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Lung volume reduction surgery (LVRS) represents an important treatment option in carefully selected patients with end-stage lung emphysema. The aim of this study was to assess the efficacy and safety of nonintubated LVRS compared to intubated LVRS in patients with preoperative hypercapnia and lung emphysema. Between April 2019 and February 2021, n = 92 patients with end-stage lung emphysema and preoperative hypercapnia undergoing unilateral video-assisted thoracoscopic LVRS (VATS-LVRS) performed in epidural anesthesia and mild sedation (nonintubated, group 1) or conventional general anesthesia (intubated, control, group 2) were prospectively enrolled in this study. Data were retrospectively analyzed. In all patients, low-flow veno-venous extracorporeal lung support (low-flow VV ECLS) was applied as a bridge through LVRS. Ninety-day mortality was considered as the primary outcome. Secondary endpoints included: chest tube duration, hospital stay, intubation and conversion to general anesthesia. Intergroup analysis showed no significant difference between the baseline data and patients' demographics. N = 36 patients underwent nonintubated surgery. VATS-LVRS under general anesthesia was performed in n = 56 patients. The mean duration of postoperative VV ECLS support was 3 ± 1 day in group 1 compared to 4 ± 1 in group 2. The 90-day mortality rate was 3% in group 1 compared to 7% in group 2. In group 1, all chest tubes were removed 5 ± 1 day (range 4-32 days) and 8 ± 1 day (range 4-44 days) in the control group after the surgery ( p < 0.02). Prolonged chest tube therapy (>8 days) was observed in n = 3 patients in group 1 and n = 11 patients in the control group. The mean ICU stay was 4 ± 1 days in group 1 compared to 8 ± 2 days in the control group ( p = 0.04). The mean hospital stay was significantly shorter in the nonintubated group 1 (6 ± 2 days vs. 10 ± 4 days, p = 0.01). Conversion to general anesthesia was necessary in one patient due to severe pleural adhesions. Nonintubated VATS-LVRS in patients with end-stage lung emphysema and hypercapnia is effective and well tolerated. Compared to general anesthesia, a reduction in mortality, chest tube duration, ICU and hospital stay and lower rate of prolonged air leak was observed. VV ECLS increases intraoperative safety and mitigates postoperative complications in such "high-risk" patients.

Lung volume reduction surgery (LVRS) represents a standard surgical approach for patients with severe pulmonary emphysema. One of the relevant risk factors for LVRS is the presence of pulmonary arterial hypertension (PAH). The aim of this study is to assess the postoperative changes in pulmonary arterial pressure (PAP) after LVRS for patients with severe pulmonary emphysema compared with preoperative measures. N = 61 consecutive patients with severe pulmonary emphysema and preoperative evidence for PAH (pulmonary arterial systolic pressure [PASP] ≥ 35 mmHg) were prospectively included into this study. In all patients, thoracoscopic LVRS was performed. PASP was assessed by echocardiography before surgery, early postoperatively, and 3 months after surgery. Data were prospectively recorded and analyzed retrospectively. Primary end points were the postoperative changes in PASP as well as the 90 day mortality rate. Secondary endpoints included: pulmonary function test, exercise capacity, quality of life, and dyspnea symptoms (Borg scale). Early after surgery, a significant reduction in PASP was observed at the day of discharge and at 3 month follow-up. In n = 34 patients, no tricuspid valve regurgitation was detectable anymore suggesting normal PAP. In n = 3 patients, venovenous extracorporeal lung support (VV ECLS) was already implemented preoperatively. In the remaining cases, VV ECLS was applied intraoperatively and continued postoperatively. Mean duration of postoperative ECLS support was 2 days. Four patients died due to acute right heart failure, two patients from sepsis with multiorgan failure, and one patient from acute pulmonary embolism. Ninety day mortality was 11.5 %. A significant improvement was postoperatively observed regarding the performance status, dyspnea scale, as well as quality of life. This study suggests a beneficial effect of LVRS on PAP, which may ultimately help to protect and stabilize right ventricular function. Further studies, implementing pre- and postoperative right heart catheterizations including invasive PAP evaluation, are necessary to support the findings in this study in greater detail., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Objective: Patients with severe manifestations of COVID-19 might exhibit characteristics of a sepsis-like syndrome that can progress to multiple organ failure and ultimately death. Underlying mechanism have been explored and suggest a profound dysregulation of the immune system associated with hyperinflammation, hemodynamic instability and respiratory failure. Besides standard intensive care treatment, approaches modulating the dysregulated immune response, such as CytoSorb hemoadsorption, have been used. However, data of ECMO-dependent patients in comparison to a control cohort remain scarce., Methods: Included were 26 critically ill COVID-19 patients requiring high-flow veno-venous extracorporeal membrane oxygenation (high-flow VV ECMO) therapy due to severe acute respiratory distress syndrome (ARDS), of whom 16 were additionally treated with an extracorporeal hemoadsorption device, and compared to a control group of 10 patients. Assessed were levels of inflammatory markers, vasopressor requirements, oxygenation parameters, as well as clinically relevant outcome variables. Data were prospectively recorded and retrospectively analyzed., Results: Treatment with the applied multimodal therapy approach resulted in a stabilization in hemodynamics, a control of the hyperinflammatory response as evidenced by a significant reduction in inflammatory mediators, as well as a marked improvement in lung function. No device related adverse events were observed while treatment appeared safe and feasible., Conclusion: Treatment of a critically ill COVID-19 ARDS patients with combined VV ECMO support and hemoadsorption therapy led to a rapid and sustained hemodynamic stabilization, a control of the uncontrolled inflammatory response and an improvement in oxygenation. Given these signals pointing toward a patient-oriented benefit of extracorporeal hemoadsorption therapy in those patients, future controlled, randomized studies should focus on the investigation of the appropriate timing and dosing of this promising treatment modality.

