The use of skin needling for the delivery of a eutectic mixture of local anesthetics.

AIM: The use of skin needling is believed to aid the transdermal delivery of drugs, even if it is mostly used for skin collagen induction. The aim of this paper was to use skin needling, combined with a local anesthetic EMLA (eutectic mixture of lidocaine and prilocaine), as a way to enhance transdermal drug penetration and optimize the analgesic effects of common local anesthesia. METHODS: We recruited 15 patients. For each patient of our study we defined a skin area of 3 cm2 from two forearms: on one side, we used skin needling first and immediately thereafter applied the EMLA in occlusion for 60 minutes; on the other one, we only applied EMLA in occlusion for 60 minutes. Then, pain was induced in each patient's forearm by introducing a 27 G needle into the skin 4 mm deep three times. Lastly, pain sensation measures were registered and a middle value was calculated. RESULTS: When skin needling is used in conjunction with EMLA applied in occlusion for 60 minutes on skin forearms, the level of pain sensation registered was significantly reduced on a Visual Analogue Scale compared to the application of EMLA alone. CONCLUSION: The use of skin needling can improve the transdermal delivery of an emulsion-like eutectic mixture of local anesthetics (EMLA) and can introduce the use of this method for delivering topical molecules in dermatology.

Topical lidocaine enhanced by laser pretreatment: a safe and effective method of analgesia for facial rejuvenation.

BACKGROUND: Injectable forms of anesthesia for nonsurgical facial rejuvenation, although efficacious, are uncomfortable for the patient. Preclinical studies have demonstrated that laser pretreatment at low energies enhances absorption of topical lidocaine. OBJECTIVES: The authors assess the safety and efficacy of laser-assisted transdermal delivery of topical anesthetic. METHOD: Ten patients were split into 2 groups (A and B). All patients received 15 g of BLT (20% benzocaine, 6% lidocaine, and 4% tetracaine triple anesthetic cream) for 20 minutes with no occlusion. Then the cream was removed and the first blood draw taken. Group A patients were pretreated with the full ablative laser and group B patients with a fractional ablative laser to the full face. A further 15 g BLT was applied for another 20 minutes. Group A patients then underwent full ablative laser treatment, and group B received fractionated ablative laser treatment. Blood draws were taken at 60, 90, 120, 180, and 240 minutes after the initial topical anesthetic application, and the serum was analyzed for lidocaine and monoethylglycinexylidide (MEGX) levels. Patients were asked to rate the pain felt at intervals during the procedure. RESULTS: No patient required supplemental nerve blocks. Pain scores were equivalent at the end of the first pass for both groups (P = .436). Group A patients had significantly lower pain scores at the start of the second laser treatment (P = .045), but pain scores became equivalent by the end (P = .323). Combined serum lidocaine and MEGX levels were significantly higher in group A patients up to 90 minutes (peak average of 0.61 µg/mL for group A and 0.533 µg/mL for group B; P = .0253), which corresponded to greater initial analgesic effect. CONCLUSIONS: Data from this study demonstrate that topical anesthetic for facial rejuvenation can be enhanced with laser pretreatment while maintaining safe blood serum levels. Further studies should examine optimal application amount and time to allow safe multipass facial rejuvenation without the need for invasive nerve blocks.

Balanced anesthesia and constant-rate infusions in horses.

Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions. This review summarizes the different drug combinations used in horses, and provides calculated recommended doses based on the pharmacokinetics of individual drugs.

The effects of combined epidural and general anesthesia on the autonomic nervous system and bioavailability of nitric oxide in patients undergoing laparoscopic pelvic surgery.

