Edward Vincent S. Faustino

Relationship between hypoglycemia and mortality in critically ill children

Objectives: To determine the prevalence of hypoglycemia in critically ill nondiabetic children and the association of hypoglycemia with mortality and worsening organ function in critically ill children. Design: Retrospective cohort study with matched-cohort analysis. Setting: Academic pediatric intensive care unit. Patients: A total of 899 nondiabetic patients <18 yrs old admitted to the pediatric intensive care unit for >1 day with at least one blood glucose measurement. Forty-two patients with a blood glucose level of <50 mg/dL (<2.8 mmol/L) were matched with 126 nonhypoglycemic patients. Interventions: None. Measurements and Main Results: Hypoglycemia, based on point-of-care blood glucose measurements, occurred in 2.2% (<40 mg/dL [<2.2 mmol/L]) to 7.5% (<60 mg/dL [<3.3 mmol/L]) of the patients. Hypoglycemia was more common in patients on mechanical ventilation and/or vasopressor support. Severity of hypoglycemia correlated with an increased mortality rate. The highest odds ratio of mortality was 4.49 (95% confidence interval [CI], 1.69–11.96; p < .01) at a blood glucose level of <40 mg/dL (<2.2 mmol/L). In the matched analysis, hypoglycemia was an independent risk factor for mortality. The unadjusted, covariate-adjusted, and propensity score–adjusted odds ratios of mortality were 3.69 (95% CI, 1.78–7.68; p < .01), 4.16 (95% CI, 1.53–11.32; p < .01), and 8.45 (95% CI, 1.75–40.86; p < .01), respectively. Hypoglycemia was associated with worsening organ function in the covariate-adjusted model (odds ratio, 2.37; 95% CI, 1.12–5.01; p = .02) but not in the unadjusted and propensity-score adjusted models. Conclusions: Hypoglycemia is common in critically ill children. It is associated with increased mortality rates in critically ill nondiabetic children. Our data suggest that hypoglycemia is also associated with worsening organ function. Hypoglycemia may merely be a marker of severity of illness. Further investigations are needed to establish the mortality risk with hypoglycemia due to insulin compared to spontaneous hypoglycemia.

Central venous catheter-related thrombosis and thromboprophylaxis in children: a systematic review and meta-analysis

In preparation for a pediatric randomized controlled trial on thromboprophylaxis, we determined the frequency of catheter‐related thrombosis in children. We also systematically reviewed the pediatric trials on thromboprophylaxis to evaluate its efficacy and to identify possible pitfalls in the conduct of these trials.

Incidence and Acute Complications of Asymptomatic Central Venous Catheter–Related Deep Venous Thrombosis in Critically Ill Children

OBJECTIVE To determined the current incidence and acute complications of asymptomatic central venous catheter (CVC)-related deep venous thrombosis (DVT) in critically ill children. STUDY DESIGN We performed a prospective cohort study in 3 pediatric intensive care units. A total of 101 children with newly inserted untunneled CVC were included. CVC-related DVT was diagnosed using compression ultrasonography with color Doppler. RESULTS Asymptomatic CVC-related DVT was diagnosed in 16 (15.8%) children, which equated to 24.7 cases per 1000 CVC-days. Age was independently associated with DVT. Compared with children aged <1 year, children aged >13 years had significantly higher odds of DVT (aOR, 14.1, 95% CI, 1.9-105.8; P = .01). Other patient demographics, interventions (including anticoagulant use), and CVC characteristics did not differ between children with and without DVT. Mortality-adjusted duration of mechanical ventilation, a surrogate for pulmonary embolism, was statistically similar in the 2 groups (22 ± 9 days in children with DVT vs 23 ± 7 days in children without DVT; P = .34). Mortality-adjusted intensive care unit and hospital lengths of stay also were similar in the 2 groups. CONCLUSION Asymptomatic CVC-related DVT is common in critically ill children. However, the acute complications do not seem to differ between children with and without DVT. Larger studies are needed to confirm these results. Future studies should also investigate the chronic complications of asymptomatic CVC-related DVT.

