Background and objective: The effects of administering albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% on oxygen transport and left ventricular function were prospectively investigated in different experimental conditions: baseline, fluid load, after 10 min of myocardial ischaemia and after reperfusion.

Methods: Twenty-seven rabbits received at random one of three colloids in escalating boluses over 10–15 min to achieve left ventricular end-diastolic pressures (LVEDP) between 8 and 10 mmHg. A branch of the left anterior descending coronary artery was then temporarily occluded by a ligature and released after 10 min. Myocardial function was assessed using left ventricular pressure recordings and dimension data obtained from ultrasound crystals inserted onto the ventricular wall. Blood was sampled for the determination of oxygen delivery and consumption, the oxygen extraction ratio, acid-base status, and glucose and lactate concentrations.

Results: Administration of the colloids similarly increased oxygen delivery and improved left ventricular function in all groups. Peak rate of pressure development (dP/dtmax) and oxygen delivery were reduced during ischaemia and reperfusion. The decrease in dP/dtmax was more pronounced in the hydroxyethylstarch group.

Conclusions: Administration of albumin 5%, hydroxyethylstarch 6% and succinylated gelatine 4% had similar effects on oxygen delivery and myocardial function. After ischaemia and during reperfusion, the decrease in myocardial function was most pronounced with hydroxyethylstarch 6%.

Severe complications such as spinal epidural haematoma and an array of adverse neurological events leading to temporary or permanent disability have been ascribed to central neuraxial blocks. Infections (meningitis, abscesses), chemical injuries and very rarely cerebral ischaemia or haemorrhage, or both, have also been ascribed directly or indirectly to spinal and/or epidural anaesthesia. Some case reports, and very few retrospective studies, have focused their attention on the fact that central nerve blocks can cause, albeit rarely, permanent damage to the spinal cord or nerve roots, or both. The cause of this damage in many cases remains unclear. The attention of investigators and practitioners is focused both on understanding the causative mechanisms of such accidents and in identifying 'alarm events' that can arise during the administration of a central block, if any. We reviewed the international literature for the neurological complications of central neuraxial blocks to identify some events that, if they occurred during the block procedure, could be perceived as dangerous.

Background and objective: Cost consciousness has become increasingly important in anaesthesia as elsewhere in healthcare. Cost-minimization with uncompromised patient safety and quality requires systematic comparisons of alternative techniques. Inhalation anaesthesia with desflurane or sevoflurane is compared in this study with propofol delivered by the target controlled infusion technique. Directly measured drug consumption and costs and emergence times are compared.

Methods: Consumed anaesthetics were measured during elective arthroscopy of the knee, and costs were calculated for ASA I–II patients (n = 102) randomized to 3 groups: one group received anaesthesia using propofol administered by target controlled infusion, the others inhalation anaesthesia with either desflurane or sevoflurane in combination with nitrous oxide. A partial rebreathing system was used with a laryngeal mask airway. Vaporizers were weighed before and after each anaesthetic.

Results: Aaesthetic duration, postoperative pain and emesis as well as discharge time did not differ between groups. Inhaled anaesthetic techniques with desflurane or sevoflurane were associated with 2–3min shorter emergence times (P < 0.001) and approximately 45% lower cost for consumed anaesthetics as compared with propofol technique based on target controlled infusion. The inclusion of waste costs improved the cost reduction to 55%.

Conclusions: For this patient group, use of inhalation anaesthesia reduced drug costs by half and shortened emergence times compared to target controlled infusion with propofol with equal perioperative patient conditions.

Cocaine abuse is increasing, particularly among young people. It is no longer a drug used exclusively by higher socio-economic groups. This review highlights the dangers of both acute and chronic cocaine abuse and its lethal potential even on the first encounter. The systemic effects of cocaine are described along with the possible pathology that may present itself to the attending clinician.

Background and objective: Similar doses of ketamine are employed in regional and general anaesthesia. In contrast to commonly used local anaesthetic agents, accidental systemic application of local anaesthetic doses of ketamine will not result in seizure, dysrhythmia or cardiovascular depression. However, there is some doubt about the quality of regional analgesia induced by ketamine. As human sodium channels constitute an important molecular target of local anaesthetics, the study was designed to establish concentration-dependent effects of ketamine on conductance, steady-state activation and steady-state inactivation of human neuronal sodium channels. This information — that has, so far, not been published — will help to characterize further local anaesthetic properties of ketamine.