Background: Postsurgical pleural infection is a life-threatening complication after implantation of artificial devices such as ventricular assist devices (VADs). The treatment can be challenging and the evidence in the literature is very limited. Here we report our multidisciplinary approach of the management of pleural infection after VAD implantation., Methods: Between March 2014 and December 2019, 33 patients developed postoperative pleural infection after VAD implantation and underwent thoracic surgical intervention at our institution. All patients were prospectively enrolled in this analysis. Data were retrospectively analyzed. Primary outcome was the 90-day mortality rate. Length of ICU stay related to pleural infection, chest tube duration, re-thoracotomy rate and length of ventilatory support represented secondary outcomes., Results: The 90-day mortality rate was 6% (2 patients). The mean ICU stay related to the pleural infection was 6 days (2-24 days). Video-assisted thoracoscopic surgery (VATS) was performed in all patients. Conversion to thoracotomy was necessary in 12 cases. Decortication and parietal pleurectomy in addition to hematoma and empyema removal was performed in all patients. Due to diffuse bleeding, packing of the thoracic cavity with temporary thoracic closure was necessary in 10 patients. Depacking was performed after a mean of 3 days (3-7 days). Recurrent empyema or bleeding after definitive chest closure was not observed. Lung resection was performed in 3 patients., Conclusions: Thoracic surgical management of pleural infection in patients after VAD implantation is challenging and complicated due to the inevitable anticoagulative therapy. A perioperative multidisciplinary management which includes the early involvement of thoracic surgical expertise helps to improve survival in this very complex patient cohort., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-20-2886). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

The coronavirus disease 2019 (COVID-19) has spread rapidly worldwide and leads to high morbidity and mortality. Clinical experience regarding the surgical management in COVID-19 patients is limited. We report the interdisciplinary approach in a COVID-19 patient with severe thoracic trauma and pulmonary symptoms, who was admitted to the emergency unit after blunt chest trauma with dislocated serial rib fractures and concomitant hemothorax.

Background: High morbidity and mortality are frequently reported in intensive care patients suffering from severe sepsis with systemic inflammation. With the development of severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is often required. In this study, cytokine adsorption therapy in combination with ECMO is applied in patients with acute respiratory distress syndrome (ARDS) due to severe pneumogenic sepsis. The efficacy of this therapy is evaluated compared with a historical cohort without hemoadsorption therapy., Methods: Between January and May 2018, combined high-flow venovenous ECMO and CytoSorb therapy (CytoSorb filter connected to ECMO circuit) was applied in patients ( n  = 13) with pneumogenic sepsis and ARDS. These patients were prospectively included (CytoSorb group). Data from patients ( n  = 7) with pneumogenic sepsis and ECMO therapy were retrospectively analyzed (control group)., Results: All patients survived in the CytoSorb group, where the 30-day mortality rate reached 57% in the control group. After CytoSorb therapy, we instantly observed a significant reduction in procalcitonin (PCT) and C-reactive protein (CRP) levels compared with the control group. Within 48 hours, the initial high doses of catecholamine could be weaned off only in the CytoSorb group., Conclusions: Our results indicate that CytoSorb in combination with ECMO is an effective therapy to prevent escalation of sepsis with rapid weaning off high-dose catecholamine infusions and quick reduction in PCT and CRP levels. Optimal timing of immunomodulatory therapy and impact on ECMO-related inflammation still need to be furtherly investigated., Competing Interests: None., (Thieme. All rights reserved.)

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival., Methods: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V‑V ECMO (PRESERVE) Score, and 30-day survival., Results: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605., Conclusions: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V‑V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.

Extracorporeal lung support (ECLS) represents an essential support tool especially for critically ill patients undergoing thoracic surgical procedures. Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we report the efficacy of veno-venous ECLS (VV ECLS) as a bridge to or through LVRS in patients with end-stage lung emphysema and severe hypercapnia. Between January 2016 and May 2017, 125 patients with end-stage lung emphysema undergoing LVRS were prospectively enrolled into this study. Patients with severe hypercapnia caused by chronic respiratory failure were bridged to or through LVRS with low-flow VV ECLS (65 patients, group 1). Patients with preoperative normocapnia served as a control group (60 patients, group 2). In group 1, VV ECLS was implemented preoperatively in five patients and in 60 patients intraoperatively. Extracorporeal lung support was continued postoperatively in all 65 patients. Mean length of postoperative VV ECLS support was 3 ± 1 day. The 90 day mortality rate was 7.8% in group 1 compared with 5% in group 2 (p = 0.5). Postoperatively, a significant improvement was observed in quality of life, exercise capacity, and dyspnea symptoms in both groups. VV ECLS in patients with severe hypercapnia undergoing LVRS is an effective and well-tolerated treatment option. In particular, it increases the intraoperative safety, supports de-escalation of ventilatory strategies, and reduces the rate of postoperative complications in a cohort of patients considered "high risk" for LVRS in the current literature.

Purpose: The usefulness of chest wall stabilization after blunt chest wall trauma with unstable rib fractures has recently been intensely discussed. Thereby, the surgical approach seems to influence outcome, mortality and the long-term complication rate including chronic chest pain, thoracic deformity and quality of life. Here, we present the outcome after surgical stabilization of unstable rib fractures using intramedullary splints and plate osteosynthesis., Methods: n = 50 patients were enrolled in this trial. Surgical stabilization was performed using intramedullary splints and/or plate osteosynthesis. Video-assisted thoracoscopy was performed in all patients for the inspection of the thoracic cavity and to exactly localize the fractured ribs. The pre- and postoperative pain course was documented using the visual analog scale., Results: A total of n = 50 patients (10 females, mean age 63 years) were included into the analysis. All patients presented with traumatic serial rib fractures with a mean of 3 fractured ribs (range 2-8 ribs) and an unstable thorax wall. Rib osteosynthesis was performed using intramedullary splints (n = 17 patients), locking plates (n = 17 patients), or a combined use of both procedures (n = 16 patients). Mean operating time was 80 min (31-161 min). No major complications were seen intra- and postoperatively. Mean hospital stay was 8 ± 2 days (2-21 days). In all patients, excellent chest wall stability was achieved. Moreover, a significant reduction of pain was observed (2.6 ± 0.3 postoperatively vs. 8 ± 1.15 preoperatively, p < 0.0001) already during the hospital stay., Conclusions: Rib osteosynthesis is a safe and effective treatment option for patients with unstable rib fractures after blunt chest wall trauma. It leads to a significant reduction of the trauma-associated pain caused by the rib fractures and supports a quick recovery of the patients.

