Search

The primary aim of this study was to assess the incidence of a difficult airway and emergency tracheostomy in patients with orofacial infections originating in the mandible, and a secondary aim was to determine the potential predictors of difficult intubation. This retrospective single-center study included all patients who were referred between 2015 and 2022 with an orofacial infection originating in the mandible and who were surgically drained under intubation anesthesia. The incidence of a difficult airway regarding ventilation, laryngoscopy, and intubation was analyzed descriptively. Associations between potential influencing factors and difficult intubation were examined via multivariable analysis. A total of 361 patients (mean age: 47.7 years) were included in the analysis. A difficult airway was present in 121/361 (33.5%) patients. Difficult intubation was most common in patients with infections of the massetericomandibular space (42.6%), followed by infections of the mouth floor (40%) and pterygomandibular space (23.5%). Dyspnea and stridor were not associated with the localization of infection (p = 0.6486/p = 0.4418). Multivariable analysis revealed increased age, restricted mouth opening, higher Mallampati scores, and higher Cormack–Lehane classification grades as significant predictors of difficult intubation. Higher BMI, dysphagia, dyspnea, stridor and a non-palpable mandibular rim did not influence the airway management. Patients with a difficult airway were more likely to be admitted to the ICU after surgery than patients with regular airway were (p = 0.0001). To conclude, the incidence of a difficult airway was high in patients with orofacial infections originating in the mandible. Older age, limited mouth opening, a higher Mallampati score, and a higher Cormack–Lehane grade were reliable predictors of difficult intubation.

ZusammenfassungEine der größten Limitationen in der Anwendung von Lokalanästhetika liegt in ihrer begrenzten Wirkdauer. In den letzten Jahren wurden liposomale Formulierungen mit prolongierter Freisetzungskinetik entwickelt, um die pharmakologische Wirkdauer der einzeitigen peripheren Regionalanästhesie („Single-shot-Verfahren“) zeitlich „zu strecken“ und somit eine verlängerte Therapiedauer zu bewirken. Im Fokus stehen hierbei insbesondere das Erreichen einer postoperativen Schmerzfreiheit von mindestens 24 h (oder besser sogar 48 h) und dadurch eine frühzeitige Mobilisation der Patienten unter Bedarfsmedikation bei allenfalls geringfügig erhaltener sensorischer Blockade und ohne motorische Einschränkungen (so zumindest die Idealvorstellung). Eine solche moderne pharmakologische Option mit theoretisch deutlich verlängerter Wirkdauer findet sich hierbei in der Gruppe der Amidlokalanästhetika, das liposomale Bupivacain. Bedingt durch einen multivesikulären Liposomenaufbau führt die retardierte Freisetzung der aktiven Komponente Bupivacain-HCl zu einer theoretischen pharmakologischen Wirksamkeit bis zu 72 h. In bisherigen Studien zeigte sich dabei konsistent ein vergleichbares Sicherheitsprofil zum herkömmlichen Bupivacain-HCl. Seit 2011 ist das liposomale Bupivacain unter dem Handelsnamen Exparel© (Fa. Pacira Pharmaceuticals, Parsippany, NJ, USA) von der amerikanischen Food and Drug Administration (FDA) zugelassen. Die Anwendung ist derzeit jedoch auf lokale Wundinfiltration, „Transversus-abdominis-plane“(TAP)-Blockaden und interskalenäre Nervenblockaden des Plexus brachialis beschränkt. Im Jahr 2020 erteilte auch die Europäische Arzneimittel-Agentur (EMA) dem Einsatz des liposomalen Bupivacains für Blockaden des Plexus brachialis oder des N. femoralis sowie als Feldblock bzw. zur Wundinfiltration zur Behandlung postoperativer Schmerzen eine Zulassung. Bislang zeigte sich die Studienlage zur klinischen Effektivität des liposomalen Bupivacains stark heterogen. Aktuelle Metaanalysen, welche die Ergebnisse randomisierter, kontrollierter Studien zur analgetischen Wirksamkeit des liposomalen Bupivacains in verschiedenen Anwendungsbereichen zusammenfassen, weisen nun konsensuell keinen klinisch relevanten Benefit durch die neue liposomale Formulierung nach und erbringen ausreichend Evidenz, um den Diskurs um das liposomale Bupivacain beenden zu können. Ziel dieser Arbeit ist es, dem Leser einen aktuellen evidenzbasierten Überblick zu dieser Substanz zu geben.