Methods: Whole-cell patch-clamp recordings were made of sodium channels natively expressed in human neuroblastoma SH-SY5Y cells.

Results: The sodium channels activated at a threshold of −60 mV and exhibited a maximal peak current at −10 mV. The voltage of half-maximal activation was −20 mV. The Na+ currents depended on the prepulse potential. The voltage of half-maximal inactivation was —80 mV. Ketamine inhibited the sodium conductance in a concentration-dependent manner (IC50 = 1140 µmol). A concentration-dependent hyperpolarizing shift of both steady-state activation and steady-state inactivation accounted for at most 5 mV.

Conclusions: The effects of ketamine on these human ion channels occur at clinical concentrations. They are consistent with the local anaesthetic action of ketamine. Whether ketamine helps to decrease the incidence of severe side-effects during regional anaesthesia needs to be addressed in further clinical studies.

Background and objective: We investigated whether an increase in anaesthesia staffing to permit induction of anaesthesia before the previous case had ended (‘overlapping’) would increase overall efficiency in the operating room. Hitherto, the average duration of operating sessions was too long, thus impeding the timely commencement of physicians' ward duties.

Methods: The investigation was designed as a prospective, non-randomized, interrupted time-series analysis divided into three phases: (a) a baseline of 3.5 months, (b) a 2.5 month intervention phase, in which anaesthesia staffing was increased by one attending physician and one nurse, and (c) a further 2 months under baseline conditions. Data focussed on process management were collected from operating room staff, anaesthesia personnel and surgeons using a structured questionnaire collected daily during the entire study.

Results: Turnover time between consecutive operations decreased from 65 to 52 min per operation (95% CI: 9; 17; P = 0.0001). Operating room occupancy increased from 4:28 to 5:27 h day−1 (95% CI: 50; 68; P = 0.005). The surgeons began their work on the ward 35 min (95% CI: 30; 40) later than before the intervention and their overtime increased from 22:36 to 139:50 h.

Conclusions: The time between surgical operations decreased significantly. Increased operating room efficiency owing to overlapping induction of anaesthesia allows more intense scheduling of operations. Thus, physicians and nurses can be released to spend more time with their patients in the ward. Improving the efficiency of the operating room alone is insufficient to improve human resource management at all levels of a surgical clinic.

Background and objective: Thiopental in clinically relevant concentrations inhibits the oxidative function of neutrophils, whereas only very high, non-therapeutic concentrations of methohexital induce a similar effect. The study characterized the molecular basis of this differential action of oxy- and thiobarbiturates on neutrophils.

Methods: Neutrophils were incubated in vitro with thiopental or methohexital using concentrations within the therapeutic range. Neutrophil responses were induced using different stimuli: N-formyl-L-methionyl-Lleucyl-L-phenylalanine (FMLP), C5a and 1,2-dioctanoyl-sn-glycerol (DiC8-DAG). FMLP and C5a bind to specific G-protein-coupled receptors that share the same second messenger cascade. In contrast, DiC8-DAG, an activator of protein kinase C, bypasses the signal transduction pathway downstream of the receptors. Hydrogen peroxide production by neutrophils was assessed using flow cytometry. To characterize the localization of the interaction site, FMLP receptor expression and cytosolic-free calcium were further analysed.

Results: FMLP and C5a-induced hydrogen peroxide production were both significantly impaired by thiopental, but not by methohexital. When postreceptor signalling was bypassed, by stimulation with DiC8-DAG, neither thiopental nor methohexital affected hydrogen peroxide production. Additionally, neither of the barbiturates impaired the cytosolic Ca2+ response.

Conclusions: We conclude that neither protein kinase C nor the hydrogen peroxide-generating enzymes are affected by thiopental or methohexital. The unimpaired Ca2+ response suggests that the function of the receptors and G-proteins were also unimpaired. Taken together, this indicates that the site of action of thiopental is in the cellular signalling upstream of protein kinase C.

