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Clinical pharmacology of midazolam in infants and children
1Division of Pediatric Pharmacology and Critical Care, Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
Insights
Midazolam, a fast-acting benzodiazepine, offers sedation and amnesia by enhancing GABA neurotransmission. Careful dosing in children is crucial due to potential adverse events like hypoventilation.
Area of Science:
- Pharmacology
- Pediatric Anesthesiology
Background:
- Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant, and anticonvulsant properties.
- It acts by enhancing gamma-aminobutyric acid (GABA) neurotransmission.
- Midazolam exhibits a faster onset and shorter duration of action compared to other benzodiazepines.
Purpose of the Study:
- To review the properties, pharmacokinetics, and dosing of midazolam in pediatric patients.
- To highlight potential adverse events and safe administration practices.
Main Methods:
- Literature review of midazolam's pharmacological and pharmacokinetic properties.
- Analysis of pediatric dosing guidelines and adverse event profiles.
Main Results:
- Midazolam's efficacy is linked to its ability to cross the blood-brain barrier and its metabolism via the cytochrome P450 system.
- Key adverse events in children include hypoventilation, decreased oxygen saturation, apnea, and hypotension.
- Pediatric dosing requires careful calculation on a mg/kg basis, with specific recommendations for different age groups.
Conclusions:
- Midazolam is an effective agent for procedural sedation in children.
- Appropriate dosing and monitoring are essential to minimize risks and ensure patient safety.
Abstract:
Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant and anticonvulsant properties. The drug exerts its clinical effect by binding to a receptor complex which facilitates the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam. The most serious adverse events associated with midazolam in children include hypoventilation, decreased oxygen saturation, apnoea and hypotension. It is water soluble in the commercially prepared formulation but becomes lipid soluble at physiological pH and can then cross the blood brain barrier. It is metabolised in the liver by the cytochrome P450 system, and its chief metabolite is 1-hydroxymethyl midazolam. The latter is conjugated to the glucuronide form, and it has only minimal biological activity. Midazolam is excreted primarily by the kidney. Its half-life in children over 12 months is reported to be 0.8 to 1.8 hours, with a clearance of 4.7 to 19.7 ml/min/kg. Doses given to children must be calculated on a mg/kg basis. For children 6 months to 5 years of age the initial dose is 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg titrated slowly may be necessary to achieve the desired endpoint. For children 6 to 12 years of age the initial dose is 0.025 to 0.05 mg/kg with a total dose up to 0.4 mg/kg to achieve the desired end-point.