One of the main limitations concerning the use of local anesthetics is due to their restricted duration of action. In recent years, liposomal formulations with prolonged release kinetics have been developed to extend the pharmacological duration of action of the 1‑stage peripheral regional anesthesia (single-shot procedure) and thus bring about a longer duration of action. The focus here is particularly on achieving postoperative freedom from pain for at least 24 h (or even better 48 h) and thus early mobilization of patients using on-demand medication causing (at most) minor local sensory blockade without causing motor impairments (at least that is the ideal). Therefore, methods of utilizing slow-release drugs as seen in liposomal carrier systems have experienced increasing scientific attention in the last few years. A common modern pharmacological example with a theoretically significantly longer duration of action is liposomal bupivacaine, an amide local anesthetic. Due to a multivesicular liposome structure, the retarded release of the active component bupivacaine HCl leads to a theoretical pharmacological effectiveness of up to 72 h. Previous studies consistently showed a safety profile comparable to conventional bupivacaine HCl. Liposomal bupivacaine has been approved by the U.S. Food and Drug Administration (FDA) under the trade name Exparel© (Pacira Pharmaceuticals, Parsippany, NJ, USA) since 2011; however, its use is currently limited to local wound infiltration, transverse abdominis plane (TAP) blocks, and interscalene nerve blocks of the brachial plexus. In 2020, the European Medicines Agency (EMA) also approved the use of liposomal bupivacaine for blockade of the brachial plexus or the femoral nerve and as a field block or for wound infiltration to treat postoperative pain. So far, studies on the clinical effectiveness of liposomal bupivacaine have been very heterogeneous and there have been no conclusive meta-analyses with sufficient rigor or significance. Recent systematic reviews and meta-analyses, combining the results of clinical studies regarding the analgesic efficiency of liposomal bupivacaine in different fields of application, consistently refuted any benefit of clinical relevance provided by the liposomal formulation. There is currently sufficient evidence to now end the ongoing debate around liposomal bupivacaine. The aim of this work is to give the reader a current, evidence-based overview of this substance.Eine der größten Limitationen in der Anwendung von Lokalanästhetika liegt in ihrer begrenzten Wirkdauer. In den letzten Jahren wurden liposomale Formulierungen mit prolongierter Freisetzungskinetik entwickelt, um die pharmakologische Wirkdauer der einzeitigen peripheren Regionalanästhesie („Single-shot-Verfahren“) zeitlich „zu strecken“ und somit eine verlängerte Therapiedauer zu bewirken. Im Fokus stehen hierbei insbesondere das Erreichen einer postoperativen Schmerzfreiheit von mindestens 24 h (oder besser sogar 48 h) und dadurch eine frühzeitige Mobilisation der Patienten unter Bedarfsmedikation bei allenfalls geringfügig erhaltener sensorischer Blockade und ohne motorische Einschränkungen (so zumindest die Idealvorstellung). Eine solche moderne pharmakologische Option mit theoretisch deutlich verlängerter Wirkdauer findet sich hierbei in der Gruppe der Amidlokalanästhetika, das liposomale Bupivacain. Bedingt durch einen multivesikulären Liposomenaufbau führt die retardierte Freisetzung der aktiven Komponente Bupivacain-HCl zu einer theoretischen pharmakologischen Wirksamkeit bis zu 72 h. In bisherigen Studien zeigte sich dabei konsistent ein vergleichbares Sicherheitsprofil zum herkömmlichen Bupivacain-HCl. Seit 2011 ist das liposomale Bupivacain unter dem Handelsnamen Exparel© (Fa. Pacira Pharmaceuticals, Parsippany, NJ, USA) von der amerikanischen Food and Drug Administration (FDA) zugelassen. Die Anwendung ist derzeit jedoch auf lokale Wundinfiltration, „Transversus-abdominis-plane“(TAP)-Blockaden und interskalenäre Nervenblockaden des Plexus brachialis beschränkt. Im Jahr 2020 erteilte auch die Europäische Arzneimittel-Agentur (EMA) dem Einsatz des liposomalen Bupivacains für Blockaden des Plexus brachialis oder des N. femoralis sowie als Feldblock bzw. zur Wundinfiltration zur Behandlung postoperativer Schmerzen eine Zulassung. Bislang zeigte sich die Studienlage zur klinischen Effektivität des liposomalen Bupivacains stark heterogen. Aktuelle Metaanalysen, welche die Ergebnisse randomisierter, kontrollierter Studien zur analgetischen Wirksamkeit des liposomalen Bupivacains in verschiedenen Anwendungsbereichen zusammenfassen, weisen nun konsensuell keinen klinisch relevanten Benefit durch die neue liposomale Formulierung nach und erbringen ausreichend Evidenz, um den Diskurs um das liposomale Bupivacain beenden zu können. Ziel dieser Arbeit ist es, dem Leser einen aktuellen evidenzbasierten Überblick zu dieser Substanz zu geben.

Background and aims At present, “severe acute respiratory syndrome new coronavirus” (SARS-CoV-2) affects the whole world and has led to a pandemia with almost 2.000.000 infected patients in the mid of April 2020 (WHO). Thus, health care specialists primarily focus on therapy of corona disease 2019 (COVID-19) and a lot of effort has been undertaken to get more manpower on intensive care units. However, the number of patients with life threatening diseases other than COVID-19 like heart attacks or strokes has not changed at all. With a strong focus on COVID-19, there is a marked risk of diagnostic and therapeutic delays or misdiagnoses, potentially harming those patients. In this respect, we present two of those cases with the intent to improve the medical management of “traditional“ diseases in times of corona pandemia. Methods We present two patients with diseases others than SARS-CoV-2. Both cases were treated in our institution, a tertiary care hospital in the Southwest of Germany. Results One patient had a prolonged treatment on intensive care unit (ICU) because of heart failure following voluntary isolation because of fearing COVID-19 and subsequent shortage of medication. Another patient with hypothesis of COVID-19 of primary care physician because of fever and a history of skiing in a high risk region for SARS-CoV-2 was sent home for isolation. After disease progression, the patient presented in an external hospital with fever, pain in the right ear and tachypnea. Immediately, antibiotics were started at same day, but nevertheless, he developed a septic shock, leading to multi organ failure. In blood samples, bacteria Streptococcus pyogenes was found, without any signs of SARS-CoV-2-infection. Despite adequate antibiosis, the patient developed fixed pupils, brain edema and died because of massive brain edema. Conclusion Focusing only on COVID-19 may lead to delayed diagnosis and therapy in patients with “traditional diseases”. These two cases impressively clarify medical challenges in times of SARS-CoV-2 pandemia. It is important to emphasize that physicians and health care professionals have not only to focus on COVID-19 and virus associated diseases, but also on adequate drug supply, intake and monitoring and differential diagnoses, respectively.

A 59 year old male patient was admitted to our hospital diagnosed with COVID-19 associated pneumonia. Upfront treatment with hydroxychloroquine and azithromycin was started. Because of clinical deterioration with ARDS, circulatory shock and increased hyperinflammatory markers six days later, a cytokine storm rose to the top of differential diagnosis and off-label treatment with IL 6 receptor antagonist Tocilizumab was initiated. Subsequently we observed a dramatic rise of D-dimers indicating coagulopathy. Perimyocarditis with severe cardiac arrhythmia occurred after a second dose was administered. Later the patient died due to multi organ failure. Exacerbation of cytokine storm following treatment with Tocilizumab could not be ruled out, despite a hitherto unreported relationship with COVID-19.

