Paediatric drugs
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Review
Pharmacokinetic/pharmacodynamic modeling of anesthetics in children: therapeutic implications.
Modeling the pharmacokinetics and pharmacodynamics of anesthetics in children is performed as a response to the clinical need for safe and efficacious administration of drugs with a low therapeutic index. Rates and concentrations of these drugs, which are the primary parameters used by anesthesiologists, depend on physiologic parameters that are markedly affected by development. Volatile anesthetics have been used for >50 years in pediatric patients. ⋯ Pharmacodynamic interactions between general anesthesia and regional anesthesia need to be modeled. This is one of the future tasks for pharmacokineticists. Methods such as the Dixon up-and-down allocation and the isobolographic technique are promising in this field.
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The management of children with end-stage chronic liver disease and acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but studies and publications have mainly concerned adult patients. Therapeutic approaches to complications of end-stage chronic liver disease and acute liver failure (e.g. refractory ascites, hepatorenal syndrome, encephalopathy, and cerebral edema) that may be applied to children are reviewed in this article. ⋯ There are no specific medical therapies or devices that can correct all of the functions of the liver. Apart from a few metabolic diseases presenting with severe liver dysfunction for which specific medical therapies may preclude the need for liver transplantation, liver transplantation still remains the only definitive therapy in most instances of end-stage chronic liver disease and acute liver failure. Future research should focus on gaining a better understanding of the mechanisms responsible for liver cell death and liver regeneration, as well as developments in hepatocyte transplantation and liver-directed gene therapy.
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This article reviews relevant pharmacologic and clinical information gathered for valproate since it was introduced into clinical practice 37 years ago and the application of this information for the treatment of childhood epilepsy. Valproate is available for oral and parenteral use. Oral forms are almost completely bioavailable but the rate of absorption varies between formulations. ⋯ Gastrointestinal intolerance is a relatively frequent, dose-related adverse effect of the drug in children. Bodyweight increase and tremor may be observed in older children and adolescents. Despite the challenge of newer drugs, valproate remains a gold standard antiepileptic drug for the treatment of children.
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Probiotics, defined as microbial cell preparations or components of microbial cells that have a beneficial effect on the health and well being of the host, have traditionally been used to treat and prevent a variety of infections. Beneficial effects of probiotics in acute infectious diarrhea in children seem to be: (i) moderate; (ii) strain-dependent; (iii) dose dependent; (iv) significant in watery diarrhea and viral gastroenteritis, but non-existent in invasive, bacterial diarrhea; and (v) more evident when treatment with probiotics is initiated early in the course of disease. Three large, randomized controlled trials (RCTs) provide evidence of a very modest effect (statistically significant, but of questionable clinical importance) of some probiotic strains (Lactobaccillus GG, Lactobaccillus reuteri, Bifodobacterium lactis) on the prevention of community-acquired diarrhea. ⋯ Only very few probiotic strains have been tested rigorously in RCTs. Many questions remain to be answered. Future clinical trials should evaluate carefully selected, precisely defined probiotic strains and address clinically important endpoints.
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The management of pain in the palliative care of children is somewhat different from that in adults. It also differs in approach from the management of other types of acute and chronic pain in childhood. Whereas once opioids were thought to be highly dangerous drugs, unsuitable for use in children, they have now taken their place as the mainstay for provision of good analgesia to manage moderate-to-severe pain in both malignant and non-malignant life-limiting conditions. ⋯ On saying that, early research in children does suggest some significant differences in opioid pharmacokinetics, particularly with respect to morphine clearance, which seems to be faster in adults. Thus, the use of opioids in pediatric palliative care presents some unique challenges. Confident and rational use of opioids by pediatricians, illustrated by the WHO guidelines, is essential for the adequate management of pain complicating the palliative phase in children with life-limiting conditions.