Prevalence of pre-operative anaemia in surgical patients: a retrospective, observational, multicentre study in Germany.

Anaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time-period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in-hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre-operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non-anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13-6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83-19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre-operative anaemia (OR 2.08 (95%CI 1.42-3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09-5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98-1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86-2.69); p = 0.07). Pre-operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes.

High-throughput screening of multifunctional nanocoatings based on combinations of polyphenols and catecholamines.

Biomimetic surface coatings based on plant polyphenols and catecholamines have been used broadly in a variety of applications. However, the lack of a rational cost-effective platform for screening these coatings and their properties limits the true potential of these functional materials to be unleashed. Here, we investigated the oxidation behavior and coating formation ability of a library consisting of 45 phenolic compounds and catecholamines. UV-vis spectroscopy demonstrated significant acceleration of oxidation and polymerization under UV irradiation. We discovered that several binary mixtures resulted in non-additive behavior (synergistic or antagonistic effect) yielding much thicker or thinner coatings than individual compounds measured by ellipsometry. To investigate the properties of coatings derived from new combinations, we used a miniaturized high-throughput strategy to screen 2,532 spots coated with single, binary, and ternary combinations of coating precursors in one run. We evaluated the use of machine learning models to learn the relation between the chemical structure of the precursors and the thickness of the nanocoatings. Formation and stability of nanocoatings were investigated in a high-throughput manner via discontinuous dewetting. 30 stable combinations (hits) were used to tune the surface wettability and to form water droplet microarray and spot size gradients of water droplets on the coated surface. No toxicity was observed against eukaryotic HeLa cells and Pseudomonas aeruginosa (strain PA30) bacteria after 24 h incubation at 37 °C. The strategy introduced here for high-throughput screening of nanocoatings derived from combinations of coating precursors enables the discovery of new functional materials for various applications in science and technology in a cost-effective miniaturized manner.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

[Perioperative treatment of patients with long QT syndrome]. / Perioperative Betreuung von Patienten mit Long-QT-Syndrom.

Long QT syndrome (LQTS) is caused by a change in cardiac repolarization due to functional ion channel dysfunction which is associated with an elongation of the QT interval (hence the name) in the electrocardiogram and a predisposition to cardiac rhythm disorders (e.g. torsade de pointes, TdP) as well as cardiac events up to sudden cardiac death. There is a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The prevalence of cLQTS is 1 in 2000 but aLQTS is much more common and includes a grey area due to many asymptomatic patients. The LQTS is, therefore, more common than malignant hyperthermia which is much discussed in anesthesiology and has a reported prevalence in the population of 1:3000. Considering the prevalence of both aLQTS as well as cLQTS the importance of the LQTS seems to be underestimated in current perioperative care. Potential perioperative risks of such patients can be significantly reduced by appropriate patient management. This includes adequate preoperative preparation, the correct choice of anesthetic medication as well as adequate perioperative monitoring and preparedness for immediate pharmaceutical and electrical intervention in case of typical cardiac rhythm disturbances, such as TdP arrhythmia.

Efficacy and safety of 10% HES 130/0.4 versus 10% HES 200/0.5 for plasma volume expansion in cardiac surgery patients.

AIM: Hydroxyethyl starch (HES) solutions are frequently used for perioperative volume replacement. Whereas older HES specimen tended to accumulate in the plasma and to cause negative effects on hemostasis, more recent products, e.g., HES 130/0.4, are characterised by improved pharmacological properties. The present study was designed to compare the efficacy and safety of 10% HES 130/0.4 and 10% HES 200/0.5. METHODS: In this post-hoc analysis of a prospective, randomised, double-blind, multi-center therapeutic equivalence trial, 76 patients undergoing elective on-pump cardiac surgery received perioperative volume replacement using either 10% HES 130/0.4 (N.=37) or 10% HES 200/0.5 (N.=39) up to a maximum dose of 20 mL kg-1. RESULTS: Equivalent volumes of investigational medication were infused until 24 hours after the first administration (1577 vs. 1540 mL; treatment difference 37 [-150; 223] mL; P<0.0001 for equivalence). Whereas standard laboratory tests of coagulation were comparable between groups, von Willebrand factor activity on the first postoperative morning tended to be higher following treatment with 10% HES 130/0.4 as compared to 10% HES 200/0.5 (P=0.025) with this difference being statistically significant only in the per-protocol analysis (P=0.02). Treatment groups were comparable concerning other safety parameters and the incidence of adverse drug reactions. In particular, renal function was well preserved in both groups. CONCLUSION: Ten percent HES 130/0.4 was equally effective and safe as compared to 10% HES 200/0.5 for volume therapy in patients undergoing cardiovascular surgery. Postoperative coagulation and renal function, as measured by standard laboratory tests, were similar among groups.