Zusammenfassung Hintergrund und Fragestellung Ziel der Untersuchung war es, die Rolle der Videolaryngoskopie (VL) im individuellen Atemwegsmanagement von Notärzten zu evaluieren, wenn eine Vielzahl von Hilfsmitteln zur Atemwegssicherung verfügbar ist. Material und Methoden Mittels Online-Umfrage wurde neben den verfügbaren Hilfsmitteln der persönliche Algorithmus zur Atemwegssicherung erfragt (5 mögliche Schritte, 6 verfügbare Hilfsmittel: endotracheale Intubation ggf. mit Einführhilfe [ETI], VL, supraglottische Atemwegshilfe [SGA], McCoy-Spatel [McC], Masken-Beutel-Beatmung [MB], chirurgischer Atemweg [CHIR]). Dieser wurde mit der aktuellen Handlungsempfehlung zum präklinischen Atemwegsmanagement verglichen. Ergebnisse 155 Teilnehmer zeigten insgesamt 65 verschiedene Vorgehensweisen (ETI-VL-SGA-MB-CHIR am häufigsten [20%]). Die VL wurde meistens als 2. (31%) oder 3. Wahl (25%) nach der ETI verwendet und in 9% als 1. Wahl. Somit vergrößerte sich die Anzahl an Algorithmusschritten unter Nutzung der VL signifikant, was eine nachrangigere Anwendung von SGA und CHIR bedingte. 80% der erfassten Vorgehensweisen wichen von dem Algorithmus aus 2012 ab. Diskussion Der erwartete höhere Stellenwert der VL in der kommenden Handlungsempfehlung sollte zu einem höheren Einhaltungsgrad führen. Nach ihrer Umsetzung sollten Einhaltung bzw. Abweichung sowie individuelle Gründe für die verwendeten Atemwegshilfsmittel untersucht werden, ebenso, ob die VL primär oder als Rückfallebene verwendet wird.

Local anesthetics, especially bupivacaine, have myotoxic effects in clinically used concentrations and context. Detailed mechanisms of these effects are unknown, but an increase in intracellular calcium levels is suspected to be the most important trigger. Dantrolene and caffeine modify cellular calcium release from the sarcoplasmic reticulum. The aim of our study was to investigate the effect of dantrolene and caffeine on bupivacaine-induced myotoxicity in vitro.A cell culture model of primary muscle cells of BALB/c AnNCrl mice was established. Cells were incubated simultaneously with increasing concentrations of bupivacaine, dantrolene, and caffeine. The fraction of dead cells was calculated after staining with propidium iodide and analysis by flow cytometry. The half-maximal inhibitory concentration of bupivacaine was calculated for each concentration. Group differences were determined by using 1-way analysis of variances with subsequent post hoc 1-way Dunnett t test.Both dantrolene and caffeine alone had no effect on muscle cell survival. Increasing concentrations of bupivacaine caused increasing cell death. Dantrolene dose-dependently reduced the fraction of necrotic cells, whereas caffeine dose-dependently increased the fraction of dead cells.Dantrolene attenuated, and caffeine enhanced, bupivacaine-induced myotoxicity, presumably by modifying sarcoplasmic calcium release. This indicates that intracellular calcium release is an important factor for local anesthetic-induced cell death.

In den letzten Jahren zeichnet sich ein deutlicher Trend ab, dass anasthesiologische Leistungen vermehrt auch auserhalb des OP-Saals durchgefuhrt werden. In diesem Kapitel sollen nun neben allgemeinen Uberlegungen zu personellen, raumlichen und apparativen Anforderungen sowie zu geeigneten Anasthesie- und Sedierungstechniken die Besonderheiten der im Ausenbereich durchgefuhrten Eingriffe dargestellt werden.

Background The use of lipid emulsions to reduce cardiac toxicity of local anaesthetics (LAs) has shown success in experimental studies and some clinical cases, and thus has been implemented in clinical practice. However, lipid treatment is usually given after the occurrence of neurological or cardiovascular symptoms of systemic intoxication. The aim of this study was to determine if pretreatment with lipid emulsion reduces cardiac toxicity produced by bupivacaine or mepivacaine. Methods Isolated rat hearts were perfused with or without lipid emulsion (0.25 ml kg −1 min −1 ) before administration of equipotent doses of bupivacaine (250 µM) or mepivacaine (1000 µM). Haemodynamic parameters and times from start of perfusion LA to a 1 min period of asystole and recovery were determined. Results Pretreatment with lipid emulsion extended the time until occurrence of asystole and decreased times to recovery in bupivacaine-induced cardiac toxicity but not in mepivacaine-induced cardiac toxicity compared with control. Lipid pretreatment impaired rate–pressure product recovery in mepivacaine-intoxicated hearts. Conclusions This study confirms that pretreatment with a lipid emulsion reduces cardiac toxicity of LAs. The efficacy of pretreatment with lipid emulsion was LA-dependent, so pharmacokinetic properties, such as lipophilicity, might influence the effects of lipid emulsion pretreatment.

Intraarticular injections of local anesthetics are frequently used as part of multimodal pain regimens. However, recent data suggest that local anesthetics affect chondrocyte viability. In this study, we assessed the chondrotoxic effects of mepivacaine, ropivacaine, and bupivacaine. We hypothesized that specific cytotoxic potencies directly correlate with analgesic potencies, and that cytotoxic effects in intact cartilage are different than in osteoarthritic tissue.Human articular chondrocytes were exposed to equal and equipotent concentrations of bupivacaine, ropivacaine, and mepivacaine for 1 hour. Cell viability, apoptosis, and necrosis were determined at predefined time points using flow cytometry, live-dead staining, and caspase detection. Intact and osteoarthritic human cartilage explants were treated with equipotent concentrations of named drugs to determine cell viability applying fluorescence microscopy.Chondrotoxic effects increased from ropivacaine to mepivacaine to bupivacaine in a time-dependent and concentration-dependent manner. Compared with control, bupivacaine 0.5% decreased chondrocyte viability to 78% ± 9% (P = 0.0183) 1 hour and 16% ± 10% (P0.0001) 24 hours later, as determined by live-dead staining in monolayer cultures. Viability rates were reduced to 80% ± 7% (P = 0.0475) 1 hour and 80% ± 10% (P = 0.0095) 24 hours after treatment with ropivacaine 0.75%. After exposure to mepivacaine 2%, viable cells were scored 36% ± 6% (P0.0001) after 1 hour and 30% ± 11% (P0.0001) after 24 hours. Ropivacaine treatment was less chondrotoxic than bupivacaine (P = 0.0006) and mepivacaine exposure (P = 0.0059). Exposure to concentrations up to 0.25% of bupivacaine, 0.5% of ropivacaine, and 0.5% of mepivacaine did not reveal significant chondrotoxicity in flow cytometry. However, chondrotoxicity did not correlate with potency of local anesthetics. Immediate cell death was mainly due to necrosis followed by apoptosis. Cellular death rates were clearly higher in osteoarthritic compared with intact cartilage after bupivacaine, mepivacaine, and ropivacaine treatment in a decreasing order.Bupivacaine, ropivacaine, and mepivacaine are chondrotoxic in a time-dependent, concentration-dependent, and drug-dependent manner. Chondrotoxic and analgesic potencies do not directly correlate. Cellular death rates were higher in osteoarthritic compared with intact cartilage after local anesthetic treatment.