BACKGROUND: Pneumoperitoneum during laparoscopic surgery is known to affect visceral blood flow and result in oxidative stress. Whether epidural anesthesia will effectively reduce visceral ischemia and oxidative stress by blocking the sympathetic nervous system (SNS) during laparoscopic surgery has not been proven. METHODS: Forty-five patients who were to undergo robot-assisted laparoscopic prostatectomy were randomly assigned to the combined general-epidural anesthesia group (group GE, n = 22) or to the general anesthesia group (group G, n = 23). Blood pressure, heart rate, and the balance between sympathetic and parasympathetic nervous system activity as measured by heart rate variability were recorded at 10 min after induction of anesthesia (T1), 60 (T2) and 120 (T3) min after intra-abdominal CO(2) insufflation, and 10 min after returning the patient to the supine position following CO(2) exsufflation (T4). Arterial blood gas analysis and blood sampling for measurements of nitrite (NO(2-)) and malondialdehyde (MDA) were performed at all time points. RESULTS: Intraoperative mean blood pressure was significantly lower in group GE compared with group G. The low-frequency to high-frequency ratio was significantly increased after induction of pneumoperitoneum in group G but was unchanged in group GE. Plasma levels of nitrite decreased after pneumoperitoneum induction in group G while there was no change in group GE. A significant increase in MDA levels was seen in group G after pneumoperitoneum induction and were higher than group GE at T3 and T4. The 24-h urine output was higher in group GE than in group G on POD 1. The 24-h CrCl was higher in group GE on POD 1 but was not different between groups on POD 2. CONCLUSIONS: Combined epidural and general anesthesia effectively blocks SNS stimulation during laparoscopic surgery and reduces NO inactivation and oxidative stress.

Absorption characteristics of epidural levobupivacaine with adrenaline and clonidine in children.

AIM: To determine if the addition of adrenaline, clonidine, or their combination altered the pharmacokinetic profile of levobupivacaine administered via the caudal epidural route in children. METHODS: Children aged <18 years old scheduled to undergo sub-umbilical surgery were administered caudal levobupivacaine plain 2.5 mg · ml(-1) or with adjuvants adrenaline 5 mcg · ml(-1) or clonidine 2 mcg · ml(-1) or their combination. Covariate analysis included weight and postnatal age (PNA). Time-concentration profile analysis was undertaken using nonlinear mixed effects models. A one-compartment linear disposition model with first-order input and first-order elimination was used to describe the data. The effect of either clonidine or adrenaline on absorption was investigated using a scaling parameter (Fabs(CLON), Fabs(ADR)) applied to the absorption half-life (Tabs). RESULTS: There were 240 children (median weight 11.0, range 1.9-56.1 kg; median postnatal age 16.7, range 0.6-167.6 months). Absorption of levobupivacaine was faster when mixed with clonidine (Fabs(CLON) 0.60; 95%CI 0.44, 0.83) but slower when mixed with adrenaline (Fabs(ADR) 2.12; 95%CI 1.45, 3.08). The addition of adrenaline to levobupivacaine resulted in a bifid absorption pattern. While initial absorption was unchanged (Tabs 0.15 h 95%CI 0.12, 0.18 h), there was a late absorption peak characterized by a Tabs(LATE) 2.34 h (95%CI 1.44, 4.97 h). The additional use of clonidine with adrenaline had minimal effect on the bifid absorption profile observed with adrenaline alone. Neither clonidine nor adrenaline had any effect on clearance. The population parameter estimate for volume of distribution was 157 l 70 kg(-1). Clearance was 6.5 l · h(-1) 70 kg(-1) at 1-month PNA and increased with a maturation half-time of 1.6 months to reach 90% of the mature value (18.5 l · h(-1) 70 kg(-1)) by 5 months PNA. CONCLUSIONS: The addition of adrenaline decreases the rate of levobupivacaine systemic absorption, reducing peak concentration by half. Levobupivacaine concentrations with adrenaline adjuvant were reduced compared to plain levobupivacaine for up to 3.5 hours. Clonidine as an adjuvant results in faster systemic absorption of levobupivacaine and similar concentration time profile to levobupivacaine alone. Adding adrenaline with clonidine does not alter the concentration profile observed with adrenaline alone.

Development of lidocaine-coated microneedle product for rapid, safe, and prolonged local analgesic action.

