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2.
Anaesthesia ; 71(3): 306-14, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26682512

RESUMO

One advantage of effect-site target-controlled infusion is the administration of a larger initial dose of propofol to speed up the induction of anaesthesia. This dose is determined by the combination of the pharmacokinetic model parameters, the target setting and the blood-effect time-constant, ke0 . With the help of computer simulation, we determined the ke0 values required to deliver a range of initial doses with three pharmacokinetic models for propofol. With an effect site target of 4 µg.ml(-1) , in a 35-year-old, 170-cm tall, 70-kg male subject, the ke0 values delivering a dose of 1.75 mg.kg(-1) with the Marsh, Schnider and Eleveld models were 0.59 min(-1) , 0.20 min(-1) and 0.26 min(-1) , respectively. These ke0 values have the attractive feature that, when used to simulate the administration schemes used in two previous studies, predicted effect site concentrations at loss of consciousness were close to those required for maintenance of anaesthesia.


Assuntos
Anestésicos Intravenosos/farmacocinética , Propofol/farmacocinética , Adulto , Anestésicos Intravenosos/administração & dosagem , Estado de Consciência/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Infusões Intravenosas , Masculino , Propofol/administração & dosagem
3.
Anaesthesia ; 69(6): 550-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24720380

RESUMO

We compared the predictive performance of the existing Diprifusor and Schnider models, used for target-controlled infusion of propofol, with a new modification of the Diprifusor model (White) incorporating age and sex covariates. The bias and inaccuracy (precision) of each model were determined using computer simulation to replicate the infusion profiles in an earlier study of 41 patients undergoing surgery with propofol administered by target-controlled infusion and in which timed, measured blood propofol concentrations were available. Bias with the White model (5%) was significantly less (p < 0.0001) than with the Diprifusor (16%) or Schnider (15%) models. The White model showed a significant improvement in accuracy (inaccuracy 19%, p < 0.0001) relative to the Diprifusor (26%). Temporal changes were such that with all three models, bias differed at induction and recovery. None of the models accounted fully for the extent of inter-individual variation in propofol clearance, but the improved performance with the White model suggests it has merit.


Assuntos
Anestésicos Intravenosos/farmacocinética , Propofol/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos
4.
Anaesthesia ; 69(5): 420-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24738799

RESUMO

Debate continues over the most appropriate blood-brain equilibration rate constant (ke0) for use with the Marsh pharmacokinetic model for propofol. We aimed to define the optimal ke0 value. Sixty-four patients were sedated with incremental increases in effect-site target concentration of propofol while using six different ke0 values within the range 0.2-1.2 min(-1). Depth of sedation was assessed by measuring visual reaction time. A median 'apparent ke0' value of 0.61 min(-1) (95% CI 0.37-0.78 min(-1)) led to the greatest probability of achieving a stable clinical effect when the effect-site target was fixed at the effect-site concentration displayed by the target-controlled infusion system, at the time when a desired depth of sedation had been reached. By utilising a clinically relevant endpoint to derive this value, inter-individual pharmacokinetic and pharmacodynamic variability may be accounted for.


Assuntos
Anestésicos Intravenosos/farmacocinética , Modelos Biológicos , Propofol/farmacocinética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Anaesthesia ; 69(5): 429-35, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24738800

RESUMO

We studied the use of a new ke0 value (0.6 min(-1)) for the Marsh pharmacokinetic model for propofol. Speed of induction and side-effects produced were compared with three other target-controlled infusion systems. Eighty patients of ASA physical status 1-2 were studied in four groups in a prospective, randomised study. Median (IQR [range]) induction times were shorter with the Marsh model in effect-site control mode with a ke0 of either 0.6 min(-1) (81 (61-101 [49-302])s, p < 0.01), or 1.2 min(-1) (78 (68-208 [51-325])s, p < 0.05), than with the Marsh model in blood concentration control (132 (90-246 [57-435])). The Schnider model in effect-site control produced induction times that were longer (298 (282-398 [58-513])s) than those observed with the Marsh model in blood control (p < 0.05), or either effect-site control mode (p < 0.001). There were no differences in the magnitude of blood pressure changes or frequency of apnoea between groups.


Assuntos
Anestesia Geral/métodos , Anestésicos Intravenosos/farmacocinética , Modelos Biológicos , Propofol/farmacocinética , Adolescente , Adulto , Anestésicos Intravenosos/sangue , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Propofol/sangue , Estudos Prospectivos , Adulto Jovem
6.
Br J Anaesth ; 102(5): 626-32, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19297371

RESUMO

BACKGROUND: This study has compared the predictive performance of four pharmacokinetic models, two of which are currently incorporated in commercial target-controlled infusion pumps for the administration of propofol. METHODS: Arterial propofol concentrations and patient characteristic data were available from nine patients who, in a published study, had received a standardized infusion of propofol. Predicted concentrations with 'Diprifusor' (Marsh), 'Schnider', 'Schuttler', and 'White' models were obtained by computer simulation. The predictive performance of each model was assessed overall and over the following phases: rapid infusion (1-5 min), early (1-21 min), maintenance (21-min end-infusion), and recovery (2-20 min post-infusion). RESULTS: The overall assessment, based on 29-36 samples from each patient, indicated that all four models were clinically acceptable. However, the negligible bias (-0.1%) with the 'Schnider' model was accompanied by overprediction in the rapid infusion phase and underprediction during recovery. This changing bias over time was not detected as 'divergence' when assessed on absolute performance error (APE), (1.4% h(-1)) but became significant (13.2% h(-1)) when based on changes in signed PE over time. The 'Schuttler' model performed well at most phases but overpredicted concentrations during recovery. The White model led to a marginal improvement over 'Diprifusor' and would be expected to reduce the positive bias usually seen with 'Diprifusor' systems. CONCLUSIONS: In assessing the predictive performance of pharmacokinetic models, additional information can be obtained by analysis of bias at different phases of an infusion. The evaluation of divergence should involve linear regression analysis of both absolute and signed PEs.


