Background and objective: Clinical studies suggest that lidocaine may induce irreversible neurological damage after spinal application in human beings. The mechanisms underlying the possible cytotoxic action of lidocaine have only been suggested from animal studies. This study aimed to investigate if lidocaine exhibited cytotoxic action in a human model widely used for the study of neuronal apoptosis. This is important to know as it may help one to judge on possible neurotoxic risks imposed by the spinal application of lidocaine.

Methods: The concentration- and time-dependent effects of lidocaine on retinoic acid-differentiated human neuroblastoma SH-SY5Y cells were quantified by trypan blue staining, the release of lactate dehydrogenase, immunocytochemistry and flow cytometry.

Results: The local anaesthetic caused a significant increase in the number of cells staining positive for trypan blue, a significant increase of LDH release into the incubation medium, and a significant increase of 7AAD and annexin V binding. Lidocaine induced apoptosis already at 3 mm. At a concentration of 10 mmol 47% of the cells and at 30 mmol 98% of the cell population was necrotic. Both necrosis and apoptosis were time-dependent.

Conclusions: The results demonstrate that lidocaine exhibited neurotoxic effects in a human model established for the study of drug-induced neuronal apoptosis. The results were consistent with the neurotoxic clinical effects of lidocaine. These effects may be produced by more than a single mechanism.

Background and objective: Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects. Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks. It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on haemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery.

Methods: Testing E 047/1 was performed prospectively in two consecutive phase II open, clinical studies. Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, haemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg−1 (pilot study, n = 15) or randomized to a 2 or 3 mg kg−1 bolus of E 047/1, followed by a 1 mg kg−1 h−1 continuous infusion for 2 h (n = 10 in each group). Dysrhythmias, PQ, QTc intervals and haemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation.

Results: At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per minute. Within the first 2–3 min of application in the pilot trial E 047/1induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment. The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per hour. In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per hour after a 3 mg bolus. Approximately 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients. In only three patients did the incidence of dysrhythmias return to inclusion criteria levels. In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCW I in both groups. E 047/1 did not cause QTc prolongation.

Conclusions: E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.

Background and objective: Previous studies have shown that general anaesthetic agents modulate the production of hypothalamic prostaglandins (PG) D2 and E2, which are mediators of sleep and wakefulness respectively. Although flurbiprofen, a cyclo-oxygenase inhibitor, is used clinically as a non-steroidal anti-inflammatory agent and postoperative analgesic, it reduces prostaglandin production. Thus, this agent may affect the depth of sedation during general anaesthesia. In this study, we examined if flurbiprofen affects the bispectral index, which correlates with sedation levels.

Methods: Fifteen patients who underwent elective surgery under total intravenous anaesthesia with propofol and fentanyl were studied. The sedation level was monitored using a bispectral index monitor. On attainment of stable haemodynamics and a bispectral index, patients were given flurbiprofen axetil 50 mg intravenously. A bispectral index and 95% spectral edge frequency were recorded before and 5, 10, 15, 20 and 30 min after flurbiprofen axetil intravenously.

Results: Bispectral indexes of 51.7 (95% CI: 47.3–56.8), 51.7 (47.1–56.3), 51.3 (46.3–56.3), 50.3 (45.8–54.2), 48.9 (43.6–54.1) and 50.3 (45.5–55.2) at 0, 5, 10, 15, 20, 30 min after flurbiprofen axetil intravenously were observed. There was no change in this or 95% spectral edge frequency.

Conclusions: Clinical dose of flurbiprofen axetil does not alter the bispectral index and 95% spectral edge frequency under total intravenous anaesthesia with propofol and fentanyl.

Background and objective: Epidural analgesia is the most effective method for pain relief during labour. The aim was to elucidate the efficacy of ropivacaine 0.05% and bupivacaine 0.05%, which were both combined with fentanyl 0.00015% to provide analgesia in labour.

