Airway Management of Orofacial Infections Originating in the Mandible.

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.

Machine learning for the prediction of preclinical airway management in injured patients: a registry-based trial.

OBJECTIVE: The aim of this study was to determine the feasibility of using machine learning to establish the need for preclinical airway management for injured patients based on a standardized emergency dataset. METHODS: A registry-based, retrospective analysis was conducted of adult trauma patients who were treated by physician-staffed emergency medical services in southwestern Germany between 2018 and 2020. The primary outcome was to assess the feasibility of using the random forest (RF) and Naive Bayes (NB) machine learning algorithms to predict the need for preclinical airway management. The secondary outcome was to use a principal component analysis to determine the attributes that can be used and advanced for future model development. RESULTS: In total, 25,556 adults with multiple injuries were identified, including 1,451 patients (5.7%) who required airway management. Key attributes were auscultation, injury pattern, oxygen therapy, thoracic drainage, noninvasive ventilation, catecholamines, pelvic sling, colloid infusion, initial vital signs, preemergency status, and shock index. The area under the receiver operating characteristics curve was between 0.96 (RF; 95% confidence interval [CI], 0.96-0.97) and 0.93 (NB; 95% CI, 0.92-0.93; P<0.01). For the prediction of airway management, RF yielded a higher precision-recall area than NB (0.83 [95% CI, 0.8-0.85] vs. 0.66 [95% CI, 0.61-0.72], respectively; P<0.01). CONCLUSION: To predict the need for preclinical airway management in injured patients, attributes that are commonly recorded in standardized datasets can be used with machine learning. In future models, the RF algorithm could be used because it has robust prediction accuracy.

[Liposomal bupivacaine-No breakthrough in postoperative pain management]. / Liposomales Bupivacain ­ kein Durchbruch in der postoperativen Schmerztherapie.

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 1­stage 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.

Collateral damages in the SARS-CoV-2 pandemia- two cases.

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.

Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 vitro myotoxic effects of bupivacaine on rhabdomyosarcoma cells, immortalized and primary muscle cells.

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 < 0.01). RESULTS: The total number of cultured cells was similar for the different local anesthetics and examined concentrations. Increasing concentrations of bupivacaine led to a decrease in survival of muscle cells. IC50 was highest for immortalized cells, followed by rhabdomyosarcoma cells and differentiated cells. Exposure time, but not recovery time, had an influence on survival. CONCLUSION: Bupivacaine has clear but different cytotoxic effects on various muscle cell types in vitro. Differentiated primary cells seem to be more vulnerable than tumor cells possibly because of more differentiated intracellular structures.

Cytotoxicity of local anesthetics on human mesenchymal stem cells in vitro.

PURPOSE: The purpose of this study was to investigate the cytotoxic potency of local anesthetics on human mesenchymal stem cells (MSCs) before and after chondrogenic differentiation. METHODS: MSCs were exposed to equal and equipotent concentrations of bupivacaine, ropivacaine, and mepivacaine for 1 hour. Cell viability, apoptosis, and necrosis were determined using flow cytometry and live/dead staining. After chondrogenic differentiation, MSC viability was determined in aggregates exposed to equipotent concentrations of the named agents, applying fluorescence microscopy. RESULTS: All local anesthetics showed detrimental cytotoxic effects on MSC monolayer cultures in a concentration- and time-specific manner. Minimum viability rates were found 96 hours after a 1-hour exposure. Bupivacaine 0.5% caused a reduction of vital MSCs to 5% ± 1%. Sixteen percent ± 2% viable cells were detected after treatment with 0.75% ropivacaine. Exposure to 2% mepivacaine decreased vitality rates to 1% ± 0%. Ropivacaine was significantly less cytotoxic than were bupivacaine and mepivacaine. Immediate cell death was mainly caused by necrosis followed by apoptosis afterward. Viability rates of MSCs embedded in cartilaginous tissue after chondrogenic differentiation were not reduced by local anesthetic treatment. CONCLUSIONS: Local anesthetics are cytotoxic to MSCs in a concentration-, time-, and agent-dependent manner in monolayer cultures but not in whole-tissue probes. CLINICAL RELEVANCE: MSCs are applied for treatment of cartilage defects. Intra-articular application of local anesthesia is a common procedure in pain management and has shown chondrotoxic effects. Therefore, it is crucial to evaluate the impact of local anesthetics on human MSCs and regenerative cartilage tissue engineering.

