Dexmedetomidine: Paediatric Applications and Limitations
Despite lack of paediatric labelling, contributions to the literature on paediatric applications of dexmedetomidine have increased over recent years. Dexmedetomidine possesses many properties that are advantageous for a sedative and anaesthetic; it has been reported to provide sedation that parallels natural sleep, anxiolysis, analgesia, sympatholysis, and an anaesthetic-sparing effect with minimal respiratory depression. In addition, there is increasing evidence supporting its organ-protective effects against ischaemic and hypoxic injury. These favourable physiological effects combined with a limited adverse effect profile make dexmedetomidine an attractive adjunct to anaesthesia (general and regional) for a variety of procedures in paediatric operating rooms. A comprehensive understanding of the pharmacological, pharmacokinetic, and pharmacodynamic effects of dexmedetomidine is critical to maximize its safe, efficacious, and efficient paediatric perioperative applications. This review focuses on the current paediatric perioperative and periprocedural applications of dexmedetomidine and its limitations, with a consideration for the future.
The ideal anaesthetic for perioperative application would be fast in onset and offset, with limited lipid solubility, predictable in response, easy to titrate, reliable in achieving a targeted level of sedation, able to preserve airway tone, and sparing of respiratory effects. This ideal agent would be neuroprotective and exhibit minimal cardiovascular effects. Unfortunately, such an ideal agent does not exist. Dexmedetomidine (DEX; Precedex;® Hospira, Lake Forest, IL, USA; and Dexdor; Orion Corporation, Espoo, Finland) possesses some of the desirable properties mentioned. In rodents and humans, DEX, through action on α2-adrenergic receptors in the locus coeruleus, provides relatively fast onset of sedative properties paralleling natural sleep, with minimal respiratory depression.
In some studies, DEX has been shown to be neuroprotective, reducing apoptosis in animals and humans. To date, DEX has no known active or toxic metabolites. Currently, it is United States Food and Drug Administration (FDA) approved in the USA for sedation via i.v. bolus and continuous infusion for up to 24 h on intubated adults and for adult procedural sedation in areas outside the intensive care unit (ICU) and operating room setting. In Europe, it is approved for adults (intubated or non-intubated) in the ICU via continuous i.v. infusion, at higher doses than approved in the USA, and without a restriction on duration of administration. Currently, worldwide, there is no approval for administration to the paediatric population. Despite the lack of paediatric labelling, DEX for paediatric use has been described for almost a decade in the literature. The favourable physiological effects of DEX combined with its limited adverse effect profile have facilitated its introduction into the perioperative setting. The α2-adrenergic effects of DEX, relative contraindications, and biphasic effect on blood pressure in both children and adults should be well understood by any provider who administers or cares for a patient receiving DEX.
This review focuses on the diverse and most recent applications of DEX in the perioperative period in the paediatric population. We will summarize its current use as a premedication for anxiolysis, as an adjunctive drug both during and after surgery, and as an adjunct to attenuate emergence agitation, postoperative pain, and shivering. We will also discuss the clinical limitations, challenges, and relative contraindications to its use.
A summary of the current paediatric perioperative and periprocedural applications of DEX and the varying dosing regimens, doses, and routes of administration are provided in Table 1 and Table 2, respectively.
Abstract and Introduction
Abstract
Despite lack of paediatric labelling, contributions to the literature on paediatric applications of dexmedetomidine have increased over recent years. Dexmedetomidine possesses many properties that are advantageous for a sedative and anaesthetic; it has been reported to provide sedation that parallels natural sleep, anxiolysis, analgesia, sympatholysis, and an anaesthetic-sparing effect with minimal respiratory depression. In addition, there is increasing evidence supporting its organ-protective effects against ischaemic and hypoxic injury. These favourable physiological effects combined with a limited adverse effect profile make dexmedetomidine an attractive adjunct to anaesthesia (general and regional) for a variety of procedures in paediatric operating rooms. A comprehensive understanding of the pharmacological, pharmacokinetic, and pharmacodynamic effects of dexmedetomidine is critical to maximize its safe, efficacious, and efficient paediatric perioperative applications. This review focuses on the current paediatric perioperative and periprocedural applications of dexmedetomidine and its limitations, with a consideration for the future.
Introduction
The ideal anaesthetic for perioperative application would be fast in onset and offset, with limited lipid solubility, predictable in response, easy to titrate, reliable in achieving a targeted level of sedation, able to preserve airway tone, and sparing of respiratory effects. This ideal agent would be neuroprotective and exhibit minimal cardiovascular effects. Unfortunately, such an ideal agent does not exist. Dexmedetomidine (DEX; Precedex;® Hospira, Lake Forest, IL, USA; and Dexdor; Orion Corporation, Espoo, Finland) possesses some of the desirable properties mentioned. In rodents and humans, DEX, through action on α2-adrenergic receptors in the locus coeruleus, provides relatively fast onset of sedative properties paralleling natural sleep, with minimal respiratory depression.
In some studies, DEX has been shown to be neuroprotective, reducing apoptosis in animals and humans. To date, DEX has no known active or toxic metabolites. Currently, it is United States Food and Drug Administration (FDA) approved in the USA for sedation via i.v. bolus and continuous infusion for up to 24 h on intubated adults and for adult procedural sedation in areas outside the intensive care unit (ICU) and operating room setting. In Europe, it is approved for adults (intubated or non-intubated) in the ICU via continuous i.v. infusion, at higher doses than approved in the USA, and without a restriction on duration of administration. Currently, worldwide, there is no approval for administration to the paediatric population. Despite the lack of paediatric labelling, DEX for paediatric use has been described for almost a decade in the literature. The favourable physiological effects of DEX combined with its limited adverse effect profile have facilitated its introduction into the perioperative setting. The α2-adrenergic effects of DEX, relative contraindications, and biphasic effect on blood pressure in both children and adults should be well understood by any provider who administers or cares for a patient receiving DEX.
This review focuses on the diverse and most recent applications of DEX in the perioperative period in the paediatric population. We will summarize its current use as a premedication for anxiolysis, as an adjunctive drug both during and after surgery, and as an adjunct to attenuate emergence agitation, postoperative pain, and shivering. We will also discuss the clinical limitations, challenges, and relative contraindications to its use.
A summary of the current paediatric perioperative and periprocedural applications of DEX and the varying dosing regimens, doses, and routes of administration are provided in Table 1 and Table 2, respectively.
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