Sheila J. Hanson

Incidence and risk factors for venous thromboembolism in critically ill children after trauma.

BACKGROUND Venous thromboembolism (VTE) causes major morbidity in adults after trauma, occurring in up to 50% of patients without prophylaxis. The incidence of VTE after trauma is lower in children. No study has measured the incidence of and risk factors for VTE in critically ill children after trauma. METHODS Nested case-control study of children, younger than 18 years, admitted to the pediatric intensive care unit at a level I trauma center. Three controls were selected for each identified VTE case. RESULTS Nine of 144 children admitted to the pediatric intensive care unit after trauma developed VTE (incidence 6.2%, 95% confidence interval [CI] 2.3-10.2), with a median age of 8.6 years (range, 2.3-17.9). VTE was diagnosed at a median of 9 days after admission, with 67% of VTE located at the site of previous or existing central venous line (CVL). Significant risk factors for thrombosis included parenteral nutrition (odds ratio [OR] 20, 95% CI 1.9-227), CVL (OR 19, 95% CI 2-178), deep sedation (OR 13, 95% CI 1.6-48), neuromuscular blockade (OR 10, 95% CI 1.4-70), inotropic support (OR 10, 95% CI 1.7-59), and recombinant factor VIIa administration (p = 0.012, OR not calculable). Logistic analysis found a 7.9-fold increase in the odds of developing VTE for each additional CVL (p = 0.005), a threefold increase with each additional risk factor present (p = 0.009), and a 1.3-fold increase for an increase in injury severity (p = 0.03). VTE was not associated with sepsis, spinal cord injury, fracture, or elevated D-dimer level. CONCLUSIONS VTE is not a rare event in critically ill children after trauma. Most patients developing thrombosis have multiple risk factors, including poor perfusion, immobility, and presence of a CVL.

Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma.

BACKGROUND: Historically, 6% of critically ill children developed clinically apparent venous thromboembolism (VTE) after trauma at our Level I pediatric trauma center. We hypothesized that implementation of clinical guidelines for thrombosis prophylaxis incorporating both VTE risk and bleeding risk would reduce VTE incidence without increased bleeding. METHODS: VTE, both clinically apparent and those only detected by guideline-directed screening, were prospectively identified for all children admitted to the intensive care unit after trauma during three time periods: preimplementation of guidelines for VTE thromboprophylaxis (PRE; April 1, 2006–June 30, 2007), the intervening period (ROLL OUT; July 1, 2007–November 4, 2008), and postguideline implementation (POST; November 5, 2008–June 1, 2010). For patients classified as high risk for VTE, anticoagulation was recommended. For those patients at high risk of VTE with high risk of bleeding, anticoagulation was deferred and screening ultrasound performed. RESULTS: Fourteen of 546 subjects developed VTE. There was a decrease in total VTE (p = 0.041) and clinical VTE (p = 0.001) after guideline implementation. The nine VTE PRE (5.2%) were clinically symptomatic, while the three VTE POST (1.8%) were detected by guideline-directed screening ultrasound. Implementation of guidelines did not increase overall thromboprophylaxis, with decreased anticoagulation in patients at low risk of VTE. No bleeding complications occurred. No patients classified by the guidelines as low risk for VTE developed VTE. CONCLUSION: The incidence of clinical VTE and total VTE decreased after implementation of clinical guidelines for thromboprophylaxis in critically ill children after trauma. This decrease in VTE was not associated with increased prophylactic anticoagulation nor increased bleeding. The guidelines were predictive in identifying patients at low risk for VTE. LEVEL OF EVIDENCE: II, therapeutic study.

Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients.

