Population pharmacokinetic analysis of vancomycin in pediatric continuous renal replacement therapy.

BACKGROUND AND OBJECTIVES: Dosing of vancomycin in pediatric patients undergoing continuous venous-venous hemodiafiltration (CVVHDF) is challenging. Characterization of vancomycin pharmacokinetics can assist with dosing and attainment of goal serum concentrations. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients less than 19 years of age who received vancomycin and had post-dose vancomycin concentrations while undergoing CVVHDF were identified. Data collection included the following: patient demographics, vancomycin dosing and serum concentrations, CVVHDF variables, serum creatinine (SCR), blood urea nitrogen (BUN), albumin, hematocrit, and urine output. Fat-free mass was calculated. Data were summarized with descriptive statistical methods, and population pharmacokinetic analysis was performed with NONMEM 7.2 and PDx-Pop 5.2. Simulation was performed to identify dosing regimens with the highest percentage of goal serum concentration < 20 mg/L and AUC0-24:MIC ≥ 400 attainment. RESULTS: A total of 138 patients met study criteria (45.6% male, median age 4.9 years (IQR (1.0, 14.5))). Mean vancomycin dose was 14.3 ± 1.6 mg/kg/dose (19.5 ± 3.0 mg/kg/dose by FFM). Patients had a median of six (IQR 2, 12) vancomycin serum concentrations sampled 13.6 ± 8.4 h after the dose, and the mean vancomycin serum concentration was 11.3 ± 3.4 mg/L. Vancomycin pharmacokinetics were characterized by a two-compartment model with allometric scaling on fat-free mass and significant covariates of SCR, BUN, dialysate flow rate, and ultrafiltration rate on clearance. Simulation identified doses of 40-50 mg/kg/day that divided every 8-12 h had the highest percentage of patients with a serum concentration < 20 mg/L and an AUC0-24:MIC ≥ 400. CONCLUSIONS: Vancomycin pharmacokinetics are characterized by fat-free mass, serum creatinine, blood urea nitrogen, dialysate flow rate, and ultrafiltration rate in the pediatric CVVHDF population. Dosing of 40-50 mg/kg/day on fat-free mass divided every 8-12 h with frequent vancomycin serum sampling is recommended.

Incidence and treatment of chylothorax after cardiac surgery in children: analysis of a large multi-institution database.

OBJECTIVE: There is limited information regarding the true incidence of and risk factors for chylothorax after pediatric cardiac surgery. The objective of this study was to determine, from a large multi-institution database, incidence, associated factors, and treatment strategy in patients undergoing pediatric cardiac surgery. METHODS: All patients younger than 18 years in the Pediatric Health Information System (PHIS) database who underwent congenital heart surgery or heart transplant from 2004 to 2011 were included. Procedure complexity was assessed by Risk Adjustment for Congenital Heart Surgery-1. RESULTS: In all, 77,777 patients (55% male) of median age 6.7 months were included. Overall incidence of chylothorax was 2.8% (n = 2205), significantly associated with increased procedure complexity, younger age, genetic syndromes, vein thrombosis, and higher annual hospital volume. Patients with multiple congenital procedures had the highest incidence. Incidence increased with time, from 2% in 2004 to 3.7% in 2011 (P < .0001). Chylothorax was associated with longer stay (P < .0001), increased adjusted risk for in-hospital mortality (odds ratio, 2.13; 95% confidence interval, 1.75-2.61), and higher cost (P < .0001), regardless of procedure complexity. Of all patients with chylothorax, 196 (8.9%) underwent thoracic duct ligation or pleurodesis a median of 18 days after surgery. Total parenteral nutrition, medium-chain fatty acid supplementation, and octreotide were used in 56%, 1.7%, and 16% of patients, respectively. CONCLUSIONS: Chylothorax is a significant problem in pediatric cardiac surgery and is associated with increased mortality, cost, and length of stay. Strategies should be developed to improve prevention and treatment.

Possible digoxin toxicity associated with concomitant ciprofloxacin therapy.

