Related Experiment Videos
Plasma concentrations of midazolam after i.v., nasal or rectal administration in children
J M Malinovsky1, C Lejus, F Servin
1Département d'Anesthésie-Réanimation Chirurgicale, Hôtel-Dieu, CHRU, Nantes, France.
Insights
Nasal midazolam (intranasal) offers faster plasma concentrations in children compared to rectal administration for premedication. Both non-parenteral routes show similar midazolam levels to intravenous administration after 45 minutes.
Area of Science:
- Pediatric Anesthesiology
- Pharmacokinetics
- Drug Administration
Background:
- Midazolam is a common choice for pediatric premedication.
- Non-parenteral routes are preferred for ease of administration in children.
Purpose of the Study:
- To compare plasma concentrations of midazolam following nasal, rectal, and intravenous administration in pediatric patients.
- To evaluate the pharmacokinetic profile of different midazolam administration routes in children undergoing minor urological surgery.
Main Methods:
- A randomized study involving 45 children (aged 2-9 years) receiving midazolam (0.2 mg kg-1) via nasal, rectal, or intravenous routes.
- Plasma midazolam concentrations were measured using gas chromatography and electron capture detection up to 360 minutes post-administration.
- Standard general anesthesia protocols were followed, including halothane, nitrous oxide, atropine, and fentanyl.
Main Results:
- Nasal midazolam achieved a Cmax of 182 ng ml-1 within 12.6 minutes, while rectal administration resulted in a Cmax of 48 ng ml-1 within 12.1 minutes.
- Rectal administration yielded lower plasma concentrations compared to the nasal route.
- Plasma concentrations after nasal and intravenous midazolam administration became similar around the 45-minute mark.
Conclusions:
- Nasal midazolam provides rapid absorption and achieves therapeutic plasma concentrations quickly in pediatric patients.
- Nasal administration is a viable and effective non-parenteral route for midazolam premedication in children, comparable to intravenous administration after 45 minutes.
Abstract:
Midazolam is used frequently for premedication in children, preferably by non-parenteral administration. We have compared plasma concentrations of midazolam after nasal, rectal and i.v. administration in 45 children (aged 2-9 yr; weight 10-30 kg) undergoing minor urological surgery. General anaesthesia consisted of spontaneous respiration of halothane and nitrous oxide in oxygen via a face mask. After administration of atropine and fentanyl i.v., children were allocated randomly to receive midazolam 0.2 mg kg-1 by the nasal, rectal or i.v. route. In the nasal group, children received 50% of the dose of midazolam in each nostril. In the rectal group, midazolam was given rectally via a cannula. Venous blood samples were obtained before and up to 360 min after administration of the drug. Plasma concentrations of midazolam were measured by gas chromatography and electron capture detection. After nasal and rectal administration, midazolam Cmax was 182 (SD 57) ng ml-1 within 12.6 (5.9) min, and 48 (16) ng ml-1 within 12.1 (6.4) min, respectively. Rectal administration resulted in smaller plasma concentrations. In the nasal group, a plasma concentration of midazolam 100 ng ml-1 occurred at about 6 min. After 45 min, the concentration curves after i.v. and nasal midazolam were similar.