Assuntos
Anestésicos Intravenosos/sangue , Modelos Biológicos , Propofol/sangue , Adulto , Anestésicos Intravenosos/administração & dosagem , Constituição Corporal , Simulação por Computador , Quimioterapia Assistida por Computador/métodos , Feminino , Humanos , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Adulto Jovem
7.
Anaesthesia ; 64(1): 32-8, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19087003

RESUMO

The utility of two-choice visual reaction time testing using a specially programmed mobile telephone as a measure of sedation level was investigated in 20 healthy patients sedated with target controlled infusions of propofol. At gradually increasing target concentrations visual reaction time was compared with patient-assessed visual analogue scale sedation scores and an observer-rated scale. Propofol sedation caused dose-dependent increases in visual reaction time and visual analogue scale scores that were statistically significant when the calculated effect-site concentration reached 0.9 microg.ml(-1) (p < 0.05) and 0.5 microg.ml(-1) (p < 0.01) respectively. While visual analogue scale scores were more sensitive at lower levels of sedation than visual reaction time, the latter demonstrated marked increase in values at higher levels of sedation. Visual reaction time may be useful for identifying impending over-sedation.


Assuntos
Telefone Celular , Sedação Consciente/métodos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Tempo de Reação/efeitos dos fármacos , Adulto , Comportamento de Escolha/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Percepção de Forma/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Propofol/administração & dosagem
8.
J Med Chem ; 23(12): 1350-7, 1980 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7452689

RESUMO

Following our discovery of the intravenous (iv) anesthetic activity of 2,6-diethylphenol in mice, a series of alkylphenols was examined in this species and the most active analogues were further evaluated in rabbits. The synthesis of compounds which were not commercially available was accomplished by adaptations of standard ortho-alkylation procedures for phenols. Structure-activity relationships were found to be complex, but, in general, potency and kinetics appeared to be a function of both the lipophilic character and the degree of steric hindrance exerted by ortho substituents. The most interesting compounds were found in the 2,6-dialkyl series, and the greatest potency was associated with 2,6-di-sec-alkyl substitution. In particular, 2,6-diisopropylphenol (ICI 35 868) emerged as a candidate for further development and has subsequently been shown to be an effective iv anesthetic agent in man.


Assuntos
Anestésicos/síntese química , Fenóis/síntese química , Anestesia Intravenosa , Animais , Fenômenos Químicos , Química , Hipnóticos e Sedativos , Dose Letal Mediana , Masculino , Camundongos , Fenóis/administração & dosagem , Fenóis/farmacologia , Relação Estrutura-Atividade
9.
Lab Anim ; 14(3): 207-11, 1980 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7431835

RESUMO

A minimum fresh gas flow of 1 litre per minute per mask and an inspired concentration of 2-3% halothane was required in induce anesthesia in rats in 1-2 min. Anaesthesia was maintained with an inspired concentration of 1.5-2% halothane. Arterial carbon dioxide concentration increased during anaesthesia and was reduced by increasing the flow of fresh gas. Using the apparatus described here, halothane vapour concentration in the operator's breathing zone was 5 ppm. Prior to its introduction, levels of 250 ppm had been recorded in a poorly-ventilated animal room.


Assuntos
Anestesia por Inalação/veterinária , Ratos , Poluição do Ar/prevenção & controle , Anestesia por Inalação/instrumentação , Animais , Gasometria/veterinária , Halotano
10.
Lab Anim ; 18(1): 42-4, 1984 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10628786

RESUMO

A number of design modifications have been made to an extraction system for use with inhalation anaesthesia techniques in rats and other small laboratory animals. These changes necessitated a re-evaluation of the effectiveness of this equipment in limiting the operator's exposure to the anaesthetic vapours used. With a given fresh gas flow, the halothane vapour concentration in the operator's breathing zone was dependent on the design of the oronasal mask. With the optimum configuration the atmospheric concentration of halothane was less than 1 ppm.


Assuntos
Anestesia por Inalação/veterinária , Animais de Laboratório/fisiologia , Máscaras/veterinária , Ratos/fisiologia , Anestesia por Inalação/instrumentação , Animais
11.
Vet Rec ; 148(7): 198-203, 2001 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-11265996

RESUMO

The performance of a modified target-controlled infusion system was investigated in 16 dogs undergoing routine dental work, by comparing the predicted concentrations of propofol in venous blood samples with direct measurements; the optimum targets for the induction and maintenance of anaesthesia were also identified. The performance of a target-controlled infusion system is considered clinically acceptable when the median prediction error, a measure of bias, is not greater than +/-10 to 20 per cent, and the median absolute performance error, a measure of the accuracy, is not greater than 20 to 30 per cent. The results fell within these limits indicating that the system performed adequately. The optimal induction target was 3 microg/ml, and anaesthesia of adequate depth and satisfactory quality was achieved with maintenance targets of between 2.5 and 4.7 microg/ml propofol. The system was easy to use and the quality of anaesthesia was adequate for dental work.


Assuntos
Anestesia Intravenosa/métodos , Anestésicos Intravenosos/administração & dosagem , Assistência Odontológica/veterinária , Propofol/administração & dosagem , Anestésicos Intravenosos/farmacocinética , Animais , Simulação por Computador , Cães , Feminino , Bombas de Infusão/veterinária , Masculino , Propofol/farmacocinética
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