The pharmacokinetics of ropivacaine after four different techniques of brachial plexus blockade.

Arterial plasma concentrations of ropivacaine were measured after brachial plexus blockade using four different approaches: lateral interscalene (Winnie), posterior interscalene (Pippa), axillary and vertical infraclavicular. Four groups of 10 patients were given a single 3.75 mg.kg(-1) injection of ropivacaine 7.5 mgxml(-1). The pharmacokinetics of ropivacaine were evaluated for 1 h after local anaesthetic injection. The supraclavicular techniques (lateral and posterior) were associated with earlier and higher peak plasma concentrations of local anaesthetic than the infraclavicular techniques (axillary and vertical infraclavicular): mean (SD) values = 3.30 (0.65) microgxml(-1) vs 2.55 (0.62) microgxml(-1) (p = 0.001) in 13.4 (6.9) min vs 25.0 (10.8) min (p = 0.0002). More ropivacaine is taken up by the systemic circulation in the first hour after the supraclavicular approaches; the mean (SD) area under the concentration-time curve was larger: 2.63 (0.51) microgxml(-1).h vs 2.10 (0.49) microgxml(-1).h (p = 0.002). These results show that the technique used for brachial plexus blockade significantly influences the systemic uptake of ropivacaine.

Lumbar epidural catheter insertion: the midline vs. the paramedian approach.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the characteristics of epidural catheter insertion via the midline or the paramedian approach with regard to ease of catheter insertion, incidence of paraesthesias and efficacy of epidural block. In addition to the type of approach, the prognostic value of Patients characteristics variables with regard to the incidence of paraesthesias was assessed. METHODS: Thirty patients scheduled for surgery under epidural anaesthesia were randomly assigned to one of two groups of 15 patients each. Epidural anaesthesia was performed via a midline or paramedian approach using loss of resistance to saline. Variables measured were: time needed to identify the epidural space, time needed for and ease of epidural catheter insertion and the incidence of paraesthesias. After completion of these observations, epidural anaesthesia was established with 150 mg ropivacaine 1%. Efficacy of the epidural block was assessed by the need for intraoperative analgesics and by the patient on a three-point scale (good/fair/poor). RESULTS: Quality of sensory blockade was adequate in both groups. Catheter insertion was significantly faster using the paramedian approach. The difference between the two approaches with regard to the incidence of paraesthesias was not significant, however, there was a trend towards more paraesthesias in the midline group. In the multivariate analysis, type of approach was an independent significant predictor of paraesthesias and we found a trend towards a higher incidence of paraesthesias in female patients. CONCLUSIONS: Catheter insertion was faster in the paramedian group and we found a trend towards a higher incidence of paraesthesias with the midline approach.

Effect of age on the clinical profile and systemic absorption and disposition of levobupivacaine after epidural administration.

BACKGROUND: Pharmacokinetic and/or pharmacodynamic changes, which may occur with increasing age, could alter the clinical profile of the new local anaesthetic levobupivacaine. We investigated the effect of age on the absorption and disposition kinetics and the neural block characteristics after epidural administration of levobupivacaine 0.75%. METHODS: Thirty-one patients were enrolled in one of three age groups (Group 1, 18-44 yr; Group 2, 45-70 yr; Group 3, >70 yr). Twenty-five minutes after epidural administration of levobupivacaine (127.5 mg), they received approximately 25 mg deuterium-labelled levobupivacaine (D(3)-levobupivacaine) intravenously. Arterial blood samples were collected until 24 h after the epidural administration. Plasma concentrations were determined using liquid chromatography mass spectrometry. Plasma concentration-time data were analyzed by compartmental and non-compartmental analysis. Assessments of analgesia and motor block were made at set intervals until complete regression of the block. RESULTS: The upper levels of analgesia in the two oldest groups of patients were 3 dermatomes (95% confidence interval (95% CI): 0.5-5.0 dermatomes) higher than in the youngest group. The fraction absorbed (F(1)) was 0.07 (95% CI: 0.02-013) smaller and the absorption half-life (t(1/2,a1)), characterizing the initial fast absorption phase, 3.6 min (95% CI: 0.8-6.4) shorter in the oldest group compared with the youngest group. CONCLUSIONS: Age influences the pharmacokinetics, in particular the early absorption kinetics, and the neural block characteristics after epidural administration of levobupivacaine. Changes in the upper level of analgesia are best explained by anatomical considerations and possibly pharmacodynamic changes in the elderly.

[Bispectral analysis of the electroencephalogram: a new method for recording the level of consciousness during anaesthesia]. / Bispectraalanalyse van het elektro-encefalogram: een nieuwe methode van bewustzijnsregistratie tijdens anesthesie.