CASE (DESCRIPTION): A 27 year old female with a complex history of congenital heart disease, cardiac surgery, heart failure, and arrhythmias was admitted for a Pseudomonas aeruginosa sternal wound infection and treated with intravenous antibiotics. After discharge and completion of an outpatient course of intravenous antibiotics, suppressive antibiotic therapy with ciprofloxacin was initiated. She presented to clinic with nausea and anorexia within a few days of addition of ciprofloxacin to her current regimen of medications, which included digoxin. The digoxin was discontinued, with all other medications remaining the same, and the symptoms resolved in 48 h. The dose of digoxin was restarted at 50 % of the previous dose with no further complications. The proposed cause of the nausea and anorexia was digoxin toxicity secondary to a drug-drug interaction with ciprofloxacin. CONCLUSION: Patients receiving ciprofloxacin and digoxin should be monitored closely for the risk of digoxin toxicity.

Response to intravenous potassium chloride supplementation in pediatric cardiac intensive care patients.

Potassium chloride (KCl) supplementation is common among critically ill children. Intravenous (IV) KCl supplementation for pediatric patients is poorly characterized. This study aimed to examine the efficacy and safety of IV KCL and to determine factors affecting patient responses to IV KCL in the pediatric cardiac intensive care unit (CICU). A retrospective review of 211 children (794 KCl doses) undergoing cardiac surgery or a hospital stay for heart failure in the CICU of a tertiary care teaching and referral children's hospital in 2011 was performed. Demographic data, weight, height, creatinine, and concomitant medications during each KCl dose were recorded and analyzed. Body surface area (BSA), creatinine clearance, and change in [K(+)] were calculated. The median age of the children was 4 months (range, 10 days-18 years). In this study, 151 KCl doses were administered to neonates (19 %), 307 doses (39 %) to females, and 510 doses (64 %) to patients with a BSA smaller than 0.33 m(2) (a group with relative renal insufficiency). The mean KCl dose was 0.97 ± 0.006 mEq/kg. No adverse events were associated with IV KCl administration. Blood/plasma [K(+)] increased 0.8 ± 0.02 mEq/L. The responses to KCl did not differ significantly between males and females, between neonates and children, or between patients with a BSA smaller than 0.33 m(2) and those with a BSA of 0.33 m(2) or larger. The responses to IV KCl were attenuated by concomitant furosemide (p = 0.01), amphotericin B (p < 0.01), and KCl in parenteral nutrition (p < 0.01). The responses were augmented by concomitant enalapril (p = 0.03), ethacrynic acid (p < 0.001), and hemodialysis (p < 0.01). Intravenous KCl can be administered safely for CICU patients. Responses to KCl are altered when it is given with certain medications. Intravenous KCl should be used cautiously in children receiving angiotensin-converting enzyme inhibitors. Future studies are needed for further characterization of factors affecting responses to IV KCl in children.

Enteral potassium supplementation in a pediatric cardiac intensive care unit: evaluation of a practice change.

BACKGROUND: Potassium supplementation is a common practice in critically ill children, especially those with heart disease. Intravenous potassium supplementation is the standard route of administration in most intensive care units. Although the enteral route is safer and thus may be a reasonable alternative, data on the efficacy of enteral potassium administration are lacking. METHODS: A change of practice to encourage use of enteral potassium was instituted in the cardiac intensive care unit at Texas Children's Hospital, and a review of this practice change was undertaken. The primary outcome of interest was the comparable efficacy of enteral and intravenous potassium administration. Patient demographic data, including urine output, diuretic use, route of potassium administration, and adverse events were documented and analyzed. RESULTS: Seventy-six patients met inclusion criteria and received 399 bolus doses of potassium (166 intravenous and 233 enteral). No patients became hyperkalemic after either route of administration. The increase in serum potassium was similar in both groups of patients. Side effects of the two routes of administration were not different. CONCLUSIONS: The efficacy of enteral potassium is comparable to intravenous potassium for potassium replacement in pediatric patients after congenital heart surgery.

Treatment of acute rheumatic carditis with choline magnesium trisalicylate in a patient needing surgery.

Acute rheumatic fever is a post-infectious illness characterized by diffuse inflammation. Typically, high-dose anti-inflammatory agents are used as primary therapy for this disorder. In addition to their anti-inflammatory properties, these agents, most frequently aspirin, also have anti-platelet properties. We describe the case of an 11-year-old patient with rheumatic fever who needed to undergo surgery. The use of traditional anti-inflammatory agents would have posed a potential problem with post-surgical bleeding, so a lesser-used anti-inflammatory agent (i.e., choline magnesium trisalicylate) was selected.