Context and objectives The present study was designed to investigate whether 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') increases the sensitivity of the contractile apparatus to calcium in muscle fibres from malignant hyperthermia-susceptible and malignant hyperthermia-negative pigs, whether it causes calcium ion release from the sarcoplasmic reticulum and whether it inhibits calcium reuptake into the sarcoplasmic reticulum. Design Experimental study, using a model of porcine saponin-skinned fibres. Results Administration of MDMA in concentrations of 1, 2 and 4 mmol l(-1)l did not result in relevant force transients in skinned muscle fibres of malignant hyperthermia-susceptible or malignant hyperthermia-negative pigs. Furthermore, MDMA in these concentrations did not alter calcium ion loading of the sarcoplasmic reticulum in either group. With regard to changes in the calcium ion sensitivity of the contractile proteins, however, MDMA dose-dependently increased (pCa50) values (negative decadic logarithm of [Ca2+] at which isometric force is half-maximal) in both groups. Conclusion In the present study, we were able to demonstrate that MDMA dose-dependently increases the sensitivity of the contractile apparatus to calcium in both malignant hyperthermia-susceptible and malignant hyperthermia-negative fibres. Consequently, the malignant hyperthermia status should not affect the calcium sensitivity of the contractile apparatus. However, the increased calcium sensitivity is an important finding that must be appreciated, particularly in relation to the agonistic effect of MDMA at the nicotinic acetylcholine receptor, which increases intracellular calcium ion concentrations.

Background In the immature brain, neuronal Ca2+ oscillations are present during a time period of high plasticity and regulate neuronal differentiation and synaptogenesis. In this study we examined the long-term blockade of hippocampal Ca2+ oscillations, the role of the N-methyl-D-aspartate (NMDA) receptors and the effects of S(+)-ketamine on neuronal synapsin expression. Methods Hippocampal neurons were incubated at day 15 in culture with the specific NMDA receptor antagonists dizocilpine (MK 801, 100 μM) or S(+)-ketamine (3 μM to 25 μM) for 24 hours. Terminal-deoxynucleotidyl-transferase (TUNEL) and activated caspase3 were used to detect apoptotic neurons. Ca2+ oscillations were detected after loading the neurons with the Ca2+-sensitive dye fura-2AM, and dual wavelength excitation fluorescence microscopy was performed. Ca2+/calmodulin kinase II (CaMKII) was measured using Western blots. Synapsin was identified with confocal antisynapsin immunofluorescence. Results Blocking the NMDA receptor with MK 801 or 25 μM S(+)-ketamine resulted in a significant increase in apoptotic neurons. MK 801 led to a significant increase in cytosolic Ca2+ concentration and reduction of the amplitude and frequency of the Ca2+ oscillations. Similar to MK 801, the long-term application of S(+)-ketamine resulted in a significant increase in cytosolic Ca2+ concentration 24 hours after washout. This was associated with a down-regulation of the CaMKII and a reduction of the synapsin 24 hours after washout. Conclusion Neuronal Ca2+ oscillations mediate neuronal differentiation and synaptogenesis via activating CaMKII. By acting via the NMDA receptor, S(+)-ketamine exerts its toxic effect through the suppression of neuronal Ca2+ oscillations, down-regulation of the CaMKII, and consecutively reduced synaptic integrity.

Okonomische Fragestellungen und Handlungsinstrumente werden im Zuge knapper werdender personeller (Pflege und Arzte) und finanzieller Ressourcen fur die Medizin immer bedeutender. Um einen gewissen Grad an Autonomie fur einzelne klinische Abteilungen und deren Leiter gegenuber Sozialversicherungstragern und Klinikverwaltungen zu wahren, ergibt sich fur Arzte daher die zunehmende Notwendigkeit, wirtschaftliche Planungen und Konzepte erarbeiten und verstehen zu konnen. Die vorliegende Arbeit bietet in diesem Zusammenhang einen Ansatz zur Planung einer anasthesiologischen Abteilung mithilfe einer ”Strengths“, ”Weaknesses“, ”Opportunities“ und ”Threats“ (SWOT)-Analyse. Hierzu werden die Verfahren der strategischen Planung beispielhaft dargestellt und anhand einer fiktiven exemplarischen Klinik praktisch verdeutlicht.