Objective: To evaluate the incidence and risk factors associated with venous thromboembolism (VTE) in children admitted to pediatric intensive care units (PICUs). Design: Prospective observational study. Setting: Eleven tertiary care PICUs in the United States. Patients: Children who were admitted to PICUs and had radiographically confirmed VTE over a rolling 6-month period were enrolled in the study. Demographic, patient-related, and outcomes data were collected and compared with all children admitted during the same period. Interventions: None. Results: Sixty-six symptomatic VTE were documented in sixty-two patients among 6653 patients admitted to 11 PICUs. Thirteen (19.7%) of the thrombi were present on admission. The incidence rate was 0.74% (range, 0–2.7% per PICU) with a point prevalence of 0.93%. Doppler ultrasound was most frequently used to diagnose or confirm a suspected VTE. Variables associated with unadjusted risk for VTE include: younger age (3.8 months for patients with VTE vs. 51 months for non-VTE patients, p < .001), cardiac diagnosis (41% in VTE cases vs. 15% in non-VTE, p < .001), pre-/post-operative status (63% in VTE cases vs. 40% in non-VTE, p = .001), presence of central venous catheter (88% in VTE case vs. 17% in non-VTE, p < .001), or mechanical ventilation (85% in VTE cases vs. 30% non-VTE, p < .001). Multivariate analysis showed increased risk of VTE with CVC (odds ratio 6.9; confidence interval 2.7–17.5) and mechanical ventilation (odds ratio 2.8; confidence interval 0.98–7.93). Children with VTE were sicker (Pediatric Index of Mortality 2 score risk of mortality of 3.0% vs. 0.9%; p<0.0001), stayed longer in the ICU (21.2 days vs. 1.6 days; p < .0001) and had increased mortality (10.2% vs. 2.6; p < .0001). Conclusions: Children admitted to the PICU have an increased risk of VTE. The presence of a CVC is the strongest risk factor for VTE in this PICU population. Children with VTE were younger, sicker, stayed longer in PICU, and had a higher mortality rate.

Effect of Volume Resuscitation on Regional Perfusion in Dehydrated Pediatric Patients as Measured by Two-Site Near-Infrared Spectroscopy

Objective: The aim of this study was to measure the change of cerebral and somatic regional oxygen saturation (rSO2) using near-infrared spectroscopic (NIRS) monitoring during volume resuscitation of dehydrated children. Methods: This prospective, observational study enrolled 17 moderately dehydrated children presenting to the emergency department in a tertiary care pediatric hospital. Pulse oximetry and 2-site rSO2 using forehead and flank NIRS probes were monitored continuously during intravenous rehydration. Results: Prehydration and posthydration data were summarized as mean (SD) and analyzed by paired 2-sided Student t test. Significance was defined as a P < 0.05. Pulse oximetry and cerebral rSO2 remained unchanged throughout rehydration. The somatic rSO2 increased from 79% (13) to 87% (9) (P < 0.01) with rehydration, and the somatic-cerebral rSO2 difference increased from 5% (7) to 13% (6) (P < 0.001). The high-volume rehydration group (33-40 mL/kg) showed a greater increase in somatic rSO2 with rehydration when compared with the low-volume rehydration group (20 mL/kg). The measured increase in somatic rSO2 was greatest in children weighing less than 15 kg. Conclusions: In children with acute dehydration, cerebral rSO2 is preserved in moderate dehydration. Somatic tissue beds show an increase in rSO2 by NIRS oximetry with rehydration. Two-site NIRS monitoring is a continuous, noninvasive quantitative method for early detection of regional hypoperfusion in dehydrated children.

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.

Multicenter Analysis of the Factors Associated With Unplanned Extubation in the PICU.

Objective: To identify factors associated with unplanned extubation in PICUs. Design: A prospective, case-controlled multicenter study. Setting: Eleven Pediatric Intensive Care Units collaborating through the National Association of Children’s Hospitals and Related Institutions PICU focus group. Patients: Patients with unplanned extubation events and control patients without unplanned extubation. Interventions: Unplanned extubation events were prospectively tracked for 1 year at 11 centers. When an unplanned extubation occurred, up to four controls were randomly identified of other intubated patients in the unit. For each event and control, data associated with unplanned extubation events, reintubation, and outcomes were collected. Measurements and Main Results: One hundred eighty-nine unplanned extubation events occurred out of 25,500 endotracheal tube days in the study (0.74 unplanned extubations/100 endotracheal days; 95% CI, 0.64–0.85), with 654 associated controls. Unplanned extubation rates ranged by site from 0.3 to 2.1 unplanned extubations/100 endotracheal days. Children less than 6 years had an increased rate of unplanned extubation (0.83 for < 6 yr vs 0.45 for ≥ 6 yr; p = 0.001). After multivariate analysis, inadequate patient sedation (odds ratio, 9.1; 95% CI, 4.5–18.5), loose or slimy endotracheal tube (odds ratio, 10.4; 95% CI, 5.0–22.2), a planned extubation in the next 12 hours (odds ratio, 2.3; 95% CI, 1.3–4.1), and a nurse pulled from another unit (odds ratio, 3.8; 95% CI, 1.4–9.9) were associated with unplanned extubation. Sixty percent of unplanned extubations required reintubation. Conclusions: The rate of unplanned extubation is higher in patients aged less than 6 years. Patient factors, such as decreased level of sedation, loose or slimy endotracheal tube, and staffing factors such as floating nurse from another unit, contribute to unplanned extubation in children.