"Enhanced Recovery after Surgery" programs have been developed for thoracic surgery over the last couple of years. Besides minimally invasive surgical techniques, there are a number of anaesthesiological aspects like the choice of short acting anaesthetics, the use of regional analgesia, a balanced intraoperative fluid therapy, the avoidance of postoperative nausea and vomiting and, most importantly, protective ventilation, that need to be considered. In patients undergoing thoracic surgery procedures with preexisting severe limitations in pulmonary function, protective ventilation under the conditions of one lung ventilation often leads to severe dysfunction of pulmonary gas exchange. In this situation, establishing veno-venous membrane oxygenation (vvECMO) is a sufficient and safe method to facilitate perioperative treatment of these patients. Postoperatively, patients benefit from the continuation of the conscious vvECMO by augmentation of necessary therapeutic procedures such as physical and respiratory therapy or early mobilisation as well as healing of air leakage of the operated lung. To avoid bleeding complications, ECMO can be operated without anticoagulation intraoperatively with heparin-coating of the tube system. Postoperatively, heparin, argatroban or bivalirudin are options for anticoagulation. New techniques like minimally-invasive thoracic surgery under regional anaesthesia and sedation can potentially be developed further using vvECMO support in the future., Competing Interests: MB hat Honorare für wissenschaftliche Vorträge und Sponsoring von Studien von der Fa. Mitsubishi Tanabe Pharma erhalten., (Georg Thieme Verlag KG Stuttgart · New York.)

Extracorporeal membrane oxygenation (ECMO) and extracorporeal life support are increasingly used for treating various forms of shock, lung failure, protected interventions and life support including resuscitation. Most patients on ECMO are affected by a systemic inflammatory response caused by the underlying disease as well as the ECMO support itself, which contributes to vasoplegia, multi-organ failure, deterioration and death. Unfortunately, effective strategies for control of inflammation and related organ failure and shock on ECMO are lacking. Recently, a new polystyrene-based device for hemoadsorption, which aims to reduce excessive levels of inflammatory molecules such as interleukins, cytokines as well as damage- and pathogen-associated molecular patterns, has become available. Here we summarize the rationale, available data and technical aspects of polystyrene-based hemoadsorption during ECMO support, and give recommendations based on existing experience., (The Author(s). Published by S. Karger AG, Basel.)

Lung volume reduction surgery (LVRS) is an important treatment option for end-stage lung emphysema in carefully selected patients. Here, we first describe the application of low-flow venovenous extracorporeal CO2 removal (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute failure of the breathing pump. Between March and October 2015, n = 4 patients received single-site LFVV-ECCO2R as bridge to LVRS. Indication for extracorporeal lung support was severe hypercapnia with respiratory acidosis and acute breathing pump failure. Two patients required continuous mechanical ventilation over a temporary tracheostomy and were bed ridden. The other two patients were nearly immobile because of severe dyspnea at rest. Length of preoperative ECCO2R was 14 (1-42) days. All patients underwent unilateral LVRS. Anatomical resection of the right (n = 3) or left (n = 1) upper lobe was performed. Postoperatively, both patients with previous mechanical ventilatory support were successfully weaned. ECCO2R in patients with end-stage lung emphysema experiencing severe hypercapnia caused by acute breathing pump failure is a safe and effective bridging tool to LVRS. In such patients, radical surgery leads to a significant improvement of the performance status and furthermore facilitates respiratory weaning from mechanical ventilation.

Purpose: Many institutions perform peripheral femoral and/or sciatic nerve blocks for analgesia after total knee arthroplasty. The aim of the present investigation was to compare the analgesic effect of an intermittent sciatic block (boluses on demand only) with a continuous infusion., Methods: One hundred and forty patients receiving a femoral and a sciatic nerve block (SNB) by catheter were assessed. The femoral catheter was infused continuously in both groups. In the continuous group (n = 70), the sciatic catheter was used continuously as well. In the intermittent group (n = 70), after a single injection of 20 ml ropivacaine 0.75 %, injections into the sciatic catheter were performed on demand only. Frequency of injections, ventral and dorsal numerical pain scores (NRSs) of the knee, functional outcome (degree of flexion/extension) and additional opioid requirements were assessed during the post-operative period., Results: In both groups, dorsal and ventral NRSs were below 3 at rest and below 5 during mobilisation over the complete period of assessment. Differences between the groups could not be observed. The cumulative number of supplemental injections into the sciatic catheter was higher in the intermittent group (52) compared with the continuous group (24; p < 0.05). Groups did not differ from each other with regard to functional outcome and opioid consumption., Conclusions: The use of a sciatic block performed as intermittent bolus injection on demand only did not affect post-operative outcome parameters with regard to pain scores, functional outcome or opioid requirements. This approach might therefore be considered as an alternative to a continuous infusion concept. ClinicalTrials.gov Identifier: NCT01843153.

The application of extracorporeal lung support (ECLS) in patients with acute respiratory distress syndrome is a well-established concept. In patients receiving ECLS therapy, hemodynamic monitoring is often required. However, less is known about the effect of ECLS on hemodynamic measurements. In the present work, the influence of single-site low-flow veno-venous ECLS (LFVV-ECLS) on hemodynamic monitoring by transpulmonary thermodilution (TPTD) was prospectively investigated. Five consecutive patients undergoing single-site LFVV-ECLS for severe hypercapnic respiratory failure were included in this study. For single-site LFVV-ECLS, a 22 Fr twin-port double-lumen cannula was inserted percutaneously into the right jugular vein. Hemodynamic monitoring was performed using the Pulse index Continuous Cardiac Output system. Before ECLS initiation, baseline measurements of cardiac index, systemic vascular resistance, mean arterial pressure, and extravascular lung water (EVLW) were performed. During the first 3 days of ECLS therapy, repeated hemodynamic measurements at different ECLS flow rates were performed. No significant differences were seen in hemodynamic measurements. With respect to EVLW, a significant decrease over the duration of ECLS therapy was observed. This study demonstrates that LFVV-ECLS does not interfere with TPTD. It needs to be further studied if these findings also apply to other ECLS modes.