Methods: Forty nulliparous females were enrolled into the study. After insertion of an epidural catheter, patients were randomly assigned into two groups. Once the os uteri had dilated to 4–5 cm, a bolus of bupivacaine 0.125% 10 mL + fentanyl 50 μg (1 mL) in Group 1 patients, and ropivacaine 0.125% 10 mL + fentanyl 50 μg (1 mL) in Group 2 patients was administered via the epidural catheter. Then, patient-controlled epidural analgesia was started with a basal infusion of bupivacaine 0.05% 10 mL h−1 + fentanyl 0.00015% 1.5 μg mL−1 in Group 1, and ropivacaine 0.05% + fentanyl 1.5 μg mL−1 in Group 2. When needed, a 10 mL bolus infusion could be given and the lockout time was 20 min. Maternal and fetal haemodynamic variables were monitored before induction and subsequently at 5 min intervals. Using a visual analogue scale assessed the degree of pain.

Results: Maternal haemodynamic variables and Apgar scores were not different between the two groups. The second stage of the labour was shorter in Group 2 (P < 0.01). There were no significant differences in patients’ assessment of motor block or mode of delivery between groups.

Conclusions: An epidural infusion (10 mL h−1) of bupivacaine 0.05% or ropivacaine 0.05% together with fentanyl 1.5 μg mL−1 provided good and safe analgesia during labour.

Background and objective: Ventilation of the lungs with positive end-expiratory pressure during pneumoperitoneum has been shown to improve the arterial partial pressure of oxygen. The implications of spontaneous breathing on pulmonary gas exchange remain unknown in this setting. We therefore sought to examine the influence of pressure-support ventilation with spontaneous breathing on gas exchange during simulated laparoscopy.

Methods: Ten pigs were subjected to pneumoperitoneum at a pressure of 15 cmH2O. Animals received, in a random order, pressure-support and pressure-controlled ventilation for 60 min per mode. Inert gas and haemodynamic measurements were performed before changing to a subsequent mode.

Results: Pressure-support ventilation was more efficient than pressure-controlled ventilation regarding perfusion of normal VA/Q lung areas (78 ± 4% vs. 72 ± 5%) (P < 0.05), alveolar-arterial partial pressure of oxygen difference (9.73 ± 1.3 vs. 11.2 ± 1.2 kPa) and arterial partial pressure of oxygen (14.93 ± 1.6 vs. 13.7 ± 2.0 kPa) (P < 0.05).

Conclusions: Pressure-support ventilation resulted in significantly better gas exchange than pressure-controlled ventilation in this model of simulated laparoscopy.

Background and objective: It was previously reported that topical ketamine inhibits albumin extravasation in a rat chemical peritonitis model. Using the same model, the present study investigated whether intravenous ketamine inhibited this extravasation.

Methods: Twenty-four rats anaesthetized with pentobarbital (75 mg kg−1) were randomly assigned to two groups: ketamine and a 0.9% NaCl (saline) group (n = 12 each). Ketamine 1% or saline 0.1 mL kg−1 min−1 was given intravenously for 60 min to the respective group. After the abdomen had been opened, peritonitis was elicited by topically applying a filter paper containing 0.02 M HCl 0.07 mL onto the surface of the appendix or caecum for 5 min. Fifteen minutes after removal of the filter paper, Evans' blue dye (50 mg kg−1) was injected intravenously. The extravasated dye was colorimetrically quantified by a spectrophotometer at 620 nm.

Results: The infusion of ketamine significantly reduced Evans' blue extravasation: 5.26 (range 4.18–6.34) μg per 100 mg tissue compared with the saline group control: 6.81 (5.93−7.69) μg per 100 mg tissue (P < 0.05).

Conclusions: It is suggested that ketamine anaesthesia may reduce albumin extravasation in inflammatory tissues.

