Off-Label Use of Medications in Children Undergoing Sedation and Anesthesia

Smith, Michael C.; Williamson, Julie; Yaster, Myron; Boyd, Geoffrey J. C.; Heitmiller, Eugenie S.

doi:10.1213/ane.0b013e3182501b04

Cited by 37 publications

(21 citation statements)

References 14 publications

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“…However, they most likely describe the typical patients and medicine utilization in the study wards. The medicine utilization pattern was also close to those described in other similar paediatric units in Europe, Australia, and in the USA …”

Section: Discussionsupporting

confidence: 82%

Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation

et al. 2013

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Section: Discussionsupporting

confidence: 82%

Prescribing for off-label use and unauthorized medicines in three paediatric wards in Finland, the status before and after the European Union Paediatric Regulation

et al. 2013

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“…Despite the above, there have been supporting, and discouraging literature regarding its use in children. The use of propofol in certain age groups continues to be off-label as it has Food Drug and Administration (FDA) approval for maintenance of anesthesia only in children ≥ 2 months of age and for induction of anesthesia in children ≥ 3 years of age[7]. There are a number of review articles covering the features of propofol [8, 9], but not a comprehensive one covering its present use in pediatric anesthesia, which is the main focus of this review.…”

Section: ) Introductionmentioning

confidence: 99%

Propofol: A Review of its Role in Pediatric Anesthesia and Sedation

2015

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Propofol is an intravenous agent used commonly for induction and maintenance of anesthesia, procedural and critical care sedation in children. The mechanisms of action on the central nervous system involve interactions at various neurotransmitter receptors, especially gamma-aminobutyric acid A receptor. Approved for use in the United States by the Federal Drugs and Administration (FDA) in 1989, its use for induction of anesthesia in children less than 3 years of age still remains off-label. Despite its wide use in pediatric anesthesia, there is conflicting literature about its safety and serious adverse effects in particular subsets of children. Particularly as children are not “little adults”, in this review, we emphasize the maturational aspects of propofol pharmacokinetics. Despite the myriad of propofol pharmacokinetic-pharmacodynamic studies and the ability to use allometrical scaling to smooth out differences due to size and age, there is no optimal model that can be used in target controlled infusion pumps for providing closed loop total intravenous anesthesia in children. As the commercial formulation of propofol is a nutrient-rich emulsion, the risk for bacterial contamination exist despite the FDA mandating addition of antimicrobial preservative, calling for manufacturers’ directions to discard open vials after six hours. While propofol has advantages over inhalation anesthesia like less postoperative nausea and emergence delirium in children, pain on injection remains a problem even with newer formulations. Propofol is known to depress mitochondrial function by its action as an uncoupling agent in oxidative phosphorylation. This has implications for children with mitochondrial diseases and the occurrence of propofol-related infusion syndrome, a rare but seriously life-threatening complication of propofol. At the time of this review, there is no direct evidence in humans for propofol induced neurotoxicity to the infant brain; however, current concerns of neuroapoptosis in developing brains induced by propofol persist and continue to be a focus of research.

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“…As a result of decades of this policy, and despite efforts to reverse the policy, clinical trial data about efficacy and safety of medications in children are not available for many widely used medications. This has led, in turn, to a general lack of pediatric labeling for many drugs and the widespread off‐label use of medications in children . Other factors include limitations in extrapolating data from studies conducted in adults to children because of the many differences between adults and children with regard to organ development, metabolism, absorption, pharmacokinetics and pharmacodynamics, and the increase in the numbers of medications used by children, as well as the numbers of children using medications on a regular basis.…”

Section: Introductionmentioning

confidence: 99%