Protein biomarkers for incident deep venous thrombosis in critically ill adolescents: An exploratory study.

BACKGROUND: There are no tests to identify critically ill children at high risk of deep venous thrombosis (DVT). In this exploratory study, we aimed to identify proteins that are associated with incident DVT in critically ill adolescents. PROCEDURE: Plasma samples were obtained from critically ill adolescents within 24 hours after initiation of cardiopulmonary support. The adolescents were followed with ultrasound to detect the development of DVT of the lower extremity and clinically for bleeding. Thrombin-antithrombin complex and prothrombin fragment 1+2 were measured using immunosorbent assays, whereas procoagulation and anticoagulation factors were measured using multiplex assays. Plasma samples were also analyzed using SOMAscan, an aptamer-based capture assay. The associations between DVT and the log-transformed level of the proteins were assessed using logistic regression adjusting for the presence of femoral venous catheter and severity of illness. Associations were expressed as odds ratio (OR) for every log-fold increase in level of the protein with 95% confidence interval (CI). RESULTS: Plasma from 59 critically ill adolescents, of whom 9 developed incident DVT, was analyzed. The median age of the adolescents was 15.1 years (interquartile range, 14.0-16.7 years). Higher levels of thrombin-antithrombin complex (OR: 31.54; 95% CI: 2.09-475.92) and lower levels of factor XIII (OR: 0.03; 95% CI: 0.002-0.44) were associated with DVT. CD36, MIC-1, and EpoR were marginally associated with DVT. Only factor XIII was associated with clinically relevant bleeding (OR: 0.27; 95% CI: 0.08-0.97). CONCLUSIONS: We identified candidate protein biomarkers for incident DVT. We plan to validate our findings in adequately powered studies.

Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children.

OBJECTIVES: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children. DESIGN: Nested case-control study. SETTING: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia. PATIENTS: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia. CONCLUSIONS: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Epidemiology of Clinically Relevant Bleeding in Critically Ill Adolescents.

OBJECTIVES: The epidemiology of clinically relevant bleeding in critically ill adolescents, particularly those who are at high risk of venous thromboembolism, is unclear. In preparation for a randomized clinical trial of pharmacologic prophylaxis against venous thromboembolism, we characterized the epidemiology of clinically relevant bleeding in critically ill adolescents. DESIGN: Post hoc analysis of data from a pediatric multicenter observational study of venous thromboembolism. SETTING: Six PICUs. PATIENTS: Adolescents 13-17 years old who received cardiac or pulmonary support for at least 48 hours were eligible. Those admitted with venous thromboembolism or receiving therapeutic anticoagulation were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Adolescents (n = 88) were followed daily for the development of any bleeding event. The severity of the event was categorized based on the definitions by the International Society on Thrombosis and Haemostasis. The frequency of clinically relevant bleeding was 29.5% (95% CI, 20.3-40.2%) or 3.7 events (95% CI, 2.5-5.4 events) per 100 patient-days. Adolescents with venous thromboembolism were more likely to develop clinically relevant bleeding (hazard ratio, 2.06; 95% CI, 1.08-3.94). Age was negatively associated with clinically relevant bleeding (hazard ratio for every 1-year increase in age: 0.68; 95% CI, 0.58-0.79). In contrast, predicted risk of mortality (hazard ratio for every 0.10 increase in risk: 1.35; 95% CI, 1.05-1.74) and admission for trauma or surgery (hazard ratio: 2.04; 95% CI, 1.21-3.44) were positively associated with clinically relevant bleeding. The association of clinically relevant bleeding with medications, interventions, or laboratory tests, including mechanical ventilation and pharmacologic prophylaxis with anticoagulation, did not reach statistical significance. Adolescents with clinically relevant bleeding stayed in the hospital longer than those without clinically relevant bleeding. CONCLUSIONS: Clinically relevant bleeding is common in critically ill adolescents who are at high risk of venous thromboembolism. Admission for trauma or surgery can be used to stratify the risk of clinically relevant bleeding in these adolescents.

Central Venous Catheter-Associated Deep Venous Thrombosis in Critically Ill Children.

