No abstract

BackgroundEpithelial and endothelial barrier integrity, essential for homeostasis, is maintained by cellular boarder structures known as tight junctions (TJs). In critical illness, TJs may become disrupted, resulting in barrier dysfunction manifesting as capillary leak, pulmonary edema, gut bacterial translocation, and multiple organ failure. We aim to provide a clinically focused overview of TJ structure and function and systematically review and analyze all studies assessing markers of endothelial and epithelial TJ breakdown correlated with clinical outcomes in critically ill humans.MethodsWe systematically searched MEDLINE, EMBASE, and PubMed. Additional articles were identified by targeted searches. We included studies that looked at the relationship between biomarkers of endothelial or epithelial TJ structure or function and critical illness. Results were qualitatively analyzed due to sample size and heterogeneity.ResultsA total of 5297 abstracts met search criteria, of which 150 articles met requirements for full text review. Of these, 30 studies met inclusion criteria. Fifteen of the 30 reports investigated proteins of endothelial tight junctions and 15 investigated epithelial TJ markers, exclusively in the gastrointestinal epithelium. No studies investigated TJ-derived proteins in primary cardiac or pulmonary pathology.ConclusionsTJ integrity is essential for homeostasis. We identified multiple studies that indicate TJs are disrupted by critical illness. These studies highlight the significance of barrier disruption across many critical disease states and correlate TJ-associated markers to clinically relevant outcomes. Further study on the role of multiple tissue-specific claudins, particularly in the setting of respiratory or cardiac failure, may lead to diagnostic and therapeutic advances.Systematic review registrationThis systematic review is registered in the PROSPERO database: CRD42017074546.Electronic supplementary materialThe online version of this article (10.1186/s40635-018-0203-4) contains supplementary material, which is available to authorized users.

Objective Delayed enteral nutrition (EN), defined as EN started ≥ 48 hours after admission to the pediatric intensive care unit (PICU) is associated with an inability to achieve full EN and worse outcomes in critically ill children. We reviewed nutritional practices in 6 medical-surgical PICUs and determined risk factors associated with delayed EN in critically ill children. Design Retrospective cross-sectional study using medical records as source of data Setting Six medical-surgical PICUs in northeastern United States Patients Children < 21 years old admitted to the PICU for ≥ 72 hours excluding those awaiting or recovering from abdominal surgery. Measurements/Main Results A total of 444 children with a median age of 4.0 years were included in the study. EN was started at a median time of 20 hours after admission to the PICU. There was no significant difference in time to start EN among the PICUs. Of those included, 88 (19.8%) children had delayed EN. Risk factors associated with delayed EN were: non-invasive (odds ratio [OR]: 3.37; 95% CI: 1.69-6.72) and invasive positive pressure ventilation (OR: 2.06; 95% CI: 1.15-3.69), severity of illness, (OR for every 0.1 increase in Pediatric Index of Mortality 2 score: 1.39; 95% CI: 1.14-1.71) as well as procedures (OR 3.33; 95% CI: 1.67-6.64) and; gastrointestinal disturbances (OR: 2.05; 95% CI: 1.14-3.68) within 48 hours after admission to the PICU. Delayed EN was associated with failure to reach full EN while in the PICU (OR 4.09; 95% CI: 1.97-8.53). Nutrition consults were obtained in less than half of the cases and none of the PICUs employed tools to assure the adequacy of energy and protein nutrition. Conclusions Institutions in this study initiated EN for a high percentage of patients by 48 hours of admission. Non-invasive positive pressure ventilation was most strongly associated with delay EN. A better understanding of these risk factors and assessments of nutritional requirements should be explored in future prospective studies.