Until recently, no measure was available that provided objective and reproducible information on the level of consciousness in patients under general anaesthesia. Several decades of research to find a reliable measure for determining the depth of anaesthesia has now led to the clinical introduction of the bispectral index scale (BIS), a parameter derived from the electroencephalogram. Implementation of the BIS-monitor in anaesthetic practice leads to a reduced use of hypnotic agents, a more rapid recovery phase and possibly a reduced incidence of awareness.

The systemic absorption and disposition of levobupivacaine 0.5% after epidural administration in surgical patients: a stable-isotope study.

BACKGROUND AND OBJECTIVE: Absorption and disposition kinetics can be studied with a stable-isotope method. The aim of this study was to validate a stable-isotope method for levobupivacaine and to derive the relevant pharmacokinetics after epidural administration. METHODS: Eight volunteers (18-32 yr) received approximately 23 mg of both levobupivacaine and deuterium-labelled levobupivacaine simultaneously by intravenous infusion. Venous blood samples were taken for 8 h. Fifteen patients (23-85 yr) received 19 mL levobupivacaine 0.5% (including a 3 mL test dose) epidurally and, 25 min later, approximately 25 mg deuterium-labelled levobupivacaine (D3-levobupivacaine) intravenously. Arterial blood samples were collected for 24 h. Plasma concentrations were determined using liquid chromatography-mass spectrometry. Plasma concentration-time data were analysed by compartmental and non-compartmental analysis. RESULTS: Based on the ratio of the normalized areas under the curve of unlabelled and deuterium-labelled levobupivacaine in volunteers, as determined by both compartmental (mean ratio: 1.02, 90% CI: 1.00-1.04) and non-compartmental analysis (mean ratio: 1.02, 90% CI: 1.00-1.03) the two formulations were considered equivalent. In surgical patients the elimination half-life (mean +/- SD: 196 +/- 65 min), total body clearanc (349 +/- 114 mL min(-1)) and volume of distribution at steady state (56 +/- 14 L), derived by compartmental analysis, were similar to those obtained by non-compartmental analysis. The absorption was bi-phasic. The fractio absorbed and half-life of the fast absorption process were 0.22 +/- 0.06 and 5.2 +/- 2.7 min, respectively. Th values for the slow absorption process were 0.84 +/- 0.14 and 386 +/- 91 min, respectively. CONCLUSIONS: D3-levobupivacaine is pharmacokinetically equivalent to unlabelled levobupivacaine and can be used to study the absorption and disposition kinetics after perineural administration of levobupivacaine in a single experiment.

Predictive performance of computer-controlled infusion of remifentanil during propofol/remifentanil anaesthesia.

BACKGROUND: The predictive performance of the available pharmacokinetic parameter sets for remifentanil, when used for target-controlled infusion (TCI) during total i.v. anaesthesia, has not been determined in a clinical setting. We studied the predictive performance of five parameter sets of remifentanil when used for TCI of remifentanil during propofol anaesthesia in surgical patients. METHODS: Remifentanil concentration-time data that had been collected during a previous pharmacodynamic interaction study in 30 female patients (ASA physical status I, aged 20-65 yr) who received a TCI of remifentanil and propofol during lower abdominal surgery were used in this evaluation. The remifentanil concentrations predicted by the five parameter sets were calculated on the basis of the TCI device record of the infusion rate-time profile that had actually been administered to each individual. The individual and pooled bias [median performance error (MDPE)], inaccuracy [median absolute performance error (MDAPE)], divergence and wobble of the remifentanil TCI device were determined from the pooled and intrasubject performance errors. RESULTS: A total of 444 remifentanil blood samples were analysed. Blood propofol and remifentanil concentrations ranged from 0.5 to 11 micro g ml(-1) and 0.1 to 19.6 ng ml(-1) respectively. Pooled MDPE and MDAPE of the remifentanil TCI device were -15 and 20% for the parameter set of Minto and colleagues (Anesthesiology 1997; 86: 10-23), 1 and 21%, -6 and 21%, and -6 and 19% for the three parameter sets described by Egan and colleagues (Anesthesiology 1996; 84: 821-33, Anesthesiology 1993; 79: 881-92, Anesthesiology 1998; 89: 562-73), and -24 and 30% for the parameter set described by Drover and Lemmens (Anesthesiology 1998; 89: 869-77). CONCLUSIONS: Remifentanil can be administered by TCI with acceptable bias and inaccuracy. The three pharmacokinetic parameter sets described by Egan and colleagues resulted in the least bias and best accuracy.