[Perioperative monitoring of the QT interval]. / Perioperatives Monitoring des QT-Intervalls.

The feasibility of routine perioperative monitoring of the QT interval is demonstrated for the first time in two patients suffering from acquired long QT syndrome. These cases demonstrate that automatic perioperative monitoring of the QT interval is simple and easy to achieve. Besides sufficient premedication, normalized electrolytes, a calm and quiet atmosphere, avoiding QT prolonging drugs and the possibility of immediate defibrillation, monitoring of the QT interval should be considered in the perioperative treatment of these cardiac risk patients.

[Perioperative pharmacological myocardial protection. Systematic literature-based process optimization]. / Perioperative medikamentöse Kardioprotektion. Systematische Literaturübersicht als rationale Grundlage zur Prozessoptimierung.

Patients with major cardiac risk factors have been suggested to benefit from perioperative beta-blockade. However, the scientific literature on perioperative beta-blockade needs to be interpreted carefully. So far treatment recommendations for millions of patients are based on heterogeneous data from randomized trials with divergent study results. The evidence for a beneficial effect of perioperative beta-blockers is sufficient only for a limited subpopulation of high cardiac risk patients undergoing vascular surgery. Perioperative beta-blocker treatment is not useful in patients with intermediate risk and may even be harmful in patients with low cardiac risk. Therefore, an individualized risk-benefit analysis is an important prerequisite for a rational therapy that may be based on a standardized protocol including the Revised Cardiac Risk Index. Such a protocol is presented in this article. A recently reported trial (POISE) demonstrated that perioperative treatment with high doses of oral metoprolol efficiently reduces the incidence of cardiovascular events. However, due to severe adverse effects (hypotension, bradycardia, stroke) the total mortality was increased. Thus, dose adjustments, safety aspects, and monitoring of beta-blocker therapy seem to be mandatory. So far evidence from relevant trials about how to best implement perioperative beta-blockade is lacking. This article offers a simple clinical concept for this purpose.

Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis.

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.

Inhibition of HERG channels by the local anaesthetic articaine.

BACKGROUND AND OBJECTIVE: Articaine is an amide local anaesthetic widely used in dentistry. Human ether-a-go-go-related gene (HERG) potassium channels constitute potential targets involved in cardiotoxic side-effects of various pharmacological agents including amide local anaesthetics. The aim of this study was to determine the sensitivity of HERG channels to the inhibitory action of articaine and to further evaluate the effect of the mutations Y652A and F656A in the putative drug-binding region of HERG on the sensitivity for articaine. METHODS: We examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells by articaine. Whole cell patch-clamp recordings were performed at room temperature. RESULTS: Inhibition of HERG wild-type and HERG Y652A channels by articaine was concentration dependent and reversible. The concentration-response data were described by Hill functions (wild type: IC50 = 224 +/- 6 micromol L-1, Hill coefficient h = 1.17 +/- 0.03, n = 23; Y652A: IC50 = 360 +/- 48 micromol L-1, h = 0.93 +/- 0.08, n = 26). The mutation Y5652A decreased the sensitivity by factor 1.6. The mutation F656A decreased inhibition of inward tail currents by 300 micromol L-1 articaine in 100 mmol extracellular K+ 3-fold. CONCLUSIONS: Our results indicate that the local anaesthetic articaine does not inhibit HERG channels at clinically relevant concentrations. Articaine may therefore constitute a safer alternative for local and regional anaesthesia. The aromatic amino acid F656 rather than Y652 in the S6 region might play a role in interaction of the drug with the channel.

[Thalidomide for the treatment of recurrent gastrointestinal blood loss due to intestinal angiodysplasias]. / Thalidomide als behandeling bij recidiverend gastro-intestinaal bloedverlies op basis van intestinale angiodysplasieën.

