Intravenous paracetamol and intraocular pressure reduction: Mannitol may also be involved

Karel Allegaert1,2 1Intensive Care, Department of Surgery, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands; 2Department of Development and Regeneration, KU Leuven, BelgiumI read, with great interest, the paper on the intraocular pressure-lowering properties of intravenous paracetamol (acetaminophen) recently published in this journal by van den Heever and Meyer.1 The authors documented a decrease from baseline in mean intraocular pressure of 15.7% in a 6-hour time interval following intravenous paracetamol (1 g Perfalgan®, Bristol-Myers Squibb, New York, NY, USA) administration. This mean decrease was moderate but relevant when compared to, for example, topical timolol (–25.3%, single drop 0.5% timolol maleate) or oral acetazolamide (–23.1%, 250 mg). Although the authors provided potential relevant mechanistic arguments in support of a link between paracetamol administration and intraocular pressure through the endocannabinoid system, we would like to draw attention to the fact that – when intravenous paracetamol is administered – a relevant amount of mannitol is coadministered.View the original paper by van den Heever and Meye

Catch-Up growth in former preterm neonates: no time to waste

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Individualized dosing of aminoglycosides in neonates: mission accomplished or work in progress?

We have read with great interest the paper of Sherwin et al. on individualized dosing of amikacin based on a population pharmacokinetic and-dynamic (PKPD) study in 80 neonates [1]. To the very best of our knowledge, this is the first PD study (outcome indicator sepsis) of aminoglycosides in neonates. We fully support the clinical need to evaluate both PK and PD of drugs, including aminoglycosides in neonates. The recent review on aminoglycosides in neonates in this journal hereby illustrates that clinical pharmacologists are aware of and interested in the specific needs and characteristics of this patient population [2]. We are, however, intrigued by the dosing suggestions formulated by the authors: 15 mg/kg at 36-h intervals for neonates with a postmenstrual age (PMA)≤28 weeks, 14 mg/kg at 24-h intervals for neonate

Acute Maternal Fasting or Fluid Abstention Does Not Significantly Affect the Macronutrient Composition of Human Milk: Clinical and Clinical Research Relevance

There are guidelines on lactation following maternal analgo-sedative exposure, but these do not consider the effect of maternal fasting or fluid abstention on human milk macronutrient composition. We therefore performed a structured search (PubMed) on ‘human milk composition’ and screened title, abstract and full paper on ‘fasting’ or ‘abstention’ and ‘macronutrient composition’ (lactose, protein, fat, solids, triglycerides, cholesterol). This resulted in six papers and one abstract related t

Rational Use of Antibiotics in Neonates: Still in Search of Tailored Tools

Rational medicine use in neonates implies the prescription and administration of age-appropriate drug formulations, selecting the most efficacious and safe dose, all based on accurate information on the drug and its indications in neonates. This review illustrates that important uncertainties still exist concerning the different aspects (when, what, how) of rational antibiotic use in neonates. Decisions when to prescribe antibiotics are still not based on robust decision tools. Choices (what) on empiric antibiotic regimens should depend on the anticipated pathogens, and the available information on the efficacy and safety of these drugs. Major progress has been made on how (beta-lactam antibiotics, aminoglycosides, vancomycin, route and duration) to dose. Progress to improve rational antibiotic use necessitates further understanding of neonatal pharmacology (short- and long-term safety, pharmacokinetics, duration and route) and the use of tailored tools and smarter practices (biomarkers, screening for colonization, and advanced therapeutic drug monitoring techniques). Implementation strategies should not only facilitate access to knowledge and guidelines, but should also consider the most effective strategies (‘skills’) and psychosocial aspects involved in the prescription process: we should be aware that both the decision not to prescribe as well as the decision to prescribe antibiotics is associated with risks and benefits

Clinical pharmacokinetics of vancomycin in the neonate: a review

Neonatal sepsis is common and is a major cause of morbidity and mortality. Vancomycin is the preferred treatment of several neonatal staphylococcal infections. The aim of this study was to review published data on vancomycin pharmacokinetics in neonates and to provide a critical analysis of the literature. A bibliographic search was performed using PubMed and Embase, and articles with a publication date of August 2011 or earlier were included in the analysis. Vancomycin pharmacokinetic estimates, which are different in neonates compared with adults, also exhibit extensive inter-neonatal variability. In neonates, several vancomycin dosing schedules have been proposed, mainly based on age (i.e., postmenstrual and postnatal), body weight or serum creatinine level. Other covariates [e.g., extracorporeal membrane oxygenation (ECMO), indomethacin or ibuprofen, and growth restriction] of vancomycin pharmacokinetics have been reported in neonates. Finally, vancomycin penetrates cerebrospinal fluid (range = 7-42%). Renal function drives vancomycin pharmacokinetics. Because either age or weight is the most relevant covariate of renal maturation, these covariates should be considered first in neonatal vancomycin dosing guidelines and further adjusted by renal dysfunction indicators (e.g., ECMO and ibuprofen/indomethacin). In addition to the prospective validation of available dosing guidelines, future studies should focus on the relevance of therapeutic drug monitoring and on the value of continuous vancomycin administration in neonates