The presence of a central venous catheter and admission to the intensive care unit are the most important risk factors for deep venous thrombosis (DVT) in children. At least 18% of critically ill children with a catheter develop radiologically confirmed catheter-associated thrombosis. Clinically apparent thrombosis occurs in 3% of critically ill children with a catheter and is associated with 8 additional days of mechanical ventilation. Even when the thrombus is initially asymptomatic, 8 to 18% of critically ill children with catheter-associated thrombosis develop postthrombotic syndrome. Thrombosis is uncommon within 24 hours after insertion of a nontunneled catheter in critically ill children, but nearly all thrombi have developed by 4 days after insertion. Hypercoagulability during or immediately after insertion of the catheter plays an essential role in the development of thrombosis. Pharmacologic prophylaxis, including local anticoagulation with heparin-bonded catheter, has not been shown to reduce the risk of catheter-related thrombosis in children. Systemic anticoagulation in critically ill children started soon after the insertion of the catheter, however, may be beneficial. A multicenter clinical trial that is testing this hypothesis is currently underway.

Epidemiology of Lower Extremity Deep Venous Thrombosis in Critically Ill Adolescents.

OBJECTIVE: To determine the epidemiology of lower extremity deep venous thrombosis (DVT) in critically ill adolescents, which currently is unclear. STUDY DESIGN: We performed a multicenter, prospective, cohort study. Adolescents aged 13-17 years who were admitted to 6 pediatric intensive care units and were anticipated to receive cardiopulmonary support for at least 48 hours were eligible, unless they were admitted with DVT or pulmonary embolism or were receiving or anticipated to receive therapeutic anticoagulation. While patients were in the unit, serial sonograms of the lower extremities were performed, then centrally adjudicated. Bayesian statistics were used to leverage the similarities between adults and adolescents. RESULTS: A total of 88 adolescents were enrolled, from whom 184 lower extremity sonograms were performed. Of these, 9 adolescents developed DVT, with 1 having bilateral DVT. The frequency of DVT was 12.4% (95% credible interval: 6.1%, 20.1%), which ranged from 6.3% to 19.8% with a variability of 41.0% across units. All cases of DVT occurred in adolescents who received invasive mechanical ventilation (frequency: 16.5%; 95% credible interval 8.1%, 26.6%). DVT was associated with femoral central venous catheterization (OR 15.44; 95% credible interval 1.62, 69.05) and severe illness (OR for every 0.1 increase in risk of mortality 3.11; 95% credible interval 1.19, 6.85). DVT appears to be associated with prolonged days on support. CONCLUSIONS: Our findings highlight the similarities and differences in the epidemiology of DVT between adults and adolescents. They support the conduct and inform the design of a trial of pharmacologic prophylaxis in critically ill adolescents.

Hemoglobin Levels Across the Pediatric Critical Care Spectrum: A Point Prevalence Study.

OBJECTIVES: To determine the prevailing hemoglobin levels in PICU patients, and any potential correlates. DESIGN: Post hoc analysis of prospective multicenter observational data. SETTINGS: Fifty-nine PICUs in seven countries. PATIENTS: PICU patients on four specific days in 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients' hemoglobin and other clinical and institutional data. Two thousand three hundred eighty-nine patients with median age of 1.9 years (interquartile range, 0.3-9.8 yr), weight 11.5 kg (interquartile range, 5.4-29.6 kg), and preceding PICU stay of 4.0 days (interquartile range, 1.0-13.0 d). Their median hemoglobin was 11.0 g/dL (interquartile range, 9.6-12.5 g/dL). The prevalence of transfusion in the 24 hours preceding data collection was 14.2%. Neonates had the highest hemoglobin at 13.1 g/dL (interquartile range, 11.2-15.0 g/dL) compared with other age groups (p < 0.001). The percentage of 31.3 of the patients had hemoglobin of greater than or equal to 12 g/dL, and 1.1% had hemoglobin of less than 7 g/dL. Blacks had lower median hemoglobin (10.5; interquartile range, 9.3-12.1 g/dL) compared with whites (median, 11.1; interquartile range, 9.0-12.6; p < 0.001). Patients in Spain and Portugal had the highest median hemoglobin (11.4; interquartile range, 10.0-12.6) compared with other regions outside of the United States (p < 0.001), and the highest proportion (31.3%) of transfused patients compared with all regions (p < 0.001). Patients in cardiac PICUs had higher median hemoglobin than those in mixed PICUs or noncardiac PICUs (12.3, 11.0, and 10.6 g/dL, respectively; p < 0.001). Cyanotic heart disease patients had the highest median hemoglobin (12.6 g/dL; interquartile range, 11.1-14.5). Multivariable regression analysis within diagnosis groups revealed that hemoglobin levels were significantly associated with the geographic location and history of complex cardiac disease in most of the models. In children with cancer, none of the variables tested correlated with patients' hemoglobin levels. CONCLUSIONS: Patients' hemoglobin levels correlated with demographics like age, race, geographic location, and cardiac disease, but none found in cancer patients. Future investigations should account for the effects of these variables.