Higher doses of low-molecular-weight heparin (enoxaparin) are needed to achieve target anti-Xa concentrations in critically ill children*.

Objectives: To demonstrate that low-molecular-weight heparin (enoxaparin) can be used in critically ill pediatric patients to achieve target anti-factor Xa concentrations and determine appropriate dosing corrected for age and illness severity. Design: Retrospective cohort study. Setting: Single tertiary level PICU. Patients: One hundred ninety-two children age 1 day through 18 years admitted to PICU undergoing every 12-hour enoxaparin therapy with at least one anti-factor Xa concentration obtained. Patients receiving renal replacement therapy or infants with corrected gestational age less than 37 weeks were excluded. Interventions: None. Measurements and Main Results: We collected patient characteristics including age, weight, height/length, gender, corrected gestational age, illness severity markers, diagnosis, creatinine, enoxaparin dose and times of administration, anti-factor Xa concentrations, and collection times. Only 42% of critically ill children (80 of 192) and only 29% of children (9 of 31) on inotropes achieved recommended target range of anti-factor Xa concentrations on initial recommended enoxaparin dosing (1.5 mg/kg/dose < 2 mo; 1 mg/kg/dose > 2 mo), but 81% were ultimately within target range with dose titration. Increased enoxaparin dose was required to reach target concentrations in younger patients and those with worse illness severity as evidenced by concurrent use of inotropes, previous ICU admission, mechanical ventilation, cardiac surgery, and increased risk of mortality defined by severity-of-illness scores. Conclusions: Enoxaparin can be used to reach recommended target range of anti-factor Xa concentrations in the PICU patient. However, younger patients and patients with higher illness severity are less likely to achieve target concentrations using currently recommended dosing and may require higher doses of enoxaparin to reach target anti-factor Xa concentrations. Starting enoxaparin dose at least 1.3 mg/kg dosed every 12 hours for treatment of thromboembolic disease in critically ill patients aged 61 days to 1 year or those requiring inotropic support should be confirmed in prospective study.

The Need for Evidence Based Nutritional Guidelines for Pediatric Acute Lymphoblastic Leukemia Patients: Acute and Long-Term Following Treatment

High survival rates for pediatric leukemia are very promising. With regard to treatment, children tend to be able to withstand a more aggressive treatment protocol than adults. The differences in both treatment modalities and outcomes between children and adults make extrapolation of adult studies to children inappropriate. The higher success is associated with a significant number of children experiencing nutrition-related adverse effects both in the short and long term after treatment. Specific treatment protocols have been shown to deplete nutrient levels, in particular antioxidants. The optimal nutrition prescription during, after and long-term following cancer treatment is unknown. This review article will provide an overview of the known physiologic processes of pediatric leukemia and how they contribute to the complexity of performing nutritional assessment in this population. It will also discuss known nutrition-related consequences, both short and long term in pediatric leukemia patients. Since specific antioxidants have been shown to be depleted as a consequence of therapy, the role of oxidative stress in the pediatric leukemia population will also be explored. More pediatric studies are needed to develop evidence based therapeutic interventions for nutritional complications of leukemia and its treatment.

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

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

Prevalence of heparin-dependent platelet antibodies in children after cardiopulmonary bypass.

27,000. Several risk factors have been associated with VTE in injured children, including older age, injury severity, obesity, central venous catheter (CVC) use, mechanical ventilation, inotrope use, blood transfusion, pelvic or lower extremity fracture, spinal cord injury, and intensive care unit stay. However, it is not clear in any individual pediatric patient when the benefit of pharmacologic prophylaxis to reduce the risk of VTE outweighs the risk, particularly the risk of bleeding. The efficacy of anticoagulation to prevent VTE is unknown in this population. In addition, there are no pediatric studies on the effectiveness of mechanical prophylaxis to prevent VTE. In contrast, VTE prophylaxis with lowmolecular-weight heparin (LMWH) is routinely recommended for injured adults. Despite the paucity of evidence, medical providers from different specialties are routinely called upon to make management decisions regarding the use of VTE prophylaxis in injured children. We proposed to survey experts in the field of pediatric trauma and thrombosis to develop consensus regarding the prevention of VTE in pediatric trauma patients.