Objectives Malignant hyperthermia susceptibility is an important risk factor during general anesthesia. Affected patients have an asymptomatic but potentially lethal hypermetabolic reaction after contact with volatile anesthetics or succinylcholine. Classic symptoms include hemodynamic instability, combined with acidosis, rigor, and hyperthermia. During cardiopulmonary bypass, these signs may be obscured, delaying correct diagnosis and lifesaving treatment. Malignant hyperthermia–susceptible individuals are more sensitive to heat and stress, so rewarming and catecholamine administration may trigger an episode, necessitating prophylactic measures. Methods This systematic review identified typical malignant hyperthermia symptoms during cardiopulmonary bypass and investigated other factors in cardiac surgery that might trigger an episode in susceptible individuals. Approaches used to treat and prevent malignant hyperthermia during cardiopulmonary bypass were systematically analyzed. We conducted a systematic search for reports about malignant hyperthermia and cardiopulmonary bypass. Search terms included malignant hyperthermia and cardiopulmonary bypass, extracorporeal circulation, or cardiac surgery. Results We found 24 case reports and case series including details of 26 patients. In 14 cases, malignant hyperthermia crises during or shortly after cardiopulmonary bypass were described. Fourteen reports discussed prevention of an episode. Early symptoms of a malignant hyperthermia episode include excessive carbon dioxide production and metabolic acidosis. Massively increased creatine kinase levels are a strong indicator of a malignant hyperthermia reaction. Rewarming is associated with development of clinical signs of malignant hyperthermia. Conclusions In potentially susceptible patients, apart from avoiding classic trigger substances, aggressive rewarming should not be applied. Hemodynamic instability in conjunction with the described symptoms should result in a diagnostic algorithm.

Background Worsening of lung function in patients awaiting lung transplantation can lead to ventilation-refractory hypoxemia or hypercapnia and respiratory acidosis. This report describes the successful use of different extracorporeal circulatory systems as a bridge to transplantation at remote centers. Methods Between January 2003 and December 2009, we had 10 requests for implantation of extracorporeal circulatory systems (pumpless extracorporeal lung assist [PECLA] or extracorporeal membrane oxygenation [ECMO]) in patients decompensating on the waiting list to bridge to transplantation at three different transplant centers between 150 km and 570 km apart. Cannulas were inserted percutaneously with Seldinger's technique. Results The median patient age was 36 years (range, 24 to 53). Three patients were supported with PECLA and 7 with ECMO. The median duration of support was 23 days (range, 5 to 73). Two patients were initially provided with ECMO and then changed to PECLA after hemodynamic stabilization in the face of persisting pulmonary failure. Two patients died of multiorgan failure on ECMO while on the waiting list. One PECLA patient was successfully weaned and waiting for LTx. Before transplantation, 5 patients (4 PECLA and 1 ECMO) were successfully weaned from mechanical ventilation, and 3 PECLA patients were successfully weaned from the system. Seven patients were successfully bridged and transplanted. Five of 7 patients were discharged from the transplant centers. Conclusions This report suggests that implantation of extracorporeal circulatory systems is a safe method to bridge patients decompensating on the waiting list for transplantation. Support intervals of several weeks are possible.

The minimized extracorporeal circulation (ECC) is a safe alternative for coronary artery bypass grafting (CABG) and allows a reduction of the negative effects associated with conventional extracorporeal circulation. Experimental and clinical data indicate that the anesthetic regime might influence the ischemia-reperfusion injury in CABG surgery. The aim of our retrospective study was to investigate the cardioprotective effects of two different minimized ECC systems in combination with two different anesthetic concepts and to determine the impact on oxygen consumption during aortic cross-clamping (ACC). Data of 1,182 patients who underwent elective isolated CABG with minimized ECC from January 1, 2003, to December 31, 2008, were enrolled in a retrospective manner. Patients were allocated either to sevoflurane-based volatile anesthesia using PRECiSe system (SEVO group) or to propofol-based intravenous anesthesia using MECC system (PROP group). Postoperatively, the SEVO group showed lower concentrations of myocardial fraction of creatine kinase compared with the PROP group (p < 0.001). During the period of ACC, the values of systemic vascular resistance (SVR) were higher in SEVO group (p < 0.005). Also, the SEVO group showed lower oxygen consumption at each time point ACC (p < 0.0001). In conclusion, PRECiSe system using a microporous capillary oxygenator in combination with sevoflurane-based volatile anesthetic regimen seem to provide lower postoperative myocardial cell damage and to allow improved perfusion with higher SVRs and lower oxygen consumption during ACC.

Securing the airway is a rarely performed procedure in the out-of-hospital setting. In recent years evidence has been accumulated indicating that out-of-hospital airway management is more challenging as compared to elective situations even for experienced health care providers. Furthermore, several authors have questioned the benefit of out-of-hospital tracheal intubation. This review argues the problems regarding out-of-hospital airway management studies and discusses potential solutions which may improve out-of-hospital health care.

BACKGROUND Minimized extracorporeal circulation (MECC) is a promising alternative to standard extracorporeal circulation (ECC) and its use is increasing in routine coronary bypass surgery. We analyzed the clinical outcome of patients with reduced left ventricular function who underwent coronary artery bypass surgery with MECC or with standard ECC. METHODS From January 2003 to September 2008, 238 patients with a left ventricular function < 30 % underwent bypass surgery with ECC or MECC. The primary end point of our retrospective observational study was 30-day mortality. Secondary endpoints were the transfusion requirements, as well as intensive care and the in-hospital course. RESULTS Demographic data, comorbidities and left ventricular function were similar in the study groups. MECC patients had a tendency towards a lower 30-day mortality rate, a better postoperative renal function and reduced ventilation times. Extracorporeal circulation time and postoperative high-dose inotropic support were significantly lower in the MECC group, while the stays in the intensive care unit and in hospital were comparable between the two groups. In our study, age in the ECC group, and previous infarction and New York Heart Association grade IV in the MECC group were preoperative risk factors associated with a higher mortality. CONCLUSION Coronary bypass surgery using MECC is feasible and safe for patients with severely impaired left ventricular function. It is a promising alternative to ECC with a low mortality rate and a more favorable postoperative course.

Seit dem Ausbruch der Finanz- und Wirtschaftskrise in Deutschland steht der Staat vor neuen Herausforderungen: Zusatzlich zur Finanzierung und Aufsicht von Betrieben mit infrastrukturellen Aufgaben ist die kurzfristige Stabilisierung von sogenannten systemrelevanten Unternehmen getreten. Der Beitrag stellt mit Public Equity eine Strategie zur Investitionspolitik der offentlichen Hand vor, die klassische Beteiligungsformen mit privatwirtschaftlichen Elementen verbindet. Es wird beschrieben, welche Methoden eingesetzt werden, welche Aktivitaten und Investitionen fur den Aufbau von Public Equity Management notig sind und warum staatliche Akteure so flexibler auf veranderte wirtschaftspolitische Rahmenbedingungen reagieren konnen.

