Increased Fracture Risk with Furosemide Use in Children with Congenital Heart Disease.

OBJECTIVES: To determine the association of furosemide therapy with the incidence of bone fractures in children with congenital heart disease. STUDY DESIGN: We conducted a retrospective cohort study with data extracted from the 2008-2014 Texas Medicaid databases. Pediatric patients aged <12 years diagnosed with congenital heart disease, cardiomyopathy, or heart failure were included. Patients taking furosemide were categorized into a furosemide-adherent group (medication possession ratio of ≥70%), and a furosemide-nonadherent group (medication possession ratio of <70%). A third group of patients was matched to the furosemide user groups by using propensity score matching. A multivariate logistic regression and Cox proportional hazard model with a Kaplan-Meier plot (time-to-fracture) were used to compare the 3 groups, controlling for baseline demographics and clinical characteristics. RESULTS: After matching, 3912 patients (furosemide adherent, n = 254; furosemide nonadherent, n = 724; no furosemide, n = 2934) were identified. The incidence of fractures was highest for the furosemide-adherent group (9.1%; 23 of 254), followed by the furosemide-nonadherent group (7.2%; 52 of 724), which were both higher than for patients who did not receive furosemide (5.0%; 148 of 2934) (P < .001). Using logistic regression, both furosemide groups were more likely to have fractures than the no furosemide group: furosemide-adherent OR of 1.9 (95% CI, 1.17-2.98; P = .009); furosemide nonadherent OR of 1.5 (95% CI, 1.10-2.14; P = .01). In the Cox proportional hazard model, the risk of fractures for the furosemide-adherent group was significantly higher compared with the no furosemide group (HR, 1.6; 95% CI, 1.00-2.42; P = .04). CONCLUSIONS: Furosemide therapy, even with nonconsistent dosing, was associated with an increased risk of bone fractures in children with congenital heart disease.

Cardiac Arrest in Pediatric Patients Receiving Azithromycin.

OBJECTIVE: To compare outcomes of pediatric patients treated with azithromycin compared with penicillin or cephalosporin. We hypothesized that azithromycin use would not be associated with increased cardiac mortality in the pediatric population. STUDY DESIGN: Retrospective cohort study from the Pediatric Health Information System database between 2008 and 2012. Patients <19 years of age with a principal diagnosis of community-acquired pneumonia who received an antibiotic were included. Primary outcomes were cardiopulmonary resuscitation (CPR) and mortality. Secondary outcomes were ventricular arrhythmias incidences and readmission for ventricular arrhythmia. Statistical analysis was performed with the χ2 test. Multivariable analysis was performed to control for potential confounders among patient, event, and treatment characteristics. RESULTS: A total of 82 982 patients (54.3% males) met study criteria. Median age was 2.6 years (IQR 1.2-5.9 years) and median length of stay was 2 days (IQR 2-4 days). Azithromycin was used in 5039 (6.1%); penicillin or cephalosporin was used in 77 943 (93.9%). Overall prevalence of antibiotic-associated CPR was 0.14%. Patients receiving a macrolide antibiotic had a lower prevalence of CPR compared with patients receiving a penicillin or cephalosporin (0.04% vs 0.14%, P = .04), and there was no difference in mortality. Multivariable analysis did not find an association between macrolide use and CPR. CONCLUSIONS: In contrast to recent adult studies, among children hospitalized for community-acquired pneumonia, azithromycin use was not associated with a greater prevalence of cardiac arrest compared with penicillin or cephalosporin use.

Readmissions for Heart Failure in Children.

