Joana Tala

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.

The temporal kinetics of circulating angiopoietin levels in children with sepsis.

Objective: Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin-1 and angiopoietin-2, play opposing roles in capillary stabilization in patients with sepsis. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios when compared with nonseptic PICU patients over a 7-day period. Design: Prospective observational study. Patients were classified within 24 hours of admission into non–systemic inflammatory response syndrome, systemic inflammatory response syndrome/sepsis, or severe sepsis/shock. Plasma levels of angiopoietin-1 and angiopoietin-2 were measured via enzyme-linked immunosorbent assay. The angiopoietin-2/1 ratio was graphically plotted and determined whether patients fell into “constant” or “variable” patterns. Setting: Tertiary care center PICU. Patients: Critically ill pediatric patients with varying sepsis severity. Interventions: None. Measurements and Main Results: Forty-five patients were enrolled (nine non–systemic inflammatory response syndrome, 19 systemic inflammatory response syndrome/sepsis, and 17 severe sepsis/shock). Gender, age, weight, comorbidities, and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p < 0.05). Admission angiopoietin-2 levels and angiopoietin-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p < 0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p ⩽ 0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of systemic inflammatory response syndrome/sepsis and 82% of severe sepsis/shock had variable angiopoietin-2/1 ratio patterns compared with none in the control group (p < 0.001). Conclusions: Pediatric patients with severe sepsis and septic shock possess significantly elevated angiopoietin-2/1 ratios during their first 3 days of illness, which peak at day 2 of illness. A subset of these patients demonstrated variable angiopoietin-2/1 ratio patterns.

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.

Prevalence of post-thrombotic syndrome after cardiac catheterization.

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

Blood glucose as a marker of venous thromboembolism in critically ill children.

The ability to predict the development of venous thromboembolism is highly desirable.

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.

Frequency of Desaturation and Association with Hemodynamic Adverse Events during Tracheal Intubations in PICUs

Objectives: Oxygen desaturation during tracheal intubation is known to be associated with adverse ICU outcomes in critically ill children. We aimed to determine the occurrence and severity of desaturation during tracheal intubations and the association with adverse hemodynamic tracheal intubation–associated events. Design: Retrospective cohort study as a part of the National Emergency Airway Registry for Children Network’s quality improvement project from January 2012 to December 2014. Setting: International PICUs. Patients: Critically ill children younger than 18 years undergoing primary tracheal intubations in the ICUs. Interventions: tracheal intubation processes of care and outcomes were prospectively collected using standardized operational definitions. We defined moderate desaturation as oxygen saturation less than 80% and severe desaturation as oxygen saturation less than 70% during tracheal intubation procedures in children with initial oxygen saturation greater than 90% after preoxygenation. Adverse hemodynamic tracheal intubation–associated event was defined as cardiac arrests, hypo or hypertension requiring intervention, and dysrhythmia. Measurements and Main Results: A total of 5,498 primary tracheal intubations from 31 ICUs were reported. Moderate desaturation was observed in 19.3% associated with adverse hemodynamic tracheal intubation–associated events (9.8% among children with moderate desaturation vs 4.4% without desaturation; p < 0.001). Severe desaturation was observed in 12.9% of tracheal intubations, also significantly associated with hemodynamic tracheal intubation–associated events. After adjusting for patient, provider, and practice factors, the occurrence of moderate desaturation was independently associated with hemodynamic tracheal intubation–associated events: adjusted odds ratio 1.83 (95% CI, 1.34–2.51; p < 0.001). The occurrence of severe desaturation was also independently associated with hemodynamic tracheal intubation–associated events: adjusted odds ratio 2.16 (95% CI, 1.54–3.04; p < 0.001). Number of tracheal intubation attempts was also significantly associated with the frequency of moderate and severe desaturations (p < 0.001). Conclusions: In this large tracheal intubation quality improvement database, we found moderate and severe desaturation are reported among 19% and 13% of all tracheal intubation encounters. Moderate and severe desaturations were independently associated with the occurrence of adverse hemodynamic events. Future quality improvement interventions may focus to reduce desaturation events.

Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness

Abstract Background Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza–MRSA pneumonia and evaluated antibiotic use. Methods We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008–5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. Results We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza–MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza–MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8–22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. Conclusions Influenza–MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.

Pediatric Adverse Tracheal Intubation Associated Events Following Noninvasive Ventilation Failure

Objective: To determine if children intubated after failed Noninvasive Ventilation (NIV) have a higher occurrence of Tracheal Intubation Associated Events (TIAEs) compared to those intubated immediately. Methods: We conducted a retrospective study of all Tracheal Intubations (TIs) in a tertiary pediatric intensive care unit from 1/2013 to 12/2015. Data were collected from National Airway Registry for Kids, Virtual PICU System, and chart review. We excluded TI in children on chronic NIV, endotracheal tube exchange, nonemergent TI for procedures, and cases with insufficient documentation. We defined NIV as continuous or bilevel pressure ≥5 cm H2O or high flow nasal cannula ≥4L/min for infants and ≥5L/min for children. NIV failure was defined as TI after >1h of exposure to NIV; it was further characterized as acute (1-4h) or delayed (>4h). Our primary outcome was occurrence of severe TIAEs and/or desaturation (SpO2 drop >20%). Data were analyzed using Fisher’s Exact Test, Chi Square, Mann-Whitney U Test, and logistic regression. Results: One-hundred-forty-four of 192 intubations (75%) were included, of which 48 (33%) were primary TIs and 96 (67%) were after NIV failure. The median duration of NIV prior to failure was 14h (IQR 5, 45). TIAEs/desaturation occurred in 33% of intubations and were not different between the two groups after adjusting for potential confounders (25% vs. 38%; p=0.134, aOR 2.15, 95% CI 0.77-6.03). Additionally, there was no difference between occurrence of severe TIAEs/ desaturation in acute compared to delayed NIV failure (26% vs. 19%; p=0.558). Conclusion: TI after NIV failure is common. However, there was no difference in the occurrence of severe TIAEs/desaturation in primary TI versus TI after NIV failure, suggesting NIV failure does not increase the risk of TIAEs. Correspondence to: Christina Walsh, MD, Yale University, 333 Cedar St, PO Box 208064, New Haven, CT 06520-8064, Tel: 203-785-4651; E-mail: Christina.walsh@yale.edu