Diuretics in the treatment of hypertension.

Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

Improving Pneumococcal Vaccination Rates in High-risk Children in Specialty Clinics.

BACKGROUND AND OBJECTIVES: Pediatric patients with immunocompromising or certain chronic medical conditions have an increased risk of acquiring invasive pneumococcal disease (IPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients ≥2 years at high risk for IPDs. The aim of this project was to improve PPSV23 vaccination rates for children at high risk for IPD who were seen in 3 specialty clinics from ∼20% to 50% over a 12-month period. METHODS: The project team included quality improvement champions from the divisions of rheumatology, infectious diseases, and pulmonology in addition to leaders from our population health management subsidiary. Several initiatives were implemented, starting with review of patient inclusion criteria per the vaccination recommendations, that led to the design and deployment of an automated weekly previsit planning report. Additionally, we implemented a process to stock pneumococcal vaccines and shared best practices among the divisions. We monitored improvement through times series and run charts of PPSV23 vaccination rates. RESULTS: The initial PPSV23 vaccination rate for applicable high-risk patients was ∼20%. There was an increase in vaccination rate to ∼60%. All 3 divisions showed improvements in their individual PPSV23 vaccination rates. CONCLUSIONS: Using quality improvement methodology, we increased PPSV23 vaccination rates in 3 pediatric specialty clinics, and this improvement was sustained. We will continue to identify best practices and actively recruit additional divisions because we have the opportunity to reach >9000 high-risk patients.

Cisplatin pharmacokinetics in a child receiving peritoneal dialysis.

Cisplatin is a highly effective and frequently used drug in the chemotherapy of solid tumors in children, but there is currently no information to guide dosing in children requiring dialysis. Here, we present the case of a 2-year-old boy with end-stage renal disease managed with peritoneal dialysis and requiring cisplatin for a newly diagnosed hepatoblastoma. A pharmacokinetic study was performed to personalize the cisplatin dose with the goal of providing adequate cisplatin exposure and avoiding excessive exposure and toxicity. Accordingly, 25% of the standard cisplatin dose was infused intravenously over 4 h. Serial blood and peritoneal fluid samples were obtained, and free cisplatin levels were subjected to noncompartmental pharmacokinetic analysis. The disposition of free cisplatin was significantly altered as compared to that of normal children. Despite a 75% dose reduction, our patient showed a fourfold increase in free cisplatin exposure (AUC = 64.1 h mcg/mL) compared with the AUC observed in children with normal kidney (15 + or - 9 h mcg/mL) function. When a subsequent dose was decreased to 8.7% of the standard dose, the free cisplatin AUC measured 29.7 h mcg/mL and more closely approximated the exposure observed in children with normal kidney function.

Use of the multipurpose drainage catheter for the provision of acute peritoneal dialysis in infants and children.

BACKGROUND: Prior experience with the Cook (Cook Inc, Bloomington, IN) Teflon rigid catheter (CTC) showed it to be a suboptimal access for acute peritoneal dialysis (PD) treatment in infants and children because of the frequency of catheter-related complications associated with its use. The objective of this study is to report our experience with the bedside-placed flexible Cook Mac-Loc Multipurpose Drainage catheter (CMMDC) for acute PD in critically ill infants, comparing it with the historic Tenckhoff catheter (TC) and CTC use. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: All patients with acute renal failure (ARF) seen in our institution between December 2003 and April 2005 who underwent CMMDC placement for acute PD are included. PREDICTOR: CTCs versus CMMDCs versus TCs. OUTCOMES & MEASUREMENTS: Catheter-related complications and catheter-free survival. RESULTS: 21 infants and children with ARF were treated with acute PD using a CMMDC; 16 patients were post-cardiac surgery and 5 had other diagnoses. Mean patient age was 6.9 +/- 14.4 (SD) months (range, 4 days to 5.2 years; median, 1.6 months). Of 21 catheters, 3 had complications, and in 2 patients, this precluded continuation of PD therapy. In the remaining 18 patients, catheter use continued until recovery from ARF or nonrenal death. All patients achieved target fluid and solute removal with no catheter-related infectious complications. Mean complication-free survival of CMMDCs was 10.5 +/- 7.9 days (range, 2 to 29 days), with the 90% probability of survival at 14 days. Although there was no significant difference between lengths of complication-free survival of CMMDCs and TCs (58 days; P = 0.57), the difference between CMMDCs and CTCs (6 days) was significant (P < 0.001). Likewise, incidences of catheter-related complications with TCs and CMMDCs were similar, and in both cases, significantly less than the incidence associated with CTCs (49%; P < 0.01). LIMITATIONS: Small number of patients and comparison with historic experience. CONCLUSIONS: Use of CMMDCs is associated with the provision of effective dialysis with a satisfactory complication-free survival and should be considered when bedside placement of an acute PD access in infants and children is desired.

Outcome of infants born to women with chronic kidney disease.

Pregnancy in women with chronic kidney disease is not uncommon and is not without risk to the mother and child. This article reviews the literature on the outcome of infants from pregnancies in women with chronic kidney disease (CKD), including those receiving dialysis and those living with a functional kidney transplant. Pregnancy in women with CKD and end-stage renal disease (ESRD) is associated with a higher rate of premature birth and small-for-gestational-age (SGA) infants, with resultant increase in neonatal mortality. Although congenital anomalies or long-term developmental issues do not appear to be a significant risk, these areas deserve further study, especially as newer immunosuppressive medications are employed in kidney transplant recipients.