Accuracy of an Extubation Readiness Test in Predicting Successful Extubation in Children With Acute Respiratory Failure From Lower Respiratory Tract Disease.

OBJECTIVE: Identifying children ready for extubation is desirable to minimize morbidity and mortality associated with prolonged mechanical ventilation and extubation failure. We determined the accuracy of an extubation readiness test (Randomized Evaluation of Sedation Titration for Respiratory Failure extubation readiness test) in predicting successful extubation in children with acute respiratory failure from lower respiratory tract disease. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial, a pediatric multicenter cluster randomized trial of sedation. SETTING: Seventeen PICUs in the intervention arm. PATIENTS: Children 2 weeks to 17 years receiving invasive mechanical ventilation for lower respiratory tract disease. INTERVENTION: Extubation readiness test in which spontaneously breathing children with oxygenation index less than or equal to 6 were placed on FIO2 of 0.50, positive end-expiratory pressure of 5 cm H2O, and pressure support. MEASUREMENTS AND MAIN RESULTS: Of 1,042 children, 444 (43%) passed their first extubation readiness test. Of these, 295 (66%) were extubated within 10 hours of starting the extubation readiness test, including 272 who were successfully extubated, for a positive predictive value of 92%. Among 861 children who were extubated for the first time within 10 hours of performing an extubation readiness test, 788 passed their extubation readiness test and 736 were successfully extubated for a positive predictive value of 93%. The median time of day for extubation with an extubation readiness test was 12:15 hours compared with 14:54 hours for extubation without an extubation readiness test within 10 hours (p < 0.001). CONCLUSIONS: In children with acute respiratory failure from lower respiratory tract disease, an extubation readiness test, as described, should be considered at least daily if the oxygenation index is less than or equal to 6. If the child passes the extubation readiness test, there is a high likelihood of successful extubation.

Epidemiology of Bleeding in Critically Ill Children.

OBJECTIVE: To determine the epidemiology of bleeding in critically ill children. STUDY DESIGN: We conducted a cohort study of children <18 years old admitted to the pediatric intensive care unit for >24 hours and without clinically relevant bleed (CRB) on admission. CRB was defined as resulting in severe physiologic derangements, occurring at a critical site or requiring major therapeutic interventions. Using a novel bleeding assessment tool that we developed, characteristics of the CRB were abstracted from the medical records independently and in duplicate. From the cohort, we matched each child with CRB to 4 children without CRB based on onset of CRB. Risk factors and complications of CRB were identified from this matched group of children. RESULTS: We analyzed 405 children with a median age of 35 months (IQR 7-130 months). A total of 37 (9.1%) children developed CRB. The median number of days with CRB was 1 day (IQR 1-2 days). Invasive ventilation (OR 61.35; 95% CI 6.27-600.24), stress ulcer prophylaxis (OR 2.70; 95% CI 1.08-6.74), surgical admission (OR 0.29; 95% CI 0.10-0.84), and aspirin (OR 0.04; 95% CI 0.002-0.58) were associated with CRB. CRB was associated with longer time to discharge from the unit (hazard ratio 0.20; 95% CI 0.13-0.33) and the hospital (hazard ratio 0.49; 95% CI 0.33-0.73). Children with CRB were on vasopressor longer and transfused more red blood cells after the CRB than those without CRB. CONCLUSIONS: Our findings suggest that bleeding complicates critical illness in children.

