RESUMEN
OBJECTIVES: To compare fentanyl infusion pharmacokinetic variables in obese children and nonobese children. DESIGN: A pharmacokinetic simulation study. SETTING: We used a semi-physiologically based pharmacokinetic model to generate fentanyl pharmacokinetic variables. SUBJECTS: Simulations of pharmacokinetic variables were based on historical inpatient demographic data in less than 18-year-olds. INTERVENTIONS: Obese children were defined as children less than 2 years with weight-for-length greater than or equal to 97.7th percentile or body mass index-for-age greater than or equal to 95th percentile for greater than or equal to 2-17-year-olds. MEASUREMENTS AND MAIN RESULTS: Overall, 4,376 patients were included, with 807 (18.4%) classified as obese children. The majority (52.9%) were male, with a median age of 8.1 years (interquartile range, 4.3-13.0 yr). The differences in total clearance (CLS), volume of distribution at steady-state values, weight-normalized CLS, and weight-normalized volume of distribution at steady state were assessed in obese children and nonobese children. Multivariable analyses indicated that obesity was significantly associated with a higher CLS in obese children greater than 6-year-olds (p < 0.0375). However, there was an 11-30% decrease in weight-normalized CLS in obese children versus nonobese children in all age groups (p < 0.05). Both volume of distribution at steady state and weight-normalized volume of distribution at steady state increased significantly in obese children compared with nonobese children (p < 0.05). Fentanyl plasma concentration-time profiles of obese children and nonobese children pairs (ages 4, 9, and 15) receiving 1 µg/kg/hr using total body weight were also compared. Steady-state concentrations of the obese children using similar weight-based dosing increased by 25%, 77%, and 44% in comparison to nonobese children 4-, 9-, and 15-year-olds, respectively. Time to steady state and elimination half-lives were two- to four-fold longer in obese children. An additional simulation was conducted for 15-year-old obese children and nonobese children using a fixed dose of 50 µg/hr and it provided similar pharmacokinetic profiles. CONCLUSIONS: CLS may increase less than proportional to weight in obese children greater than 6-year-olds, while volume of distribution at steady state increases more than proportional to weight in all obese children compared with nonobese children. Weight-based dosing in obese children may cause an increase in steady-state concentration while prolonging the time to steady state. Exploring alternative dosing strategies for obese children is warranted.
Asunto(s)
Fentanilo/farmacocinética , Obesidad/epidemiología , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Simulación por Computador , Femenino , Fentanilo/administración & dosificación , Humanos , Masculino , Tasa de Depuración MetabólicaRESUMEN
Objectives: Limited data on performing bilateral pulmonary artery banding (BPAB) before stage 1 Norwood procedure suggest that some patients may benefit through the postponement of the major cardiopulmonary bypass procedure. The objective of this study was to evaluate the effectiveness of BPAB in the surgical management of high-risk patients with hypoplastic left heart syndrome (HLHS). Methods: A retrospective review of all high-risk neonates with HLHS who underwent BPAB at our institution was performed. No patients, including those with intact or highly restrictive atrial septum (IAS), were excluded. Results: Between October 2015 and April 2021, 49 neonates with HLHS (including 6 with IAS) underwent BPAB, 40 of whom progressed to the Norwood procedure. Risk factors for not progressing to the Norwood procedure after BPAP include low birth weight (P = .043), the presence of multiple extracardiac anomalies (P = .005), and the presence of genetic disorders (P = .028). Operative mortality was 7.5% (3/40). IAS was associated with operative mortality (P = .022). Conclusions: The strategy of BPAB prestage 1 Norwood procedure was successful in identifying at-risk patients and improving Norwood survival. Although not all patients will need this hybrid approach, a significant number can be expected to benefit from this tactic. These results support the need for a substantial hybrid strategy, in addition to a primary stage 1 Norwood surgical strategy, in the management of HLHS.
RESUMEN
Rocky Mountain spotted fever is a tick-borne illness that is prevalent in the south and the central United States, primarily during the summer months. Patients with delayed diagnosis can experience increased mortality and morbidity, particularly poor neurological outcome. We present a case of a 7-year-old girl with Rocky Mountain spotted fever who was admitted with severe neurological changes and septic shock on day 8 of illness. She was initially diagnosed with Kawasaki disease and treated with intravenous immunoglobulin. Her treatment also included doxycycline, vancomycin, and ceftriaxone due to concerns regarding Rocky Mountain spotted fever and bacterial sepsis. During hospitalization, the patient required mechanical ventilation for respiratory distress, inotropic support, and fluid resuscitation for hypotension. Titers for Rocky Mountain spotted fever were ultimately positive, with magnetic resonance imaging of the brain demonstrating numerous punctate foci of restricted diffusion within the supratentorium, including the corpus callosum and basal ganglia. Although the patient presented late in the disease course, she ultimately had a good neurological outcome. We theorized that administration of intravenous immunoglobulin prevented ongoing neurological injuries from the cerebral vasculitis, which are associated with Rocky Mountain spotted fever.
RESUMEN
Recent reports have described increased risk of acute kidney injury (AKI) in adults receiving concomitant vancomycin and piperacillin/tazobactam, but few reports exist in children. We describe an 8-year-old girl who was admitted to the pediatric intensive care unit with respiratory distress secondary to pneumonia. She began treatment with vancomycin and piperacillin/tazobactam. She developed AKI, and piperacillin/tazobactam and vancomycin were discontinued. Following a furosemide infusion, her AKI resolved and serum creatinine returned to baseline. She later resumed piperacillin/tazobactam monotherapy for multidrug-resistant tracheitis with no evidence of AKI and was eventually discharged to a long-term care facility. The Naranjo probability scale supports a probable drug-related adverse event. Clinicians must be aware of the possibility of AKI with this combination and should monitor renal function and vancomycin concentrations vigilantly. Future prospective studies are needed to explore the incidence and clinical characteristics associated with AKI after this combination in children.
RESUMEN
PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) states that "residents should participate in scholarly activity." However, there is little guidance for effectively integrating scholarly activity into residency. This study was conducted to understand how pediatric residency programs meet ACGME requirements and to identify characteristics of successful programs. METHOD: The authors conducted an online cross-sectional survey of all pediatric residency program directors in October 2012, assessing program characteristics, resident participation in scholarly activity, program infrastructure, barriers, and outcomes. Multivariate logistic regression was used to identify characteristics of programs in the top quartile for resident scholarly activity participation. RESULTS: The response rate was 52.8% (105/199 programs). Seventy-seven (78.6%) programs required scholarly activity, although definitions were variable. When including only original research, systematic reviews or meta-analyses, and case reports or series with references, resident participation averaged 56% (range 0%-100%). Characteristics associated with high-participation programs included a scholarly activity requirement (odds ratio [OR] = 5.5, 95% confidence interval [CI] = 1.03-30.0); program director belief that all residents should present work regionally or nationally (OR = 4.7, 95% CI = 1.5-15.1); and mentorship by >25% of faculty (OR = 3.6, CI = 1.2-11.4). Only 47.1% (41) of program directors were satisfied with resident participation, and only 30.7% (27) were satisfied with the quality of research training provided. CONCLUSIONS: The findings suggest that resident scholarly activity experience is highly variable and suboptimal. Identifying characteristics of successful programs can improve the resident research training experience.