated compared with adult vessels, although leukocyte flux was not different. Leukocyte rolling velocity in pups was one-half that in adults. In response to surgical trauma alone, the number of arrested pup cells was 15% that of adult cells, although again leukocyte flux was not different. An anti-L-selectin antibody inhibited rolling significantly by 60 min for both pups and adults. The effect on arrest and emigration occurred at significantly earlier times, although the effect was less in rabbit pups. A primary defect in leukocyte emigration in the rabbit pup appears to be a failure of the cell to transition efficiently from rolling to arrest. L-selectin-dependent adhesion and emigration are decreased, rolling is not, suggesting that at least part of the defect is due to events downstream of the initial tether.