Background and objective: The arterial thermodilution technique offers the ability to measure cardiac output using only central venous and arterial catheters. However, the technique has been reported to overestimate cardiac output because of a higher loss of cold indicator due to the increased distance between the sites of injection and measurement. In this study, the two techniques were compared with respect to conditions of low cardiac output in which a longer passage time may further increase loss of indicator.

Methods: Seventeen anaesthetized dogs were studied during hypovolaemic shock and fluid resuscitation. Cardiac output measurements were carried out simultaneously by arterial and pulmonary artery thermodilution techniques.

Results: One-hundred-and-two measurements were performed. The mean cardiac output was 2.28 ± 1.4 L min−1 by the pulmonary arterial technique and 2.29 ± 1.56 L min−1 by the arterial thermodilution technique. The correlation coefficient between the two measurements was 0.95, the precision −0.04 ± 0.41 L min−1 and the limits of agreement from −0.86 to 0.78 L min−1. The agreement was also consistent at low cardiac outputs.

Conclusions: The arterial thermodilution technique may serve as a less invasive cardiac output monitor in conditions of severe bleeding and shock.

Background and objective: The effects of clonidine and dopamine, both alone and together, on gastric tone were studied using an electronic barostat. This enabled volume changes to be measured in an intragastric bag with constant preset pressure.

Methods: Nine healthy male volunteers were each studied on two occasions in a randomized order. During each study period, a continuous infusion of dopamine was given, starting with a dose of 2.5 μg kg−1 min−1 and then increasing at 15-min intervals to 5.0 and 7.5 μg kg−1min 2 1. Clonidine 150 μg intravenously was given on one occasion during the infusion of dopamine (7.5 μg kg−1min−1) and on the other occasion 15 min before the dopamine infusion started.

Results: During dopamine infusion, the intragastric bag volume increased (gastric tone therefore decreasing) in a dose-related manner (total increase 290 6 114 mL). Clonidine given either during or before dopamine infusion did not influence the bag volume. When the dopamine infusion started 15 min after clonidine, the bag volume did not change until the infusion of dopamine reached 7.5 μg kg−1min−1(total increase 205 6 156 mL).

Conclusions: Dopamine reduced gastric tone in a dose-related manner, and clonidine did not influence gastric tone per se. If clonidine is given before dopamine, the effects of dopamine are reduced.

Background and objective: Non-depolarizing neuromuscular blocking agents have a shorter duration of action on the diaphragm than on skeletal muscles. It was to be tested if this also held true for rapacuronium, a shortacting, amidosteroid non-depolarizing neuromuscular blocker, lately withdrawn from the market, using a novel technique for stimulating the diaphragm and assessing its function.

Methods: Anaesthesia was induced with propofol 2 mg kg−1 and remifentanil 1 μg kg−1, and the trachea was intubated after topical anaesthesia. Rapacuronium was given at a dose of 1.5 mg kg−1. The diaphragm was stimulated by cervical magnetic stimulation of the phrenic nerves (2 Tesla, single coil) and airway pressure responses were measured at the endotracheal tube connector. The neuromuscular effects at the adductor pollicis and orbicularis oculi muscles were measured by acceleromyography.

Results: Fifteen males and five females (ASA I and II; 27 ± 8 yr; 73 ± 13 kg; mean ± SD) were recruited. Median maximal relaxation was less (P < 0.01) for the diaphragm (89%) than for the adductor pollicis or orbicularis oculi muscles (each 100%). The time to 25% recovery was shorter for the diaphragm than for adductor pollicis or orbicularis oculi (7.5 ± 3.1 versus 14.1 ± 3.7 and 15.1 ± 3.5 min, respectively, P < 0.01). Recovery from 25 to 75% was identical for the diaphragm and adductor pollicis (9.4 ± 2.9 versus 9.1 ± 3.5 min), but longer for orbicularis oculi (13.4 ± 4.2 min, P < 0.01). The median recovery time to TOF0.8 was shorter for the diaphragm (23.9 min) than for the adductor pollicis or orbicularis oculi muscles (31.5 and 28.4 min, respectively; P < 0.05).