Background and objective: Recent clinical studies comparing ropivacaine 0.25% with bupivacaine 0.25% reported not only comparable analgesia, but also comparable motor block for epidural analgesia during labour. An opioid can be combined with local anaesthetic to reduce the incidence of side-effects and to improve analgesia for the relief of labour pain. The purpose of the study was to evaluate the effects of epidural bupivacaine 0.2% compared with ropivacaine 0.2% combined with fentanyl for the initiation and maintenance of analgesia during labour and delivery.

Methods: Sixty labouring nulliparous women were randomly allocated to receive either bupivacaine 0.2% with fentanyl 2 μg mL−1 (B/F), or ropivacaine 0.2% with fentanyl 2 μg mL−1 (R/F). For the initiation of epidural analgesia, 8 mL of the study solution was administered. Supplemental analgesia was obtained with 4 mL of the study solution according to parturients’ needs when their pain was ≥4 on a visual analogue scale. Analgesia, hourly local anaesthetic use, motor block, patient satisfaction and side-effects between groups were evaluated during labour and at delivery.

Results: Sixty patients were enrolled and 53 completed the study. No differences in verbal pain scores, hourly local anaesthetic use or patient satisfaction between groups were observed. However, motor block was observed in 10 patients in the B/F group whereas only two patients had motor block in the R/F group (P < 0.05). The incidence of instrumental delivery was also higher in the B/F group than in the R/F group (P < 0.05).

Conclusions: The results suggest that epidural bupivacaine 0.2% and ropivacaine 0.2% combined with fentanyl produced equivalent analgesia for pain relief during labour and delivery. It is concluded that ropivacaine 0.2% combined with fentanyl 2 μg mL−1 provided effective analgesia with significantly less motor block and need for an instrumental delivery than a bupivacaine/fentanyl combination at the same concentrations during labour and delivery.

Background and objective: Parallels exist between the coma associated with cerebral malaria and general anaesthesia. They both produce reversible loss of consciousness. In the case of cerebral malaria and in the absence of other complications, patients recover without sequelae. General anaesthetics are so designed that patients recover from their anaesthetics very quickly and show no ‘after effects’. This study compares brain function in these two clinical conditions by examining auditory- (AEPs) and median nerve somatosensory-evoked potentials (SEPs). The AEPs studied (waves Pa and Nb) are thought to arise from the primary auditory cortex and the median nerve SEPs (waves P15, N20, P25, N35, P45) from the pons, thalamus and primary somatosensory cortices.

Methods: Six comatosed patients with malaria (three males, three females) aged between 19 and 38 yr were studied in Zimbabwe. Their Glasgow Coma Scores on admission were 4, 3, 6, 7, 7 and 11. Their AEPs and median nerve SEPs were recorded daily over 4 days. The data were compared with those previously collected in the UK on patients and volunteers anaesthetized with desflurane, isoflurane, sevoflurane and propofol.

Results: In general, patients with cerebral malaria showed AEPs and SEPs similar to those of light to moderate anaesthesia i.e. 0.5–1.25 measure of anaesthetic potency (MAC), where 1 MAC is the minimum alveolar concentration necessary to prevent movement to surgical incision in 50% of patients. The appearance of the AEPs and SEPs bore no relationship to the degree of coma. The auditory brainstem-evoked response was retained in all degrees of coma, as would be expected. Otherwise, it would not be possible to interpret the waveform. In most instances, the early cortical complex Pa/Nb/Pb of the AER was present. When comatose patients emerged from malarial coma or were stimulated by talking loudly to them, they showed changes in the Pa/Nb/Pb complex similar to those seen on awakening from anaesthesia. The somatosensory-evoked response showed clear P15, N20 and P25 peaks at the expected latencies, and in some instances the waveforms of cerebral malaria and lightly anaesthetized volunteers were very similar.

Conclusions: The sensory-evoked responses of the cerebral malaria patients recorded in this study were not markedly different from those seen in light-to-moderately anaesthetized patients and volunteers. The profound depression of the AEPs and SEPs associated with deeper levels of anaesthesia were not seen, with the exception of one patient several hours before death.

Background and objective: Clinical sedation assessment becomes insufficient in deeply sedated patients. Bispectral index as a processed electroencephalogram parameter provides a continuous and observer-independent value reported to change with sedation. The aim of this prospective observational study was to determine the reliability and possible confounding factors of the bispectral index to assess sedation in surgical intensive care patients.