Vitamin D Status After Cardiopulmonary Bypass in Children With Congenital Heart Disease.

Deficiency in 25-hydroxyvitamin D (25OHD) is associated with increased morbidity and mortality in the critically ill. Children who underwent surgery for congenital heart disease under cardiopulmonary bypass (CPB) are typically deficient in 25OHD. It is unclear whether this deficiency is due to CPB. We hypothesized that CPB reduces the levels of 25OHD in children with congenital heart disease. We conducted a prospective observational study on children aged 2 months to 17 years who underwent CPB. Serum was collected at 3 time points: immediately before, immediately after surgery, and 24 hours after surgery. 25-Hydroxyvitamin D, 1,25-dihydroxyvitamin D, 1,25(OH)2D, vitamin D binding protein, and albumin levels were measured. Levels were compared using repeated measures analysis of variance. We enrolled 20 patients, 40% were deficient in 25OHD with levels <20 ng/mL prior to surgery. Mean (±standard deviation) of 25OHD at the 3 time points was 21.3 ± 8 ng/mL, 19 ± 5.8 ng/mL, and 19.5 ± 6.6 ng/mL, respectively ( P = .02). The decrease in 25OHD was observed primarily in children with sufficient levels of 25OHD, with mean levels at the 3 time points: 26.8 ± 4.2 ng/mL, 21.5 ± 5.7 ng/mL, and 23.0 ± 4.9 ng/mL, respectively ( P < .001). Calculated means of free fraction of 25OHD at the 3 time points were 6.2 ± 2.8 pg/mL, 5.8 ± 2.2 pg/mL, and 5.5 ± 2.4 pg/mL, respectively, ( P = .04). Mean levels of 1,25(OH)2D were 63.7 ± 34.9 ng/mL, 53.2 ± 30.6 ng/mL, and 67.7 ± 23.5 ng/mL ( P = .04). Vitamin D binding protein and albumin levels did not significantly change. Cardiopulmonary bypass decreases 25OHD by reducing the free fraction. Current investigations are geared to establish whether vitamin D deficiency is associated with outcomes and if treatment is appropriate.

A regional cohort study of the treatment of critically ill children with bronchiolitis.

OBJECTIVE: To describe the treatment practices in critically ill children with RSV bronchiolitis across four regional PICUs in the northeastern United States, and to determine the factors associated with increased ICU length of stay in this population. METHODS: We conducted a retrospective cohort study of children who were admitted with RSV bronchiolitis between July 2009 and July 2011 to the PICUs of Connecticut Children's Medical Center, Yale-New Haven Children's Hospital, Maria Fareri Children's Hospital, and Baystate Children's Hospital. Data were collected regarding clinical characteristics and intensive care course among these hospitals. RESULTS: During the study period, 323 children were admitted to one of the four ICUs with RSV bronchiolitis. Despite similar mortality risk scores among ICUs, there was considerable variation in the use of therapies, particularly intubation and mechanical ventilation, in which there was greater than a 3.5-fold increased risk of intubation between sites with the highest and lowest frequency of intubation (odds ratio: 3.8; 95% confidence interval: 2.2-6.4). Albuterol was the most commonly used respiratory treatment, followed by chest physiotherapy, high-flow nasal cannula, and hypertonic saline. Longer stays in the ICU were associated with more frequent use of therapies, specifically invasive mechanical ventilation, inhaled corticosteroids, intrapulmonary percussive ventilation, and chest physiotherapy. CONCLUSIONS: 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.

Prediction of Catheter-Associated Thrombosis in Critically Ill Children.

