A Quality Initiative to Improve Appropriate Medication Dosing in Pediatric Patients with Obesity.

Introduction: Emerging evidence supports the use of alternative dosing weights for medications in patients with obesity. Pediatric obesity presents a particular challenge because most medications are dosed based on patient weight. Additionally, building system-wide pediatric obesity safeguards is difficult due to pediatric obesity definitions of body mass index-percentile-for-age via the Center for Disease Control growth charts. We describe a quality initiative to increase appropriate medication dosing in inpatients with obesity. The specific aim was to increase appropriate dosing for 7 high-risk medications in inpatients with obesity ≥2 years old from 37% to >74% and to sustain for 1 year. Methods: The Institute for Healthcare Improvement model for improvement was used to plan interventions and track outcomes progress. Interventions included a literature review to establish internal dosing guidance, electronic health record (EHR) functionality to identify pediatric patients with obesity, a default selection for medication weight with an opt-out, and obtaining patient heights in the emergency department. Results: Appropriate dosing weight use in medication ordered for patients with obesity increased from 37% to 83.4% and was sustained above the goal of 74% for 12 months. Conclusions: Implementation of EHR-based clinical decision support has increased appropriate evidence-based dosing of medications in pediatric and adult inpatients with obesity. Future studies should investigate the clinical and safety implications of using alternative dosing weights in pediatric patients.

Evaluation of an Enteral Clonidine Taper following Prolonged Dexmedetomidine Exposure in Critically Ill Children.

The aim of the current study is to evaluate the use of an enteral clonidine transition for the prevention or management of dexmedetomidine withdrawal symptoms in critically ill children not exposed to other continuous infusion sedative agents. A retrospective, single-center study was conducted in patients ≤ 18 years of age admitted to the pediatric intensive care unit who received a continuous infusion of dexmedetomidine for ≥ 24 hours and who were prescribed enteral clonidine within 72 hours of dexmedetomidine discontinuation. Predefined withdrawal terminology was established to assess for hypertension, tachycardia, agitation, tremors, and decreased sleep. A total of 105 patients were included and received enteral clonidine for prevention or management of dexmedetomidine withdrawal symptoms, with 13 patients (12.4%) requiring a taper modification to manage withdrawal symptoms. The median duration of dexmedetomidine infusion was 120.5 hours (95.5, 143.5) and median peak infusion rate was 1 µg/kg/h (1, 1.2). A higher cumulative dexmedetomidine dose of 119.2 µg/kg (96.6, 154.9) and duration of 142.9 hours (122.6, 158.3) were noted in patients who required a taper modification. Risk factors for dexmedetomidine withdrawal such as dexmedetomidine duration and cumulative dose may help predict patients at the highest risk of withdrawal that would benefit from an enteral clonidine taper to prevent dexmedetomidine withdrawal symptoms. An enteral clonidine taper can be effective in the prevention and management of dexmedetomidine withdrawal symptoms.

Post-operative Anticoagulation Strategy Following Comprehensive Stage 2 Procedure for Single Ventricle Physiology.

Thrombosis, especially thrombosis of the pulmonary artery, is a large contributor to morbidity and mortality following comprehensive stage 2 procedure for single ventricle cardiac physiology. A peri-operative management protocol was implemented at our institution in March 2010. It includes 6 weeks of therapeutic anticoagulation post-operatively to mitigate the thrombotic risks in this patient population. This is a retrospective study of hospitalized children who received post-operative anticoagulation following a comprehensive stage 2 procedure for single ventricle cardiac physiology at a free-standing children's hospital. The primary objectives are to describe our institution's anticoagulation strategy and report on the number of thromboses and major bleeding episodes in the 6 weeks post-operatively. Secondary objectives include the dose of enoxaparin required to obtain a therapeutic low-molecular weight anti-factor-Xa (AFXaLMWH) level, and the number of patients outside of the therapeutic range. A total of 71 infants were included in the final analysis. Four patients experienced a thrombosis episode and three patients experienced clinically significant bleeding. The mean dose of enoxaparin required to obtain a therapeutic AFXaLMWH level between 0.5-1 unit/mL was 1.23 mg/kg SQ every 12 h and 37% of patients achieved goal AFXaLMWH levels with the initial starting dose of enoxaparin 1 mg/kg SQ every 12 h. We describe a 9-year experience of anticoagulation after single ventricle palliation. Anticoagulation with therapeutic AFXaLMWH goals of 0.5-1 unit/mL may reduce the rates of clinically significant thrombosis post-operatively in this population and appears safe without increase in significant bleeding episodes when compared to a historical cohort. Further studies comparing this population to those who do not receive post-operative anticoagulation are warranted.

