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.

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.

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.

Bayesian analysis of the epidemiology of bleeding in critically ill children.

PURPOSE: We updated our findings on the epidemiology of clinically relevant bleeding (CRB) in critically ill children. We also determined the concordance of CRB as defined by the International Society of Thrombosis and Haemostasis, i.e., ISTH definition, and characteristics identified by pediatric intensivists in a recent survey, i.e., survey definition. METHODS: In a prospective cohort study, we included children <18 years old who were admitted to the pediatric intensive care unit for >1 day. We followed them daily for bleeding. Bayesian inference was used as the primary analytic tool to incorporate our prior findings. RESULTS: Using the ISTH definition, the estimated frequency of CRB was 10.0% (95% credible interval, CrI: 7.6%, 12.8%) from 41 of 405 children who had CRB. The estimated frequency from 4 of 12 adolescents >13 years old who received mechanical ventilation or vasopressor support and had CRB was 32.9% (95% CrI: 12.0%, 58.8%). Using the survey definition, the estimated frequency of CRB for the entire cohort was 10.8% (95% CrI: 8.3%, 13.8%). Concordance between definitions for each bleeding event was 0.40 (95% confidence interval: 0.27, 0.52). CONCLUSIONS: Our updated findings highlight the high frequency of CRB regardless of definition used for CRB.

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.

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.

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 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.

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 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 Survey of Pediatric Critical Care Providers on the Presence, Severity, and Assessment of Capillary Leak in Critically Ill Children.

Purpose To determine provider opinions on factors most commonly used to assess the presence and severity of pathologic capillary leak in critically ill children. Methods We conducted an electronic survey of pediatric critical care providers. Patient scenarios were presented to assess opinions on the risk, presence, and clinical significance of capillary leak. Responses were obtained using Likert scales and multiple-choice questions. Results A total of 160 responses were analyzed. Respondents agreed that capillary leak is present in the scenario with septic shock while respondents somewhat agreed that it is also present with poly-trauma, cardiac arrest, or cardiopulmonary bypass. They agreed that physical exam, but neither agreed nor disagreed that laboratory tests, can be used to assess and follow the severity of capillary leak in these children. Generalized edema, increase in weight, and pulmonary crackles were commonly identified parameters for assessing capillary leak. The patient factor most commonly identified with capillary leak was presence of infection, while treatment factors most commonly identified were cardiopulmonary bypass and general anesthesia. Conclusion There is agreement that capillary leak is common in critically ill children and exacerbates disease. The parameters identified in this study may facilitate a more standardized clinical evaluation of pathologic capillary leak for future studies.

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.

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.

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.

Clinical equipoise on prophylaxis against catheter-associated thrombosis in critically ill children.

PURPOSE: In preparation for a randomized controlled trial of prophylaxis against catheter-associated deep venous thrombosis in critically ill children, we aimed to determine clinical equipoise, defined as willingness to randomize children, among pediatric critical care physicians. MATERIALS AND METHODS: We conducted a cross-sectional, self-administered electronic survey of pediatric critical care physicians in the United States. The survey focused on the effect of child's age, presence of a central venous catheter, and risk (ie, presence of coagulopathy or recent surgery) and presence of bleeding on their willingness to randomize children to an anticoagulant or placebo. RESULTS: Responses from 239 (33.0%) of 725 physicians were analyzed. Respondents were willing to randomize children 1 month or older in the presence of a catheter but only those older than 13 years in the absence of a catheter. For children with coagulopathy, they would randomize those with international normalized ratio less than or equal to 2.0, partial thromboplastin time less than or equal to 50 seconds, and platelet count greater than or equal to 50000/mm(3). Respondents were willing to randomize children 2 days after most types of surgery and after 1 to 5 days of a bleeding event. CONCLUSIONS: Clinical equipoise on prophylaxis against catheter-associated thrombosis exists among pediatric critical care physicians, which ethically justifies conducting a randomized controlled trial.

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.