OBJECTIVE: We determined whether in critically ill children with an untunneled central venous catheter, the risk of catheter-associated deep venous thrombosis can be predicted within 24 hours after insertion of the catheter. DESIGN: Secondary analysis of two multicenter prospective cohort studies. SETTING: PICUs in Northeastern United States. PATIENTS: A total of 175 children admitted to the PICU within 24 hours after insertion of an untunneled central venous catheter who did not receive anticoagulation were included. Of these, 53 (30.3%) developed catheter-associated thrombosis detected with active surveillance with ultrasonography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used logistic regression (models 1 and 2) and recursive partitioning (models 3 and 4) methods to develop risk prediction models with predictors present at any time while catheterized (models 1 and 3), or within 24 hours after insertion of the catheter (models 2 and 4). Age, recent surgery, catheter in the subclavian vein, and blood product transfusion were included in models 1 and 2. Areas under the receiver operating characteristic curves were similar for these models (model 1: 0.80 vs model 2: 0.80; p = 0.44). Except for recent surgery, predictors in model 1 were identified as partitioning variables for model 3. In addition to the predictors in model 2, severity of illness was used in partitioning for model 4. The area under the curve of model 3 appeared smaller than that of model 4 (0.75 vs 0.80; p = 0.08). Groups of children at low, intermediate, and high risks of catheter-associated thrombosis were identified using model 4. CONCLUSIONS: Critically ill children at high risk of catheter-associated thrombosis can be identified within 24 hours after insertion of an untunneled central venous catheter.

Factors Associated With Continuous Low-Dose Heparin Infusion for Central Venous Catheter Patency in Critically Ill Children Worldwide.

OBJECTIVES: To identify patient, hospital, and central venous catheter factors that may influence the use of low-dose heparin infusion for central venous catheter patency in critically ill children. DESIGN: Secondary analysis of an international multicenter observational study. SETTING: Fifty-nine PICUs over four study dates in 2012, involving seven countries. PATIENTS: Children less than 18 years old with a central venous catheter who were admitted to a participating unit and enrolled in the completed Prophylaxis against Thrombosis Practice study were included. All overflow patients were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 2,484 patients in the Prophylaxis against Thrombosis Practice study, 1,312 patients had a central venous catheter. Five hundred seven of those patients used low-dose heparin infusion. The frequency of low-dose heparin infusion was compared across various patient, hospital, and central venous catheter factors using chi-square, Mann-Whitney U, and Fisher exact tests. In the multivariate analysis, age was not a significant factor for low-dose heparin infusion use. Patients with pulmonary hypertension had decreased low-dose heparin infusion use, whereas those with active surgical or trauma diagnoses had increased low-dose heparin infusion use. All centrally inserted central venous catheters were more likely to use low-dose heparin infusion when compared with peripherally inserted central venous catheters. The Asia-Pacific region showed increased low-dose heparin infusion use, along with community hospitals and smaller ICUs (< 10 beds). CONCLUSIONS: Patient, central venous catheter, and hospital factors are associated with the use of low-dose heparin infusion in critically ill children. Further study is needed to evaluate the efficacy and persistence of low-dose heparin infusion use.

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.

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.

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.

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.

Corticosteroid therapy in critically ill pediatric asthmatic patients.

OBJECTIVES: IV corticosteroids are routinely prescribed to treat critically ill children with asthma. However, no specific dosing recommendations have been made for children admitted to the PICU. We aim to determine current asthma corticosteroid dosing preferences in PICUs within North America. DESIGN: Cross-sectional, self-administered survey. SETTING: North American PICUs. SUBJECTS: Pediatric intensivists working in the United States and Canada. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 104 intensivists completed the survey. Of these, 70% worked in the United States, 67% attended in PICUs with at most 20 beds, and 79% had more than 10 years of PICU experience. The majority of asthmatics were admitted to PICUs based on clinical asthma examination/score or because the patient was receiving continuous albuterol. IV methylprednisolone is prescribed by a large majority of intensivists (96%). Of those who prescribe methylprednisolone, 66% use a starting dose of 4 mg/kg/d, whereas 31% use a starting dose of 2 mg/kg/d, and only 3% use 1 mg/kg/d. The large majority of respondents (85%) use "clinical experience" as their rationale for their preferred dosage. In multivariate logistic regression analysis, only knowledge of the National Heart, Lung, and Blood Institute guidelines was an independent predictor of prescribing an initial corticosteroid dose of 4 mg/kg/d (odds ratio, 3.69 [95% CI, 1.26-10.80]; p = 0.017). Country of practice, years of experience, and PICU size were not associated with corticosteroid dosing preference. CONCLUSIONS: 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.