Conclusions: As with other non-depolarizing muscle relaxants, the duration of the clinical effect of rapacuronium was shorter for the diaphragm than for skeletal muscle. The recovery index was identical for the diaphragm and adductor pollicis.

Background and objective: The study was conducted to compare the standard intravenous route with the intranasal route of desmopressin application and to establish the best time for initiating treatment with desmopressin with the use of the Born test and the PFA 100®-Analyzer for monitoring the therapeutic effect.

Methods: Thirty healthy volunteers (ASA I) with no known bleeding disorder were randomly assigned to an intravenous or an intranasal group in a cross-over design fashion. After obtaining baseline values, the volunteers were given 500 mg aminosalicylic acid for 3 days. On day 4, platelet function tests were performed and desmopressin (0.3 μg kg−1 body weight) was administered either intravenously or intranasally. Born tests (aggregation after stimulation with epinephrine and collagen) were conducted at 30 and 240 min, and PFA 100® bleeding time measurements were conducted at 30, 120 and 240 min after desmopressin administration. Wilcoxon signed rank sum tests or non-parametric ANOVA for repeated measures were used for statistical evaluation.

Results: All volunteers showed a marked decreased platelet function in the Born test (especially if stimulation with epinephrine was used) and an increased PFA 100® bleeding time after treatment with aminosalicylic acid. Platelet function was improved by intravenous as well as intranasal application of desmopressin (P < 0.001) after 30 min. The effect diminished after 4 h in both groups.

Conclusions: Intravenous as well as intranasal desmopressin improved platelet function in healthy volunteers with aminosalicylic acid-induced platelet dysfunction at least 30 min after application. The effect lasts up to 4 h.

Background and objective: The common parameters of the electroencephalogram quantify a shift of its power spectrum towards lower frequencies with increasing anaesthetic drug concentrations (e.g. spectral-edge frequency 95). These ad hoc parameters are not optimized for the content of information with regard to drug effect. Using semilinear canonical correlation, different frequency ranges (bins) of the power spectrum can be weighted for sensitivity to changes of drug concentration by multiplying their power with iteratively determined coefficients, yielding a new (canonical univariate) electroencephalographic parameter.

Methods: Electroencephalographic data obtained during application of volatile anaesthetics were used: isoflurane (n = 6), desflurane (7), sevoflurane (7), desflurane during surgical stimulation (12). Volatile anaesthetic end-tidal concentrations varied between 0.5 and 1.6 minimum alveolar concentration (MAC). The canonical univariate parameter and spectral-edge frequency 95 were determined and their correlation with the volatile anaesthetic effect compartment concentration, obtained by simultaneous pharmacokinetic—pharmacodynamic modelling, were compared.

Results: The canonical univariate parameter with individually optimized coefficients, but not with mean coefficients, was superior to the spectral-edge frequency 95 as a measure of anaesthetic drug effect. No significant differences of the coefficients were found between the three volatile anaesthetics or between the data with or without surgical stimulus. The coefficients for volatile anaesthetics were similar to the coefficients for opioids, but different from coefficients for propofol and midazolam.

Conclusions: The canonical univariate parameter calculated with individually optimized coefficients, but not with mean coefficients, correlates more accurately and consistently with the effect site concentrations of volatile anaesthetics than with spectral-edge frequency 95.

Background and objective: Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 8 (IL-8). We investigated whether different anaesthetic techniques alter the pro-inflammatory cytokine response to cardiac surgery.

Methods: Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomized into three groups of 10 patients. They received either volatile inhalation induction and maintenance (Group 1) or total intravenous anaesthesia with propofol and a minimal dose sufentanil (Group 2) or a moderate dose midazolam-sufentanil (Group 3). The effect of the different anaesthetic techniques on plasma levels of TNF-α, IL-6 and IL-8 were examined during and after anaesthesia.

