Population Pharmacokinetics of Vancomycin in Pregnant Women.

Objective: Vancomycin is a glycopeptide antibacterial indicated for serious gram-positive infections. Pharmacokinetics (PK) of vancomycin have not been described in pregnant women. This study aims to characterize the PK disposition of vancomycin in pregnant women based on data acquired from a database of routine hospital care for therapeutic drug monitoring to better inform dosing decisions. Methods: In this study, plasma drug concentration data from 34 pregnant hospitalized women who were administered intravenous vancomycin was analyzed. A population pharmacokinetic (PPK) model was developed using non-linear mixed effects modeling. Model selection was based on statistical criterion, graphical analysis, and physiologic relevance. Using the final model AUC0-24 (PK efficacy index of vancomycin) was compared with non-pregnant population. Results: Vancomycin PK in pregnant women were best described by a two-compartment model with first-order elimination and the following parameters: clearance (inter individual variability) of 7.64 L/hr (32%), central volume of 67.35 L, inter-compartmental clearance of 9.06 L/h, and peripheral volume of 37.5 L in a typical patient with 175 ml/min creatinine clearance (CRCL) and 45 kg fat-free mass (FFM). The calculated geometric mean of AUC0-24 for the pregnant population was 223 ug.h/ ml and 226 ug.h/ ml for the non-pregnant population. Conclusion: Our analysis suggests that vancomycin PK in pregnant women is consistent with non-pregnant adults and the dosing regimens used for non-pregnant patients may also be applicable to pregnant patients.

Characterization of drug-drug interactions on the pharmacokinetic disposition of busulfan in paediatric patients during haematopoietic stem cell transplantation conditioning.

AIM: The study objective was to develop a population pharmacokinetic model for busulfan to comprehensively examine drug-drug interactions in paediatric patients undergoing haematopoietic stem cell transplantation. Currently, there is limited evidence to substantiate potential drug-drug interactions with busulfan. METHODS: This retrospective study population was comprised of 250 patients receiving, on average, 0.8 mg/kg intravenous busulfan as pretreatment. All model analyses were conducted using nonlinear mixed effects modelling in Pumas v2.0. The metabolic pathways of primary interest were glutathione conjugation and cytochrome P450 (CYP) activity. Concomitant medications were categorized as CYP inhibitors, inducers or glutathione S-transferase depleters, and included in the model as conditional covariates. A bootstrap simulation and visual predictive check were conducted to qualify the final model. RESULTS: The final 1-compartment model incorporates covariates of weight and age in relation to their effects on both total body clearance and volume of distribution. The estimated typical values of clearance and volume were 1.138 L/h (CI: 1.095-1.179 L/h) and 3.527 L (CI: 3.418-3.621 L), respectively. No significant changes in clearance were observed when medications that alter proposed hepatic and metabolic pathways of busulfan were coadministered. CONCLUSION: To the best of our knowledge, this is the largest single centre study of busulfan in children and the first to quantify the maturation effect of both clearance and volume. This study could not demonstrate a difference in busulfan clearance when comparing patients who received medications that alter the glutathione S-transferase, CYP3A4 or CYP2C9 pathway to those who did not.

Characteristics and outcomes of children with congenital heart disease needing diaphragm plication.

BACKGROUND: Diaphragm dysfunction following surgery for congenital heart disease is a known complication leading to delays in recovery and increased post-operative morbidity and mortality. We aimed to determine the incidence of and risk factors associated with diaphragm plication in children undergoing cardiac surgery and evaluate timing to repair and effects on hospital cost and length of stay. METHODS: We conducted a multi-institutional retrospective observational cohort study. Forty-three hospitals from the Pediatric Health Information System database were included, and a total of 112,110 patients admitted between January 2004 and December 2014 were analysed. RESULTS: Patients less than 18 years of age who underwent cardiac surgery were included. Risk Adjustment for Congenital Heart Surgery was utilized to determine procedure complexity. The overall incidence of diaphragm dysfunction was 2.2% (n = 2513 out of 112,110). Of these, 24.0% (603 patients) underwent diaphragm plication. Higher complexity cardiac surgery (Risk Adjustment for Congenital Heart Surgery 5-6) and age less than 4 weeks were associated with a higher likelihood of diaphragm plication (p-value < 0.01). Diaphragmatic plication was associated with increased hospital length of stay (p-value < 0.01) and increased medical cost. CONCLUSIONS: Diaphragm plication after surgery for congenital heart disease is associated with longer hospital length of stay and increased cost. There is a strong correlation of prolonged time to plication with increased length of stay and medical cost. The likelihood of plication increases with younger age and higher procedure complexity. Methods to improve early recognition and treatment of diaphragm dysfunction should be developed.