SURVEY OF PHARMACOLOGIC THROMBOPROPHYLAXIS IN CRITICALLY ILL CHILDREN

Objective:There is lack of evidence to guide thromboprophylaxis in the pediatric intensive care unit. We aimed to assess current prescribing practice for pharmacologic thromboprophylaxis in critically ill children. Setting:Pediatric intensive care units in the United States and Canada with at least ten beds. Design:Cross-sectional self-administered survey of pediatric intensivists using adolescent, child, and infant scenarios. Participants:Pediatric intensive care unit clinical directors or section heads. Interventions:None. Measurements and Main Results:Physician leaders from 97 of 151 (64.2%) pediatric intensive care units or their designees responded to the survey. In mechanically ventilated children, 42.3% of the respondents would usually or always prescribe thromboprophylaxis for the adolescent but only 1.0% would prescribe it for the child and 1.1% for the infant. Considering all pediatric intensive care unit patients, 3.1%, 32.0%, and 44.2% of respondents would never prescribe thromboprophylaxis for the adolescent, child, and infant scenarios, respectively. These findings were significant (p < .001 for the adolescent vs. child and infant; p = .002 for child vs. infant). Other patient factors that increased the likelihood of prescribing prophylaxis to a critically ill child for all three scenarios were the presence of hypercoagulability, prior deep venous thrombosis, or a cavopulmonary anastomosis. Prophylaxis was less likely to be prescribed to patients with major bleeding or an anticipated invasive intervention. Low-molecular-weight heparin was the most commonly prescribed drug. Conclusions:In these scenarios, physician leaders in pediatric intensive care units were more likely to prescribe thromboprophylaxis to adolescents compared with children or infants, but they prescribed it less often in adolescents than is recommended by evidence-based guidelines for adults. The heterogeneity in practice we documented underscores the need for rigorous randomized trials to determine the need for thromboprophylaxis in critically ill adolescents and children.

MORTALITY-ADJUSTED DURATION OF MECHANICAL VENTILATION IN CRITICALLY ILL CHILDREN WITH SYMPTOMATIC CENTRAL VENOUS LINE-RELATED DEEP VENOUS THROMBOSIS

Objective:To determine the association between symptomatic central venous line-related deep venous thrombosis and a mortality-adjusted measure of duration of mechanical ventilation in critically ill children with central venous lines. Design:Retrospective matched cohort study. Setting:Eleven pediatric intensive care units across the United States. Patients:Twenty-nine index critically ill children with central venous line-related deep vein thrombosis from a previous prospective observational study on symptomatic venous thromboembolism were compared with 116 control children with central venous lines without venous thrombosis. Each index patient was matched to four control patients based on age group, disease category, severity of illness score, and number of days in the intensive care unit before central venous line insertion. Interventions:None. Measurements and Main Results:Index patients were appropriately matched to control patients with similar characteristics between the two groups. Index patients had fewer ventilator-free days (ie, days alive and breathing unassisted within 28 days after central venous line insertion) compared with matched control patients (16.8 ± 11.5 days vs. 22.3 ± 4.9 days, p = .040). Index patients also had less intensive care unit-free days (ie, days alive and discharged from the intensive care unit within 28 days after central venous line insertion) (9.8 ± 9.9 days vs. 17.9 ± 5.7 days, p < .001). Durations of mechanical ventilation (17.6 ± 40.6 days vs. 5.2 ± 5.5 days, p = .236) and intensive care unit stay (38.1 ± 61.7 days vs. 11.9 ± 10.9 days, p = .011) were longer in index patients. The mortality rate was statistically similar between the two groups. Conclusions:The presence of symptomatic central venous line-related deep vein thrombosis is associated with worse outcomes, particularly fewer ventilator-free days, in critically ill children. The causal relationship that deep venous thrombosis leads to impairment in lung function and delays weaning from mechanical ventilation and discharge from the intensive care unit needs to be proven prospectively. Ventilator-free days is a possible alternative outcome measure for future deep venous thrombosis studies.