Background Cardiac toxicity significantly correlates with the lipophilicity of local anesthetics (LAs). Recently, the infusion of lipid emulsions has been shown to be a promising approach to treat LA-induced cardiac arrest. As the postulated mechanism of action, the so-called "lipid sink" effect may depend on the lipophilicity of LAs. In this study, we investigated whether lipid effects differ with regard to the administered LAs. Methods In the isolated rat heart, cardiac arrest was induced by administration of equipotent doses of bupivacaine, ropivacaine, and mepivacaine, respectively, followed by cardiac perfusion with or without lipid emulsion (0.25 mL x kg(-1) x min(-1)). Subsequently, the times from the start of perfusion to return of first heart activity and to recovery of heart rate and rate-pressure product (to 90% of baseline values) were assessed. Results In all groups, lipid infusion had no effects on the time to the return of any cardiac activity. However, recovery times of heart rate and rate-pressure product (to 90% of baseline values) were significantly shorter with the administration of lipids in bupivacaine-induced cardiac toxicity, but not in ropivacaine- or mepivacaine-induced cardiac toxicity. Conclusions These data show that the effects of lipid infusion on LA-induced cardiac arrest are strongly dependent on the administered LAs itself. We conclude that lipophilicity of LAs has a marked impact on the efficacy of lipid infusions to treat cardiac arrest induced by these drugs.

Background Rhabdomyosarcoma is a rare malignant skeletal muscle tumor. It mainly occurs in children and young adults and has an unsatisfactory prognosis. Prior studies showed a direct myotoxic effect of bupivacaine on differentiated muscle cells in vitro and in vivo. Exact mechanisms of this myotoxicity are still not fully understood, but a myotoxic effect on malignant muscle tumor cells has not been examined so far. Thus, the aim of this study was to examine if bupivacaine has cytotoxic effects on rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells. Methods Cell lines of rhabdomyosarcoma cells, immortalized muscle cells and differentiated muscle cells were established. After microscopic identification, cells were exposed to various concentrations of bupivacaine (500, 1,000, 1,750, 2,500 and 5,000 ppm) for 1 and 2 h, respectively. 24 and 28 h after incubation the cultures were stained with propidium iodid and analyzed by flow cytometry. The fraction of dead cells was calculated for each experiment and the concentration with 50% cell survival (IC50) was computed. Cell groups as well as incubation and recovery time were compared (ANOVA/Bonferroni p

Obwohl das bundesdeutsche Rettungssystem mit Einbindung von Notarzten als eines der leistungsstarksten der Welt gilt, wird von aufnehmenden Kliniken immer wieder uber Mangel in der prahospitalen Versorgung berichtet. Da neben der formalen Qualifikation die Leistungsfahigkeit eines Notarztsystems von der Routine des eingesetzten Personals abhangt, wurde unter Berucksichtigung von uber 82.000 durch die MIND-Auswertung in Baden-Wurttemberg erfassten bodengebundenen und uber 47.000 durch die LIKS-Datenbank der ADAC-Luftrettung dokumentierten luftgestutzten Notarzteinsatzen untersucht, wie haufig Notarzte in Deutschland tatsachlich komplexen und anspruchsvollen Notfallsituationen prahospital begegnen. Die Ergebnisse zeigen eindrucksvoll, dass bundesdeutsche Notarzte solchen Notfallsituationen z. T. nur sehr selten begegnen: vital bedrohte Patienten mit den Tracerdiagnosen akutes Koronarsyndrom, Apoplex, Schadel-Hirn-Trauma und Polytrauma werden nur alle 0,4–14,5 Monate behandelt. Eine kardiopulmonale Reanimation und Intubation werden alle 0,5–1,5 Monate durchgefuhrt; bis zur Anlage einer Thoraxdrainage vergeht ein Zeitraum von 6 Monaten bis zu uber 6 Jahren. Gerade an Standorten mit geringer Einsatzfrequenz kann daher durch die ausschliesliche Teilnahme am Notarztdienst eine zum Management anspruchsvoller Notfallsituationen erforderliche Routine nicht erworben bzw. aufrecht erhalten werden.

Compared with bupivacaine, acute myotoxicity of ropivacaine is less severe. Thus, in this study we compared the long term myotoxic effects of both drugs in a clinically relevant setting. Femoral nerve catheters were inserted in anesthetized pigs, and either 20 mL of bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused (8 mL/h) over 6 h. Control animals were treated with corresponding volumes of normal saline. After 7 and 28 days, respectively, muscle samples were dissected at the former injection sites, and histological patterns of muscle damage were blindly scored (0 = no damage to 3 = marked lesions/myonecrosis) and compared. No morphological tissue changes were detected in control animals. In the observed period, both local anesthetics induced morphologically identical patterns of calcific myonecrosis, formation of scar tissue, and a marked rate of fiber regeneration. However, bupivacaine's effects were constantly more pronounced than those of ropivacaine. These data show that both drugs induce irreversible skeletal muscle damage in a clinically relevant model, and confirm the exceeding rate of myotoxicity of bupivacaine. However, the clinical impact of these long term myotoxic effects still has to be assessed.In a period of 4 wk after peripheral nerve block, both long-acting local anesthetics, bupivacaine and ropivacaine, produced calcific myonecrosis suggestive of irreversible skeletal muscle damage. In comparison with ropivacaine, however, the extent of bupivacaine-induced muscle lesions was significantly larger.