Methods: Following major surgery, bispectral index, body temperature and electromyographic activity of 44 ventilated patients were recorded. Sedation levels were assessed with Ramsay sedation score.

Results: Although bispectral index correlated with Ramsay sedation score (-0.64; P < 0.01) we found that in deeply sedated patients temperature instability and electromyographic activity increased bispectral index. Bispectral index correlated significantly with electromyographic activity (0.80; P < 0.01) and with an increase of body temperature (0.55; P < 0.01) not only in all patients but also in clinically deeply sedated patients (0.57; P < 0.01 and 0.46; P < 0.05).

Conclusions: Only under certain conditions, such as low muscular activity and body temperature stability, may the bispectral index be a useful addition to clinical scoring in the sedation assessment of critically ill patients.

Background and objective: Pain following the injection of propofol is a common problem. It is often treated by the coadministration of intravenous lidocaine. Iontophoresis, which facilitates the delivery of charged molecules such as lidocaine to body tissues, may be a practical alternative to lessen the pain.

Methods: The iontophoretic application of lidocaine was compared with intravenous lidocaine to assess the relative efficacy of reducing pain during propofol administration.

Results: The incidence rate of moderate or severe pain was significantly greater in the iontophoresis group (26.7 compared with 6.9% in the intravenous lidocaine group) (P < 0.05).

Conclusions: The iontophoretic administration of lidocaine 60 mg does not compare favourably with lidocaine 40 mg mixed with propofol for the reduction of pain on administration of propofol.

Background and objective: Assessment of the effects of normovolaemic haemodilution on middle cerebral artery blood flow velocity with transcranial Doppler ultrasonography, intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery.

Methods: Normovolaemic haemodilution was induced in rabbits under general anaesthesia, and the haematocrit was allowed to decrease to 30% in Group 1 (n = 6) and to 20% in Group 2 (n = 6). Peak systolic and diastolic velocities, mean blood flow velocity, and pulsatility and resistance indices of the middle cerebral artery were measured by transcranial Doppler ultrasonography. Changes in intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery were also assessed.

Results: In Group 2, middle cerebral artery blood flow velocity increased from 0.4 ± 0.01 to 0.51 ± 0.02 m s−1 after the induction of normovolaemic haemodilution (P = 0.04), while arterial oxygen content decreased from 16.2 ± 0.1 to 8.5 ± 0.1 mL dL−1 (P = 0.002). The decrease in cerebral oxygen delivery from 6.5 ± 0.2 to 4.3 ± 0.2 was also significant (P = 0.02). However, no associated changes in intracranial pressure and cerebral perfusion pressure could be demonstrated.

Conclusions: Normovolaemic haemodilution resulted in an increase in the mean blood flow velocity of the middle cerebral artery. However, this increase did not compensate for the consequences of the altered oxygen delivery to the brain when the haematocrit was reduced to 20%

Background and objective: We reviewed retrospectively the anaesthetic management and perioperative course of eight right hepatectomies for living liver donation.

Methods: After preoperative psychiatric evaluation, eight ASA I–II individuals donated the right lobe of their liver to a family member. A graft-recipient body weight ratio of 0.8–1.0% was required for patient selection. Indications for liver transplantation were: hepatitis C viral-related cirrhosis in six patients; combined hepatitis C and B viral cirrhosis in one patient; multifocal hepatocellular carcinoma – four lesions, involving both liver lobes – of hepatitis C viral-related cirrhosis in another patient. Indication for adult-to-adult living-donor liver transplantation was retained in the latter because of rapid deterioration of liver disease, rare recipient's blood group and extended, unresectable hepatocellular carcinoma. Hepatitis C viral-related cirrhosis was casually the primary indication for adult-to-adult living-donor liver transplantation in this group. The condition of the donated hepatic lobe was optimized by appropriate drug and perfusion management. Preoperative investigations included: blood tests (full cell count and film, thyroid function tests, pregnancy tests, full virological tests and bacteriological cultures, and immunological typing), chest radiograph, electrocardiogram plus Doppler cardiac ultrasound, spirometry, aminopyrine breath test, liver Doppler examination, magnetic resonance imaging, angiography and cholangiography and a volumetric study of the whole liver and the right lobe. Haemoglobin and lactate concentrations, liver function tests and international normalized ratio were measured before and after operation. The volume and weight of the resected right lobe was calculated. Anaesthesia was induced with propofol 300 mL h−1 and sufentanil 0.3 μg kg−1 intravenously; cisatracurium, 0.15 mg kg−1, was given to facilitate tracheal intubation. Anaesthesia was maintained during normocapnic ventilation of the lungs with oxygen 40% in air, isoflurane 1–1.5 MAC and sufentanil. Routine anaesthetic monitoring included electrocardiography, pulse oximetry, invasive blood pressure, central venous pressure, urine output, state of neuromuscular blockade and core temperature. Periods of hypotension (< 80% of the preoperative blood pressure) or haemodynamic instability (requiring inotropic or vasoactive support) were registered. Total blood loss and transfusion (homologous, autologous or cell-saver blood) requirements were measured; volume replacements were derived.