Population Pharmacokinetics of Vancomycin in the Pediatric Cardiac Surgical Population.

OBJECTIVE: Vancomycin is often used in the pediatric cardiac surgical population, but few pharmacokinetic data are available to guide dosing. METHODS: A retrospective, population pharmacokinetic study was performed for patients <19 years of age initiated on vancomycin after cardiac surgery in the cardiac intensive care unit from 2011-2016 in our institution. Patient data were summarized by using descriptive statistical methods, and population pharmacokinetic analysis was performed by using NONMEM. Simulation was performed to determine a dosing strategy that most frequently obtained an AUC0-24:MIC (minimum inhibitory concentration) ratio of >400. RESULTS: A total of 261 patients (281 cardiac surgical procedures, cardiopulmonary bypass 82.3%) met inclusion criteria (60.1% male, median age 0.31 [IQR, 0.07-0.77] years). Vancomycin (14.5 ± 1.7 mg/kg/dose) was administered at median postoperative day 9 (IQR, 4-14), with a mean serum concentration of 11.5 ± 5.5 mg/L at 8.9 ± 3.8 hours after a dose. Population pharmacokinetic analysis demonstrated that a 1-compartment proportional error model with allometrically scaled weight best fit the data, with creatinine clearance and postmenstrual age as significant covariates. Simulation identified that a dosing regimen of 20 mg/kg/dose every 8 hours was most likely to achieve an AUC0-24:MIC ratio > 400 at a mean trough serum concentration of 12.9 ± 3.2 mg/L. CONCLUSIONS: Vancomycin dosing in the postoperative pediatric cardiac surgical population should incorporate postmenstrual age and creatinine clearance. A vancomycin dose of 20 mg/kg every 8 hours is a reasonable empiric strategy.

Hypotensive Response to IV Acetaminophen in Pediatric Cardiac Patients.

OBJECTIVES: Acetaminophen is ubiquitously used as antipyretic/analgesic administered IV to patients undergoing surgery and to critically ill patients when enteral routes are not possible. Widely believed to be safe and free of adverse side effects, concerns have developed in adult literature regarding the association of IV acetaminophen and transient hypotension. We hypothesize that there are hemodynamic effects after IV acetaminophen in the PICU and assess the prevalence of such in a large pediatric cardiovascular ICU population using high-fidelity data. DESIGN: Observational study analyzing an enormous set of continuous physiologic data including millions of beat to beat blood pressures surrounding medication administration. SETTING: Quaternary pediatric cardiovascular ICU between January 1, 2013, and November 13, 2017. PATIENTS: All patients less than or equal to 18 years old who received IV acetaminophen. Mechanical support devices excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic vital sign data were analyzed in 5-minute intervals starting 60 minutes before through 180 minutes after completion. Hypotension defined as mean arterial pressure -15% from baseline and relative hypotension defined -10%. Only doses where patients received no other medications, including vasopressors, within the previous hour were included. t test and a correlation matrix were used to eliminate correlated factors before a logistic regression analysis was performed. Six-hundred eight patients received 777 IV acetaminophen doses. Median age was 8.8 months (interquartile range, 2-62 mo) with a dose of 12.5 mg/kg (interquartile range, 10-15 mg/kg). Data were normalized for age and reference values. One in 20 doses (5%) were associated with hypotension, and one in five (20%) associated with relative hypotension. Univariate analysis revealed hypotension associated with age, baseline mean arterial pressure, and skin temperature (p = 0.05, 0.01, and 0.09). Logistic regression revealed mean arterial pressure (p = 0.01) and age (p = 0.05) remained predictive for hypotension. CONCLUSIONS: In isolation of other medication, a hemodynamic response to IV acetaminophen has a higher prevalence in critically ill children with cardiac disease than previously thought and justifies controlled studies in the perioperative and critical care setting. The added impact on individual patient hemodynamics and physiologic instability will require further study.