Objectives: Intraoperative extracorporeal lung support (ECLS) during thoracic surgical procedures is a modern concept that is gaining increasing acceptance. So far, cardiopulmonary bypass (CPB), veno-arterial extracorporeal membrane oxygenation (v-a-ECMO) or pumpless arterio-venous interventional lung assist (iLA) were utilized for intraoperative support. Only a few case reports have described the use of veno-venous ECMO for intraoperative ECLS. Here, we report our experience with intraoperative ECLS using different veno-venous low-flow and high-flow settings adapted to the individual patient requirements., Methods: Between April 2014 and April 2015, 9 patients underwent pulmonary resections under ECLS. In 6 patients, a twin-port double-lumen cannula was inserted percutaneously into the right femoral vein for low-flow ECLS. In 3 patients, high-flow ECLS was achieved either by femoro-atrial (n = 1) or femoro-jugular cannulation., Results: Indications for ECLS were severely impaired lung function (n = 3), previous pulmonary resections including contralateral pneumonectomy (n = 4), previous single-lung transplantation (sLTX) (n = 1) and extended carinal pneumonectomy (n = 1). Procedures included segmentectomy (n = 3), extended lobectomy with bronchial and vascular anastomoses (n = 1), VATS lobectomy (n = 2), extended left-sided carinal pneumonectomy (n = 1) as well as extended metastasectomy (n = 2). Low-flow ECLS allowed for apnoea up to 45 min in patients with previous pneumonectomy (n = 3) and facilitated protective single-lung ventilation in patients (n = 3) with severely impaired pulmonary function. During trans-sternal carinal pneumonectomy (n = 1), high-flow ECLS achieved by femoro-atrial cannulation allowed for apnoea for 40 min, avoiding cross-field ventilation. In 2 patients requiring extended metastasectomy after previous lobectomy of the contralateral lower lobe (n = 1) or pulmonary metastases in the graft after sLTX for end-stage fibrosis (n = 1), high-flow ECLS by percutaneous femoro-jugular cannulation allowed for extensive metastasectomy under optimal atelectasis of the lung., Conclusions: For intraoperative ECLS, different modes may be applied depending on the intended procedures and required mechanical ventilation. In our experience, different settings of veno-venous ECLS provide sufficient partial or complete lung support, avoiding possible complications associated with other forms of extracorporeal support such as CPB or v-a-ECMO., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The intraoperative application of extracorporeal lung support devices during thoracic surgical procedures represents a modern concept with promising results. So far, pumpless extracorporeal interventional lung assist and veno-venous or veno-arterial extracorporeal membrane oxygenation via dual cannulation were utilized for complete or partial lung support throughout the surgical procedure. We report the initial intraoperative application of low-flow singular double-lumen veno-venous-extracorporeal membrane oxygenation for extracorporeal lung support during lung resections in patients with severely impaired preoperative pulmonary function. In our hands, this novel concept contributed to the safe performance of complex surgery in pulmonary compromised patients avoiding the possible complications of other forms of extracorporeal support.

Purpose: The aim of this study was to evaluate the applicability of the laryngeal tube (LT) size 2 and the classical laryngeal mask airway (LMA) size 2 in different head-neck positions under positive pressure ventilation in children by measuring leak pressures, peak pressures and the achievable tidal volumes under positive pressure ventilation., Methods: Forty children were randomized to receive airway management by either the LT or LMA as the primary device. Leak pressures, peak pressures and tidal volumes under positive pressure ventilation were measured in the neutral, anteflection, retroversion, left-rotation and right-rotation head-neck positions., Results: In all head-neck positions, the leak pressures were significantly higher for the LT than for the LMA (neutral 25.9 ± 7.0 vs. 19.1 ± 5.7 cmH2O; anteflection 29.7 ± 7.1 vs. 24.2 ± 8.9 cmH2O; retroversion 24.1 ± 7.6 vs. 17.2 ± 6.9 cmH2O). In both devices, the peak ventilation pressures were higher in the anteflection position (LT 27.1 ± 6.3 cmH2O; LMA 17.8 ± 6.7 cmH2O) than in the retroversion position (LT 13.7 ± 3.9 cmH2O; LMA 12.7 ± 3.6 cmH2O). Compared to the respirator settings, lower tidal volumes were achieved in the anteflection position (LT 65 ± 48 vs. 129 ± 38 ml, LMA 100 ± 21 vs. 125 ± 29 ml) as compared to the other positions., Conclusion: Based on our results, we suggest that in anaesthetized children, the size 2 LT, compared to the size 2 LMA, may be more suitable for positive pressure ventilation due to favorable leak and peak pressures. Both devices can be safely used in head-neck positions other than neutral. Most disadvantageous with regards to the measured parameters was the anteflection position, especially for the LT.

The time evolution of the ground state wave function of a zero-temperature Bose-Einstein condensate (BEC) gas is well described by the Hamiltonian Gross-Pitaevskii (GP) equation. Using a set of appropriately interleaved unitary collision-stream operators, a qubit lattice gas algorithm is devised, which on taking moments, recovers the Gross-Pitaevskii (GP) equation under diffusion ordering (time scales as length(2)). Unexpectedly, there is a class of initial states whose Poincaré recurrence time is extremely short and which, as the grid resolution is increased, scales with diffusion ordering (and not as length(3)). The spectral results of J. Yepez et al. [Phys. Rev. Lett. 103, 084501 (2009).] for quantum turbulence are revised and it is found that it is the compressible kinetic energy spectrum that exhibits three distinct spectral regions: a small-k classical-like Kolmogorov k(-5/3), a steep semiclassical cascade region, and a large-k quantum vortex spectrum k(-3). For most evolution times the incompressible kinetic energy spectrum exhibits a somewhat robust quantum vortex spectrum of k(-3) for an extended range in k with a k(-3.4) spectrum for intermediate k. For linear vortices of winding number 1 there is an intermittent loss of the quantum vortex cascade with its signature seen in the time evolution of the kinetic energy E(kin)(t), the loss of the quantum vortex k(-3) spectrum in the incompressible kinetic energy spectrum as well as the minimalization of the vortex core isosurfaces that would totally inhibit any Kelvin wave vortex cascade. In the time intervals around these intermittencies the incompressible kinetic energy also exhibits a multicascade spectrum.