Results: Data are presented as mean (range). There was no morbidity or mortality and no periods of intraoperative hypotension or haemodynamic instability. The operation time averaged 619 (525–780) min. Four donors were extubated in the operating room immediately after surgery; the others were extubated in the intensive care unit, where the mean extubation time was 16.3 (5–25) h after arrival. The estimated blood loss was 967 (550–1600) mL. No homologous blood was administered; five donors received autologous blood,intraoperatively; three donors received a cell-saver blood transfusion. Intraoperative fluid replacement was with crystalloids, colloids and 4% albumin. Total urine output was 1472 (700–3100)mL. Although intraoperative hypothermia occurred all subjects were normothermic at the end of operation. The pre- and immediately postoperative haemoglobin concentration averaged 13.6 (9.8–15.6) and 10.5 (6.9–13.0) g dL−1 respectively. On the first postoperative day, the haemoglobin was 11.7 (8.4–15.1) g dL−1. The donors' liver function tests were transiently elevated in the initial postoperative period. The intensive care unit discharge time was 2 (1–3) days. The hospital stay was 13 (7–17) days. There was no morbidity or mortality.

Conclusions: The study demonstrates that right-lobe living-donor surgery was well tolerated, without intraoperative hypotension or haemodynamic instability, without perioperative anaesthetic or surgical complications, and with an excellent general outcome.

Background and objective: Liver transplantation is characterized by several changes in intravascular blood volume due to vasodilatation based on neurohumoral mediators, intraoperative bleeding and anaesthesia technique effects. Today, with the transpulmonary indicator dilution technique, cardiac index (CIart) can be evaluated and preload assessed in terms of the intrathoracic blood volume index (ITBVI). The aim was to analyse in patients undergoing liver transplantation two preload variables, pulmonary artery occlusion pressure (PAOP) and ITBVI with respect to cardiac index (CIpa) and stroke volume index (SVIpa), the correlation between ITBVI and PAOP, and secondary the relationship between the changes (Δ) of ITBVI and PAOP and the changes of CIpa and SVIpa, and the relationships between ΔITBVI and ΔPAOP. The reproducibility and precision of all CIart and CIpa measurements were also evaluated.

Methods: A prospective study was performed in 60 patients monitored with a pulmonary artery catheter and with the PiCCO® system. The variables were evaluated with a linear regression model.

Results: Linear regression analysis between ITBVI-CIpa and ITBVI-SVIpa were r2 = 0.47 (P < 0.0001) and r2 = 0.55 (P < 0.0001) respectively, while PAOP poorly correlated to CIpa (r2 = 0.02), SVIpa (r2 = 0.015) and ITBVI (r2 = 0.002). Only changes in ITBVI were correlated with changes in CIpa (Δ1, r2 = 0.37; Δ2, r2 = 0.32), and SVIpa (Δ1, r2 = 0.60; Δ2, r2 = 0.47). The mean bias between CIart and CIpa was 0.13 L min−1 m−2 (2 SD = 1.04 L min−1m−2) (r2 = 0.86, P < 0.0001).

Conclusions: In comparison with PAOP, ITBVI seems a more reliable indicator of cardiac preload in patients undergoing liver transplantation.

Background and objective: Operating room management structures and interrelationships both within the operating suite and with other departments in the hospital can be very complex. Several different professional and support groups are represented that often have infrastructures of their own that may compete or conflict with the management hierarchy in the operating room. Today, there is often little actual management of the operating suite as an entity. We surveyed current operating room management in Switzerland.