The myotoxic effect of bupivacaine and ropivacaine on myotubes in primary mouse cell culture and an immortalized cell line.

BACKGROUND: The 2 local anesthetics (LAs) bupivacaine and ropivacaine have acute cytotoxic effects on different tissues. In this respect, LA-induced myotoxicity has been subject to various studies; however, the exact mechanisms are still not fully understood. Most in vitro studies use immortalized cell lines because of feasibility. Thus, establishing a primary cell line might result in more accurate results. In this study, we examined the effects of immortalization on bupivacaine- and ropivacaine-induced myotoxicity in vitro. METHODS: An immortalized (N = 6) and a primary cell line (N = 8) of the same tissue and species were established, and differentiation in myotubes was induced. Cells were exposed to increasing concentrations of bupivacaine and ropivacaine for 1 or 2 hours, respectively. Twenty-four and 48 hours after treatment, the fractions of dead and vital cells were measured using flow cytometry. Significance was tested through 1-way analysis of variance with post hoc Dunnett T3 test. Medians of dataset pairs were compared by T test. RESULTS: In both cell lines, increasing concentrations of both LAs resulted in decreased cell survival (e.g., P < 0.001 for 5000 ppm bupivacaine, 1 or 2 hours of incubation, and 24 hours recovery in both cell lines). For the same LA concentrations, survival was significantly higher in the immortalized cell culture (e.g., P < 0.001 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). In addition, equal concentrations of bupivacaine resulted in significantly fewer vital cells compared with ropivacaine (e.g., P = 0.032 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours recovery). Two hours of incubation resulted in a significantly higher rate of dead cells compared with 1 hour of incubation (e.g., P = 0.004 for C2C12 cells, 2500 ppm bupivacaine, and 24 hours recovery). CONCLUSIONS: Primary skeletal muscle cells are more vulnerable to LAs than immortalized cells. The higher myotoxic potential of bupivacaine compared with ropivacaine in vivo can be reproduced in vitro. Incubation time has an influence on cell survival.

The cytotoxicity of bupivacaine, ropivacaine, and mepivacaine on human chondrocytes and cartilage.

BACKGROUND: 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. METHODS: 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. RESULTS: 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% (P < 0.0001) 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% (P < 0.0001) after 1 hour and 30% ± 11% (P < 0.0001) 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. CONCLUSION: 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.

Shock or no shock - a question of philosophy or should intraoperative implantable cardioverter defibrillator testing be recommended?

OBJECTIVES: Implantation of implantable cardioverter defibrillators (ICDs) in patients with a high risk for life-threatening ventricular arrhythmias is a standard therapy. The development of new ICD leads, shock algorithms, high-energy defibrillators and rapid energy supply has improved the devices. Nevertheless, the discussion regarding 'shock or no shock' to test the system intraoperatively has not silenced yet. METHODS: In this study, all 718 patients (60.0 ± 14.2 years old, 570 male) who were treated with a first ICD at our institution since 2005 were analysed. The indication for implantation was primarily prophylactic in 511 patients (71.3%). Underlying diseases included ischaemic cardiomyopathy (358 patients, 50%), dilated cardiomyopathy (270 patients, 37.7%) and others (12.3%). Mean ejection fraction was 27.4 ± 11.8%. Intraoperative ventricular fibrillation was induced with a T-wave shock or burst stimulation. The primary end-point was failing the initial intraoperative testing. RESULTS: During the initial testing, 28 patients (3.9%) had a defibrillation threshold (DFT) >21 J. The mean age of these patients was 51 ± 14 years, ranging from 22 to 71 years, 20 were male, and the ejection fraction was 23.8 ± 11.8%. The indication for ICD implantation was prophylactic in 13 patients. Twenty-one of the 28 patients suffered from dilated cardiomyopathy, whereas seven patients had ischaemic cardiomyopathy. Twenty-four ICDs were implanted on the left side and four on the right side. None of the patients had been treated with amiodarone at the time of implantation. All patients achieved a sufficient DFT ≤ 21 J by changing the ICD leads, device repositioning and/or optimizing the shock configuration. CONCLUSIONS: The standard of care intraoperative ICD testing remains necessary.

