A comparison of the clinical use of the Laryngeal Tube S and the ProSeal Laryngeal Mask Airway by first-month anaesthesia residents in anaesthetised patients.

The Laryngeal Tube S and the LMA-ProSeal are supraglottic instruments with an improved airway seal and a drainage tube to protect against regurgitation and to facilitate passage of a gastric tube. We compared the feasibility of these two instruments in a randomised, controlled clinical trial. One hundred and sixty patients were randomly allocated to undergo insertion of a Laryngeal Tube S (n = 82) or an LMA-ProSeal (n = 78). All insertions were carried out by first-month anaesthesia residents. Success rates were not significantly different: Laryngeal Tube S 89%, LMA-ProSeal 95%. There was also no significant difference in leak pressure or insertion time. Insertion time decreased significantly when we compared the first with the last 10 insertions. Gastric tube placement was successful in all patients in the Laryngeal Tube S group, but failed in 12 patients in the LMA-ProSeal group (p < 0.001). Dysphagia was reported by 22% of Laryngeal Tube S group and 3% of LMA-ProSeal group (p = 0.001). These findings demonstrate the applicability of the devices and a learning effect in the hands of anaesthesia residents with limited experience.

Biphasic EEG changes in relation to loss of consciousness during induction with thiopental, propofol, etomidate, midazolam or sevoflurane.

The time course of four EEG effect variables, amplitude in the 2-5 Hz and in the 11-15 Hz band, spectral edge frequency 95% (SEF95), and bispectral index (BIS), in response to increasing concentrations of thiopental, propofol, etomidate, midazolam, or sevoflurane during a 10 min induction of anaesthesia was studied in 25 patients to determine the existence of a biphasic effect and to study the relationship of the EEG effect to the moment of loss of consciousness. A biphasic effect, that is, an initial increase of the effect variable followed by a decrease at higher concentrations, during the transition from consciousness to unconsciousness was found in EEG amplitude (both frequency bands) and in SEF95 for all anaesthetics except midazolam. There was a concentration-related decrease in BIS for all anaesthetics. There was no consistent relationship between the time of occurrence of the peak EEG effect, or the value of the EEG variable and the moment of loss of consciousness. With rapidly changing drug concentrations during the induction of anaesthesia, none of these EEG effect variables could be correlated to the moment of loss of consciousness.

Does epidural sufentanil provide effective analgesia per- and postoperatively for abdominal aortic surgery?

To assess the efficacy of epidural sufentanil in providing per- and postoperative analgesia, 40 patients undergoing elective abdominal aortic surgery received either 50 mu g sufentanil in 10 ml normal saline solution (n = 20, ES group) or 10 ml normal saline (n = 20, control group) via a thoracic epidural catheter. The study solution was given (double-blind and at random) after the patients had been anaesthetized with i.v. midazolam, sufentanil and vecuronium. Anaesthesia was maintained with 60% nitrous oxide in oxygen and halothane at a 1% inspiratory concentration. When patients showed signs of inadequate analgesia, supplementary doses of 25 mu g sufentanil were given i.v. The number of patients requiring additional i.v. sufentanil differed significantly between the two groups: 5 out of 20 patients in the ES group vs 13 out of 20 patients in the control group required additional sufentanil (P<0.05). The mean dose administered i.v. did not differ significantly between the two groups: 105 +/- 109.5 mu g vs 138.5 +/- 126.9 mu g (mean +/- SD) in 5 and 13 patients, respectively. No cardiovascular changes were observed after the epidural bolus dose. Postoperative analgesia, consisting of a continuous epidural infusion of 50 mu g sufentanil in 50 ml bupivacaine 0.125% at a rate of 6-10 ml/h after a bolus dose of 10 ml of this solution, was adequate in the majority of patients, as determined by VAS-scores assessed during the epidural treatment (4.3 +/- 1.5 days).

Quantitative electroencephalographic analysis of the biphasic concentration-effect relationship of propofol in surgical patients during extradural analgesia.

We studied effects on the EEG of propofol infused at a rate of 0.5 mg kg-1 min-1 for 10 min in 10 healthy male surgical patients under extradural analgesia. The EEG amplitude in six frequency bands was related to arterial blood propofol concentrations and responsiveness to verbal commands. The EEG amplitude showed a characteristic biphasic response to increasing blood propofol concentrations in all frequency bands. During the infusion, patients lost responsiveness when EEG amplitudes in the high frequency bands were decreasing after having reached a maximum. EEG changes were different during infusion and emergence. Pharmacodynamic modelling, using two effect compartments with dissimilar equilibration constants, resulted in satisfactory fits. We conclude that propofol exerts a biphasic effect on the EEG amplitude in all frequency bands. The dissimilarity of EEG changes during infusion and during emergence suggests that two effect compartments with different equilibration constants exert opposing effects on the EEG.