Background: Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy., Methods and Findings: We developed a "Mobile Stroke Unit", consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes., Conclusion: This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

Study Objective: To investigate the influence of duration of deep hypothermic circulatory arrest (DHCA) on recovery of the bispectral index (BIS)., Design: Prospective cohort study., Setting: Operating room of university teaching hospital., Patients: 30 adult, ASA physical status III and IV patients scheduled for cardiac surgery with extracorporeal circulation (ECC) and DHCA., Interventions: There were no study-specific interventions undertaken with the study patients., Measurements: After induction of anesthesia, propofol and sufentanil were used for maintenance. Duration until BIS values reached indices of 10, 20, and 30 after DHCA was measured. DeltaBIS was defined as the difference between BIS before the start of ECC and after DHCA at the same nasopharyngeal body temperature. Data are means + or - SD (ranges)., Main Results: Duration of DHCA was 24 + or - 15 min (8-71 min). The deepest nasopharyngeal temperature was 20.1 + or - 2.7 degrees C at the end of DHCA. BIS reduction was 1.8/ degrees C. At the end of DHCA, BIS was 2 + or - 6 and at the end of ECC, BIS was 33 + or - 11. Duration until BIS reached a value of 10 (BIS10) was 23 + or - 21 min (0-83 min); until BIS reached 20 (BIS20): 36 + or - 36 min (0-140 min); and until BIS reached 30 (BIS30): 43 + or - 29 min (1-130 min). Regression analysis between duration of DHCA and BIS10 was R = 0.76; BIS20: R = 0.67; and BIS30: R = 0.54., Conclusion: Deep hypothermia influences BIS linearly. In addition, there appears to be a reasonable correlation between recovery of BIS values and duration of DHCA., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: We compared dose-response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k(e0) values of the different anesthetics. The EEG parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as measures of the pharmacodynamic effect., Methods: With IRB approval and informed consent we analyzed the data of three studies including 61 adult patients scheduled for radical prostatectomies. At least 45 min after induction of general anesthesia, end-tidal concentrations of desflurane, sevoflurane or isoflurane were varied between 0.5 and 2 MAC. We transferred the end-tidal concentrations into age-related MAC values. The relationship between MAC effect compartment concentrations and EEG was modeled with a variation of the classical fractional sigmoid E(max) model with two linked sigmoidal curves. All parameters were calculated as a population fit by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood., Results: The k(e0) values of the population fit derived from BIS data were 0.54 min(-1) for desflurane, 0.24 min(-1) for sevoflurane and 0.16 min(-1) for isoflurane, from the Narcotrend index 0.43 min(-1) for desflurane, 0.26 min(-1) for sevoflurane and 0.18 min(-1) for isoflurane. The change between the first and the second sigmoidal curve was positioned at nearly the same Narcotrend- and BIS index values between 41 and 44., Conclusions: The first order rate constant (k(e0) value) determining the equilibration between age-related MAC values and MAC effect site concentration is substantially higher for desflurane than for sevoflurane or isoflurane.

Background: This study tested the influence of continuous medication (more than 4 weeks) with prednisolone on a rocuronium-induced neuromuscular block., Methods: The time course of a rocuronium-induced neuromuscular blockade (0.3 mg/kg) was investigated in 40 patients with chronic inflammatory bowel disease undergoing elective abdominal surgery. The primary end point was the time from the start of injection of rocuronium until recovery of the TOF ratio to 0.9. Twenty patients received continuous medication with prednisolone (group A), and 20 were without glucocorticoid medication (group B). Additionally, another 20 patients without inflammatory bowel disease and without glucocorticoid medication served as control (group C)., Results: The onset time was prolonged in group A [253 (51.2) s] compared with group B [187 (61.3) s]. Twitch height at the onset of the block was higher in group A [16.5 (0-61)%] than that in group B [5.0 (0-33)%]. The duration to 25% twitch height was shorter in group A [12.6 (0-20.7) min] compared with group B [16.7 (0-25.3) min] and group C [16.9 (0-29.3) min]. The recovery to a train-of-four ratio of 0.9 was reduced in group A [25.7 (23-34.3) min] compared with group B [34.7 (32.7-44.2) min] and group C [36.5 (31.7-42.3) min]., Conclusions: Prednisolone treatment in patients with inflammatory bowel disease is associated with a delayed onset and a shorter duration of action of rocuronium. The presence of an inflammatory bowel disease did not influence the neuromuscular block.

Cardiac surgery using cardiopulmonary bypass (CPB) causes a systemic inflammatory response. Additionally, an impairment of the responsiveness of peripheral blood mononuclear cells (PBMC) to further immunological stimuli has been observed. The aim of our present study was to evaluate the ability of antioxidant therapy with mannitol or haemofiltration during CPB to modulate this immunosuppression after CPB. Forty-five patients undergoing elective heart-surgery were prospectively enrolled and randomized into three groups (control, mannitol, haemofiltration). Blood samples were taken after induction of anaesthesia (T1), 20 min after CPB (T2) and 24 h post-operatively (T3). Expression density of the monocytic surface receptor CD14, HLA-DR expression and cytokine release (TNF-alpha and IL10) after lipopolysaccharide-stimulation were evaluated. At T2, the CD14(dim) cell population was maintained in both intervention groups while in the control group there was a decrease of this proinflammatory monocytic phenotype. No significant differences regarding HLA-DR expression or cytokine release could be demonstrated. This study shows that the suppression of the stimulated immune response after CPB can potentially be alleviated by mannitol or haemofiltration in an experimental in-vitro setting. In the light of data showing that this depression of the immune response might affect the post-operative course of patients, these results could have a potential clinical relevance.