Vancomycin disposition following intraperitoneal administration in children receiving peritoneal dialysis.

BACKGROUND: Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [e.g., automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD. METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for 29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and 3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 microg/mL.

Nephrotoxicity of over-the-counter analgesics, natural medicines, and illicit drugs.

Toxic nephropathy is a disorder whose primary feature is impairment of the normal functions of the kidney. The clinical manifestations of toxic nephropathy vary from a mild reduction in renal function to hematuria, proteinuria, and urolithiasis to a severe progressive toxicity culminating in end-stage renal disease. Although it is commonplace for adolescents to use supplemental treatments such as natural medicines and over-the-counter (OTC) analgesics, they do not often reveal the use of such treatments to physicians, nor do they fully understand their potential adverse effects. This article reviews the nephrotoxic effects of OTC analgesics, natural medicines, and illicit drugs.

Safety of the newer antihypertensive agents in children.

Hypertension is relatively uncommon in children and few children receive antihypertensive medications. This article reviews the safety of calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in children with hypertension. While the newer antihypertensive agents appear to be well-tolerated by children, further studies are needed to determine the safety profile across the developmental continuum, with chronic dosing and in children with complex hypertension.

Update on the pharmacologic treatment of hypertension in pediatrics.

J Clin Hypertens (Greenwich). 2012; 14:383-387. ©2012 Wiley Periodicals, Inc. The past decade of investigation into the pharmacologic treatment of hypertension in children has been rewarding. The studies have shown that blood pressure medications effectively reduce blood pressure in children with hypertension and that these agents are generally well tolerated with few treatment-related adverse effects. While we have advanced our capacity to make rational therapeutic decisions, future efforts must be directed towards comparing the effectiveness of the different classes of antihypertensive agents and studies evaluating the impact of antihypertensive agents on outcome.

Pharmacokinetics of olmesartan medoxomil in pediatric patients with hypertension.

BACKGROUND: The prevalence and importance of hypertension in younger patients is becoming increasingly recognized; however, only a limited number of clinical trials have been conducted in the pediatric population. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and short-term safety of olmesartan medoxomil in children and adolescents with hypertension. METHODS: An open-label, multicenter, single-dose study was conducted in children and adolescents aged 12 months-16 years who were receiving treatment for hypertension or, if not currently treated for hypertension, had either a systolic blood pressure (SBP) or diastolic blood pressure (DBP).≥95th percentile, or SBP or DBP ≥90th percentile if diabetic or with a family history of hypertension. Patients were stratified by age: 12-23 months (Group 1; none enrolled), 2-5 years (Group 2; n = 4), 6-12 years (Group 3; n = 10), and 13-16 years (Group 4; n = 10). All patients received a single oral dose of olmesartan medoxomil based on the individual's age and bodyweight. Patients aged <6 years received an oral suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to exceed 20 mg), those aged ≥6 years who weighed ≥35 kg received olmesartan medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan medoxomil 20 mg tablets. RESULTS: In Groups 2, 3, and 4, the weight-adjusted apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 ± 0.034, 0.062 ± 0.020, and 0.072 ± 0.022 L/h/kg, respectively, and the weight-adjusted apparent volume of distribution (Vd/F) was 0.32 ± 0.16, 0.33 ± 0.14, and 0.49 ± 0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not significantly different. Statistical comparisons between Groups 3 or 4 and Group 2 were not performed due to the small sample size of Group 2 (n = 4). Plasma elimination half-life and time to maximum plasma concentration were similar across the three groups. In Groups 3 and 4, considerable interindividual variability was seen in maximum plasma concentration (C(max)), area under the curve (AUC) from time zero to the last measurable concentration, and apparent clearance, with AUC and C(max) approximately 30% greater in Group 3. Four of 24 (16.7%) patients experienced treatment-emergent adverse events that were all mild in severity and considered not drug-related. No deaths, serious adverse events, or discontinuations due to adverse events occurred in the study. CONCLUSIONS: Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic profile in pediatric patients similar to that of adults when adjusted for body size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00151814

Incidence and treatment of hypertension in the neonatal intensive care unit.

The incidence and risk factors for hypertension in the neonatal intensive care unit (NICU) is inadequately defined, and the current utilization of antihypertensive medications in this specialized environment is not known. We evaluated the incidence of hypertension, associated risk factors, and utilization of antihypertensive drugs in the NICU using a large, geographically diverse pediatric database. A total of 123,847 NICU encounters were identified in the database. After exclusion of the 44,861 neonates with congenital cardiac disorders, 764 (1%) were coded with the diagnosis of hypertension. On multivariate analysis, the risk for hypertension was greatest in those neonates with a high All Patient Refined Diagnosis Related Groups (APR-DRG) severity of illness assessment (OR = 35.8), extracorporeal membrane oxygenation (OR = 3.8), coexisting renal disorder (OR = 4.7), and renal failure (OR = 2.4). Of the 441 (57.7%) infants receiving antihypertensive medication, the median duration of exposure was 10 days, and 45% were exposed to more than one antihypertensive medication. Vasodilators were used in 64.2% of hypertensive neonates, followed by angiotensin-converting enzyme inhibitors (50.8%), calcium channel blockers (24%), and alpha- and beta-blockers (18.4%). Although hypertension occurs infrequently in the NICU, certain neonates are at increased risk for this condition. Hypertensive infants are frequently exposed to antihypertensive medications, often to several different agents during their NICU course of treatment.