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.

Characteristics and outcomes of children with ductal-dependent congenital heart disease and esophageal atresia/tracheoesophageal fistula: A multi-institutional analysis.

BACKGROUND: Extracardiac birth defects are associated with worse outcomes in congenital heart disease (CHD). The impact of esophageal atresia/trachea-esophageal fistula (EA/TEF) on outcomes after surgery for ductal-dependent CHD is unknown. METHODS: Retrospective matched cohort study using the Pediatric Health Information System database from 07/2004 to 06/2015. Hospitalizations with ductal-dependent CHD and EA/TEF, undergoing CHD surgery were included as cases. Admissions with ductal-dependent CHD without EA/TEF were matched 3:1 for age at admission and Risk Adjustment for Congenital Heart Surgery-1 classification. Comparisons were performed using generalized estimating equations. RESULTS: There were 124 cases and 372 controls. Cases included 32 (25.8%) low-risk, 86 (69.3%) intermediate-risk, and 6 (4.8%) high-risk patients. Cases had more females compared to controls (53.2% vs 41.1%, P = .022). Cases were more likely to be premature (28.2% vs 13.7%, P = .001) and low birth weight (29.8% vs 11.8%, P < .001). Cases had a similar frequency of Down syndrome, and DiGeorge/Velocardiofacial syndrome, but a higher frequency of anorectal malformations (4.3% vs 2.4%, P < .001) and renal anomalies (27.4% vs 9.9%, P < .001) than controls. Cases had a higher mortality on univariate (22.0% vs 8.4%, P < .001) and multivariable analysis (odds ratio 2.45, 95%, confidence interval 1.34 - 4.49). Prematurity also was significantly associated with mortality on multivariable analysis. Cases had a longer duration of mechanical ventilation, longer hospital duration of stay, and higher total cost than controls (all P < .001). CONCLUSION: In children with ductal-dependent CHD, EA/TEF is associated with increased morbidity, mortality and resource utilization. A majority of patients undergo EA/TEF repair prior to congenital heart disease surgery. (Surgery 2017;160:XXX-XXX.).

Enhancement of diuresis with metolazone in infant paediatric cardiac intensive care patients.

BACKGROUND: Few data are available regarding the use of metolazone in infants in cardiac intensive care. Researchers need to carry out further evaluation to characterise the effects of this treatment in this population. METHODS: This is a descriptive, retrospective study carried out in patients less than a year old. These infants had received metolazone over a 2-year period in the paediatric cardiac intensive care unit at our institution. The primary goal was to measure the change in urine output from 24 hours before the start of metolazone therapy to 24 hours after. Patient demographic variables, laboratory data, and fluid-balance data were analysed. RESULTS: The study identified 97 infants with a mean age of 0.32±0.25 years. Their mean weight was 4.9±1.5 kg, and 58% of the participants were male. An overall 63% of them had undergone cardiovascular surgery. The baseline estimated creatinine clearance was 93±37 ml/minute/1.73 m2. Initially, the participants had received a metolazone dose of 0.27±0.10 mg/kg/day, the maximum dose being 0.43 mg/kg/day. They had also received other diuretics during metolazone initiation, such as furosemide (87.6%), spironolactone (58.8%), acetazolamide (11.3%), bumetanide (7.2%), and ethacrynic acid (1%). The median change in urine output after metolazone was 0.9 ml/kg/hour (interquartile range 0.15-1.9). The study categorised a total of 66 patients (68.0%) as responders. Multivariable analysis identified acetazolamide use (p=0.002) and increased fluid input in the 24 hours after metolazone initiation (p0.05). CONCLUSIONS: Metolazone increased urine output in a select group of patients. Efficacy can be maximised by strategic selection of patients.

Efficacy of sequential nephron blockade with intravenous chlorothiazide to promote diuresis in cardiac intensive care infants.