Methods: A questionnaire was sent to the chief anaesthesiologists of all public hospitals in Switzerland. It asked for information about the structure, organization and management of operating rooms as well as respondents’ opinions and expectations about management. Derived from both the literature and the results of the survey, a ‘stages of excellence’ model of best practice was developed.

Results: The overall response rate was 70%. Most anaesthesiologists were unsatisfied with current management policies and structures in their operating rooms. Of the hospitals questioned, 40% did not have an information system at all for the operating rooms. The remaining 60% had an information system that allowed rough scheduling in 71%, but only a few had more sophisticated systems that enabled dynamic scheduling (19%), user-defined conflict checking (5%), administration of a subsequent patient transfer station (postanaesthesia care units, intensive medical care, intensive care units) (10%) or other more advanced uses. All hospitals questioned offered some type of ambulatory surgery in a ‘hospital-integrated’ manner (i.e. use of the same operating room for both in- and outpatient surgery), but none had implemented a more efficient system where outpatient surgery was performed in separate facilities.

Conclusions: Current management of the operating room in Switzerland is far from best-practice standards.

Background and objective: Doppler echocardiography of diastolic transmitral flow velocity is more sensitive for the detection of myocardial ischaemia in awake patients than echocardiographic analysis of systolic wall motion. However, its diagnostic value in anaesthetized patients is unknown.

Methods: Doppler indices of diastolic transmitral flow velocity previously found to be highly sensitive for detecting ischaemia in awake patients were studied in 72 anaesthetized patients with documented coronary artery disease undergoing dobutamine stress echocardiography. These Doppler indices were compared with standard echocardiographic and electrocardiographic criteria for ischaemia.

Results: Sixty-five patients showed evidence of ischaemia by standard echocardiographic and/or electrocardiographic criteria, and seven patients did not. Regardless of evidence of ischaemia by standard criteria, the Doppler indices changed similarly in both groups. Accordingly, only a minority of anaesthetized patients displayed the changes in Doppler indices of diastolic transmitral flow previously suggested to be sensitive for detecting ischaemia.

Conclusions: The results do not confirm the diagnostic value of Doppler echocardiography of diastolic transmitral flow velocity for detecting ischaemia in anaesthetized patients undergoing dobutamine stress echocardiography during positive-pressure ventilation of the lungs.

Background and objective: To elucidate the effects of various degrees of hypotension induced by the calcitonin gene-related peptide (CGRP) on the splanchnic circulation, we investigated the renal and hepatic blood flow during hypotension induced by either the calcitonin gene-related peptide or sodium nitroprusside in the isofluraneanaesthetized dog.

Methods: Anaesthesia was maintained with 1.3% isoflurane in oxygen. After the baseline period, mean arterial pressure was reduced to 60 mmHg in the CGRP60 and nitroprusside groups, and to 50 mmHg in the CGRP50 group. The splanchnic organ blood flow was measured by hydrogen clearance.

Results: The cardiac index in the CGRP60 group increased (P < 0.01), but in the CGRP50 group it decreased (P < 0.01), and in the nitroprusside group it remained unchanged during hypotension. Mean pulmonary artery and pulmonary capillary wedge pressures in the CGRP60 group remained unchanged, but in the CGRP50 and nitroprusside groups they decreased (P < 0.01) during hypotension. Cardiac contractility in the CGRP60 group remained unchanged, whereas in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) during hypotension. Renal blood flow in the CGRP60 group was relatively well maintained but in the CGRP50 and nitroprusside groups it was reduced (P < 0.01) throughout the observation. Hepatic blood flow in all three groups was reduced (P < 0.01) during hypotension. The reductions in hepatic blood flow between the Calcitonin gene-related peptide groups were associated with a dose-dependent decrease in mean arterial pressure.

Conclusions: The results suggest that calcitonin gene-related peptide acts as an arteriolar vasodilator at low doses but as a vasodilator of the arteriolar and venous systems at higher doses, and that profound hypotension induced by the calcitonin gene-related peptide may impair splanchnic circulation.

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: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics.

Methods: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry.

Results: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations.

Conclusions: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.

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.