Results: Concentrations of TNF-α, and IL-8 were comparable in the three groups throughout all measurements. Before the start of cardiopulmonary bypass, IL-6 was significantly higher in Group 1 than in Group 2 (P = 0.009) or Group 3 (P = 0.030), but there were no differences between groups after cardiopulmonary bypass or postoperatively. In the three groups there was a positive correlation between aortic clamping time and serum concentrations of IL-6 (r = 0.54) and IL-8 (r = 0.62). Length of stay in intensive care was correlated with high levels of TNF-α (r = 0.78).

Conclusions: Albeit there is difference between the volatile induction and maintenance of the anaesthesia method and the total intravenous anaesthesia technique on the pro-inflammatory cytokine response to surgical stimulation before starting of cardiopulmonary bypass, neither technique can modify the pro-inflammatory cytokine response to ischaemia-reperfusion or extracorporeal circulation.

Background and objective: Pharmacokinetics of propofol in rats have usually been described using linear models. Furthermore, there are only a few investigations for a pharmacodynamic model of the electroencephalographic effects of propofol in rats. We investigated pharmacokinetics and pharmacodynamics of propofol in rats with special regard to linearity in pharmacokinetics and development of tolerance.

Methods: Twelve adult male Sprague-Dawley rats received propofol in three successive infusion periods of 30 min each with infusion rates of 0.5, 1 and 0.5 mg kg−1 min−1. Propofol plasma concentrations were determined from arterial blood samples. Pharmacokinetics were tested for linearity using the ratio of the concentrations at the end of the first and second infusion interval as a model independent criterion. Several linear and nonlinear models were investigated with population pharmacokinetic analysis. Pharmacodynamics were analysed using the median frequency of the electroencephalographic power spectrum as a quantitative measure of the hypnotic effect.

Results: Pharmacokinetics were found to be nonlinear and were best described by a two-compartment model with Michaelis-Menten elimination (Vm = 2.17 μg mL−1 min−1, Km = 2.65 μg mL−1, k12 = 0.30 min−1, k21 = 0.063 min−1, Vc = 0.13 L). Acute tolerance to the electroencephalographic effect of propofol was observed. The hypnotic effect was best described by a sigmoid Emax model (E0 = 17.8 Hz, Emax = 17.7 Hz, EC50 = 4.1 μg mL−1, γ = 2.3, ke0 = 0.36 min−1) with competitive antagonism of propofol and a hypothetical drug in an additional tolerance compartment.

Conclusions: For the applied infusion scheme, propofol pharmacokinetics in rats were nonlinear and a development of tolerance to the electroencephalographic effect of propofol was observed during an infusion time of 90 min.

Background and objective: Induction of general anaesthesia in combination with positive-pressure ventilation is often associated with a significant decrease of arterial pressure. A decreased preload may contribute to this phenomenon. The aim was to investigate whether a change in cardiac filling occurs following the induction of general anaesthesia with sufentanil under typical clinical conditions.

Methods: Fifteen patients scheduled for elective coronary bypass grafting were studied immediately before surgery. In addition to standard monitors, a transpulmonary double-indicator dilution technique measured in vivo intrathoracic blood volume, global end-diastolic volume and total circulating blood volume. For induction of anaesthesia 2 μg kg−1 sufentanil was given. Measurements were performed awake and after the induction of anaesthesia, intubation and mechanical ventilation of the lungs.

Results: To maintain arterial pressure during the induction period within −20% of baseline pressure, on average 22 ± 6 mL kg−1 crystalloids and 8 ± 6 mL kg−1 colloids were given. Despite these amounts of fluid, cardiac filling was decreased, whereas circulating blood volume increased significantly. Both central venous pressure and pulmonary capillary wedge pressure increased.

