E. Vincent S. Faustino

Tight glycemic control in critically Ill children

Background In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. Methods In a 35‐center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower‐target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher‐target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28. Results The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower‐target group and 353 to the higher‐target group. In the intention‐to‐treat analysis, the median number of ICU‐free days did not differ significantly between the lower‐target group and the higher‐target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per‐protocol analyses, the median time‐weighted average glucose level was significantly lower in the lower‐target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher‐target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower‐target group also had higher rates of health care–associated infections than those in the higher‐target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator‐free days. Conclusions Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF‐PINT ClinicalTrials.gov number, NCT01565941.)

Hypoglycemia in Critically Ill Children

Background: The practice of glycemic control with intravenous insulin in critically ill patients has brought clinical focus on understanding the effects of hypoglycemia, especially in children. Very little is published on the impact of hypoglycemia in this population. We aimed to review the existing literature on hypoglycemia in critically ill neonates and children. Methods: We performed a systematic review of the literature up to August 2011 using PubMed, Ovid MEDLINE and ISI Web of Science using the search terms “hypoglycemia or hypoglyc*” and “critical care or intensive care or critical illness”. Articles were limited to “all child (0–18 years old)” and “English”. Results: A total of 513 articles were identified and 132 were included for review. Hypoglycemia is a significant concern among pediatric and neonatal intensivists. Its Definition is complicated by the use of a biochemical measure (i.e., blood glucose) for a pathophysiologic problem (i.e., neuroglycopenia). Based on associated outcomes, we suggest defining hypoglycemia as <40–45 mg/dl in neonates and <60–65 mg/dl in children. Below the suggested threshold values, hypoglycemia is associated with worse neurological outcomes, increased intensive care unit stay, and increased mortality. Disruptions in carbohydrate metabolism increase the risk of hypoglycemia in critically ill children. Prevention of hypoglycemia, especially in the setting of intravenous insulin use, will be best accomplished by the combination of accurate measuring techniques, frequent or continuous glucose monitoring, and computerized insulin titration protocols. Conclusion: Studies on hypoglycemia in critically ill children have focused on spontaneous hypoglycemia. With the current practice of maintaining blood glucose within a narrow range with intravenous insulin, the risk factors and outcomes associated with insulin-induced hypoglycemia should be rigorously studied to prevent hypoglycemia and potentially improve outcomes of critically ill children.

Patterns of Sedation Weaning in Critically Ill Children Recovering From Acute Respiratory Failure.

Objective: To characterize sedation weaning patterns in typical practice settings among children recovering from critical illness. Design: A descriptive secondary analysis of data that were prospectively collected during the prerandomization phase (January to July 2009) of a clinical trial of sedation management. Setting: Twenty-two PICUs across the United States. Patients: The sample included 145 patients, aged 2 weeks to 17 years, mechanically ventilated for acute respiratory failure who received at least five consecutive days of opioid exposure. Interventions: None. Measurements and Main Results: Group comparisons were made between patients with an intermittent weaning pattern, defined as a 20% or greater increase in daily opioid dose after the start of weaning, and the remaining patients defined as having a steady weaning pattern. Demographic and clinical characteristics, tolerance to sedatives, and iatrogenic withdrawal symptoms were evaluated. Sixty-six patients (46%) were intermittently weaned; 79 patients were steadily weaned. Prior to weaning, intermittently weaned patients received higher peak and cumulative doses and longer exposures to opioids and benzodiazepines, demonstrated more sedative tolerance (58% vs 41%), and received more chloral hydrate and barbiturates compared with steadily weaned patients. During weaning, intermittently weaned patients assessed for withdrawal had a higher incidence of Withdrawal Assessment Tool-version 1 scores of greater than or equal to 3 (85% vs 46%) and received more sedative classes compared with steadily weaned patients. Conclusions: This study characterizes sedative administration practices for pediatric patients prior to and during weaning from sedation after critical illness. It provides a novel methodology for describing weaning in an at-risk pediatric population that may be helpful in future research on weaning strategies to prevent iatrogenic withdrawal syndrome.

Prevalence of post-thrombotic syndrome after cardiac catheterization.