Study Design: Prospective, double-blind, randomized, placebo-controlled study., Objective: To assess the efficacy and safety of 0.4 mg intrathecal morphine for postoperative pain control after posterior lumbar interbody fusion (PLIF) surgery., Summary of Background Data: Multiple studies have established the technique of intrathecal morphine analgesia in a wide variety of clinical settings. Several trials were conducted in patients undergoing spine surgery, generally supporting the efficacy for this type of surgery. Many exhibit methodologic problems with dosing regimes or study design., Methods: After the institutional review board-approval and written informed consent, 52 patients scheduled for PLIF-surgery were enrolled, of whom 46 could be analyzed. Patients were randomized to receive 0.4 mg morphine (M-group) or normal saline (P-group) intrathecally under direct vision before the end of surgery. Additionally, all patients received a piritramide patient-controlled-analgesia for individual pain control. Measures included visual analog scale-scores and blood-gas analysis over 20 hours after surgery. Morphine associated side effects and complications were recorded., Results: Visual analog scale-scores at rest and when the patients bent their legs were comparable between groups throughout the observation period, only being significantly lower in the M-group at rest 4 and 8 hours after surgery. Cumulative piritramide patient-controlled-analgesia requirements were significantly lower in the M-group throughout the observed 20 hours after surgery. Patients of the M-group were experiencing mild respiratory depression 4 hours after surgery not demanding any intervention, though. With respect to other morphine associated side effects or complications, there was no difference between the study groups., Conclusion: We demonstrated the efficacy of 0.4 mg intrathecal morphine after PLIF-surgery as indicated by a significantly lower cumulative piritramide requirement without any serious increase of opioid associated side effects. Therefore, morphine in a dose of 0.4 mg administered intrathecally seems to be a viable alternative therapeutic option to provide postoperative analgesia with PLIF-surgery.

Background: Although the use of pulse oximeters may be regarded a standard of care for monitoring anesthesia procedures, these monitors may be susceptible to various kinds of disturbances. Recently, it was suggested that neuronavigation equipment may interfere with pulse oximeter accuracy. In this study, we evaluated the effect of a neurosurgical image guidance system on the performance of six different pulse oximeters. Two simple shielding methods were evaluated., Methods: Twenty healthy, adult, nonsmoking volunteers were equipped with six different pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen saturation, and signal quality were assessed. After activation of the Brain Lab VectorVision Neuronavigation System, the effects on signal quality and saturation recognition were evaluated. Measurements were repeated using two different shielding techniques, a cotton blanket and aluminum sheets., Results: Activation of the image guidance system resulted in a significant disturbance of signal quality and saturation detection, which was partially reversible by both shielding techniques. Significant differences were noted among the six brands of pulse oximeters for signal quality (P < 0.001) and saturation recognition (P < 0.001), and for the response to shielding methods (P < 0.001). Coverage of the probes with aluminum foil resulted an in undisturbed saturation recognition in all subjects with almost all monitors., Conclusions: Infrared pulse waves from neurosurgical navigation equipment may interfere with pulse oximeter measurements. Shielding the probe with aluminum foil sufficiently eliminated the infrared interference.

Objective: We compared two PK/PD models, one with and one without a plateau effect. Bispectral (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, Version 4.0) indices were used as an electroencephalographic measure of desflurane drug effect., Methods: With IRB approval and informed consent we investigated 20 adult patients scheduled for radical prostatectomy. At least 45 minutes after induction of general anaesthesia, end-tidal concentrations of desflurane was varied between 3 and 10 vol%. To evaluate the relationship between concentrations and EEG indices, two different pharmacodynamic models were applied: A conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test., Results: The maximum end-tidal desflurane concentration during the two concentrations ramps was 10.0 +/- 1.4 vol%. The mean BIS and NCT values decreased significantly but slightly with increasing end-tidal desflurane concentrations between 4 and 8 vol%. Therefore a two sigmoidal curves PK/PD model including a plateau describes the effects of desflurane on BIS and Narcotrend better than a single sigmoidal curve model. The difference between the log likelihood values of the new PK/PD model with two connected sigmoidal curves and the classical E (max )model with one sigmoidal curve is 634 (P < 0.001) for the BIS monitor and 4089 (P < 0.001) for the NCT., Conclusions: BIS and Narcotrend are not useful to differentiate pharmacodynamic changes in the EEG between 4 and 9 vol% desflurane.

Exogenous administration of pineal hormone melatonin (MEL) has been demonstrated to attenuate organ damage in models of I/R and inflammation by antioxidative effects. However, specific organ-protective effects of MEL with respect to hemorrhagic shock have not been investigated yet. In the present study, we evaluated the role of MEL pretreatment for hepatic perfusion, redox state, and function after hemorrhage and resuscitation, with emphasis on MEL receptor activation. In a model of hemorrhagic shock (MAP 35 +/- 5 mmHg for 90 min) and reperfusion (2 h), we measured nicotinamide adenine dinucleotide phosphate (reduced form; NADPH) autofluorescence, hepatic microcirculation, and hepatocellular injury by intravital microscopy, as well as plasma disappearance rate of indocyanine green (PDRICG) as a sensitive maker of liver function in rat. Pretreatment with 10 mg kg(-1) MEL (i.v.) 15 min before induction of hemorrhage resulted in a significantly improved PDR(ICG) compared with controls (MEL/shock, 15.02% min(-1) +/- 2.9 SD vs. vehicle/shock, 6.18 +/- 4.6 SD; P = 0.001). Intravital microscopy after reperfusion revealed an improved hepatic perfusion index, redox state, and reduced hepatocellular injury in pretreated animals compared with the vehicle group. Melatonin receptor antagonist luzindole (LZN; 2.5 mg kg(-1)) almost completely abolished the protective effects of MEL pretreatment with respect to liver function (MEL + LZN/shock PDR(ICG), 7.31% min(-1) +/- 3.4 SD). Beneficial effects regarding hepatic perfusion, redox state, and cellular injury were not influenced by LZN, indicating that they may depend on antioxidative effects of MEL. However, liver function after hemorrhage is effectively maintained by MEL pretreatment via receptor-dependent pathways.