PURPOSE: To demonstrate rapid (~1 min) lidocaine delivery using 3M's solid microstructured transdermal system (sMTS) for prolonged, local analgesic action. METHODS: Polymeric microneedles were fabricated via injection molding and then dip-coated using an aqueous lidocaine formulation. The amount of lidocaine coated onto the microneedles was determined by high performance liquid chromatography (HPLC). To assess drug delivery and dermal pharmacokinetics, lidocaine-coated microneedles were inserted into domestic swine. Skin punch biopsies were collected and analyzed to determine lidocaine concentration in skin using HPLC-mass spectrometry (LC-MS). Commercial lidocaine/prilocaine EMLA (Eutectic Mixture of Local Anesthetic) cream was used as comparative control. RESULTS: Lidocaine dissolves rapidly off the microneedles and into skin such that the 1-min wear time achieves or exceeds lidocaine tissue levels needed to cause analgesia. This therapeutic threshold (100 ng/mg) was estimated by measuring the total amount of lidocaine and prilocaine in skin following a 1 h EMLA application. When co-formulated with 0.03 wt% vasoconstrictor-epinephrine, the concentration of lidocaine in tissue was maintained above 100 ng/mg for approximately 90 min. CONCLUSIONS: 3M's sMTS can be used to provide rapid delivery of lidocaine for local analgesia up to 90 min.

[Effect of remifentanil on propofol pharmacokinetics with target controlled infusion in elderly patients].

OBJECTIVE: To investigate the effects of remifentanil administered by target-controlled infusion (TCI) with different plasma concentration and time on pharmacokinetics of propofol in elderly patients. METHODS: Thirty-two ASA I-II patients (65-82 years old) undergoing elective lower abdominal operations were divided into 4 groups randomly: TCI propofol combined with epidural block (group A, n=8); TCI remifentanil with plasma concentration 4 µg/L and propofol (group B, n=8); TCI remifentanil with plasma concentration 7 µg/L and propofol (group C, n=8); and TCI propofol and remifentanil (plasma concentration 4 µg/L) with infusion time longer than 4 hours (group D, n=8). Propofol was infused by target-controlled infusion with plasma concentration 3 mg/L in the 4 groups. bispetral index (BIS), heart rate (HR), blood pressure (BP) were recorded during operation. Blood samples were collection from radial arterial catheter. Samples of 2 mL of arterial blood were taken at 0, 1, 3, 5, 10, 15, 30 min and then every 30 min after the start of the infusion of propofol, and at 0, 2, 4, 6, 8, 10, 15, 30, 45, 60, 120, 240, 360, 480, 720, 1440 min after the termination of the infusion of propofol. Propofol concentrations in blood were measured by reversed-phase high-performance liquid chromatography (HPLC). The pharmacokinetics analyses were performed using the nonlinear mixed-effects model approach implemented in NONMEM computer program. After obtaining the best NONMEM model with covariates, the influence of coadministered remifentanil on the model was examined. RESULTS: In all the patients, the depth of anesthesia was enough (BIS value=40-60), and the circulatory system function was stable during operation. The final model of propofol pharmacokinetics in the three groups (A+B, A+C, and A+D groups) was best described by a three-compartment mammillary model. The values of objective function (OFV) were -810.1, -714.4, and -896.4. Addition of remifentanil covariate effects to the final model resulted in no improvement in the objective function. CONCLUSION: target-controlled infusion of propofol combined with different plasma concentration of remifentanil or remifentanil infusing more than 4 hours had no effect on pharmacokinetics of propofol in elderly patients.

Use of hyaluronidase to improve chemical immobilization of free-ranging polar bears (Ursus maritimus).