BACKGROUND: Sequential nephron blockade using intravenous chlorothiazide is often used to enhance urine output in patients with inadequate response to loop diuretics. A few data exist to support this practice in critically ill infants. METHODS: We included 100 consecutive patients <1 year of age who were administered intravenous chlorothiazide while receiving furosemide therapy in the cardiac ICU in our study. The primary end point was change in urine output 24 hours after chlorothiazide administration, and patients were considered to be responders if an increase in urine output of 0.5 ml/kg/hour was documented. Data on demographic, clinical, fluid intake/output, and furosemide and chlorothiazide dosing were collected. Multivariable regression analyses were performed to determine variables significant for increase in urine output after chlorothiazide administration. RESULTS: The study population was 48% male, with a mean weight of 4.9±1.8 kg, and 69% had undergone previous cardiovascular surgery. Intravenous chlorothiazide was initiated at 89 days (interquartile range 20-127 days) of life at a dose of 4.6±2.7 mg/kg/day (maximum 12 mg/kg/day). Baseline estimated creatinine clearance was 83±42 ml/minute/1.73 m2. Furosemide dose before chlorothiazide administration was 2.8±1.4 mg/kg/day and 3.3±1.5 mg/kg/day after administration. A total of 43% of patients were categorised as responders, and increase in furosemide dose was the only variable significant for increase in urine output on multivariable analysis (p<0.05). No graphical trends were noted for change in urine output and dose of chlorothiazide. CONCLUSIONS: Sequential nephron blockade with intravenous chlorothiazide was not consistently associated with improved urine output in critically ill infants.

Outcomes in Postoperative Pediatric Cardiac Surgical Patients Who Received an Antiepileptic Drug.

BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012. Cardiac surgical patients initiated on phenobarbital, phenytoin, and levetiracetam were queried. Patients were excluded if the AED was not initiated on the admission for surgery. Patients who received 1 AED were compared to patients who received 2 AED, and differences in outcomes examined between the 3 AEDs used were evaluated. RESULTS: A total of 37 patients met the study criteria. Patients were initiated on an AED a median of 4 days following surgery and became seizure free a median of 1 day after initiation, with 65% remaining seizure free after the first dose. Half of all patients required 2 AEDs for seizure control, with a higher proportion of adolescents requiring 2 AEDs (p = 0.04). No differences were found when comparing the collected outcomes between phenobarbital, fosphenytoin, or levetiracetam. CONCLUSION: No adverse events were reported with the AEDs reviewed. Further work is necessary to evaluate long-term neurodevelopmental outcomes in this population and whether outcomes are a result of the AED or of other clinical sequelae.

Use of Continuous Infusion Hydralazine in a Pediatric Patient on Mechanical Circulatory Support.

Hydralazine is a direct peripheral arterial vasodilator used for acute hypertension. Usually administered as a bolus dose, continuous infusion has been described during pregnancy for preeclampsia and eclampsia and in limited reports in cardiac surgeries for afterload reduction. This case describes the use of continuous infusion hydralazine for afterload reduction in an infant receiving extracorporeal membrane oxygenation (ECMO) post-cardiac surgery. Postsurgery, the patient's mean arterial pressures (MAPs) could not be controlled despite escalating doses of vasodilatory medications including nitroprusside, nicardipine, and milrinone; hence, continuous infusion hydralazine was initiated. Although the initiation of a hydralazine infusion produced a decrease in MAP, the response was unsustainable. This case highlights an alternative method for managing systemic vascular resistance and cardiac output to allow for myocardial recovery after cardiac surgery and use of extracorporeal support. At the time of this writing, this is the first published case describing hydralazine administration via continuous infusion in pediatric patients. The use of continuous infusion hydralazine for afterload reduction provided a brief, non-sustained reduction in MAP in a post-cardiac surgery infant managed on ECMO support.

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.

Variability in Treatment of Post-coarctectomy Hypertension: A Multicenter Study.