Enoxaparin Dose Requirements to Achieve Therapeutic Low-molecular-weight Heparin Anti-factor Xa Levels in Infants and Young Children.

INTRODUCTION: Enoxaparin is commonly used to treat pediatric thrombosis. Several small retrospective studies have suggested that infants and young children require higher enoxaparin doses to achieve therapeutic anti-factor Xa levels compared with adults. MATERIALS AND METHODS: This is a retrospective study of hospitalized children who received enoxaparin for the treatment of thrombosis at a free-standing children's hospital. The primary objective was to ascertain the enoxaparin dose required to achieve an anti-factor Xa level of 0.5 to 1.0 U/mL among 4 age groups in a large cohort of infants and young children between 60 days and 5 years of age. RESULTS: A total of 176 infants and children were evaluated. The majority of patients were less than 1 year of age (n=104). An inverse relationship between enoxaparin dose needed to achieve therapeutic anti-factor Xa levels and patient age was noted, particularly in the first year of life. Patients who were 60 days to less than 7 months at the time of enoxaparin initiation (n=73) required the highest mean dose among the age groups at 1.73 mg/kg subcutaneously every 12 hours (P<0.0001). CONCLUSION: Infants and young children require higher doses of enoxaparin to achieve therapeutic anti-factor Xa levels compared with adults.

Efficacy of liposomal bupivacaine in pediatric patients undergoing spine surgery.

BACKGROUND: Liposomal bupivacaine may be an option for reducing opioid utilization in pediatric scoliosis surgery. The use of liposomal bupivacaine in this patient population has not been previously described. METHODS: Patients who underwent posterior spinal fusion surgery at our institution from 2011-2016 were identified. We performed a retrospective matched cohort study, matching patients who received intraoperative liposomal bupivacaine by age, gender, and extent of surgery to patients who did not. The primary endpoint was the use of morphine equivalents in the first 72 hours after surgery. Data collection included demographic and surgical data, pain medication utilization, and pain scores. Area under the curve (AUC) for pain scores was calculated. Descriptive statistical methods and univariable analysis were used to compare patients who received liposomal bupivacaine to patients who did not. RESULTS: One hundred and forty-one patients met study criteria; 47 patients who received liposomal bupivacaine were matched to 94 control patients who did not receive liposomal bupivacaine. No significant differences were noted in the patient population with the patients requiring a median of 11 segments (range 10-13 segments) fused. Patients received a mean of 56.6 ± 37.4 mg/kg of intravenous acetaminophen, a mean of 3.4 ± 2.1 mg/kg of intravenous ketorolac, and 1.9 ± 0.93 mg/kg of morphine equivalents in the first 72 hours after surgery. On univariable analysis, no differences were noted in intravenous acetaminophen use, pain score AUC, intravenous ketorolac use, or morphine equivalents (2.0 ± 98 vs 1.8 ± 0.82) in patients who did not receive liposomal bupivacaine as compared to those patient who did received liposomal bupivacaine. CONCLUSION: Liposomal bupivacaine was not associated with reductions in postoperative opioid use in pediatric spinal surgery.

MRI apparent diffusion coefficient reflects histopathologic subtype, axonal disruption, and tumor fraction in diffuse-type grade II gliomas.