Spontaneous Ca2+-oscillations are a result of periodic increases and decreases of cytosolic Ca2+. In neurons, they are thought to possess integrative properties because amplitude and frequency influence axon outgrowth, neuronal growth cone migration, and long distant wiring within the developing cortex. Ketamine stereoisomers differ in their affinities for the N-methyl-D-aspartic acid receptor and analgesic and anesthetic effects. Using a dual-excitation Ca2+ ratiometric fluorescence technique with the Ca2+-sensitive dye fura-2 AM, we detected spontaneous Ca2+-oscillations in neurons of hippocampal cell cultures. Spontaneous Ca2+-oscillations development is dependent on external Ca2+, and their amplitude and frequency increased in Mg2+-free solution. Ca2+-oscillations are glutamate dependent because blocking of the N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic, or kainate receptor resulted in a complete disruption of the oscillations. The ketamine stereoisomers dose-dependently and reversibly suppressed the amplitude and frequency of the spontaneous Ca2+-oscillations. This effect was highly stereoselective with the S+ isomer being nearly four times more potent than the R(-) enantiomer. These results correlate well with the clinical anesthetic and analgesic potency of the stereoisomers and therefore our experimental approach might represent a model system to study mechanisms of anesthetic action on Ca2+-dependent integration of neuronal information.

Studies comparing the effects of epidural local anaesthetics have been limited by the lack of knowledge of their relative potencies. In 1995 the concept of the minimum local-anaesthetic concentration (MLAC) was introduced, this has been defined primarily as the median effective analgesic concentration in the first stage of labour. Pharmacologically, this model aims to determine equipotent analgesic concentrations of local anaesthetics, to compare motor effects and to evaluate the relative toxicity during labour. However, results of recent MLAC studies are not uniform and rather confusing, and thus, the basic validity of the MLAC concept for determining local-anaesthetic potency is increasingly discussed.MLAC studies have postulated that ropivacaine is up to 40% less potent than bupivacaine, but as potent as levo-bupivacaine. Intriguingly, bupivacaine has been shown to be as effective as levo-bupivacaine in identical experimental protocols. Modified MLAC studies resulted additionally in local anaesthetic-sparing effects of epidural/intrathecal opioids, clonidine and epinephrine. MLAC studies have also been applied to compare the relative analgesic as well as relative motor-blocking potency of local anaesthetics.Relative differences in local anaesthetics' potencies derived from MLAC examinations are meaningful and correct from the pharmacological point of view, but they cannot simply be transferred to daily clinical practice. Thus, MLAC values should not be misinterpreted as these data are not suggested to be suitable to define and quantify the pharmacodynamics of local anaesthetics, nor to unequivocally predict their toxicological profile in clinically relevant concentrations.

Skeletal muscle toxicity is a rare and uncommon side effect of local anesthetic drugs. Intramuscular injections of these agents regularly result in reversible myonecrosis. The extent of muscle damage is dose dependent and worsens with serial or continuous administration. All local anesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury. The histologic pattern and the time course of skeletal muscle injury appear rather uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum, and by myocyte edema and necrosis over the next 1 to 2 days. Myoblasts, basal laminae, and connective tissue elements remain intact in most cases, which permits muscular regeneration within 3 to 4 weeks. Subcellular pathomechanisms of local anesthetic myotoxicity are still not understood in detail. Increased intracellular Ca2+ levels appear to be the most important element in myocyte injury; since denervation, inhibition of sarcolemmal Na+ channels, and direct toxic effects on myofibrils have been excluded as sites of action. In this respect, the quantitative impact of further mitochondria-mediated pathways—at least in bupivacaine toxicity—is still to be established. Although experimental myotoxic effects are impressively intense and reproducible, only a few case reports of myotoxic complications in patients after local anesthetic administrations have been published. In particular, the occurence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blocks, infiltration of wound margins, trigger point injections, and peri- and retrobulbar blocks.

Volatile Anasthetika, millionenfach weltweit taglich klinisch eingesetzt, sind mit einer seltenen, aber dann lebensbedrohlichen Komplikation behaftet, der malignen Hyperthermie. Inzwischen ist bekannt, dass mit Ausnahme von Xenon und Lachgas alle volatilen Anasthetika eine Kalzium- (Ca2+-) Freisetzung aus dem sarkoplasmatischen Retikulum induzieren und somit die Ca2+-Homoostase in Muskelzellen beeinflussen konnen. Hierbei kann sich dieser Prozess bei zu maligner Hyperthermie (MH) pradisponierten Patienten verselbstandigen. Bisher wurden diese Effekte der Inhalationsanasthetika hauptsachlich durch Studien der Ca2+-aktivierten Kraftentwicklungen von Muskelfasern und durch Studien an isolierten intrazellularen Ca2+-Freisetzungskanalen (Ryanodinrezeptoren) untersucht. Die Verwendung hoch auflosender fluoreszenzmikroskopischer Methoden in Kombination mit raumlich und zeitlich aufgelosten mathematischen Modellen erlaubt nun erstmals Effekte von volatilen Anasthetika auf funktionelle Einheiten von Ryanodinrezeptoren in Skelettmuskelfasern von Saugern in situ zu bestimmen.Die Kombination der Untersuchung zellularer Ca2+-aktivierter Kraftentwicklung und der Einzelkanaleigenschaften isolierter Ryanodinrezeptoren mit der mathematischen Modellierung ermoglicht somit die molekularen Grundlagen der Anasthetikawirkung auf die Ca2+-Freisetzung in ihrer naturlichen zellularen Umgebung unter Seit uber 20 Jahren ist bekannt, dass alle klassischen volatilen Anasthetika aus der halogenierten Kohlenwasserstoffgruppe, wie Halothan, Isofluran oder Enfluran, eine Kalzium- (Ca2+-) Freisetzung aus dem sarkoplasmatischen Retikulum (SR) von Skelettmuskelfasern und Herzmuskelfasern auslosen konnen [20, 21]. Diese Tatsache ist deshalb so wichtig, weil die Pathogenese der malignen Hyperthermie direkt mit den intrazellularen Ca2+-Freisetzungskanalen,den Ryanodinrezeptoren (RyR), des SR in Verbindung gebracht werden konnte [14, 15].Es physiologischen Bedingungen zu bestimmen. Dies ist von theoretischem wissenschaftlichen Interesse fur das Verstandnis der Anasthetikawirkung auf die intrazellulare Ca2+-Homoostase in Muskel- und vermutlich auch Nervenzellen.Auserdem besteht direkte klinische Bedeutung bei der Pathogenese der malignen Hyperthermie, da in jungster Zeit Mutationen am Ryanodinrezeptor und einem daraus resultierenden erhohtem Ca2+-Ausstrom unter Anasthetikagabe pathophysiologisch diskutiert werden.