Many pharmacologic therapies are available for treatment of post-coarctectomy hypertension in pediatric patients, which may lead to variability in care. Evaluation of trends in pharmacotherapy is necessary to evaluate quality of care. The Pediatric Health Information System database was queried from 2004 to 2013 for patients >30 days of age who had an ICD-9 code for coarctation of the aorta repair of coarctation by end-to-end anastomosis and had a RACHS-1 score of 2. Patients were excluded if they were admitted for >30 days, underwent mechanical circulatory support, or expired during the admission. Patient demographic and hospital data were collected along with antihypertensive pharmacotherapy. Trends in antihypertensive, analgesic, and sedative pharmacotherapy were evaluated, and multivariable statistical analysis was used to determine variables that significantly influenced cost. A total of 1636 patients [66.6 % male, median age 1.5 years (IQR 0.31-5.3)] met study criteria. Patients received a median of 3 (IQR 2-4) antihypertensive medications for a median of 8 days (IQR 5-11). Intravenous antihypertensive therapy was prescribed for a median 3 days (IQR 2-5) and oral therapy for a median of 1 day (IQR 1-2). Antihypertensive therapy was continued at discharge in 79.8 % of patients. Hospital cost increased by 36 % over the study period (p < 0.01), and nicardipine, dexmedetomidine, and intravenous acetaminophen were most strongly associated with increased cost (p < 0.001). Variability in the pharmacotherapy of post-coarctectomy hypertension in pediatric patients exists, and the use of newer agents may be influencing the cost of care.

Prostaglandin Availability and Association with Outcomes for Infants with Congenital Heart Disease.

Data regarding availability of prostaglandin E1 (PGE) and its impact on the stabilization, transport, critical care course, and surgical outcome of infants with ductal-dependent congenital heart disease in the current pediatric healthcare environment are unknown. We sought to determine the proportion of hospitals in Texas that stock PGE and to investigate associations between PGE availability and clinical outcomes. All birth institutions listed with the Texas Department of Health and Human Services were contacted to determine PGE availability as of 2011. Outcomes of all infants admitted to our institution from 2007 to 2012 who received PGE for ductal-dependent lesions were evaluated. PGE was stocked in 50 % (n = 139) of hospitals that performed deliveries in Texas in 2011 representing 79.1 % (303, 481) of births. Hospitals that did not stock PGE had less annual births and were located a further distance from a center that provided pediatric cardiac surgical services. Patients born at a hospital that did not stock PGE had significantly greater serum lactate and creatinine (p = 0.002) and serum lactate on admission (p < 0.001). The PGE availability was not associated with hospital length of stay, postoperative length of stay, or mortality. When stratifying in TGA and HLHS subgroups, lack of PGE availability remained associated with higher creatinine, higher lactate, lower glucose, and lower pH. PGE is not universally available in all healthcare institutions providing obstetrical services. Lack of availability of PGE at an outlying hospital was associated with increased morbidity, but was not associated with mortality or length of stay.

Adherence to Anticoagulant Therapy in Pediatric Patients Hospitalized With Pulmonary Embolism or Deep Vein Thrombosis: A Retrospective Cohort Study.

OBJECTIVES: The American College of Chest Physicians recommends anticoagulant therapy for at least 3 months in children hospitalized for venous thromboembolism. The objectives of the study were to evaluate the medication utilization patterns and predictors of adherence to anticoagulant therapy in pediatric population. METHODS: Texas Medicaid medical and prescription claims from September 1, 2007 to December 12, 2012 were extracted for children (<18 years) hospitalized for pulmonary embolism (PE) or deep vein thrombosis (DVT). The index date was defined as the date of the first prescription of an anticoagulant given within 14 days of discharge. Proportion of days covered (≥80% vs <80%) was used to assess adherence to anticoagulants while controlling for demographics, cause of hospitalization, history of nonsteroidal anti-inflammatory drug use, anticoagulant use, malignancy, drug type, and Charlson comorbidity index (CCI). KEY FINDINGS: The patients (n = 60) had a mean (± standard deviation [SD]) age of 14.2 (±4.8) years, were primarily female (56.7%), African American (55.0%), enoxaparin users (58.3%), and had a mean (±SD) CCI of 18.3 (±37.7). The mean (±SD) adherence rates for warfarin and enoxaparin were 85.5% (±22.7%) and 78.7% (±27.8%), respectively. Overall, 66.7% were adherent (≥80%) to anticoagulant therapy. Logistic regression showed that increasing age was significantly associated with adherence to anticoagulant therapy, after controlling for other covariates (odds ratio = 1.5, 95% confidence interval = 1.13-1.85). CONCLUSION: Nearly one-third of the pediatric patients on anticoagulant therapy after discharge from PE or DVT were still nonadherent. Further research is needed to highlight the factors responsible for nonadherence in pediatric patients.

Evaluating the Safety of Intraoperative Antiarrhythmics in Pediatric Cardiac Surgery Patients.