We assessed the efficacy and safety of hyaluronidase to improve chemical immobilization of free-ranging polar bears (Ursus maritimus) captured from helicopter by remote drug delivery along the Ontario coast line of northwestern James Bay and southern Hudson Bay during September 2005 and October 2007. We used a single blind study design in which one person prepared and loaded all darts without the shooter knowing whether hyaluronidase (150 IU per dart) or sterile water was added to the immobilizing drug mixture of xylazine and zolazepam-tiletamine (XZT). We found that we often required more than one dart to immobilize bears in the control group (XZT+sterile water; >1 dart for 15 of 28 captures) versus the treatment group (XZT+hyaluronidase; >1 dart for seven of 26 captures). As a consequence, treatment bears were generally immobilized with smaller XZT dosages (7.9 vs. 9.4 mg/kg; P = 0.08) and shorter induction (10 vs. 15 min; P = 0.004) than control bears. We found no differences in vital rates and serum biochemistry results between control and treatment bears. We did find, however, that induction times correlated directly with rectal temperature at

Response surface model predictions of emergence and response to pain in the recovery room: An evaluation of patients emerging from an isoflurane and fentanyl anesthetic.

INTRODUCTION: Sevoflurane-remifentanil interaction models that predict responsiveness and response to painful stimuli have been evaluated in patients undergoing elective surgery. Preliminary evaluations of model predictions were found to be consistent with observations in patients anesthetized with sevoflurane, remifentanil, and fentanyl. This study explored the feasibility of adapting the predictions of sevoflurane-remifentanil interaction models to an isoflurane-fentanyl anesthetic. We hypothesized that model predictions adapted for isoflurane and fentanyl are consistent with observed patient responses and are similar to the predictions observed in our previous work with sevoflurane-remifentanil/fentanyl anesthetics. METHODS: Twenty-five patients scheduled for elective surgery received a fentanyl-isoflurane anesthetic. Model predictions of unresponsiveness were recorded at emergence, and predictions of a response to noxious stimulus were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. Results were also compared with our previous predictions after the administration of a sevoflurane-remifentanil/fentanyl anesthetic. RESULTS: Although patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). After the termination of the anesthetic, model predictions of responsiveness well described the actual fraction of patients observed to be responsive during emergence. Half of the patients woke within 2 min of the 50% model-predicted probability of unresponsiveness; 70% woke within 4 min. Similarly, predictions of a response to a noxious stimulus were consistent with the number of patients who required fentanyl in the recovery room. Model predictions after the administration of an isoflurane-fentanyl anesthetic were similar to model predictions after a sevoflurane-remifentanil/fentanyl anesthetic. DISCUSSION: The results confirmed our study hypothesis; model predictions for unresponsiveness and no response to painful stimuli, adapted to isoflurane-fentanyl were consistent with observations. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic.

An evaluation of remifentanil-sevoflurane response surface models in patients emerging from anesthesia: model improvement using effect-site sevoflurane concentrations.

INTRODUCTION: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions. METHODS: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However, after termination of the anesthetic, models exhibited a wide range of predictions at emergence (1%-97%). Although wide, the Ce-based predictions of responsiveness were better distributed over a percentage ranking of observations than the ET-based predictions. For the ET-based model, 45% of the patients awoke within 2 min of the 50% model predicted probability of unresponsiveness and 65% awoke within 4 min. For the Ce-based model, 45% of the patients awoke within 1 min of the 50% model predicted probability of unresponsiveness and 85% awoke within 3.2 min. Predictions of a response to a painful stimulus in the recovery room were similar for the Ce- and ET-based models. DISCUSSION: Results confirmed, in part, our study hypothesis; accounting for the lag time between Ce and ET sevoflurane concentrations improved model predictions of responsiveness but had no effect on predicting a response to a noxious stimulus in the recovery room. These models may be useful in predicting events of clinical interest but large-scale evaluations with numerous patients are needed to better characterize model performance.

The rate of alveolar-capillary uptake of sevoflurane and nitrous oxide following anaesthetic induction.

The rate of anaesthetic gas uptake from the breathing system has been extensively measured, but this does not reflect the true rate of early gas uptake by pulmonary blood, which drives inhalational induction of anaesthesia. In eight patients undergoing coronary bypass surgery, we measured the rate of alveolar-capillary uptake of anaesthetic gases up to 30 min following introduction of 0.5% sevoflurane and 33% nitrous oxide using the reverse Fick method, in which blood partial pressures were measured using a headspace equilibration technique. Simultaneous measurements of gas uptake from the breathing system were made by indirect calorimetry. Measured rates of sevoflurane and nitrous oxide uptake from the breathing system agreed well with previously described formulae when adjusted for inspired concentration. The time course of alveolar-capillary gas uptake followed a characteristic rising curve peaking at 3-4 min and then exponentially declining, and for nitrous oxide was significantly higher than previously estimated.