Conclusions: Induction of general anaesthesia with positive-pressure ventilation is regularly associated with a blood volume shift from intra- to extrathoracic compartments. Even in low-dose opioid monoanaesthesia with sufentanil – often regarded as relatively inert in haemodynamic terms – the phenomenon could be demonstrated as the primary cause of the often-observed decrease of arterial pressure. It seems, therefore, rationally justified to restore cardiac filling by generous administration of intravenous fluids, at least in patients with unaffected cardiac pump function. During induction of anaesthesia, central venous pressure and pulmonary capillary wedge pressure do not reliably indicate cardiac filling.

Background and objective: Thymol is a naturally occurring phenol derivative used in anaesthetic practice as a stabilizer and preservative of halothane, usually at a concentration of 0.01%. Although analgesic effects have long been described for thymol and its structural homologue menthol, a molecular basis for these effects is still lacking. We studied the blocking effects of thymol and menthol on voltage-activated sodium currents in vitro as possible molecular target sites.

Methods: Whole cell sodium inward currents via heterologously (HEK293 cells) expressed rat neuronal (rat type IIA) and human skeletal muscle (hSkM1) sodium channels were recorded in the absence and presence of definite concentrations of either thymol or menthol.

Results: When depolarizing pulses to 0 mV were started from a holding potential of-70 mV, halfmaximum blocking concentrations (IC50) for the skeletal muscle and the neuronal sodium channel were 104 and 149 µmol for thymol and 376 and 571 µmol for menthol. The blocking potency of both compounds increased at depolarized holding potentials with the fraction of inactivated channels. The estimated dissociation constant K d for thymol and menthol from the inactivated state was 22 and 106 µmol for the neuronal and 23 and 97 µmol for the skeletal muscle sodium channel, respectively.

Conclusions: The results suggest that antinociceptive and local anaesthetic effects of thymol and menthol might be mediated via blockade of voltage-operated sodium channels with the phenol derivative thymol being as potent as the local anaesthetic lidocaine.

Background and objective: The study investigated the effect of acute normovolaemic haemodilution on haemodynamics, blood flow and oxygen transport variables with regard to skeletal muscle tissue oxygenation in a canine model.

Methods: Twenty foxhounds were anaesthetized, mechanically ventilated with 30% oxygen in air and underwent first-step normovolaemic haemodilution with Ringer's lactate solution to haematocrit (Hct) 30 and 25% and second-step acute normovolaemic haemodilution with 6% Hetastarch 70 000/0.5 to Hcts of 20, 15 and 10%. Catheters were inserted into femoral arteries and veins and into the pulmonary artery for measurements of haemodynamics, temperature, and sampling of arterial and mixed-venous blood. A flow probe was placed around the left femoral artery. Skeletal muscle tissue oxygen tension (tPO2) was measured in the gastrocnemius muscle using a stepwise driven polarographic needle probe creating histograms from 200 single tPO2 measurements.

Results: Until a Hct of 25% was reached, the heart rate, mean arterial pressure, global and muscular oxygen delivery and consumption remained constant, while the cardiac index and oxygen extraction ratio were significantly increased when compared with baseline. The median tPO2 was significantly decreased at Hcts 15 and 10%, despite increased cardiac index and regional blood flow. The ratio of tPO2 and cardiac index as a marker for efficiency of acute normovolaemic haemodilution started to decline beyond Hcts of 25% (change of slope).

Conclusions: In acute normovolaemic haemodilution to the level of Hct of 25%, the ratio between tPO2 and cardiac index decreases in the healthy dog, indicating an uneconomic relation at the threshold of Hct of 25%.

Background and objective: Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate, a selective dopamine (DA1) agonist, would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping.

Methods: A prospective, randomized, double blind controlled clinical trial was performed. Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied. According to random allocation, patients received either fenoldopam (0.1 μg kg−1 min−1) or placebo intravenously prior to surgical skin incision until release of the aortic clamp. Plasma creatinine, creatinine clearance, urinary output, fractional excretion of sodium, and free water clearance were measured: (a) prior to admission to hospital; (b) during the period from insertion of the urinary catheter until application of the aortic cross-clamp; (c) during the period of aortic cross-clamping; (d) 0-4 h, and (e) 4-8 h after release of the clamp and on days 1, 2, 3, and 5 postoperatively.