Cardiac arrhythmias occurring during the intraoperative period for cardiac surgery have been associated with excess morbidity and mortality. Several antiarrhythmics have been utilized for the management of intraoperative arrhythmias. These antiarrhythmic medications can cause undesirable adverse outcomes in the intensive care setting. The incidence and treatment of adult intraoperative arrhythmias have been studied. In addition, the prevalence, risk factors, and optimal treatment of pediatric postoperative arrhythmias have also been studied. However, the literature has not been published on intraoperative antiarrhythmia treatment during pediatric cardiac surgery. The purpose of this study was to determine the safety of intraoperative antiarrhythmic medications utilized in pediatric cardiac surgery patients. This was a retrospective review of all patients who received an intraoperative antiarrhythmic in the cardiovascular operating room at Texas Children's Hospital. Patients were included if they underwent cardiovascular surgery from November 2008 to July 2013 and were excluded if antiarrhythmics were given intraoperatively for other indications (i.e., esmolol for hypertension) or if patients were older than 18 years of age. Safety of antiarrhythmic treatment was determined by the absence or presence of adverse events. Control or recurrence of the arrhythmia was analyzed as a secondary measure to help determine antiarrhythmic efficacy. A total of 45 patients were identified (53.3 % male). Patients were a median of 0.52 years at the time of surgery. Primary surgery types were tetralogy of Fallot repair (n = 6; 13.3 %) and ventricular septal defect closure (n = 5, 11.1 %). Thirty-one patients (68.9 %) had documented adverse events after the administration of antiarrhythmics. Most of these adverse events occurred after the administration of amiodarone (n = 16; 51.6 %) followed by esmolol (n = 15; 48.4 %). Fifty-one percent of the arrhythmias resolved in the operating room (n = 23), and nearly half (n = 19) of all patients were discharged home on an antiarrhythmic medication. A high incidence of adverse events was associated with intraoperative administration of antiarrhythmic medications.

Agreement among measurements and estimations of glomerular filtration in children with cancer.

BACKGROUND: Glomerular filtration is an important route of elimination for many types of chemotherapy. Accurate estimation of glomerular filtration at the bedside is essential in the management of children with cancer. Bedside formulae for the estimation of glomerular filtration have not been validated in children with cancer. We investigated the accuracy of three formulae (the original Schwartz, Counahan-Barratt, and revised Schwartz equations) against measurement of the glomerular filtration rate (GFR) in a cohort of children with cancer. PROCEDURE: This was a retrospective review of existing data from a single institution. The electronic medical record was queried for subjects meeting inclusion criteria during a 3.5 year time frame. Bland-Altman analyses were used to assess agreement among current formulae and estimating the GFR compared to the measured, or index GFR. Logistic regression was performed to identify potential variables with an effect on the estimation of GFR. RESULTS: None of the three estimation formulae provided a reliable estimate of the index GFR. The mean difference was lowest between the revised Schwartz and the index GFR compared to the other two formulae and the index GFR. For the original Schwartz equation, age and prior receipt of chemotherapy were significant predictors of under- and overestimation. For the revised Schwartz equation, one age group (6-12 years) and a diagnosis of neuroblastoma actively receiving chemotherapy were positive risk factors for overestimation of the GFR. CONCLUSION: Currently available estimation formulae for GFR may not be appropriate for children with cancer.

Dexmedetomidine utilisation and outcomes of children with trisomy 21 undergoing congenital heart disease surgery.

INTRODUCTION: The diagnosis of trisomy 21 in children has been associated with failed extubation after CHD surgery. Dexmedetomidine may be a useful agent to improve postoperative outcomes in these patients, such as ventilator time, ICU length of stay, or hospital length of stay. MATERIALS AND METHODS: The Pediatric Health Information System database was queried from January, 2008 to December, 2010 for patients with trisomy 21 who underwent CHD surgery. Patients who received dexmedetomidine were matched to patients who did not by propensity score. The primary outcome was ventilator days charged, and secondary outcomes included ICU and hospital length of stay. RESULTS: A total of 1088 patients (544 matched pairs) met inclusion criteria. Patient characteristics were similar, with the exception of more patients in the dexmedetomidine group undergoing repair of complete atrioventricular canal and fewer undergoing mechanical valve replacement (p<0.01). More patients in the dexmedetomidine group were administered milrinone, epinephrine, vasopressin, benzodiazepines, opiates, and adjunct pain and sedative medications (p<0.01). The dexmedetomidine group had greater time on the ventilator [7 (4.5-11) versus 6 (4-10) days (median, interquartile range) p<0.01] and similar ICU length of stay, hospital length of stay, and mortality compared with controls. Mixed-effects modelling clustered on institution did not show beneficial effect of dexmedetomidine on ventilator time, ICU stay, or hospital length of stay. CONCLUSIONS: The use of dexmedetomidine was not associated with the decreased ventilatory time. Routine use of dexmedetomidine is not warranted in this patient population.