Two female patients, 86 and 80 years of age, had been treated with blood transfusions for several years and several months, respectively, due to iron-deficiency anaemia caused by gastrointestinal blood loss. Angiodysplasias were detected and subsequently coagulated in the course of repeated gastroscopies and colonoscopies. Due to the failure of this treatment, treatment with thalidomide was started. Thereafter, the gastrointestinal bleeding stopped and there was no longer any need for blood transfusions. Treatment with thalidomide seems an effective therapy for patients with frequently recurring gastrointestinal blood loss due to angiodysplasias who no longer tolerate conventional and invasive procedures due to their physical condition.

Role of colonoscopic biopsy in distinguishing between Crohn's disease and intestinal tuberculosis.

BACKGROUND: The histological differential diagnosis of Crohn's disease and intestinal tuberculosis can be very challenging, as both are chronic granulomatous disorders with overlapping histological features. AIM: To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis. METHODS: 25 patients with Crohn's disease and 18 patients with intestinal tuberculosis were selected for this study on the basis of established clinical, radiological and histological criteria. Clinical data and selected histological parameters in colonoscopic biopsy specimens were assessed retrospectively. A total of 103 and 41 biopsy sites were evaluated in patients with Crohn's disease and intestinal tuberculosis, respectively. RESULTS: Clinical parameters helpful in differentiating intestinal tuberculosis from Crohn's disease included chest radiographic features of tuberculosis (56% v 0%), perianal fistulae (0% v 40%) and extraintestinal manifestations of Crohn's disease (0% v 40%). Histopathological features that seemed to reliably differentiate between intestinal tuberculosis and Crohn's disease included confluent granulomas, > or =10 granulomas per biopsy site and caseous necrosis (in biopsy samples of 50%, 33% and 22% of patients with intestinal tuberculosis, respectively, v 0% of patients with Crohn's disease). Features that were observed more often in patients with intestinal tuberculosis than in those with Crohn's disease included granulomas exceeding 0.05 mm(2) (67% v 8%), ulcers lined by conglomerate epithelioid histiocytes (61% v 8%) and disproportionate submucosal inflammation (67% v 10%). CONCLUSION: Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.

Decreased levels of mucosal detoxification enzymes in the pouch of patients with familial adenomatous polyposis.

BACKGROUND: Adenomas can develop in the pouch after colectomy with ileal pouch-anal anastomosis (IPAA) in patients with familial adenomatous polyposis (FAP). Glutathione S-transferases (GSTs) have a protective role in carcinogenesis. GST activity is much higher in the ileum than in the colon. The present study examined the hypothesis that the protective capacity of GSTs may be lowered as a result of colonic metaplasia of the ileal pouch. METHODS: Levels of GSTs, glutathione and cysteine, and the degree of inflammation and colonic metaplasia were quantified in biopsies from the pouch and afferent loop of 26 patients with FAP. RESULTS: GST enzyme activity, and levels of GST alpha, glutathione and cysteine in the pouch were significantly lower than those in the afferent loop (308 versus 398 nmol per min per mg protein (P<0.001), 4604 versus 5286 ng per mg protein (P=0.010), 27.1 versus 34.8 nmol per mg protein (P=0.023) and 0 versus 4.8 nmol per mg protein (P=0.009) respectively). No correlation was found between inflammation or colonic metaplasia of the pouch and GST enzyme activity in the pouch. CONCLUSION: After IPAA, GST detoxification activity in the pouch is significantly lower than that in the afferent ileal loop, which may promote tumorigenesis.

[Fast-track surgery in radical retropubic prostatectomy. First experiences with a comprehensive program to enhance postoperative convalescence]. / Radikale retropubische "Fast-track-Prostatektomie". Erste Erfahrungen mit einem interdisziplinären, multimodalen Behandlungskonzept zur Beschleunigung der postoperativen Rehabilitation.

Fast-track surgery is a comprehensive program for the optimization of perioperative care in elective surgery reducing potential postoperative complications and speeding up convalescence. Recent data from randomized colon resection trials emphasize that fast-track surgery is possible in most major operations. Our initial results in radical retropubic prostatectomy fast-track surgery have been encouraging. Fast-track surgery in major urological operations needs validation using randomized trials.

Local anaesthetic sensitivities of cloned HERG channels from human heart: comparison with HERG/MiRP1 and HERG/MiRP1 T8A.