The effect of intra-articular bupivacaine on postoperative pain following arthroscopy has been intensively studied for the knee joint but no data are currently available for the hip joint. The aim of the present prospective, randomized and double-blind study was to evaluate a possible effect of intra-articular bupivacaine on postoperative pain intensity following hip arthroscopy. A total of 26 patients were included: 13 received 20 ml of 0.25% bupivacaine through the trocar at the end of surgery and 13 patients received 20 ml of 0.9% NaCl as placebo. Postoperative pain intensity was assessed using a visual analogue scale (VAS) at 0.5 h, 4 h, 8 h, 12 h, 16 h and 20 h, at rest and during movement of the joint and on the basis of additional piritramide requirements. Furthermore, a mean VAS was calculated as the arithmetic mean of all VAS scores assessed over the whole study period. In the bupivacaine group, a significantly lower mean VAS was recorded at rest (17.5 vs 27.5, p=0.05) and during movement of the hip joint (23 vs. 46, p=0.001). The additional piritramide consumption tended to be higher in the placebo group. In conclusion, intra-articular bupivacaine following arthroscopic hip surgery reduces pain in the postoperative period mainly during movement and thus may possibly allow earlier mobilization.

Background: Hypertonic-hyperoncotic solutions may be an effective treatment for systemic inflammatory response syndrome (SIRS). With regard to the immunomodulatory effects of these drugs, previous studies demonstrated controversial results. Therefore, the present study investigated the influence of different hyperoncotic and hypertonic-hyperoncotic solutions on polymorphonuclear neutrophil leukocyte (PMNL) count, elastase and superoxide-anion production in patients undergoing elective coronary artery bypass grafting (CABG) with cardiopulmonary bypass., Methods: Fifty patients scheduled for elective CABG with cardiopulmonary bypass were randomly assigned to five groups: (i) NaCl 0.9%, 750 ml/m(2) body surface area (BSA); (ii) hydroxyethylic starch 10%, 250 ml/m(2) BSA and NaCl 0.9%, 400 ml/m(2) BSA; (iii) dextran 10%, 250 ml/m(2) BSA and NaCl 0.9%, 300 ml/m(2) BSA; (iv) hypertonic sodium chloride 7.2%/hyperoncotic hydroxyethylic starch 10%, 150 ml/m(2) BSA; and (v) hypertonic sodium chloride 7.2%/hyperoncotic dextran 10%, 150 ml/m(2) BSA. Blood samples were drawn from arterial, central venous and coronary artery sinus catheters peri-operatively. PMNL count, superoxide-anion production and elastase were recorded., Results: PMNL counts and elastase activity increased in all groups after reperfusion. Superoxide-anion production showed only minor changes. Between groups, no significant differences were demonstrated., Conclusions: Infusion of clinically relevant doses of hypertonic-hyperoncotic solution did not affect PMNL count, elastase- or superoxide-anion production during elective CABG with cardiopulmonary bypass.

Objective: Impedance Cardiography (ICG) has been shown to be a feasible and accurate method for non-invasive measurement of cardiac index (CI). Aim of this investigation was the correlation of hemodynamic variables under exercise as measured by a specific ICG-monitor (Solar IKG-Modul, Version 3.0, GE-Healthcare, Freiburg, Germany) with metabolic variables., Methods: Ten healthy volunteers were included in the investigation doing ergometer exercise (5 min equilibration followed by 5 min each at 50, 75, 100 and 125 W). Hemodynamic parameters were obtained by ICG. Metabolic variables were assessed by indirect calorimetry with the Deltatrac II Metabolic monitor using a helmet system for spontaneous respiration., Results: CI increased throughout exercise (baseline: 3.0 +/- 0.4 l/min/m(2); 125 W: 4.8 +/- 0.5 l/min/m(2)). Heart rate (baseline: 87.2 +/- 13.4 bpm; 125 W: 152.7 +/- 22.4 bpm) and contractility (velocity index) (baseline: 48.9 +/- 9.3/1000 s; 125 W: 70.5 +/- 10.0/1000 s) showed a continuous rise while the stroke index decreased after an initial rise (baseline: 35.0 +/- 4.6 ml/m(2); 50 W: 37.6 +/- 4.9 ml/m(2); 75 W: 41.2 +/- 5.9 ml/m(2); 125 W: 32.3 +/- 6.1 ml/m(2)). VO(2) (baseline: 335.2 +/- 84.1 ml/min; 125 W: 1298.9 +/- 282.3 ml/min) and VCO(2)(baseline: 255.4 +/- 74.5 ml/min; 125 W: 1342.5 +/- 282.5 ml/min) increased throughout exercise. There was a good correlation in the individual fits between hemodynamic and metabolic variables., Conclusion: CI in healthy volunteers, as measured by the Solar IKG-Modul, correlates well with O(2)-consumption and CO(2)-production in individual subjects, thus indicating the metabolic needs under exercise conditions in healthy individuals.

Background: Sepsis may lead to the suppression of stimulated cytokine release after Gram-negative stimuli, correlating with a fatal outcome. Treatment of sepsis includes adequate therapy with antibiotics. The aim of this study was to investigate the role of antibiotics in the modulation of the lipopolysaccharide (LPS)-stimulated cytokine response of human monocytes., Methods: In this ex vivo, in vitro study, whole blood samples were taken from 10 healthy volunteers, stimulated with LPS in the presence or absence of various antibiotics (penicillin, amoxicillin, cefuroxime, ceftazidime, cefotaxime, piperacillin/tazobactam, imipenem/cilastatin, gentamicin, netilmicin, ciprofloxacin, vancomycin) and cultured for 24 h. Thereafter, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). Furthermore, CD14 and HLA-DR expression on monocytes was assessed using flow cytometry., Results: All cephalosporins decreased LPS-stimulated IL-10 release. Cefuroxime and cefotaxime also decreased the expression density of the LPS recognition molecule CD14 on monocytes. An increase in LPS-stimulated IL-10 release was observed with vancomycin. A suppression of LPS-stimulated TNF-alpha and IL-10 release was observed in the presence of ciprofloxacin., Conclusion: These results indicate a modulation of the expression density of CD14 on monocytes, together with a shift from a balanced to an inflammatory cytokine release pattern, by cefuroxime and cefotaxime. Vancomycin changes the response to an anti-inflammatory release pattern. After ciprofloxacin, a profound unresponsiveness of immune-competent cells to LPS stimulation is observed. Because of the critical role of a balanced innate immune response, these data may be of importance for the selection of antibiotics in septic patients.