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine.

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2 mg/kg) or S-ketamine (1.1 mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13 min after ketamine administration. Arterial blood gases were evaluated 5 min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.

Percutaneous penetration kinetics of lidocaine and prilocaine in two local anesthetic formulations assessed by in vivo microdialysis in pigs.

The aim of this study was to characterize and compare the percutaneous penetration kinetics of lidocaine (L) and prilocaine (P) in two local anesthetic formulations by in vivo microdialysis coupled with HPLC. The microdialysis system for studying lidocaine and prilocaine was calibrated by a no-net-flux method in vitro and retrodialysis method in vivo, respectively. A dosage of 0.2 g/cm2 of an in-house P-L formulation (2.5% lidocaine and 2.5% prilocaine, methylcellulose-based) and commercially available Eutectic Mixture of Local Anesthesia (EMLA, 2.5% lidocaine and 2.5% prilocaine, carbopol-based) was separately but symmetrically applied in the dorsal region of pigs. Saline (0.9%, w/v) was perfused into the linear microdialysis probe at a flow rate of 1.5 microl/min. Dialysate was collected upon topical application up to 6 h at 20-min intervals and assessed by HPLC. The results demonstrated the area under the concentration-time curve (AUC(0-6 h)) of lidocaine and prilocaine in EMLA was 71.95+/-23.36 microg h/ml and 38.01+/-14.8 microg h/ml, respectively, in comparison to 167.11+/-56.12 microg h/ml and 87.02+/-30.38 microg h/ml in the P-L formulation. The maximal concentrations (Cmax) of lidocaine and prilocaine in the dermis were 29.2+/-9.08 microg/ml and 16.54+/-5.31 microg/ml in EMLA and 80.93+/-17.98 microg/ml and 43.69+/-12.87 microg/ml in the P-L formulation, respectively. This study indicates a well-calibrated microdialysis system can provide vital real-time information on percutaneous drug delivery and specifically a methylcellulose-based P-L formulation can increase percutaneous absorption of both lidocaine and prilocaine in pigs compared to carbopol-based EMLA.

Infusão alvo-controlada com Propofol e Remifentanil: estudo experimental em cães / Target-controlled infusion with propofol and remifentanil in dogs

Os modernos sistemas de infusão alvo-controlada (TCI), usados para a indução e manutenção da anestesia, permitem que a velocidade de infusão seja ajustada através da utilização de avançados softwares alimentados com parâmetros farmacocinéticos, de modo a assegurar uma adequada profundidade da anestesia e uma rápida e eficiente recuperação. O objetivo inicial deste estudo foi determinar a concentração plasmática calculada de propofol (CPcalculada) determinada por meio de estimulação sétrica (50V, 50 Hz e 10 ms). Na segunda fase, o objetivo foi investigar a performance do uso de um sistema de infusão alvo-controlada de propofol usado isoladamente ou associado ao remifentanil. Paralelamente foram avaliados as respostas hemodinâmicas e o período de recuperação. A Performance é determinada pela Mediana da Performance do erro (MDPE), e a Mediana Absoluta da Performance do erro (MDAPE), sendo considerada clinicamente aceitável uma MDPE de até 20% e a MDAPE de até 40%. Seis cães adultos saudáveis (26,6 mais ou menos 3,6kg) foram alocados aleatoriamente em 2 grupos com um intervalo de uma semana entre os experimentos. GI igual TCI de propofol e G3 II igual TCI de propofol mais remifentanil. Os resultados foram analisados estatisticamente através da análise de variância seguida pelo teste t-Student. Foi considerado como significante um p menor que 0,05. Houve uma redução na frequência cardíaca e índice cardíaco em GII, enquanto a pressão venosa central e a pressão de oclusão da artéria pulmonar aumentaram significativamente em GII comparado a GI. Os resultados obtidos para o grupo propofol foram de MDPE igual 16,3% e MDAPE igual 32,1% e para o grupo propofol mais remifentanil foram de MDPE igual 6,8% e MDAPE igual 36,5%.

