Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures.

AIMS: The aim of this study was to describe ketamine pharmacokinetics when administered orally to children suffering from burn injury in >10% body surface area. METHODS: Children (n = 20) were given ketamine 5 or 10 mg·kg(-1) orally 20 min prior to presentation for surgical procedures. Anesthesia during procedures was maintained with a volatile anesthetic agent. Additional intravenous ketamine was given as a bolus (0.5-1 mg·kg(-1)) to nine children during the procedure while a further nine children were given an infusion (0.1 mg·kg(-1)·h(-1)) continued for 4-19 h after the procedure. Blood was assayed for ketamine and norketamine on six occasions over the study duration of 8-24 h. Data were pooled with those from an earlier analysis (621 observations from 70 subjects). An additional time-concentration profile from an adult given oral ketamine was gleaned from the literature (17 observations). A population analysis was undertaken using nonlinear mixed-effects models. RESULTS: The pooled analysis comprised 852 observations from 91 subjects. There were 20 children who presented for procedures related to burns management (age 3.5 sd 2.1 years, range 1-8 years; weight 14.7 sd 4.9 kg, range 7.9-25 kg), and these children contributed 214 ketamine and norketamine observations. A two-compartment (central, peripheral) linear disposition model fitted data better than a one-compartment model. Bioavailability of the oral formulation was 0.45 (90% CI 0.33, 0.58). Absorption half-time was 59 (90% CI 29.4, 109.2) min and had high between-subject variability (BSV 148%). Population parameter estimates, standardized to a 70-kg person, were central volume 21.1 (BSV 47.1%) l·70 kg(-1), peripheral volume of distribution 109 (27.5%) l·70 kg(-1), clearance 81.3 (46.1%) l·h(-1)·70 kg(-1), and inter-compartment clearance 259 (50.1%) l·h(-1)·70 kg(-1). Under the assumption that all ketamine was converted to norketamine, the volume of the metabolite was 151.9 (BSV 39.1%) l·70 kg(-1) with an elimination clearance of 64.4 (BSV 63.4%) l·h(-1) ·70 kg(-1) and a rate constant for intermediate compartments of 26.2 (BSV 52.1%) h(-1)·70 kg(-1). CONCLUSIONS: The ketamine pharmacokinetics in children with minor burns are similar to those without burns. The peak ratio of norketamine/ketamine at 1 h is 2.8 after oral administration allowing an analgesic contribution from the metabolite at this time. There is low relative bioavailability (<0.5) and slow variable absorption. Dose simulation in a child (3.5 years, 15 kg) suggests a dose regimen of oral ketamine 10 mg·kg(-1) followed by intravenous ketamine 1 mg·kg(-1) i.v. with the advent of short-duration surgical dressing change at 45 min.

A prospective randomized trial comparing supraglottic airways for flexible bronchoscopy in children.

OBJECTIVE: A prospective randomized, controlled trial was conducted comparing supraglottic airways (SGA) for flexible bronchoscopy in 100 children. BACKGROUND: Pediatric flexible bronchoscopy is commonly performed using a SGA as both a ventilation device and a conduit for flexible bronchoscopy. We observed that some disposable SGAs were associated with increased resistance to bronchoscope manipulation compared to the LMA Classic (cLMA). METHODS: We compared the cLMA to the Ambu Aura Once, Portex Soft Seal, Boss Systems disposable silicone laryngeal mask, and LMA Unique. We recorded the subjective resistance of the bronchoscope manipulation within the SGA by linear analog score and measured the time to insert the bronchoscope from the proximal end of the SGA to the right upper lobe. We also scored the view of the larynx through the bronchoscope and measured SGA cuff pressures. RESULTS: Resistance to bronchoscope manipulation during pediatric flexible bronchoscopy was higher using polyvinyl chloride (PVC) disposable SGAs (Ambu, Unique, and Portex) than the silicone re-usable cLMA (P < 0.0001). The Unique and Ambu laryngeal masks were clinically inferior to the cLMA at all levels of the airway (P < 0.0001). The Portex Soft Seal was not different above the larynx but was significantly statistically inferior at (P < 0.04) and below the larynx (P < 0.006) and inferior overall (P < 0.007). Boss Systems single-use laryngeal mask was as effective as the cLMA. CONCLUSION: In this trial, PVC single-use laryngeal masks were inferior to the silicone cLMA and Boss Systems laryngeal masks for flexible bronchoscopy in children.