Background: Vocal cord injuries, postoperative hoarseness, and sore throat are common complications after general anesthesia. One-lung ventilation can be achieved via two techniques: double-lumen endotracheal tube or endobronchial blocker such as the Arndt blocker. The current study was designed to assess the impact of these techniques for one-lung ventilation on the incidence and severity of postoperative hoarseness, vocal cord lesions, and sore throat., Methods: In this prospective trial, 60 patients were randomly assigned to two groups. One-lung ventilation was achieved with either an endobronchial blocker (blocker group) or a double-lumen-tube (double-lumen group). Postoperative hoarseness and sore throat were assessed at 24, 48, and 72 h after surgery. Bronchial injuries and vocal cord lesions were examined by bronchoscopy immediately after surgery., Results: In 56 included patients, postoperative hoarseness occurred significantly more frequently in the double-lumen group compared with the blocker group: 44% versus 17%, respectively (P = 0.046). Similar findings were observed for vocal cord lesions: 44% versus 17%, respectively (P = 0.046). The incidence of bronchial injuries was comparable between groups (P = 0.540). Cumulative number of days with hoarseness and sore throat were significantly increased in the double-lumen group compared with the blocker group (P < 0.01). No major complications such as bronchial ruptures were observed., Conclusions: Clinicians should be aware of an increased incidence of minor airway injuries that may impair patient satisfaction when using a double-lumen tube instead of an endobronchial blocker for one-lung ventilation.

Reduction of the perioperative cardiovascular risk with pharmacological interventions plays a prominent role in routine anesthesia practice. For example, perioperative beta-blockade is well established in anesthesiological treatment of patients. There is a growing body of evidence supporting the cardioprotective effects of volatile anesthetics known as anesthetic-induced preconditioning. There are numerous and complex data from animal studies. The mechanisms of anesthetic-induced preconditioning have been extensively studied but have still not been clearly identified. Initial clinical data show the cardioprotective effects of volatile agents by looking at parameters of myocardial function and laboratory values and therefore, the question of the relevance of these data for routine clinical practice has been raised. This review gives a summary of the currently available data focusing on the mechanisms of anesthesiological preconditioning and clinical studies.

Many drugs currently used in anaesthesia practice modify cholinergic transmission, therefore, acetylcholinesterase inhibitors are a part of anaesthetic pharmacology. Besides its well established use in the antagonism of neuromuscular blockades and the therapy of central anticholinergic syndrome (CAS), results of controlled studies and case reports suggest other favourable indications such as the prevention and therapy of postanaesthetic shivering and the treatment of various types of intoxication and delirium. Cholinesterase inhibitors may also have analgesic properties. This review summarises the pharmacological and physiological background and describes favourable indications of this class of drugs.

Induction of heme oxygenase (HO)-1 may confer hepatocellular protection, e.g., in reperfusion injury. Previous reports suggest that intracellular cAMP up-regulates HO-1. The aim of the present study was to assess the role of adrenoceptor agonists as a means to induce HO-1 and to assess molecular mechanisms of HO-1 gene expression by adrenoceptor agonists. Induction of HO-1 in primary cultures of hepatocytes and in rat liver in vivo was assessed by Northern blot, Western blot, and immunohistochemistry. The beta-receptor agonists (+/-)isoproterenol and (-)isoproterenol induced HO-1 in primary cultures of hepatocytes but not the inactive enantiomer (+)isoproterenol. No induction of HO-1 was observed after alpha1, alpha2, beta2, or beta 3 agonists. beta1-Receptor agonists dobutamine and xamoterol induced HO-1 dose dependently, whereas the beta1-receptor antagonist metoprolol attenuated HO-1 induction by beta1-receptor agonists. Furthermore, 8 Br-cAMP and forskolin induced HO-1. Inhibition of protein kinase A (PKA) abolished induction by dobutamine and 8 Br-cAMP. Parallel changes were observed for the transcription factor AP-1. In vivo infusion of dobutamine for 6 h induced HO-1 in rat livers. Immunohistochemical detection of HO-1 revealed a pericentral expression pattern of HO-1 in hepatocytes, i.e., the area at risk for ischemia/reperfusion injury. These results suggest induction of HO-1 by beta1-adrenoceptor agonists via the PKA pathway in hepatocytes, reflecting a potential means for "pharmacological preconditioning."

Molecular biology has revolutionized medicine by increasing our understanding of the pathophysiological mechanisms of disease and the ability to assess genetic risk. Individual differences in disease manifestation and course in intensive care medicine often cannot be explained by known phenotypic risk factors alone. Recent data suggest an association between specific genotypes and the risk of adverse clinical outcomes. This includes inflammatory responses (i.e. TNF-alpha, Il-10), infectious diseases such as pneumonia or meningitis, sepsis, ARDS, as well as the mortality of critically injured patients (polytrauma, severe brain trauma). Continued identification of such allotypes and haplotypes may not only provide insight as to why the response to treatment varies amongst individuals in the intensive care unit, but also may potentially decrease morbidity and mortality through improved risk assessment and the administration of prophylactic therapy.

Melagatran is a direct inhibitor of thrombin and-like its oral prodrug ximelagatran-a newly developed dipetide with high antithrombotic efficacy. They present a linear dose-response, a short plasma half-life and the therapeutic range may be advantageous compared with classic anticoagulants such as heparins or vitamin K antagonists. The results of clinical studies for prevention and treatment of thromboembolic complications are encouraging. The use of melagatran and ximelagatran will gain significance in the perioperative management, thus being of particular importance for anaesthesiology and critical care medicine in the near future.