Successful protocol of anaesthesia for measuring transepithelial nasal potential difference in spontaneously breathing mice.

Numerous difficulties arise during in vivo measurements of transepithelial nasal potential difference (PD) in mice, such as inadequate duration and depth of anaesthesia, bronchoaspiration of solutions perfused in the nose, and respiratory and/or cardiovascular depression. Anaesthesia was induced in adult C57 mice with intraperitoneal injection of a combination of fentanyl, droperidol and medetomidine, each of these at either a small dose (0.20, 10 and 0.33 mg/kg, respectively) or at a large dose (0.40, 20 and 0.40 mg/kg, respectively), combined with a fixed dose of 0.375 microg clonidine. In order to establish a pharmacokinetic-pharmacodynamic relationship, blood concentrations of the first three drugs were measured in 24 animals by liquid-chromatography tandem mass spectrometry. At the end of the experiment, naloxone, a competitive morphinic antagonist, and atipamezole, an alpha-2 adrenergic antagonist, were administered. Bronchoaspiration was prevented by tilting the animal head downwards and by absorbing the excess fluid from the opposite nostril and from the oral cavity. Optimal assessment of anaesthesia associated with regular respiration, loss of blink, pupillary and pedal withdrawal reflexes was obtained with doses of fentanyl, droperidol and medetomidine corresponding to 0.20, 20 and 0.40 mg/kg, respectively. Blood concentrations of fentanyl around 17 ng/mL induced loss of respiratory efforts and were followed by death during the experiment. Integrity of ion transport was demonstrated under continuous perfusion by successive depolarization after amiloride and repolarization after chloride-free solution. The combination investigated in this study lead to adequate surgical anaesthesia (stage III, plane 2) for prolonged nasal PD measurements in spontaneously breathing mice.

The performance of a target-controlled infusion of propofol in combination with remifentanil: a clinical investigation with two propofol formulations.

Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery lasting longer than 1 h received a combined TCI of propofol (Marsh parameter set; propofol randomly either dissolved with long- or middle-/long-chain triglycerides) and remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived electroencephalogram variables were determined at various stages before, during, and after surgery. Measured propofol plasma concentrations exceeded the predicted values by 59%, and 48% when recalculated with the Schnider parameter set. Pharmacokinetic population analysis showed a small central volume of distribution (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were the only variables that had a significant influence on propofol pharmacokinetics. In a second step, a new pharmacokinetic variable set for propofol was determined in the first 27 patients. Post hoc performance analysis of the remaining 27 patients showed improved accuracy using the new variable set. Our results show that when remifentanil and propofol are combined, the Marsh and Schnider parameter sets systematically underestimate propofol plasma concentrations. Presented, in part, at the Annual Meeting of the European Society of Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12, 1999.

The use and assessment of ketamine-medetomidine-butorphanol combinations for field anaesthesia in wild European badgers (Meles meles).

OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN: Prospective randomized 'blinded' experimental trial. METHODS: The quality of induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed in 93 badgers, given either one of three ketamine (K)-medetomidine (M)-butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B - M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1), or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the combination administered. Physiological variables (heart and respiratory rates and rectal temperature) were measured at 5-minute intervals during anaesthesia. Gingival mucus membrane colour was also recorded. RESULTS: Induction to anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality did not differ between techniques. Ketamine used alone gave the poorest score for anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane colour were higher in animals anaesthetized with ketamine alone. Rectal temperature did not differ significantly between the techniques at any time during anaesthesia. Ketamine used alone produced the poorest quality of recovery. CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame several side effects associated with ketamine anaesthesia, but at the expense of more variable induction times, lower HRs, and poorer mucus membrane coloration.