Efficacy of digoxin in comparison with propranolol for treatment of infant supraventricular tachycardia: analysis of a large, national database.

INTRODUCTION: Digoxin or propranolol are used as first-line enteral agents for treatment of infant supraventricular tachycardia. We used a large national database to determine whether enteral digoxin or propranolol was more efficacious as first-line infant supraventricular tachycardia therapy. MATERIALS AND METHODS: The Pediatric Health Information System database was queried over 10 years for infants with supraventricular tachycardia initiated on enteral digoxin or propranolol monotherapy. Patients were excluded for Wolff-Parkinson-White, intravenous antiarrhythmics (other than adenosine), or death. Success was considered as discharge on the initiated monotherapy. Risk factors for successful monotherapy and risk factors for readmission for supraventricular tachycardia for patients discharged on monotherapy were determined. RESULTS: A total of 374 patients (59.6% male) met the study criteria. Median length of stay was 7 days (interquartile range of 3-16 days). Patients had CHD (n=199, 53.2%) and underwent cardiac surgery (n=123, 32.9%), ICU admission (n=238, 63.6%), mechanical ventilation (n=146, 39.0%), and extracorporeal membrane oxygenation (n=3, 0.8%). Pharmacotherapy initiation was at median 37 days of life (interquartile range of 12-127 days) and 47.3% were initiated on digoxin. Success was similar between digoxin (73.1%) and propranolol (73.5%). Initial therapy with digoxin was not associated with success (odds ratio 1.01, 95% CI 0.64-1.61, p=0.93). Multivariable analysis demonstrated hospital length of stay (odds ratio 0.98, 95% CI 0.98-1.00) and involvement of a paediatric cardiologist (odds ratio 0.46, 95% CI 0.29-0.75) associated with monotherapy failure, and male gender (odds ratio 1.66, 95% CI 1.03-2.67) associated with monotherapy success. No variables were significant for readmission on multivariable analysis. DISCUSSION: Digoxin or propranolol may be equally efficacious for inpatient treatment of infant supraventricular tachycardia.

National prescribing trends for heart failure medications in children.

BACKGROUND: The treatment of acute decompensated heart failure (ADHF) in adults has changed considerably over the past decade, and these changes have coincided with a reduction in inpatient mortality. At this time, national trends in medication prescribing among children hospitalized with ADHF are unknown. METHODS: The Pediatric Health Information System (PHIS) database was queried to identify all patients ≤21 years of age who were admitted from 2001 to 2010 with ADHF and a diagnosis of cardiomyopathy. Patients were excluded for potential infectious or inflammatory etiologies of heart failure, congenital heart disease, cardiovascular surgery, acute heart transplant rejection, or isolated diastolic dysfunction. Only the index admission was used, and descriptive statistical methods were employed. RESULTS: A total of 1773 patients (55.8% male) met study criteria (mortality 6.9%). Median length of stay was 9 days (IQR 4-16 days). Vasopressor or inotropic agents were used in 63.6% of patients (milrinone in 82.9% of these) and diuretics in 90.1% (furosemide in 98.4% of these). At discharge, a beta-blocker was prescribed in 36.8% of patients (carvedilol in 77.1% of these), and an angiotensin-converting enzyme (ACE) inhibitor was prescribed in 69.6% (enalapril in 59.9% of these). A wide variability in prescribing practices over time and by pediatric hospital was noted, along with a trend for decreased inotrope use and an increase in beta-blocker discharge prescribing. CONCLUSIONS: This is the first national evaluation of prescribing trends in pediatric ADHF medication. A large degree of variability in medication use for ADHF and low rates of beta-blocker and ACE inhibitor use at discharge were identified.