Hospital-acquired venous thromboembolism during invasive mechanical ventilation in children: a single-center, retrospective cohort study.

BACKGROUND: Invasive mechanical ventilation (IMV) has been independently associated with hospital-acquired venous thromboembolism (HA-VTE) among critically ill children, including extremity deep venous thrombosis and pulmonary embolism. OBJECTIVES: We aimed to characterize the frequency and timing of HA-VTE following IMV exposure. METHODS: This was a single-center, retrospective cohort study including children aged <18 years, hospitalized in a pediatric intensive care unit, undergoing mechanical ventilation for >24 hours from October 2020 through April 2022. Encounters with an existing tracheostomy or receiving treatment for HA-VTE prior to endotracheal intubation were excluded. The primary outcomes characterized clinically-relevant HA-VTE, including timing after intubation, location, and the presence of known hypercoagulability risk factors. Secondary outcomes were IMV exposure magnitude, defined by IMV duration and ventilator parameters (ie, volumetric, barometric, and oxygenation indices). RESULTS: Of 170 consecutive, eligible encounters, 18 (10.6%) experienced HA-VTE at a median of 4 days (IQR, 1.4-6.4) following endotracheal intubation. Those with HA-VTE had an increased frequency of a prior venous thromboembolism (27.8% vs 8.6%, P = .027). No differences in frequency of other HA-VTE risk factors (ie, acute immobility, hematologic malignancy, sepsis, and COVID-19-related illness), presence of a concurrent central venous catheter, or the magnitude of IMV exposure were noted. CONCLUSION: Children undergoing IMV experience HA-VTE at markedly higher rates than previously estimated in the general pediatric intensive care unit population after endotracheal intubation. While prospective validation is needed, these findings are an important step toward informing the development of risk-stratified thromboprophylaxis trials in critically ill children.

Recommendations for standardized definitions, clinical assessment, and future research in pediatric clinically unsuspected venous thromboembolism: Communication from the ISTH SSC subcommittee on pediatric and neonatal thrombosis and hemostasis.

Clinically unsuspected venous thromboembolism (VTE) in children is defined as a VTE diagnosed via imaging test performed for surveillance (i.e., with an intent to identify clinically silent VTEs) or incidentally found (most often via imaging performed for evaluation of regional pathology unrelated to VTE) in the absence of any VTE-associated signs or symptoms. Our understanding of the clinical significance of these events in children is limited by a paucity of data on the epidemiology and outcomes of this complication. There is an urgent need for further research in this area to inform optimal management. Recognizing this knowledge gap, this Task Force has previously published a systematic review of the literature in this topic. We now provide guidance recommendations for standardization of definitions and identify future research needs on clinically unsuspected VTE in children. These recommendations will serve to enhance the quantity and quality of evidence on the topic and facilitate the design and execution of cooperative observational studies, and interventional trials of risk-stratified management approaches aimed at preventing and optimizing long-term outcomes of clinically unsuspected VTE in children.

Practical considerations and consensus opinion for children's hospital-based inpatient hemostasis and thrombosis (HAT) consultative services: Communication from the ISTH SSC Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis.

Caring for children and adolescents with disorders of hemostasis and thrombosis (HAT) has become more specialized and requires a unique skill set that many providers are not able to obtain in standard pediatric hematology/oncology/bone marrow transplant fellowship training programs. The influx of numerous therapeutic advances and increasing medical complexity has expanded the need for experienced HAT providers and subspecialty collaboration in the inpatient setting due to the nuances in the management of patients with HAT complications and concerns. While there are data highlighting the benefits of an inpatient hemostasis, thrombosis, and anticoagulation management service in adult hospitals, there are limited pediatric data supporting such programs. In this article, we summarize the current practices of various pediatric institutions in the inpatient management of HAT patients and provide a consensus opinion for the development of a pediatric inpatient HAT service at tertiary care referral centers.