OBJECTIVE: To assess the frequency of inpatient 30-day readmission for heart failure in children with cardiomyopathy discharged after an admission for heart failure and the impact of discharge pharmacotherapy on readmissions. STUDY DESIGN: The Pediatric Health Information System Database was queried for patients ≤18 years of age with an International Classification of Diseases, Ninth Revision code for heart failure (428.xx) or cardiomyopathy (425.xx) discharged from 2004 to 2013. Patients were excluded if they had congenital heart disease, expired on the initial admission, or underwent cardiac surgery. Patient admission characteristics were documented and discharge medications were captured. Frequency of 30-day readmission for heart failure was identified, and mixed effects multivariable logistic regression analysis was performed to determine factors significant for readmission. RESULTS: A total of 2386 patients met study criteria (52.1% male, median age 8.1 years [IQR 1.2-14.6 years]). Vasoactive medications were used in 70.3% of patients on initial admission, the most common of which was milrinone (62.8%). Angiotensin converting enzyme inhibitors and beta-blockers were given at discharge to 67.4% and 35.9%, respectively. Frequency of 30-day readmission for heart failure was 12.9%. Duration of milrinone or beta-blocker use at discharge and institutional heart failure patient volume were associated with a greater odds of 30-day readmission, whereas mechanical ventilation on initial admission was associated with decreased odds of readmission. CONCLUSIONS: Pediatric patients with cardiomyopathy and heart failure have a high frequency of heart failure-related 30-day readmission. Outpatient pharmacotherapy at discharge does not appear to influence readmission.

Antithrombin Concentrate Use in Children Receiving Unfractionated Heparin for Acute Thrombosis.

OBJECTIVE: To characterize features of antithrombin concentrate (ATC) use in children receiving unfractionated heparin (UFH) therapy for acute thrombosis. STUDY DESIGN: All pediatric patients at Texas Children's Hospital who received ATC in the context of UFH therapy for acute thrombosis during February 2011 to May 2013 were analyzed. RESULTS: Fifty-one children received ATC during UFH therapy for acute thrombosis. Median age was 3 months (IQR 1 to 18 months). Clinical indications included venous (53%), arterial (37%), venous and arterial (6%), and intracardiac (4%) thrombosis. Median baseline antithrombin (AT) level was 61% and UFH dose was 26 U/kg/h. The median dose of ATC was 49.9 IU/kg (IQR 32.6 to 50.0 IU/kg). Although most patients (86%) did not undergo a change in UFH dose, there was a significant increase in both AT and anti-factor Xa level after the first dose of ATC (P < .001 for both). There was no correlation between ATC dose or increment in AT level above baseline and the achievement of targeted anticoagulation by anti-factor X activity level. Adverse bleeding events occurred in 10% of patients. CONCLUSIONS: There was a significant change in AT and anti-factor Xa activity level after a single dose of ATC despite little to no change in dose of UFH. ATC appears to facilitate anticoagulation with UFH in some children with acute thrombosis but the degree of response is variable and dependent on factors identified in this study. Bleeding and other theoretical risks must be carefully considered.

Efficacy and safety of high-dose propranolol for the management of infant supraventricular tachyarrhythmias.

OBJECTIVE: To report our experience with high-dose propranolol monotherapy for prophylaxis and treatment of infant supraventricular arrhythmias (SAs). STUDY DESIGN: Patients <1 year of age initiated on enteral propranolol as inpatients for management of SA were identified during a 10-year time period from the Texas Children's Hospital pharmacy database. Patients were included if they received propranolol monotherapy for SA. Propranolol therapy was considered successful when patients were initiated and discharged on monotherapy, without documented recurrence of arrhythmia or requiring additional antiarrhythmic medication. Patients discharged on propranolol were followed as outpatients until therapy was discontinued or a year from initiation, whichever came first. RESULTS: A total of 287 patients met study criteria (59.2% male). Propranolol therapy was initiated at a median of 17 days of age (IQR 6-33 days) at a total daily dose of 3.6 ± 1.0 mg/kg/day. Propranolol was successful in controlling SA throughout the inpatient stay in 67.3% of patients. Only one patient experienced a clinically significant adverse event that required propranolol discontinuation. A multivariable logistic regression analysis identified the presence of congenital heart disease (OR 0.42, 95% CI 0.19-0.94, P = .04) and Wolff-Parkinson-White (OR 0.42, 95% CI 0.21-0.87, P = .01) as factors for nonsuccessful inpatient propranolol monotherapy. Of 190 patients discharged on propranolol monotherapy, 87.7% were recurrence free during follow-up. CONCLUSIONS: High-dose propranolol is safe and reasonably successful in the treatment of infant SA. Inpatient control may be a predictor of continued outpatient efficacy.

Trends in pharmacotherapy for neonatal hypotension.