As the survival of children with cardiac disease increases, chronic complications of deep venous thrombosis from cardiac catheterization, particularly post‐thrombotic syndrome, may be important to monitor for and treat, if needed. We aimed to determine the prevalence of this syndrome in children who underwent cardiac catheterization.

Prevention of Hospital-Acquired Venous Thromboembolism in Children: A Review of Published Guidelines

Venous thromboembolism, which includes deep venous thrombosis and pulmonary embolism, is a potentially preventable condition in children. In adults, pharmacologic prophylaxis has been shown to significantly reduce the incidence of venous thromboembolism in distinct patient cohorts. However, pediatric randomized controlled trials have failed to demonstrate the efficacy of pharmacologic prophylaxis against thrombosis associated with central venous catheters, the most important risk factor for venous thromboembolism in children. Despite the lack of supporting evidence, hospital-based initiatives are being undertaken to try to prevent venous thromboembolism in children. In this study, we sought to review the published guidelines on the prevention of venous thromboembolism in hospitalized children. We identified five guidelines, all of which were mainly targeted at adolescents and used various risk-stratification approaches. In low-risk children, ambulation was the recommended prevention strategy, while mechanical prophylaxis was recommended for children at moderate risk and pharmacologic and mechanical prophylaxis were recommended for the high-risk group. The effectiveness of these strategies has not been proven. In order to determine whether venous thromboembolism can be prevented in children, innovative clinical trial designs are needed. In the absence of these trials, guidelines can be a source of valuable information to inform our practice.

Control of serum glucose concentration in critical illness.

Purpose of review Hyperglycemia is a significant problem for children in the ICU. Use of tight glycemic control (TGC) to manage hyperglycemia remains controversial, especially given the potential risk of insulin-induced hypoglycemia. This review will address the latest evidence regarding TGC in critically ill children. Recent findings Two randomized controlled trials (RCT) involving primarily postoperative cardiac surgery patients demonstrated the feasibility and safety of TGC in pediatric patients. The trials, however, had discrepant results with regards to the benefit of TGC. There is also uncertainty about the generalizability of these results to nonpostoperative cardiac patients. There is only one published study addressing the long-term safety of TGC in children. In this study, hypoglycemia was not associated with adverse effects on neurocognitive development. In contrast, articles from adult studies demonstrate increased risk of death with hypoglycemia. Summary Although the clinical benefit of TGC in critically ill children is still unclear, TGC can be done safely in this population.

Racial and Ethnic Disparities in Parental Refusal of Consent in a Large, Multisite Pediatric Critical Care Clinical Trial

Objective To evaluate whether race or ethnicity was independently associated with parental refusal of consent for their childs participation in a multisite pediatric critical care clinical trial. Study design We performed a secondary analyses of data from Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), a 31‐center cluster randomized trial of sedation management in critically ill children with acute respiratory failure supported on mechanical ventilation. Multivariable logistic regression modeling estimated associations between patient race and ethnicity and parental refusal of study consent. Result Among the 3438 children meeting enrollment criteria and approached for consent, 2954 had documented race/ethnicity of non‐Hispanic White (White), non‐Hispanic Black (Black), or Hispanic of any race. Inability to approach for consent was more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic children (13.2%). Among those offered consent, parents of Black (29.5%) and Hispanic children (25.9%) more frequently refused consent than parents of White children (18.2%, P < .0167 for each). Compared with parents of White children, parents of Black (OR 2.15, 95% CI 1.56‐2.95, P < .001) and Hispanic (OR 1.44, 95% CI 1.10‐1.88, P = .01) children were more likely to refuse consent. Parents of children offered participation in the intervention arm were more likely to refuse consent than parents in the control arm (OR 2.15, 95% CI 1.37‐3.36, P < .001). Conclusions Parents of Black and Hispanic children were less likely to be approached for, and more frequently declined consent for, their childs participation in a multisite critical care clinical trial. Ameliorating this racial disparity may improve the validity and generalizability of study findings. Trial registration ClinicalTrials.gov: NCT00814099.

Assessing the benefits and risks of tight glycemic control in critically ill children

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