Results: Fenoldopam (0.1 μg kg−1 min−1) administration was not associated with haemodynamic instability. On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo (83 ± 20 to 42 ± 29 mLmin−1 (mean ± SD)) (P < 0.01) but not in the fenoldopam group, and this decrease persisted for at least 8 h after release of the cross-clamp (83 ± 20 to 54 ± 33 mLmin−1 (mean ± SD)) (P < 0.05). Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group (87 ± 12 to 103 ± 28 μmol L−1 (mean ± SD)) (P < 0.01) but not in the fenoldopam group.

Conclusions: These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping.

Background and objective: Patients' perception of limb position during regional anaesthesia is frequently incorrect. The incidence and nature of this phenomenon has not yet been completely described. The aim of this prospective study was to assess phantom sensation in patients undergoing a brachial plexus block.

Methods: Axillary block was performed in 81 patients with the aid of a peripheral nerve stimulator. Immediately after the block, patients were allocated randomly to two groups (Group 1, n = 40; Group 2, n = 41) to have the blocked limb placed either on their thorax or in abduction. Fifteen minutes later, when the block was complete, the position of the limb was changed, without the knowledge of the patient, to a new position of abduction and flexion of the forearm. Patients were questioned about the new limb position. Fifteen minutes later, the limb was then transiently shown to the patient and further placed ‘blindly’ to another position. Patients were once more questioned about this new position.

Results: Correct perception was more frequently observed in both groups following the first interview. Thirty-two and 34 patients gave at least one erroneous response about their limb position when it was initially placed on the thorax or in abduction respectively. Transient visualization of the limb position did not improve the rate of correct response.

Conclusions: Patients' perception of the position of the limb after axillary block in the majority of instances was probably due to persisting sensory inputs from the shoulder joint, which is not involved in this block. This in contrast to supraclavicular or interscalene blocks. A significant number of patients experienced phantom limb sensation. They reported an arm position in fact related to the position of their arm before the axillary block.

Background and objective: Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line.

Methods: Cells were cultured for 2, 6 or 24 h in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-βglucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. Infrared analysis and fluoride microdetermination allowed crystal components.

Results: At 5 mmol after 24 h, fluoride decreased cell numbers (−14%, *P < 0.05), protein content (−16%*), leucine incorporation (−54%*), Na-K-2Cl activity (−84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24 h and after 2 h at 5 mmol. Crystal formation in mitochondria occurred after 6 h at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride.

Conclusions: The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.

Background and objective: A critical factor that delays patient discharge following day-surgery is severe postoperative pain and the requirement for strong analgesics. Laparoscopic sterilization is a day case procedure and is associated with additional postoperative pain compared with diagnostic laparoscopy. This pain, associated with application of Filshie clips, may be ischaemic or spasmodic in aetiology. Papaverine relaxes smooth muscle, and the aim of the study was to investigate if papaverine would be effective in improving postoperative pain if administered directly to the Fallopian tubes. Bupivacaine is used commonly in day-surgery and so we compared the effect of this local anaesthetic with saline placebo.

Methods: Sixty-six ASA I-II females undergoing laparoscopic sterilization were entered into the prospective, randomized, double-blind, placebo-controlled clinical trial. They received intrauterine papaverine (30 mg) or bupivacaine (0.375% 30 mL) or normal saline (30 mL) via the transcervical route before application of Filshie clips.

Results: There were no significant differences in the postoperative period between the three groups in the number of patients needing analgesia in the first 60 min postoperatively, the time to first analgesia, the rescue analgesic or antiemetic consumption, the incidence of postoperative nausea and vomiting, and the sedation and visual analogue pain scores.

Conclusions: From the data presented, we would not recommend routine transcervical administration of papaverine or bupivacaine for pain following laparoscopic sterilization.