Optimal Furosemide Therapy in Critically Ill infants

Furosemide as continuous infusion is used in infants after cardiopulmonary bypass (CPB) surgery and during extracorporeal membrane oxygenation (ECMO). The currently used regimens which start with low dose (0.05 - 0.1 mg/kg.hr) may not be optimal in this group of patients with varying renal function. In an observational study the pharmacokinetics/pharmacodynamics (PK/ PD) of continuous furosemide therapy were evaluated in infants after CPB surgery. The study confirmed that the effects of furosemide are dependent on renal function. Therefore it was hypothesized that furosemide therapy may be more effective when the infusion is started at a higher dose. With the data from the observational study a PK/PD model was developed. The proposed furosemide regimen (loading bolus: 1-2 mg/kg; infusion rate 0.2 mg/kg.hr) by the PK/PD model was evaluated in infants after CPB surgery. Since adaptation of the furosemide doses was hardly needed, the proposed regimen seems rational. In a retrospective study furosemide regimens used in neonates during ECMO were evaluated. The regimens varied widely in continuous and intermittent doses. Given the wide variety of doses used, the regimens might not be optimal. Therefore more standardized and efficacious dosing regimens should be developed. As CPB and ECMO are comparable procedures the PK/PD model developed for infants after CPB surgery might also be applicable for infants on ECMO. In a prospective study the proposed furosemide regimen (loading bolus: 1-2 mg/kg; infusion rate 0.2 mg/kg.hr) by the PK/PD model was evaluated in infants during ECMO. The results suggest that the proposed furosemide dose was too high, since the dose had to be decreased in the majority of the patients. Therefore a novel PK/PD model should be developed for infants on ECMO. In conclusion the evaluated continuous furosemide regimens are safe and effective to augment urine production in critically ill infants. The PK/PD model developed for infants after CPB surgery should be used with caution in infants treated with ECMO

Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review

BackgroundObesity and its related complications are increasing health issues. Since generally only minor weight loss is obtained with lifestyle intervention, additional pharmacological therapies such as metformin are often used.ObjectiveWe conducted a systematic review to provide an overview of the efficacy of ≥ 6 months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM).MethodsIn September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss. Prospective studies reporting weight/body mass index (BMI) as a primary or secondary outcome in patients with overweight/obesity with ≥ 6 months’ metformin treatment were included. Included subjects were children and adults with overweight/obesity who received ≥ 6 months of metformin and/or lifestyle intervention, and/or placebo and/or lifestyle intervention, and/or standard care. Studies were independently screened by two reviewers. Data were extracted by one and verified by the other reviewer, and both reviewers assessed the risk of bias using the Cochrane risk-of-bias tool.ResultsOur review includes 15 pediatric and 14 adult studies. In children, after 6 months, more than half the studies reported a greater reduction in BMI with metformin versus controls. Only six studies had an intervention of > 6 months, and these studies found no further improvement in BMI in the metformin users, though their BMI was lower than that of controls. Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group. Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention. In 11 of 14 studies, a greater reduction in weight/BMI was observed with metformin than with placebo. Progression toward T2DM was significantly reduced in adults using metformin, ranging from 7 to 31%. The safety and tolerability of metformin, withdrawal of participants, and comparison with other drugs were not taken into account.ConclusionsThe effects of metformin on weight/BMI vary, with smaller reductions in children than in adults. This could be because of differences in adherence, daily dosage, and insulin status. Metformin significantly reduced the progression toward T2DM in adults. Therefore, metformin should be considered as a treatment for obesity and its related complications.Pharmacolog

Skin autofluorescence in children with and without obesity

Pharmacolog

Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study

Pharmacolog

Increased Arterial Stiffness in Adolescents With Obesity

FWN – Publicaties zonder aanstelling Universiteit Leide

Diuretics in pediatrics: Current knowledge and future prospects

This review summarizes current knowledge on the pharmacology, pharmacokinetics, pharmacodynamics, and clinical application of the most commonly used diuretics in children. Diuretics are frequently prescribed drugs in children. Their main indication is to reduce fluid overload in acute and chronic disease states such as congestive heart failure and renal failure. As with most drugs used in children, optimal dosing schedules are largely unknown and empirical. This is undesirable as it can potentially result in either under- or over-treatment with the possibility of unwanted effects. The pharmacokinetics of diuretics vary in the different pediatric age groups as well as in different disease states. To exert their action, all diuretics, except spironolactone, have to reach the tubular lumen by glomerular filtration and/or proximal tubular secretion. Therefore, renal maturation and function influence drug delivery and consequently pharmacodynamics. Currently advised doses for diuretics are largely based on adult pharmacokinetic and pharmacodynamic studies. Therefore, additional pharmacokinetic and pharmacodynamic studies for the different pediatric age groups are necessary to develop dosing regimens based on pharmacokinetic and pharmacodynamic models for all routes of administration

Evaluation of a bedside device to assess the activated partial thromboplastin time for heparin monitoring in infants

Perioperative Medicine: Efficacy, Safety and Outcom

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands

Aim The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. Methods A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at least one OAD dispensing were identified. Age-adjusted and age-specific incidence (1999-2011) and prevalence (1998-2011) rates of OAD use were calculated. Trends over time were assessed using joinpoint regression software. A subset of PHARMO Database Network (including community pharmacy dispensing records linked to general practitioner data (OPD-GP database)) was used to assess indications for OADs. Results In 2011, the overall age-adjusted incidence and prevalence rates of OAD use were 20.7/100 000 (95% CI 19.2, 22.1) person-years (PY) and 53.8/100 000 (95% CI 51.5, 56.1) persons, respectively. The average annual percentage change (AAPC) in the overall age-adjusted incidence rates from 1999 to 2011 was 18.9% (95% CI 4.5, 35.2). The incidence and prevalence rates of OAD use were higher among females and older age categories. The increases in rates of OAD use were mainly driven by metformin. For only 50% of the 98 patients in the OPD-GP database, indications for OAD prescriptions were reported with type 1 diabetes (n = 20), type 2 diabetes (n = 16), and overweight/obesity (n = 10). Conclusions Incidence and prevalence rates of OAD use in children and adolescents substantially increased in the Netherlands, especially among older age categories (10-14 and 15-19 years) and females. The main indications for use of OADs were type 1 and 2 diabetes and overweight/obesity