A multinational study of thromboprophylaxis practice in critically ill children.

Objectives:Although critically ill children are at increased risk for developing deep venous thrombosis, there are few pediatric studies establishing the prevalence of thrombosis or the efficacy of thromboprophylaxis. We tested the hypothesis that thromboprophylaxis is infrequently used in critically ill children even for those in whom it is indicated. Design:Prospective multinational cross-sectional study over four study dates in 2012. Setting:Fifty-nine PICUs in Australia, Canada, New Zealand, Portugal, Singapore, Spain, and the United States. Patients:All patients less than 18 years old in the PICU during the study dates and times were included in the study, unless the patients were 1) boarding in the unit waiting for a bed outside the PICU or 2) receiving therapeutic anticoagulation. Interventions:None. Measurements and Main Results:Of 2,484 children in the study, 2,159 (86.9%) had greater than or equal to 1 risk factor for thrombosis. Only 308 children (12.4%) were receiving pharmacologic thromboprophylaxis (e.g., aspirin, low-molecular-weight heparin, or unfractionated heparin). Of 430 children indicated to receive pharmacologic thromboprophylaxis based on consensus recommendations, only 149 (34.7%) were receiving it. Mechanical thromboprophylaxis was used in 156 of 655 children (23.8%) 8 years old or older, the youngest age for that device. Using nonlinear mixed effects model, presence of cyanotic congenital heart disease (odds ratio, 7.35; p < 0.001) and spinal cord injury (odds ratio, 8.85; p = 0.008) strongly predicted the use of pharmacologic and mechanical thromboprophylaxis, respectively. Conclusions:Thromboprophylaxis is infrequently used in critically ill children. This is true even for children at high risk of thrombosis where consensus guidelines recommend pharmacologic thromboprophylaxis.

Risk Factors for Delayed Enteral Nutrition in Critically Ill Children.

Objective: Delayed enteral nutrition, defined as enteral nutrition started 48 hours or more after admission to the PICU, is associated with an inability to achieve full enteral nutrition and worse outcomes in critically ill children. We reviewed nutritional practices in six medical-surgical PICUs and determined risk factors associated with delayed enteral nutrition 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 less than 21 years old admitted to the PICU for 72 hours or more excluding those awaiting or recovering from abdominal surgery. Measurements and Main Results: A total of 444 children with a median age of 4.0 years were included in the study. Enteral nutrition was started at a median time of 20 hours after admission to the PICU. There was no significant difference in time to start enteral nutrition among the PICUs. Of those included, 88 children (19.8%) had delayed enteral nutrition. Risk factors associated with delayed enteral nutrition were noninvasive (odds ratio, 3.37; 95% CI, 1.69–6.72) and invasive positive-pressure ventilation (odds ratio, 2.06; 95% CI, 1.15–3.69), severity of illness (odds ratio for every 0.1 increase in pediatric index of mortality 2 score, 1.39; 95% CI, 1.14–1.71), procedures (odds ratio, 3.33; 95% CI, 1.67–6.64), and gastrointestinal disturbances (odds ratio, 2.05; 95% CI, 1.14–3.68) within 48 hours after admission to the PICU. Delayed enteral nutrition was associated with failure to reach full enteral nutrition while in the PICU (odds ratio, 4.09; 95% CI, 1.97–8.53). Nutrition consults were obtained in less than half of the cases, and none of the PICUs used tools to assure the adequacy of energy and protein nutrition. Conclusions: Institutions in this study initiated enteral nutrition for a high percentage of patients by 48 hours of admission. Noninvasive positive-pressure ventilation was most strongly associated with delay enteral nutrition. A better understanding of these risk factors and assessments of nutritional requirements should be explored in future prospective studies.

Clinical equipoise regarding glycemic control: a survey of pediatric intensivist perceptions.

