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.

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.

Serum Neuronal Biomarkers in Neonates With Congenital Heart Disease Undergoing Cardiac Surgery.

BACKGROUND: Newborns with congenital heart disease have associated brain damage that affects short-and long-term neurodevelopment. Several neuronal biomarkers exist that could predict brain damage. We investigated the pattern of neuron-specific enolase (NSE) and s100B levels after cardiopulmonary bypass surgery in neonates with congenital heart disease. METHODS: We completed a prospective observational study of neonates with congenital heart disease who were undergoing cardiopulmonary bypass surgery. NSE and s100B levels were measured from serum samples obtained preoperatively, immediately postoperatively, and once daily on postoperative days one to seven. Cranial ultrasounds were obtained preoperatively and postoperatively and findings were scored using an internally developed scoring system. RESULTS: Eighteen neonates were included. Immediate postoperative and peak levels of both NSE (58.0 [21.6] and 68.1 [55.7] µg/L) and s100B (0.14 [0.3] and 0.14 [0.3] µg/L) were significantly increased when compared with preoperative levels (34.0 [21.6] µg/L; P < 0.01 and 0.08 [0.1] µg/L; P < 0.02). By postoperative day seven, NSE and s100B levels were lower than preoperative levels: NSE (18 [5.7]; P = 0.09) and s100B (0.03 [0.05]; P < 0.01). Postoperative s100B levels were negatively correlated with age at surgery and positively correlated with circulatory arrest time. Although there was no significant correlation between either NSE or s100B levels and intensive care unit length of stay, hospital length of stay, and pediatric cerebral performance category score, there was a negative correlation between postoperative levels of NSE and ventriculomegaly. CONCLUSIONS: NSE and s100B levels increase after bypass surgery and return below preoperative baseline levels by postoperative day seven. The levels of s100B were positively correlated with circulatory arrest time and negatively correlated with age at time of surgery. This finding may be supportive of pre-existing prenatal brain injury that could be enhanced by longer surgical times but also of some brain protection effect associated with longer wait until surgery.

Advances in monitoring and management of shock.

Early recognition and treatment of pediatric shock, regardless of cause, decreases mortality and improves outcome. In addition to the conventional parameters (eg, heart rate, systolic blood pressure, urine output, and central venous pressure), biomarkers and noninvasive methods of measuring cardiac output are available to monitor and treat shock. This article emphasizes how fluid resuscitation is the cornerstone of shock resuscitation, although the choice and amount of fluid may vary based on the cause of shock. Other emerging treatments for shock (ie, temperature control, extracorporeal membrane oxygenation/ventricular assist devices) are also discussed.