Ventricular assist device implantation in patients on percutaneous extracorporeal life support without switching to conventional cardiopulmonary bypass system.

OBJECTIVES: Ventricular assist device (VAD) implantation using cardiopulmonary bypass (CPB) is an established procedure. However, the well-described complications of CPB may exacerbate multiple organ failure and increase blood product transfusions especially in end-stage heart failure patients. METHODS: We describe our successful experience in six consecutive patients with profound cardiogenic shock, who were provided on an emergency basis with a percutaneous extracorporeal life support (ECLS) system via the peripheral vessels. After stabilization, a VAD was implanted using ECLS without switching to a conventional CPB system to reduce its side effects. We compared the data with those of 11 patients in whom the VAD was placed with the aid of an additional CPB system. RESULTS: The six patients demonstrated a shorter duration of operating room time compared with the patients requiring CPB for device placement. During and after surgery, blood loss and blood product transfusions were lower in these patients. The need for mechanical ventilation and inotropic support was shorter and the survival rate (100% at 30 days, 83.3% at 3 months and 83.3% at 6 months) was higher when compared with patients who were operated upon with CPB. Two patients were successfully bridged to transplantation. One patient died due to cerebral bleeding after 7 weeks. CONCLUSIONS: Our experience suggests that VAD implantation using percutaneous ECLS without switching to conventional CPB is a safe alternative in the bridge to bridge concept, especially in high-risk patients with cardiogenic shock who would benefit from the avoidance of the adverse sequels associated with conventional CPB.

Late reoperations after repaired acute type A aortic dissection.

OBJECTIVE: Late complications can develop in patients after surgery for aortic type A dissection, mandating redo surgery on the ascending aorta and arch. METHODS: From 2006 to 2010, 23 patients (aged 41-69 years) who had late complications related to previous aortic surgery for acute type A dissection underwent redo surgery. Initial surgery included ascending aorta replacement in all cases. RESULTS: The main indications for reoperation were progressive enlargement of the false lumen of the aortic arch or descending aorta and suture line dehiscence in 10 patients each. All patients with progressive aneurysm formation in nonresected aortic segments had persistent dissection within the aortic arch since initial surgery. Suture line dehiscence led to a localized hematoma in most cases. Three patients presented with graft infection and extensive perigraft hematoma. The average time interval from the initial repair to the redo procedure was 71±56 months. Exchange of the formerly implanted Dacron graft in the ascending aorta was the most frequently used surgical procedure. Implantation of a valved conduit was deemed necessary in 4 cases, and isolated aortic valve replacement was necessary in 2 cases. A hybrid stent graft was used in 6 patients. All patients survived surgery, and 1 patient died of postoperative low output cardiac failure in hospital. Only 1 major stroke was noted. CONCLUSIONS: Complex reoperations for repaired acute type A dissection can be performed safely. The concern for the reoperative risk should not dictate the operative strategy during the initial procedure in acute type A dissection.

3,4-Methylenedioxymethamphetamine (Ecstasy) increases the sensitivity of the contractile apparatus to calcium ions in both malignant hyperthermia-susceptible and normal skeletal muscle fibres.

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.

[Strategic planning: an important economic action for German hospitals]. / Strategische Planung - Eine wichtige ökonomische Handlungsweise für deutsche Krankenhäuser.

In medical systems, economic issues and means of action are in the course of dwindling human (physicians and nurses) and financial resources are more important. For this reason, physicians must understand basic economic principles. Only in this way, there may be medical autonomy from social systems and hospital administrators. The current work is an approach to present a model for strategic planning of an anesthesia department. For this, a "strengths", "weaknesses", "opportunities", and "threats" (SWOT) analysis is used. This display is an example of an exemplary anaesthetic department.

The toxic effects of s(+)-ketamine on differentiating neurons in vitro as a consequence of suppressed neuronal Ca2+ oscillations.

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.

Cardiopulmonary bypass in malignant hyperthermia susceptible patients: a systematic review of published cases.

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.

Extracorporeal circulatory systems as a bridge to lung transplantation at remote transplant centers.

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.

Myocardial protection in patients undergoing coronary artery bypass grafting surgery using minimized extracorporeal circulation in combination with volatile anesthetic.

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.