Hintergrund. Die Anlage einer Thoraxdrainage wird bei der Versorgung von Polytraumatisierten als notarztliche Routinemasnahme gefordert. Die Koniotomie und der intraossare Zugang sind dagegen seltener indizierte Masnahmen, deren Beherrschung aber in Einzelfallen fur das Uberleben des Patienten entscheidend sein kann. Da ein Grosteil der Notfallmediziner nur unzureichende Erfahrung im Umgang mit diesen Techniken aufweist, war es Ziel dieser Arbeit, ein mogliches Ausbildungskonzept zur Erlernung dieser Techniken vorzustellen und zu evaluieren. Methodik. Im November 2001 wurde von unserer Institution in Zusammenarbeit mit dem Anatomischen Institut II der Universitat Heidelberg erstmals der Workshop “Invasive Notfalltechniken (INTECH): Thoraxdrainage – Koniotomie – intraossarer Zugang” veranstaltet. Nach Darstellung der anatomischen Grundlagen und Besonderheiten der relevanten Korperregionen wurden die Techniken der Thoraxdrainage, der Koniotomie sowie des intraossaren Zugangs im Detail vorgestellt. Im Anschluss an diesen theoretischen Veranstaltungsabschnitt bildeten Videodemonstrationen sowie praktische Ubungen an der Leiche den Schwerpunkt. Abschliesend wurden die Teilnehmer zum Grund ihrer Kursteilnahme und ihren bisherigen Erfahrung mit diesen Notfalltechniken in schriftlicher anonymisierter Form befragt sowie gebeten, das didaktische Konzept dieser Veranstaltung zu bewerten (1=sehr gut; 6=sehr schlecht). Ergebnisse. Insgesamt wurden die Fragebogen von 66 der 86 Teilnehmer (77%) ausgewertet. Hiervon waren 40 Teilnehmer mit 13±8 (4–30) Einsatzen pro Monat seit 6,5±6,3 (0,5–22) Jahren notarztlich tatig. Als Grund fur die Kursteilnahme wurde am haufigsten (52%) mangelnde Praxis genannt: 98% der Notarzte hatten vor der Veranstaltung noch keine Koniotomie, 85% noch keinen intraossaren Zugang und 28% noch keine Thoraxdrainage praklinisch durchgefuhrt. Die Ausbildungsabschnitte “Anatomische Grundlagen”, “Koniotomie”, “i.o.-Zugang” und “Thoraxdrainage” des Theorieteils wurden mit 2,3±0,8, 1,7±0,7, 1,5±0,5 bzw. 1,7±0,7, die Abschnitte “Koniotomie”, “i.o.-Zugang”, “Thoraxdrainage” des Praxisteiles mit 1,9±0,7 bzw. jeweils 1,6±0,8, die “Lagedemonstration” mit 1,7±0,8 sowie die praktischen Ubungen insgesamt mit 1,4±0,7 bewertet. Schlussfolgerung. Diese Ergebnisse zeigen, dass – obwohl im Rahmen des Polytraumamanagements gefordert – selbst langjahrig tatige Notarzte haufig keine ausreichenden Kenntnisse im Legen einer Thoraxdrainage haben. Erfahrungen mit anderen im Einzelfall als lebensrettend empfohlenen notarztlichen Masnahmen liegen bei uber 80% der Notfallmediziner ebenfalls nicht vor. Trotz des Einwandes, dass es sich bei den Workshop-Teilnehmern um eine selektionierte Studiengruppe handelt, scheinen diese Zahlen jedoch die Realitat widerzuspiegeln: Aufnehmende Zentren berichten uber erhebliche und gravierende Versorgungsmangel bei notarztlich versorgten Polytraumatisierten. In Zusammenarbeit mit anatomischen Instituten konnten streng praxisorientierte Workshops diese Ausbildungslucke schliesen. Da es sich in anatomischen Instituten in der Regel um fixierte Leichenpraparate handelt, muss allerdings auf etwaige Unterschiede zur Durchfuhrung beim Lebenden hingewiesen werden. Trotz dieser geringen Einschrankungen konnen praktische Ubungen dem Defizit bei der Versorgung von Notfallpatienten entgegenwirken und sollten daher in zukunftige Ausbildungskonzepte fest integriert werden.

Background Bupivacaine produces skeletal muscle damage in clinical concentrations. It has been suggested that this may be caused by an increased intracellular level of [Ca2+]. Therefore, the aim of this study was to investigate direct intracellular effects of bupivacaine on Ca2+ release from the sarcoplasmic reticulum (SR), on Ca2+ uptake into the SR, and on Ca2+ sensitivity of the contractile proteins. Methods Saponin skinned muscle fibers from the extensor digitorum longus muscle of BALB/c mice were examined according to a standardized procedure described previously. For the assessment of effects on Ca2+ uptake and release from the SR, bupivacaine was added to the loading solution and the release solution, respectively. Force transients and force decays were monitored, and the position of the curve relating relative isometric force free [Ca2+] was evaluated in the presence or absence of bupivacaine. Results Bupivacaine induces Ca2+ release from the SR. In addition, the Ca2+ loading procedure is suppressed, resulting in smaller caffeine-induced force transients after loading in the presence of bupivacaine. The decay of caffeine-induced force transients is reduced by bupivacaine, and it also shifts [Ca2+]-force relation toward lower [Ca2+]. Conclusions These data reveal that bupivacaine does not only induce Ca2+ release from the SR, but also inhibits Ca2+ uptake by the SR, which is mainly regulated by SR Ca2+ adenosine triphosphatase activity. It also has a Ca2+ -sensitizing effect on the contractile proteins. These mechanisms result in increased intracellular [Ca2+] concentrations and may thus contribute to its pronounced skeletal muscle toxicity.

Bei kardiovaskular wirksamen Medikamenten handelt sich hier um eine Vielzahl von Substanzen mit uneinheitlicher chemischer Struktur und mit unterschiedlichen pharmakologischen Wirkmechanismen.