Clinical observations on the neuromuscular blocking action of Org 9426, a new steroidal non-depolarizing agent.

The neuromuscular blocking effects of Org 9426, the 2-morpholino, 16-allyl-pyrrolidino derivative of the 3-desacetoxy analogue of vecuronium have been investigated in anaesthetized patients. Based on data from a pilot study, two doses, 250 and 500 micrograms kg-1 (estimated as the ED90 and 2 x ED90, respectively) were chosen. Org 9426 appeared to be six to eight times less potent than vecuronium and showed a faster rate of development of neuromuscular block, with good to excellent intubation conditions within 60 s after administration of a dose of 500 micrograms kg-1. The duration of action and the recovery index appeared to be similar to those of vecuronium. Side effects were not noted. Org 9426 may have advantages over existing non-depolarizing neuromuscular blocking agents with respect to rate of development of good intubating conditions, and is stable in aqueous solutions.

Predictability of processed electroencephalography effects on the basis of pharmacokinetic-pharmacodynamic modeling during repeated propofol infusions in patients with extradural analgesia.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PKPD) modeling can be used to characterize the concentration-effect relation of drugs. If the concentration-effect relation of a hypnotic drug is stable over time, an effect parameter derived from the processed electroencephalographic signal may be used to control the infusion for hypnosis. Therefore, the stability of the propofol concentration-electroencephalographic effect relation over time was investigated under non-steady state conditions. METHODS: Three propofol infusions (25 mg x kg(-1) x h(-1) for 10 min, 22 mg x kg(-1) x h(-1) for 10 min, and 12.5 mg x kg(-1) x h(-1) for 20 min) were administered to 10 patients during extradural analgesia. Each successive infusion was started immediately after the patient had regained responsiveness after termination of the preceding infusion. Electroencephalography was recorded from bilateral prefrontal to mastoid leads. Electroencephalographic amplitude in the 11- to 15-Hz band and the Bispectral Index were used as electroencephalographic effect variables. PKPD parameters were calculated with use of parametric and nonparametric models based on electroencephalographic data and arterial propofol concentrations derived during the initial infusion, and these were used to predict electroencephalographic effect during the subsequent infusions. The predictability of the electroencephalographic effects was determined by the coefficient of determination (R2) and of the -2 log likelihood of the sequential infusions. RESULTS: The direction of electroencephalographic changes in response to the infusions was reproducible. Although PKPD parameters could be estimated well during the initial infusion (median [range] parametric R2 = 0.74 [0.56-0.95] for electroencephalographic amplitude and 0.90 [0.27-0.99] for Bispectral Index), none of the modeling techniques could predict accurately the electroencephalographic effect during subsequent infusions (R2 = 0.00 [-0.31-0.46] for electroencephalographic amplitude and 0.15 [-.46-0.57] for Bispectral Index; P < 0.01). CONCLUSIONS: The relation between blood propofol concentrations and the electroencephalographic effect under non-steady state conditions is not stable over time and is too complex to be modeled by any of the applied PKPD models.

Do plasma concentrations obtained from early arterial blood sampling improve pharmacokinetic/pharmacodynamic modeling?

In pharmacokinetic/pharmacodynamic (PK/PD) modeling the first blood sample is usually taken 1 to 2 min after drug administration (late sampling). Therefore, investigators have to extrapolate the plasma concentration to Time 0. Extrapolation, however, erroneously assumes instantaneous and complete mixing of drug in the central volume of distribution. We investigated whether plasma concentrations obtained from early arterial blood sampling would improve PK/PD modeling. In 14 pigs, one of five neuromuscular blocking agents (NMBAs) was administered into the right ventricle within 1 sec and arterial sampling was performed every 1.2 sec (1st min). The response of the tibialis muscle was measured mechanomyographically. The influence of inclusion of data from early arterial sampling on PK/PD modeling was determined. Furthermore, the concentrations in the effect compartment at 50% block (EC50) derived from modeling were compared to the measured concentration in plasma during a steady state 50% block. A very high peak in arterial plasma concentration was seen within 20 sec after administration of the NMBA. Extensive modeling revealed that plasma concentrations obtained from early arterial blood sampling improve PK/PD modeling. Independent of the type of modeling, the EC50 and KeO based on data sets that include early arterial blood sampling were, for all five NMBAs, significantly higher and lower respectively, than those based on data sets obtained from late sampling. Early arterial sampling shows that the mixing of the NMBA in the central volume of distribution is incomplete. A parametric PD (sigmoid Emax) model could not describe the time course of effect of the NMBAs adequately.