OBJECTIVE: To determine trends in pharmacotherapy for neonatal hypotension in all infants and in extremely low birth weight (ELBW, birth weight 300-1000 g) infants. STUDY DESIGN: We queried the Pediatric Health Information System database for all infants ≤28 days with a diagnosis code for hypotension that were discharged between January 2001 and December 2012. Patients were excluded if they had complex congenital heart disease or cardiac surgery, sepsis or meningitis, or had extracorporeal membrane oxygenation. We determined trends in pharmacotherapy for hypotension in all infants and ELBW infants, an especially vulnerable group. RESULTS: A total of 8019 hypotensive infants met study criteria. The 2 most prescribed medications were dopamine (65.3%) and dobutamine (19.9%). For 1487 hypotensive ELBW infants, the 2 most prescribed medications were dopamine (83.4%) and hydrocortisone (33%). During the study period, the use of dobutamine decreased, and hydrocortisone and vasopressin use increased for all infants and for ELBW infants. CONCLUSIONS: Treatment of neonatal hypotension varies widely between institutions and individual practitioners, and pharmacotherapy for neonatal hypotension has changed over the past decade. Although dopamine and dobutamine were the most frequently used agents, their use has declined and the uses of hydrocortisone and vasopressin have increased.

Evaluation of weight-based dosing of unfractionated heparin in obese children.

OBJECTIVE: To determine whether pediatric patients with obesity receiving weight-based dosages of unfractionated heparin (UFH) exhibit an enhanced response when dosed by actual body weight compared with nonobese patients as assessed primarily by the frequency of supratherapeutic anticoagulation. Secondary measures included UFH doses associated with therapeutic anticoagulation. STUDY DESIGN: This single-institution retrospective case-matched study included children with and without obesity, matched on a 1:1 basis, who received a weight-based continuous infusion of UFH. Therapeutic monitoring values were defined for activated partial thromboplastin time (aPTT) level (70-101 seconds) and anti-activated factor X (Xa) level (0.35-0.7 U/mL). RESULTS: The study included 50 children. The percentage of patients with supratherapeutic anticoagulation at any point in the study, as measured by either aPTT or anti-Xa level, was similar in the obese and nonobese groups (76% vs 72%; P = 1.0). However, compared with patients without obesity, those with obesity received a lower mean starting dose (17.4 vs 20.2 U/kg/hour; P = .013) and a lower mean maintenance dose (19.1 vs 24.3 U/kg/hour; P = .033) to achieve stable therapeutic monitoring test values. There was no difference in mean initial post-UFH aPTT between the 2 groups, but the mean initial anti-Xa level was higher in the obese group (0.45 vs 0.29 U/mL; P = .045). CONCLUSION: Compared with children without obesity, those with obesity who received actual body weight-based continuous UFH infusions did not exhibit a higher frequency of supratherapeutic anticoagulation, but did require lower dosages to achieve comparable anticoagulation. Our results highlight recognized discrepancies between aPTT and anti-Xa monitoring assays.

Comparison of anti-Xa levels in obese and non-obese pediatric patients receiving treatment doses of enoxaparin.

OBJECTIVE: To determine if using actual body weight to dose enoxaparin in obese pediatric patients results in higher anti-Xa levels compared with non-obese pediatric patients. STUDY DESIGN: This was a retrospective case-matched study of obese and non-obese pediatric patients receiving treatment doses of enoxaparin in a tertiary care children's hospital. Patients were included if they were initiated on treatment doses of enoxaparin, had appropriate anti-Xa levels drawn, and were between 2 and 18 years of age. Patients with renal insufficiency, hyperbilirubinemia, goal anti-Xa level <0.5 or >1 unit/mL, or receiving mechanical circulatory support were excluded. Obese patients who met study criteria were matched on a 1:1 basis with non-obese patients. RESULTS: All baseline characteristics were similar except for body mass index percentile (98.2 ± 2 vs 48.7 ± 15, P < .01). Obese patients had higher initial anti-Xa levels (0.67 ± 0.27 vs 0.53 ± 0.24 unit/mL, P = .028). Over time, obese patients required a lower mean dose to achieve therapeutic anti-Xa levels than non-obese patients (0.81 ± 0.19 vs 1.1 ± 0.4 mg/kg, P = .005). CONCLUSIONS: The mean initial anti-Xa level was higher in obese pediatric patients compared with non-obese pediatric patients, but a dosage adjustment was not required. Obese patients may need closer monitoring over time to avoid supratherapeutic levels and possible bleeding events.