BACKGROUND: Myocardial potassium channels are complexes formed by different subunits. The subunit composition may influence the cardiotoxic action of local anaesthetics. The effects of amide local anaesthetics on HERG channels co-expressed with the putative subunit MiRP1 have not been established. It is also unclear if the common polymorphism MiRP1(T8A) that predisposes individuals to drug-induced cardiac arrhythmia increases local-anaesthetic sensitivity of HERG/MiRP1 channels. This may suggest the presence of genetic risk factors for local-anaesthetic-induced cardiac arrhythmia. METHODS: Whole-cell patch-clamp recordings and site-directed mutagenesis were combined to compare local anaesthetic sensitivities of cloned and mutated human potassium channel subunits. The ion channels were activated by a protocol that approximated ventricular action potentials. RESULTS: The amide local anaesthetics bupivacaine, levobupivacaine and ropivacaine inhibited HERG channels at toxicologically relevant concentrations, with IC(50) values of 20 (SEM 2) micro M (n=29), 10 (1) micro M (n=40) and 20 (2) micro M (n=49), respectively. Hill coefficients were close to unity. There were no indications of qualitative differences in channel inhibition between the three anaesthetics. The putative subunit MiRP1 did not alter local anaesthetic sensitivity of HERG channels. The common single nucleotide polymorphism producing MiRP1(T8A) did not increase local anaesthetic sensitivity of HERG/MiRP1 channels. CONCLUSIONS: Amide local anaesthetics target HERG and HERG/MiRP1 channels with identical potency. The effects on these ion currents may significantly contribute to local-anaesthetic-induced cardiac arrhythmia. MiRP1(T8A) does not seem to confer an increased risk of severe cardiac side-effects to carriers of this common polymorphism.

Biophysical properties of Kv3.1 channels in SH-SY5Y human neuroblastoma cells.

Biophysical properties of delayed rectifier K channels in the human neuroblastoma SH-SY5Y were established using patch clamp recordings. The whole cell K+ conductance activated at membrane potentials positive to -20 mV. The midpoint of current activation was 9.6 +/- 5.1 mV, the equivalent charge was 3.7 +/-.6. Whole-cell currents inactivated slightly with time constants of 700 ms and 5 s. The K+ currents were sensitive to micromolar concentrations of TEA and 4-aminopyridine. RT-PCR experiments amplified a cDNA fragment specific for human Kv3.1 channels. Activation gating parameters in outside-out patches were shifted by approximately 14 mV in the hyperpolarizing direction.

Ketamine effects on human neuronal Na+ channels.

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 micromol). 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.

Lidocaine-induced cell death in a human model of neuronal apoptosis.

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.

Bupivacaine inhibits human neuronal Kv3 channels in SH-SY5Y human neuroblastoma cells.

BACKGROUND: Information on molecular targets that may be involved in the neurotoxicity of bupivacaine is limited. Suppression of Kv3 channels has been demonstrated to result in abnormal patterns in the electroencephalogram and in seizures. Inhibition of Kv3 channels by bupivacaine may consequently contribute to its neuroexcitatory side-effects. Data on the effects of bupivacaine on these potassium channels are lacking. We therefore characterized the effects of bupivacaine on human Kv3 channels natively expressed in SH-SY5Y cells. METHODS: Kv3 channels natively expressed in human SH-SY5Y cells were studied using a standard whole-cell patch-clamp protocol. RESULTS: Bupivacaine reversibly inhibited Kv3 channels in a concentration-dependent manner. The half-maximal inhibitory concentration (IC50) for conductance block was 57 microM and the Hill coefficient was close to unity. Bupivacaine accelerated macroscopic current decline by inducing inactivation-like behaviour. The midpoint of current activation was shifted to depolarized potentials in a concentration-dependent and reversible manner by a maximum of 26 mV. The IC50 was 47 microM and the Hill coefficient was 2.4. The free arterial plasma concentrations of bupivacaine that have been estimated to occur during convulsions in man would inhibit the Kv3 channels by at least 40% and would shift the midpoint of current activation by a minimum of 9 mV. CONCLUSIONS: Both inhibition of potassium channels and a depolarizing shift of their activation midpoint would increase neuronal excitability. The effects of bupivacaine on human Kv3 channels are thus compatible with a contributory role of Kv channel alteration in bupivacaine-induced neuronal excitation.