Pharmacokinetics of intravenous ondansetron in healthy children undergoing ear, nose, and throat surgery.

BACKGROUND: To determine the pharmacokinetics of the 5-HT3 antagonist ondansetron in children, informed written consent was obtained from the parents of 21 healthy children aged from 3 to 12 years scheduled for ear, nose, and throat surgery. METHODS: The children were stratified according to age: 3 to 7 years and 7.1 to 12 years, and a single intravenous infusion of 2 or 4 mg ondansetron, respectively, was administered over 5 minutes before induction of anesthesia. After completion of the infusion, anesthesia was induced intravenously and maintained with inhalational anesthesia. Whole blood (3 ml) was obtained before administration of ondansetron, at completion of the infusion, at the beginning and end of surgery, and at 3, 4, 6, 8, 10, and 12 hours after start of the infusion. Pharmacokinetic variables were determined with use of standard noncompartmental techniques. RESULTS: Mean plasma clearance was 0.50 L.hr-1.kg-1 and 0.39 L.hr-1.kg-1, the mean volume of distribution at steady-state was 1.70 L.kg-1 and 1.61 L.kg-1, and the mean plasma terminal half-life was 2.6 hours and 3.1 hours for the 2 mg and 4 mg groups, respectively. On a body surface area basis, mean plasma clearance was 14.0 and 13.7 L.hr-1.m-2 and mean volume of distribution was 47.7 and 55.9 L.m-2 for the 2 and 4 mg groups, respectively. There were no serious adverse events attributable to ondansetron. CONCLUSIONS: These data indicate that the pharmacokinetics of ondansetron in children from 3 to 12 years old are predictable and similar to those in adults. The elimination half-life of ondansetron increases in parallel with age. However, clearance is constant when normalized to body surface area, but the volume of distribution increases over the age range studied.

Proximate delivery of a large experimental dose from salbutamol MDI induces epithelial airway lesions in intubated rabbits.

The delivery of aerosolized drugs by metered dose inhaler (MDI) to intubated patients can be substantially improved by actuating the MDI through a narrow catheter placed inside the tracheal tube. However, the deposition of increased quantities of drug, surfactant, in particular oleic acid, and chlorofluorocarbon propellants on the lung surface could result in adverse effects not observed after oral MDI administration. To investigate this hypothesis, 42 adult intubated rabbits (six groups, n = 6 to 9/group) received Ventolin MDI, Ventolin placebo, a placebo MDI containing lecithin as surfactant, instilled salbutamol sulfate, instilled oleic acid solution, or no treatment (control). Heart rate, invasive blood pressure, and hemoglobin oxygen saturation, recorded continuously for the 3-h experiment, were unchanged from baseline (awake) values. Sections of trachea and lungs were reviewed blindly and graded using a four-point, nine-variable Ophoven scale. Blood was obtained after either 1 puff or 20 puffs MDI salbutamol to determine the pharmacokinetic profile of salbutamol. Multiple doses of both Ventolin and Ventolin placebo aerosols produced significant lesions to the epithelium of the trachea and main bronchi (p < 0.05). The histologic injury after lecithin placebo or salbutamol solution did not differ significantly from control, and all were significantly less than that observed after Ventolin MDI administration. Instilled oleic acid caused gross airway lesions. Maximum serum concentrations of salbutamol were 4.4 +/- 1.8 ng/ml after 1 puff and 419 +/- 168 ng/ml after 20 puffs. After 20 puffs, the total body clearance of salbutamol was 108 +/- 27 ml/min/kg, volume of distribution was 3.6 +/- 1.8 L/kg, and the elimination half-life was 22 +/- 7 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Capnometry and the paediatric laryngeal mask airway.

The laryngeal mask airway (LMA), an alternative to tracheal intubation in certain situations, has gained popularity in recent years. Initially designed for use in adults it has now become available in suitable sizes for paediatric anaesthesia. The objectives of this study were to identify the preferred site of sampling the end-tidal carbon dioxide (PETCO2) with the LMA and to determine the accuracy of this recording when compared with arterial CO2 (PaCO2). We studied 30 healthy children, age one to five years and weighing between 10 and 25 kg undergoing minor surgery requiring mask anaesthesia. In each case, after induction of anaesthesia, the LMA was inserted under direct vision to eliminate the possibility of epiglottic airway obstruction. The fresh gas flow was provided by a Jackson Rees modification of an Ayre's T-piece and was determined according to the following formula: 3 x (1000 + (100 x body weight)) LPM. Blood pressure, ECG, O2 saturation, temperature and end-tidal gas concentrations were recorded. The measures of peak PETCO2 were taken at pre-determined distances from the elbow connector down the LMA shaft. During the sampling sequence an arterial blood sample was taken for gas analysis. The PaCO2 was 63.5 +/- 9.3 mmHg (mean +/- SD). At any given sampling site, mean PETCO2 values were less than PaCO2 (P < 0.05). However, in eight patients PETCO2 values measured at the distal site were higher than the PaCO2 (negative P(a-ET)CO2 gradients).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral midazolam premedication in children: the minimum time interval for separation from parents.

To determine the minimum time interval between oral midazolam (0.5 mg.kg-1) premedication and separation from parents that ensures a smooth separation, 30 children were assigned randomly to one of three groups (ten children per group). The groups differed only in the time interval between administration of midazolam and separation from their parents: 10, 20 or 30 min. Heart rate, systolic blood pressure, and sedation and anxiolysis scores were assessed before midazolam premedication (baseline), at the time of separation from parents, and during the application of a face mask at the induction of anaesthesia. We found that heart rate and systolic blood pressure changes were similar for all three groups throughout the study period. Sedation scores at the time of separation from parents and on application of the mask for all three groups were greater than baseline values. Sedation scores at separation did not differ among the three groups. Anxiolysis values did not differ from baseline values at any time for all three groups. We conclude that children may be separated from their parents as early as ten minutes after receiving oral midazolam, 0.5 mg.kg-1.

Premedication of children with oral midazolam.

In a randomized, double-blind, placebo-controlled study, the safety, efficacy and feasibility of oral midazolam premedication in children were evaluated in an ambulatory surgery unit. Eighty unmedicated children (ASA PS I or II, ages 1-6 yr) were randomly assigned to one of four groups receiving midazolam 0.5, 0.75, or 1.0 mg.kg-1 or a placebo 30 min before separation from parents. Heart rate, systolic blood pressure, arterial oxygen saturation, respiratory rate, sedation and anxiolysis scores were recorded before premedication, every five minutes for 30 min and then during induction of anaesthesia and recovery. We found that heart rate, systolic blood pressure, arterial oxygen saturation and respiratory rate were unchanged during the study. Sedation and anxiolysis scores in the midazolam-treated groups were greater than those in the placebo group and that anxiolysis at the time of separation from the parents was judged excellent in 80-90% of the children who received midazolam. However, sedation and anxiolysis did not differ among the three midazolam groups. Mean times to discharge from hospital were similar for all four groups. The side effects, loss of balance and head control, blurred vision and dysphoric reactions were observed only in the 0.75 and 1.0 mg.kg-1 midazolam groups. We conclude that oral midazolam 0.5 mg.kg-1 is a safe and effective premedication and that 0.75 and 1 mg.kg-1 while offering no additional benefit, may cause more side effects.