RESUMO
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.
Assuntos
Anestesia/métodos , Halotano/efeitos adversos , Óxido Nitroso/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Propofol/efeitos adversos , Vômito/prevenção & controle , Adenoidectomia , Anestesia/efeitos adversos , Criança , Pré-Escolar , Feminino , Halotano/administração & dosagem , Humanos , Masculino , Óxido Nitroso/administração & dosagem , Estudos Prospectivos , Tonsilectomia , Vômito/epidemiologiaRESUMO
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.
Assuntos
Propofol/farmacocinética , Projetos de Pesquisa , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valores de ReferênciaRESUMO
The objective of this study was to compare intubating conditions and neuromuscular effects using smaller doses of atracurium (0.25 mg/kg and 0.3 mg/kg) with the recommended dose of 0.4 mg/kg for intubation in children anesthetized with halothane, N2O and oxygen undergoing strabismus repair. All patients (10 in each group) had good or excellent intubating conditions at 80% depression of twitch height [T1 of train-of-four (TOF) stimulation]. Mean times to intubation were 2.6 +/- 0.2 minutes following 0.25 mg/kg and 2.2 +/- 0.2 minutes following 0.3 mg/kg. These times were significantly longer (P less than 0.05) than the mean intubation time of 1.5 +/- 0.2 minutes following 0.4 mg/kg. Mean times to recovery, defined as times from injection of atracurium to return of T1 of TOF to 10%, 25%, and 95% of control measurements, were significantly shorter with the smaller doses. Atracurium at these low doses may provide an alternative to succinylcholine for intubating children during halothane anesthesia for surgical procedures lasting 20-30 min.
Assuntos
Atracúrio/administração & dosagem , Intubação Intratraqueal , Anestesia , Atracúrio/farmacologia , Pré-Escolar , Humanos , Succinilcolina/efeitos adversos , Fatores de TempoRESUMO
Pattern of drug consumption and side effects of sufentanil and alfentanil were compared to morphine, using "on-demand" patient-controlled analgesia (PCA). After a non-narcotic general anesthetic, a bolus dose of the narcotic was given intravenously towards the end of surgery. PCA was started in the recovery room. Data were retrieved postoperatively for a total of 24 h. Results showed a wide range of pattern of drug consumption and uniform acceptance of therapy by the nurses and the patients in all the groups. The frequency of use of incremental doses was greater than 2-2.5-fold for the sufentanil and alfentanil groups, respectively, compared with morphine. The bolus dose of the narcotics failed to achieve adequate analgesia for 2 h for morphine and sufentanil and for 6 h for alfentanil. Overall patients were most sedated with morphine and least sedated with sufentanil. At the time intervals sampled, there was a higher incidence of oxygen desaturation--less less than 95% with morphine and alfentanil, compared with sufentanil. There was a similar incidence of nausea in all the groups. Further study is needed to determine precisely the best dose regimens for sufentanil and alfentanil, especially in reference to optimum loading doses. Sufentanil appears to be a promising drug for PCA use.
Assuntos
Alfentanil/uso terapêutico , Analgesia Controlada pelo Paciente , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Alfentanil/administração & dosagem , Alfentanil/efeitos adversos , Humanos , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/efeitos adversos , Medição da DorRESUMO
Protamine administration for heparin reversal after cardiopulmonary bypass on occasion is associated with mild to severe hemodynamic deterioration. The route of administration may modify these reactions. A prospective randomized study was done in 68 patients undergoing isolated coronary artery bypass grafting. The route of protamine administration was randomized in a balanced fashion between right atrium, left atrium, and aorta. The preoperative and operative characteristics of the three groups were similar. Hemodynamic measurements were recorded before cannulation, after removal of the venous drainage catheter, and 1 minute, 5 minutes, and 10 minutes after protamine administration. Hypotension occurred in 11 patients with no significant difference among the three groups. The hypotension was immediate in three patients in whom route of administration was the aorta. The overall hemodynamic changes observed for the three treatment groups were not significantly different. An analysis for type II error indicated that it was unlikely that an important difference had been missed. We conclude that the route of administration does not affect the hemodynamic changes associated with protamine administration. We did not observe a case of severe hemodynamic deterioration, so that we cannot assess the effect of route of administration on the severity of an anaphylactic reaction.