Aim:To identify patients aged 10-30 years with probable hyperglycemic hyperosmolar syndrome (HHS), to describe demographic and clinical profiles, and to attempt to assess risk factors for poor outcomes. Study design: Retrospective cohort study (medical records review). Setting: A 944-bed tertiary care teaching and research hospital and a 425-bed affiliated facility. Patients: 10-30 year-old patients with a primary or secondary discharge diagnosis of HHS or diabetic ketoacidosis (DKA). Patients with a serum glucose >600 mg/dl in the absence of significant ketoacidosis (possible HHS) were profiled. Further stratification based on measured or calculated serum osmolarity >320 mOsm/kg (probable HHS) was undertaken. Interventions: Patients received treatment for hyperglycemic crises, consisting primarily of fluids, electrolyte replacement and insulin. Measurements and main results: Of the 629 admissions, 10 with a diagnosis of HHS and 33 with a diagnosis of DKA met the initial study criteria for HHS. 60% were African Americans and 89% were new-onset diabetics. From this group, 20 admissions had serum osmolarity >320 mOsm/kg. Fisher's exact test and Pearson coefficients were used to examine associations between risk factor and poor outcomes and correlations between admission data and length of hospital stay, respectively. Serious complications occurred in four patients (including two deaths, 10% mortality) and were limited to those with unreversed shock over the first 24 hours of admission and who received <40 ml/kg of intravenous fluids over the first 6 hours of treatment. Conclusions: HHS was underdiagnosed in this population and occurred disproportionately in African Americans. Serious complications occurred exclusively in those with unreversed shock and inadequate fluid resuscitation.

The observed mortality rate was in the range reported in other resource-limited settings. The initial attempt to create and implement a risk of mortality tool for this setting determined a score that could identify those patients at higher risk of mortality. In PICUs in resource-limited settings, the gathering of data and use of severity of illness tools could improve care in a number of ways.

Even within a close geographic region, there is significant variation in the treatment provided to critically ill children with RSV bronchiolitis. None of these treatments were associated with shorter durations of hospitalization in this population and some, such as mechanical ventilation, were associated with longer ICU lengths of stay.

Most intensivists administer methylprednisolone to critically ill asthmatics at doses 2 to 4 times higher than recommended by the National Heart, Lung, and Blood Institute guidelines for hospitalized asthmatic children. The rationale for these decisions is likely multifactorial, but in the absence of evidence-based data, most of them cite clinical experience as their deciding factor. Future research is needed to determine the most appropriate corticosteroid dosage in this critically ill patient population.

Objectives: Shock refractory to fluid and catecholamine therapy has significant morbidity and mortality in children. The use of methylene blue to treat refractory shock in children is not well described. We aim to collect and summarize the literature and define physicians’ practice patterns regarding the use of methylene blue to treat shock in children. Design: We conducted a systematic search of MEDLINE, Embase, PubMed, Web of Science, Cochrane for studies involving the use of methylene blue for catecholamine-refractory shock from database inception to 2019. Collected studies were analyzed qualitatively. To describe practice patterns of methylene blue use, we electronically distributed a survey to U.S.-based pediatric critical care physicians. We assessed physician knowledge and experience with methylene blue. Survey responses were quantitatively and qualitatively evaluated. Setting: Pediatric critical and cardiac care units. Patients or Subjects: Patients less than or equal to 25 years old with refractory shock treated with methylene blue. Interventions: None. Measurements and Main Results: One-thousand two-hundred ninety-three abstracts met search criteria, 139 articles underwent full-text review, and 24 studies were included. Studies investigated refractory shock induced by a variety of etiologies and found that methylene blue was generally safe and increased mean arterial blood pressure. There is overall lack of studies, low number of study patients, and low quality of studies identified. Our survey had a 22.5% response rate, representing 125 institutions. Similar proportions of physicians reported using (40%) or never even considering (43%) methylene blue for shock. The most common reasons for not using methylene blue were unfamiliarity with this drug, its proper dosing, and lack of evidentiary support. Conclusions: Methylene blue appears safe and may benefit children with refractory shock. There is a stark divide in familiarity and practice patterns regarding its use among physicians. Studies to formally assess safety and efficacy of methylene blue in treating pediatric shock are warranted.