Objectives: To assess the willingness of pediatric intensivists to conduct a pediatric trial of blood glucose control, and to determine if self-reported practices were influenced by adult-specific data over the past 4 yrs. This was a follow-up to our previous 2005 survey. Design: Electronic survey comprising a 30-item questionnaire. Setting: North American PICUs that were members of, or connected to, the Pediatric Acute Lung Injury and Sepsis Network (n = 96 targeted institutions). Participants: North American pediatric intensivists (n = 209). Interventions: None. Methods: We conducted a survey of North American PICUs using a Web-based questionnaire. Invitations were sent to 96 institutions in 37 states/provinces. Results: Response rate was 68% (141/209). The median definitions of hyperglycemia (150 mg/dL) and hypoglycemia (⩽60 mg/dL) were similar to our 2005 survey results. Self-reported practice patterns remain variable. Although 75% of clinician respondents denied a change in clinical practice based on the published literature, the preferred blood glucose target range increased from 80–110 mg/dL in 2005 to 90–140 mg/dL in 2009. Intensivists who preferred a blood glucose target of 80–110 mg/dL decreased from 43% to 6% (p < 0.001). Many respondents (45%) indicated that the acceptable severe hypoglycemia rate (% patients) for a protocol was ⩽2.5%. The majority (93%) indicated they would be willing to enroll patients in a pediatric trial of blood glucose control. Conclusions: Pediatric intensivists report that they control blood glucose with insulin in critically ill children and do not necessarily adopt adult-specific data or a single uniform blood glucose target. The published evidence does not adequately address PICU clinicians concerns. Unanswered questions and persistent variation in practice suggest a need for a multicenter clinical trial of blood glucose control in critically ill children.

Factor VIII May Predict Catheter-Related Thrombosis in Critically Ill Children: A Preliminary Study.

Objective: If we can identify critically ill children at high risk for central venous catheter-related thrombosis, then we could target them for pharmacologic thromboprophylaxis. We determined whether factor VIII activity or G value was associated with catheter-related thrombosis in critically ill children. Design: Prospective cohort study. Setting: Two tertiary academic centers. Patients: We enrolled children younger than 18 years who were admitted to the PICU within 24 hours after insertion of a central venous catheter. We excluded children with a recently diagnosed thrombotic event or those anticipated to receive anticoagulation. Children with thrombosis diagnosed with surveillance ultrasonography on the day of enrollment were classified as having prevalent thrombosis. Those who developed catheter-related thrombosis thereafter were classified as having incident thrombosis. Interventions: None. Measurements and Main Results: We enrolled 85 children in the study. Once enrolled, we measured factor VIII activity with one-stage clotting assay and determined G value with thromboelastography. Of those enrolled, 25 had incident and 12 had prevalent thromboses. The odds ratio for incident thrombosis per SD increase in factor VIII activity was 1.98 (95% CI, 1.10–3.55). The area under the receiver operating characteristic curve was 0.66 (95% CI, 0.52–0.79). At factor VIII activity more than 100 IU/dL, which was the optimal threshold identified using Youden index, sensitivity and specificity were 92.0% and 41.3%, respectively. The association between factor VIII activity and incident thrombosis remained significant after adjusting for important clinical predictors of thrombosis (odds ratio, 1.93; 95% CI, 1.10–3.39). G value was associated with prevalent but not with incident thrombosis. Conclusion: Factor VIII activity may be used to stratify critically ill children based on their risk for catheter-related thrombosis.

Recommendations for venous thromboembolism prophylaxis in pediatric trauma patients: A national, multidisciplinary consensus study.

T incidence of venous thromboembolism (VTE) has been increasing in children, although the incidence remains lower than the incidence in adults. The incidence of VTE is higher in injured children than it is in the general population of uninjured hospitalized children, ranging from 0.02% to 0.33%. Increasing scrutiny is given to hospital-acquired VTE, as quality initiatives to prevent VTE, such as Children’s Hospitals Solutions for Patient Safety, gain national priority. Children with hospital-acquired VTE have increased length of stay and excess costs of