The apparent diffusion coefficient (ADC) determined from MR diffusion tensor imaging (DTI) has shown promise for distinguishing World Health Organization grade II astrocytoma (AS) from the more prognostically favorable grade II oligodendroglioma (OD). Since mixed oligoastrocytomas (OAs) with codeletions in chromosomes 1p and 19q confer prognoses similar to those of OD, we questioned whether a previously determined ADC-based criterion for distinguishing OD and AS would hold on an independent set of gliomas that included OA with codeleted or intact 1p/19q chromosomes. We also questioned whether the ADC is associated with the tumor microstructure. ADC colormaps generated from presurgical DTI scans were used to guide the collection of biopsies from each tumor. The median normalized ADC distinguished OD from AS with 91% sensitivity and 92% specificity. 1p/19q codeleted OAs were always classified as ODs, while 1p/19q intact OAs were always classified as ASs. There were positive associations between the ADC and both the SMI-31 score of axonal disruption and the fraction of tumor cells in the biopsies. The ADC of OD and 1p/19q codeleted OA was more associated with tumor fraction, while the ADC of AS and 1p/19q intact OA was more associated with SMI-31 score. We conclude that our previously determined threshold median ADC can distinguish grade II OD and AS on a new patient cohort and that the distinctions extend to OA with codeleted and intact 1p/19q chromosomes. Further, the ADC in grade II gliomas is associated with the fraction of tumor cells and degree of axonal disruption in tumor subregions.

Choline metabolism, proliferation, and angiogenesis in nonenhancing grades 2 and 3 astrocytoma.

PURPOSE: To study choline metabolism in biopsies from nonenhancing Grade 2 (AS2) and Grade 3 (AS3) astrocytomas to determine whether (1) phosphocholine (PC) dominates in AS3, and (2) PC is associated with proliferation or angiogenesis. PC and glycerophosphocholine (GPC) are involved in phospholipid metabolism that accompanies mitosis. PC is the predominant peak in Grade 4 astrocytoma (GBM) while GPC dominates in AS2. MATERIALS AND METHODS: We used high resolution magic angle spinning magnetic resonance spectroscopy to compare the concentrations of 10 metabolites in 41 biopsies (16 AS2 and 25 AS3) from 24 tumors. Immunohistochemistry was performed on paired biopsies to determine the cell density, Ki-67 proliferation index, and vascular endothelial growth factor (VEGF) angiogenic marker expression. RESULTS: AS3 had higher PC than AS2; however, the PC:GPC was less than 1 in all cases irrespective of tumor grade. Within tumors, GPC increased with Ki-67 and PC and tCho increased with cell density. There was no association between any choline compound and VEGF. CONCLUSION: These data suggest that PC:GPC less than 1 is not unique to low grade glioma. Furthermore, the PC concentration that is a marker of aggressive glial tumors is not tightly linked to cell proliferation or angiogenesis in nonenhancing astrocytomas.

Effects of age on perioperative complications of extensive multilevel thoracolumbar spinal fusion surgery.

OBJECT: The elderly compose a substantial proportion of patients presenting with complex spinal pathology. Several recent studies have suggested that fusion of 4 or more levels increases the risk of perioperative complications in elderly patients. Therefore, the purpose of this study was to analyze the effects of age in persons undergoing multilevel (> or = 5 levels) thoracolumbar fusion surgery. METHODS: A retrospective review of all hospital records, operative reports, and clinic notes was conducted for 124 consecutive patients who underwent surgery between 2000 and 2007 with an average follow-up of 3.5 years and a minimum follow-up of 1.2 years. The most frequent preoperative diagnoses included scoliosis, tumor, osteomyelitis, vertebral fracture, and degenerative disc disease with stenosis. Complications were classified as intraoperative and major and minor postoperative as well as the need for revision surgery. Multivariate logistic regression analysis was used to determine the effects of age and other potentially prognostic factors. RESULTS: After controlling for other factors, increasing age was associated with an elevated risk for major postoperative complications (OR 1.04, 95% CI 1.00-1.10) as were increasing levels of fusion (OR 1.5, 95% CI 1.1-2.1) and male sex (OR 4.6, 95% CI 1.3-16.2). In patients 65 years of age or older, rates of intraoperative complications, major and minor postoperative complications, and reoperation were 14.1, 23.4, 29.7, and 26.6%, respectively. The number of comorbidities was associated with a greater risk for perioperative complications in elderly patients (OR 1.8, 95% CI 1.1-2.8). CONCLUSIONS: Age is a positive risk factor for major postoperative complications in extensive thoracolumbar spinal fusion surgery. Complication rates in the elderly are high, and good clinical judgment and careful patient selection are needed before performing extensive thoracolumbar reconstruction in older persons.