Vomiting and recovery after outpatient tonsillectomy and adenoidectomy in children. Comparison of four anesthetic techniques using nitrous oxide with halothane or propofol.

BACKGROUND: The authors' purpose in this study was to compare prospectively four different anesthetic induction and maintenance techniques using nitrous oxide with halothane and/or propofol for vomiting and recovery after outpatient tonsillectomy and adenoidectomy procedures in children. METHODS: Eighty unpremedicated children, aged 3-10 yr, were assigned randomly to four groups: group H/H, 0.5-2% halothane induction/halothane maintenance; group P/P, 3-5 mg.kg-1 propofol induction and 0.1-0.3 mg.kg-1.min-1 propofol maintenance; group H/P, 0.1-0.3 mg.kg-1.min-1 halothane induction/propofol maintenance; and group P/H, 3-5 mg.kg-1 propofol induction and 0.5-2% halothane maintenance. Nitrous oxide (67%) and oxygen (33%) were administered in all the groups. Other treatments and procedures were standardized intra- and postoperatively. Results of postoperative vomiting and recovery were analyzed in the first 6 h and beyond 6 h. RESULTS: Logistic regression showed that vomiting occurred 3.5 times as often when halothane was used for maintenance of anesthesia (groups H/H and P/H) compared with the use of propofol (groups P/P and H/P; Odds Ratio 3.5; 95% confidence interval 1.3 and 9.4, respectively; P = 0.012). A significant association between vomiting ( < 6 h: yes/no) and discharge times ( > 6 h: yes/no) (Odd's Ratio = 3.6; 95% confidence interval: 1.02, 12.4, respectively) (P = 0.046) was shown. However, no significant differences among the groups in the incidence of vomiting beyond 6 h, recurrent vomiting, or hospital discharge times were shown. CONCLUSIONS: After tonsillectomy and adenoidectomy procedures, despite reduced postoperative vomiting with use of propofol rather than halothane, along with nitrous oxide for anesthetic maintenance, the authors found no differences in "true" endpoints such as unplanned admissions or discharge times. Among the groups, the main factor that delayed hospital discharge beyond 6 h was vomiting within the first 6 h.

The pharmacokinetics of propofol in children using three different data analysis approaches.

BACKGROUND: Accurate dosing of propofol in children requires accurate knowledge of propofol pharmacokinetics in this population. Improvement in pharmacokinetic accuracy may depend on the incorporation of individual patient factors into the pharmacokinetic model or the use of population approaches to estimating the pharmacokinetic parameters. We investigated whether incorporating individual subject covariates (e.g., age, weight, and gender) into the pharmacokinetic model improved the accuracy. We also investigated whether the use of a mixed-effects population model (e.g., the computer program NONMEM) improved the accuracy of the pharmacokinetic model beyond the accuracy obtained with models estimated using two simple approaches. METHODS: We studied 53 healthy, unpremedicated children (28 boys and 25 girls) ranging from 3 to 11 yr of age. Twenty children only received an initial loading dose of 3 mg/kg intravenous propofol. In the remaining 33 children, an initial intravenous propofol dose of 3.5 mg/kg was followed by a propofol maintenance infusion. Six hundred fifty-eight venous plasma samples were gathered and assayed for propofol concentrations. Three different regression techniques were used to analyze the pharmacokinetics: the "standard two-stage" approach, the "naive pooled-data" approach, and the nonlinear mixed-effects modeling approach (as implemented in NONMEM). In both the pooled-data and mixed-effects approaches, individual covariates (age, weight, height, body surface area, and gender) were added to the model to examine whether they improved the quality of the fit. Accuracy of the model was measured by the ability of the model to describe the observed concentrations. RESULTS: The pharmacokinetics of propofol in children were best described by a three-compartment pharmacokinetic model. There were no appreciable differences among the pharmacokinetics estimated using the two-stage, pooled-data, and mixed-effects approaches. Weight was a significant covariate, and the weight-proportional model was supported by all three regression approaches. The pharmacokinetic parameters of the weight-proportional pharmacokinetic model (pooled-data approach) were: central compartment (V1) = 0.52 1 x kg-1; rapid-distribution compartment (V2) = 1.01 x kg-1; slow-distribution compartment (V3) = 8.2 1 x kg-1; metabolic clearance (Cl1) = 34 ml.kg-1 x min-1; rapid-distribution clearance (Cl2) = 58 ml.kg-1 x min-1; and slow-distribution clearance (Cl3) = 26 ml.kg-1 x min-1. The inclusion of age as an additional covariate of V2 statistically improved the model, but the actual improvement in the fit was small. CONCLUSIONS: The pharmacokinetics of propofol in children are well described by a standard three-compartment pharmacokinetic model. Weight-adjusting the volumes and clearances significantly improved the accuracy of the pharmacokinetics. Adjusting the pharmacokinetics for inclusion of additional patient covariates or using a mixed-effects model did not further improve the ability of the pharmacokinetic parameters to describe the observations.

Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans.

STUDY OBJECTIVE: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. DESIGN: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. SETTING: Inpatients requiring surgery at Georgetown University Medical Center. PATIENTS: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery. INTERVENTIONS: After Georgetown University Institutional Review Board approval and patient consent, patients were premedicated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of-four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED95 of ORG 9426 (570 micrograms/kg, 710 micrograms/kg, or 850 micrograms/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T1). MEASUREMENTS AND MAIN RESULTS: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T1 (T1 90% block), maximal T1 depression (onset time), intubating conditions, clinical duration (time for return of T1 to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T1 90% block was achieved rapidly (75 +/- 25 seconds to 78 +/- 18 seconds, means +/- SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 +/- 18 minutes at 570 micrograms/kg to 42 +/- 10 minutes at 850 micrograms/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 +/- 1 minutes to 6 +/- 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. CONCLUSION: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans.