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Aim of the Study: Prognosis in out-of-hospital cardiac arrest (OHCA) depends on cardiopulmonary resuscitation (CPR) duration. Therefore, the optimal biphasic defibrillation waveform shows high conversion rates besides low energy. Matthew Fishler theoretically predicted it to be truncated ascending exponential. We realised a prototypic defibrillator and compared ascending with conventional rectangular waveforms in modelled OHCA and CPR., Methods: Approved by the authorities, 57 healthy swine (Landrace ​× ​Piétrain) were randomised to ASCDefib ( n 26) or CONVDefib ( n 26). Five swine served as sham control. We induced ventricular fibrillation (VF) electrically in anaesthetised swine randomised to ASCDefib or CONVDefib and discontinued mechanical ventilation. After 5 ​min of untreated cardiac arrest, we started CPR with mechanical chest compressions and ventilation. We performed transthoracic biphasic defibrillations after 2, 4, 6 and 8 ​min CPR targeting 4 ​J/kg in either group. Depending on the randomised group, the defibrillation protocol was either three ascending followed by one rectangular waveform (ASCDefib) or three rectangular followed by one ascending waveform (CONVDefib)., Results: Under our model-specific conditions, VF was initially terminated by 13/80 ascending waveforms and 13/79 rectangular waveforms and persistent return of spontaneous circulation was achieved in 8/26 (ASCDefib) vs. 10/26 (CONVDefib) animals. Mean current rather than waveform design was predictive for defibrillation success in a generalised linear model., Conclusion: Contrary to theoretical assumptions, transthoracic biphasic defibrillation with ascending waveforms is not superior to rectangular waveforms in modelled OHCA. We advocate defibrillation dosage to be guided by current, that has proven its predictive value again., Institutional Protocol Number: 84-02.04.2017.A176., Competing Interests: T. Annecke reports research funding from Aerogen, B. Braun Foundation, CIO Koeln Bonn, CytoSorbents Europe, Medtronic and PULSION Medical Systems; outside the submitted work. Prof Steven reports research grants from Abbott, Boston and Medtronic, outside the submitted work; honoraria from Abbott and Boston Scientific, outside the submitted work. The remaining authors have disclosed that they do not have any conflicts of interest., (© 2020 The Author(s).)

Anaesthetics used during cancer surgery may influence tumour cells and immunological response. The aim of this study was to evaluate a potential influence of the anaesthetic method (inhaled anaesthetics versus total-intravenous anaesthesia using propofol) on recurrence-free and overall survival in glioblastoma patients. We retrospectively identified patients undergoing resection of contrast enhancing glioblastoma under general anaesthesia followed by standard adjuvant treatment between January 2010 and February 2017 at two University Hospitals. Matched pairs of patients receiving either balanced with volatile anaesthetics or total intravenous anaesthesia were generated according to the known prognostic factors (extent of resection, methyl-guanine-methyl-transferase (MGMT) promoter methylation, age, Karnofsky performance score). Groups were compared using chi-square and Whitney-Man-U test. Time to recurrence was calculated using Kaplan Meier estimates. Log Rank test was used to assess the influence of the anaesthetic method. One hundred and fifty-eight (79:79) patients were included. Groups showed no significant difference in recurrence-free (volatiles: 8.0 (95% CI 6.5-9.8) vs. propofol: 8.4 (95% CI 7.9-10.1) months; p = 0.54) or overall survival (propofol: 17.4 (95% CI 14.0-20.7) vs. volatiles: 16.9 (95% CI 13.9-20.1) months; p = 0.85). In contrast to potential beneficial effects in some other solid tumours, the choice of anaesthetic method had no impact on survival in patients with glioblastoma in a well-defined cohort.

Background: If transport under ongoing cardiopulmonary resuscitation (CPR) from an upper floor is indicated, the ideal CPR-method and evacuation route is unknown hitherto. We aimed to elaborate a strategy for evacuation of patients under ongoing CPR from an upper floor, comparing three different evacuation routes and manual and mechanical chest compressions., Methods: A CPR-training manikin recording CPR-quality was placed on the fifth floor and was evacuated to an ambulance via lift, turntable ladder, or staircase. Chest compressions were performed manually or with a mechanical CPR-device. Efficiency endpoints were compression depth and frequency, sufficiency of chest release, compared with European Resuscitation Council (ERC) Guidelines, and duration of the evacuation. Adverse outcomes were disconnection/dislocation of devices and hazards/accidents to the personnel., Results: For all evacuation routes, compression depth and frequency were significantly more compliant with ERC-guidelines under mechanical CPR. Manual CPR was associated with considerable deviations from correct compression depth and frequency. Chest release only slightly differed between groups. Evacuation via lift under mechanical CPR was fastest and evacuation via turntable ladder under manual CPR was slowest. No device disconnections or accidents occurred, but hazard to personnel was perceived during evacuation via ladder under manual CPR., Conclusions: In this study, a mechanical CPR-device proved to deliver better CPR-quality during evacuation from an upper floor. If a lift accessible with a stretcher is available, this route should be preferred, regardless of manual or mechanical CPR. Turntable ladders can only be meaningfully used with mechanical CPR, otherwise CPR-quality is poor and hazard to the personnel is increased. Not all evacuation routes may be useable in a specific real-life scenario., Trial Registration: German Clinical Trials Registry, www.drks.de, registration number DRKS00012885, registration date 17.08.2017.

Purpose: Pancreatic cancer is typically diagnosed in a late stage with limited therapeutic options. For those patients, ultrasound-guided high-intensity focused ultrasound (US-HIFU) can improve local control and alleviate pain. However, MRI-guided HIFU (MR-HIFU) has not yet been studied extensively in this context. To facilitate related research and accelerate clinical translation, we report a workflow for the in vivo HIFU ablation of the porcine pancreas under MRI guidance. Materials and methods: The pancreases of five healthy German landrace pigs (35-58 kg) were sonicated using a clinical MR-HIFU system. Acoustic access to the pancreas was supported by a specialized diet and a hydrogel compression device for bowel displacement. Organ motion was suspended using periods of apnea. The size of the resulting thermal lesions was assessed using the thermal threshold- and dose profiles, non-perfused volume, and gross examination. The effect of the compression device on beam path length was assessed using MRI imaging. Results: Eight of ten treatments resulted in clearly visible damage in the target tissue upon gross examination. Five treatments resulted in coagulative necrosis. Good agreement between the four metrics for lesion size and a clear correlation between the delivered energy dose and the resulting lesion size were found. The compression device notably shortened the intra-abdominal beam path. Conclusions: We demonstrated a workflow for HIFU treatment of the porcine pancreas in-vivo under MRI-guidance. This development bears significance for the development of MR-guided HIFU interventions on the pancreas as the pig is the preferred animal model for the translation of pre-clinical research into clinical application.

To date, the optimal cooling device for targeted temperature management (TTM) remains unclear. Water-circulating cooling blankets are broadly available and quickly applied but reveal inaccuracy during maintenance and rewarming period. Recently, esophageal heat exchangers (EHEs) have been shown to be easily inserted, revealed effective cooling rates (0.26-1.12°C/h), acceptable deviations from target core temperature (<0.5°C), and rewarming rates between 0.2 and 0.4°C/h. The aim of this study was to compare cooling rates, accuracy during maintenance, and rewarming period as well as side effects of EHEs with water-circulating cooling blankets in a porcine TTM model. Mean core temperature of domestic pigs ( n  = 16) weighing 83.2 ± 3.6 kg was decreased to a target core temperature of 33°C by either using EHEs or water-circulating cooling blankets. After 8 hours of maintenance, rewarming was started at a goal rate of 0.25°C/h. Mean cooling rates were 1.3 ± 0.1°C/h (EHE) and 3.2 ± 0.5°C/h (blanket, p  < 0.0002). Mean difference to target core temperature during maintenance ranged between ±1°C. Mean rewarming rates were 0.21 ± 0.01°C/h (EHE) and 0.22 ± 0.02°C/h (blanket, n.s.). There were no differences with regard to side effects such as brady- or tachycardia, hypo- or hyperkalemia, hypo- or hyperglycemia, hypotension, shivering, or esophageal tissue damage. Target temperature can be achieved faster by water-circulating cooling blankets. EHEs and water-circulating cooling blankets were demonstrated to be reliable and safe cooling devices in a prolonged porcine TTM model with more variability in EHE group.

Background: Targeted temperature management is a standard therapy for unconscious survivors of cardiac arrest. To date, multiple cooling methods are available including invasive intravascular cooling devices (IVDs), which are widely used in the clinical setting. Recently, esophageal heat exchangers (EHEs) have been developed providing cooling via the esophagus that is located close to the aorta and inferior vena cava. The objective was to compare mean cooling rates, as well as differences, to target temperature during maintenance and the rewarming period of IVD and EHE., Methods: The study was conducted in 16 female domestic pigs. After randomization to either IVD or EHE (n = 8/group), core body temperature was reduced to 33°C. After 24 hours of maintenance (33°C), animals were rewarmed using a target rate of 0.25°C/h for 10 hours. All cooling phases were steered by a closed-loop feedback system between the internal jugular vein and the chiller. After euthanasia, laryngeal and esophageal tissue was harvested for histopathological examination., Results: Mean cooling rates (4.0°C/h ± 0.4°C/h for IVD and 2.4°C/h ± 0.3°C/h for EHE; P < .0008) and time to target temperature (85.1 ± 9.2 minutes for IVD and 142.0 ± 21.2 minutes for EHE; P = .0008) were different. Mean difference to target temperature during maintenance (0.07°C ± 0.05°C for IVD and 0.08°C ± 0.10°C for EHE; P = .496) and mean rewarming rates (0.2°C/h ± 0.1°C/h for IVD and 0.3°C/h ± 0.2°C/h for EHE; P = .226) were similar. Relevant laryngeal or esophageal tissue damage could not be detected. There were no significant differences in undesired side effects (eg, bradycardia or tachycardia, hypokalemia or hyperkalemia, hypoglycemia or hyperglycemia, hypotension, overcooling, or shivering)., Conclusions: After insertion, target temperatures could be reached faster by IVD compared to EHE. Cooling performance of IVD and EHE did not significantly differ in maintaining target temperature during a targeted temperature management process and in active rewarming protocols according to intensive care unit guidelines in this experimental setting.

Purpose: The purpose of this retrospective study was to evaluate perioperative risk factors concerning difficult airway management, primary tracheostomy, and need for intensive care unit (ICU) admission in severe odontogenic space infections., Methods: Perioperative risk factors were retrospectively analyzed in 499 cases. Fisher's exact test and analysis of variance were performed to analyze associations between categorical and continuous variables. Univariate regression analysis was used for estimating predictors for ICU admission. A risk model for ICU admission was performed using multivariate regression analysis. Area-under-the-curve (AUC) was calculated by receiver-operating-characteristic (ROC) curve., Results: Airway securing in patients with restricted mouth opening led to significant use of the video laryngoscope (p < 0.001) or fiberoptic bronchoscope (p < 0.001). The use of fiberoptic bronchoscopy was significantly increased in patients with dysphagia (p = 0.005) and dyspnea (p = 0.04). Four patients (0.8%) needed primary tracheostomy. ICU admission was significantly associated with higher levels of C-reactive protein (CRP, p = 2.78 × 10 -5 ), white blood cell count (WBC, p = 0.003), dyspnea (p = 9.95 × 10 -6 ), and higher body mass index (BMI, p = 0.0003). American Society of Anesthesiologists physical status (ASA PS) class III patients (p = 0.04) and the need for the use of a video laryngoscopy (p = 0.003) or fiberoptic bronchoscopy (p = 6.58 × 10 -5 ) resulted in a more frequent ICU admission. The AUC of the model was 0.897., Conclusion: Difficult airway management was mainly dependent on limited mouth opening and elevated CRP. Elevated CRP, BMI, ASA PS III, and dyspnea were important risk factors for ICU admission. These predictors should be considered preoperatively for proper planning and preparation.

Background: Peri-operative critical events are still a major problem in paediatric anaesthesia care. Access to more experienced healthcare teams might reduce the adverse event rate and improve outcomes., Objective: The current study analysed incidences of peri-operative paediatric cardiac arrest before and after implementation of a specialised paediatric anaesthesia team and training programme., Design: Retrospective cohort study with before-and-after analysis., Setting: Department of Anaesthesiology and Intensive Care Medicine, University Hospital of Cologne, Germany., Patients: A total of 36 243 paediatric anaesthetics (0 to 18 years) were administered between 2008 and 2016., Intervention: Implementation of a specialised paediatric anaesthesia team and training programme occurred in 2014 This included hands-on supervised training in all fields of paediatric anaesthesia, double staffing for critical paediatric cases and a 24/7 emergency team. A logistic regression analysis with risk factors (age, ASA physical status, emergency) was used to evaluate the impact of implementation of the specialised paediatric anaesthesia team., Main Outcome Measures: Incidences of peri-operative paediatric cardiac arrest and anaesthesia-attributable cardiac arrest before and after the intervention., Results: Twelve of 25 paediatric cardiac arrests were classified as anaesthesia-attributable. The incidence of overall peri-operative paediatric cardiac arrest was 8.1/10 000 (95% CI 5.2 to 12.7) in the period 2008 to 2013 and decreased to 4.6/10 000 (95% CI 2.1 to 10.2) in 2014 to 2016. Likewise, the incidence of anaesthesia-attributable cardiac arrest was lower after 2013 [1.6/10 000 (95% CI 0.3 to 5.7) vs. 4.3/10 000 (95% CI 2.3 to 7.9)]. Using logistic regression, children anaesthetised after 2013 had nearly a 70% lower probability of anaesthesia-attributable cardiac arrest (odds ratio 0.306, 95% CI 0.067 to 1.397; P = 0.1263). For anaesthesia-attributable cardiac arrest, young age was the most contributory risk factor, whereas in overall paediatric cardiac arrest, ASA physical statuses 3 to 5 played a more important role., Conclusion: In this study on incidences of peri-operative paediatric cardiac arrest from a European tertiary care university hospital, implementation of a specialised paediatric anaesthesia team and training programme was associated with lower incidences of peri-operative paediatric cardiac arrest and a reduced probability of anaesthesia-attributable cardiac arrest.

Background: A severe mismatch between the supply and demand of oxygen is the common feature of all types of shock. We present a newly developed, clinically oriented classification of the various types of shock and their therapeutic implications., Methods: This review is based on pertinent publications (1990-2018) retrieved by a selective search in PubMed, and on the relevant guidelines and meta-analyses., Results: There are only four major categories of shock, each of which is mainly related to one of four organ systems. Hypovolemic shock relates to the blood and fluids compartment while distributive shock relates to the vascular system; cardiogenic shock arises from primary cardiac dysfunction; and obstructive shock arises from a blockage of the circulation. Hypovolemic shock is due to intravascular volume loss and is treated by fluid replacement with balanced crystalloids. Distributive shock, on the other hand, is a state of relative hypovolemia resulting from pathological redistribution of the absolute intravascular volume and is treated with a combination of vasoconstrictors and fluid replacement. Cardiogenic shock is due to inadequate function of the heart, which shall be treated, depending on the situation, with drugs, surgery, or other interventional procedures. In obstructive shock, hypoperfusion due to elevated resistance shall be treated with an immediate life-saving intervention., Conclusion: The new classification is intended to facilitate the goal-driven treatment of shock in both the pre-hospital and the inpatient setting. A uniform treatment strategy should be established for each of the four types of shock.

Background: Contribution of the small intestine to systemic inflammation after cardiac arrest (CA) is poorly understood. The objective was to evaluate whether an in vivo rat model of 6 min CA is suitable to initiate intestinal ischaemia-reperfusion-injury and to evaluate histomorphological changes and inflammatory processes in the small intestinal mucosa resp. in sera., Methods: Adult male Wistar rats were subjected to CA followed by cardio-pulmonary resuscitation. Proximal jejunum and serum was collected at 6 h, 24 h, 72 h and 7 d post return of spontaneous circulation (ROSC) and from a control group. The small intestine was evaluated histomorphologically. Cytokine concentrations were measured in jejunum lysates and sera., Results: Histomorphological evaluation revealed a significant increase in mucosal damage in the jejunum at all timepoints compared to controls (p < 0.0001). In jejunal tissues, concentrations of IL-1α, IL-1β, IL-10, and TNF-α showed significant peaks at 24 h and were 1.5- to 5.7-fold higher than concentrations at 6 h and in the controls (p < 0.05). In serum, a significant higher amount of cytokine was detected only for IL-1β at 24 h post-ROSC compared to controls (15.78 vs. 9.76 pg/ml)., Conclusion: CA resulted in mild small intestinal tissue damage but not in systemic inflammation. A rat model of 6 min CA is not capable to comprehensively mimic a post cardiac arrest syndrome (PCAS). Whether there is a vital influence of the intestine on the PCAS still remains unclear.

Cancer is one of the leading causes of death worldwide. New targeted and individualized therapies and drugs provide a survival benefit for an increasing number of patients, but can also cause severe side effects. An increasing number of oncology patients are admitted to intensive care units (ICU) because of cancer-related complications or treatment-associated side effects. Postoperative care, respiratory distress and sepsis are the leading causes for admission. Tumor mass syndromes and tumor lysis may require urgent treatment. Traditional anticancer chemotherapy is associated with infections and immunosuppression. Newer agents are generally well-tolerated and side effects are mild or moderate, but overwhelming inflammation and autoimmunity can also occur. Cellular treatment, such as with chimeric antigen receptor modified T‑cells, monoclonal and bispecific antibodies targeting immune effectors and tumor cells are associated with cytokine release syndrome (CRS) with hypotension, skin reactions and fever. It is related to excessively high levels of inflammatory cytokines. Immune checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as colitis and endocrine disorders. Noninfectious respiratory complications, such as pneumonitis can also occur. Recent studies revealed that short-term and medium-term survival of cancer patients is better than previously expected. In this review article we summarize diagnostic and treatment strategies for common life-threatening complications and emergencies requiring ICU admission. Furthermore, strategies for rational admission policies are presented., (© Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2018.)

Since 1975, a plethora of lectures within the context of annual meetings relevant for the clinical care has been summarized in "what's new in obstetric anesthesia" by the society for Obstetric anesthesia and Perinatology which can be recommended to everyone interested in anaesthesiology in the delivery room. After the death of Gerard W. Ostheimer, Professor of Anaesthesiology at Brigham and Women's Hospital in Boston, Massachusetts, it became renamed the Gerard W. Ostheimer "what's new in obstetric anesthesia" lecture to honor his contributions to regional anesthesia and obstetric anaesthesia. Each year the event held by selected professional representatives and their imprint in leading anesthesia journals give insight into a critical appraisal of recent literature and the possible consequences for - but not only - the anaesthetic delivery room practice.A similar event has been established in Germany for more than 16 years (first event on April 1, 2000, most recently held on February 27, 2016, in Munich): the obstetrical anesthesia symposium of the academic working group "regional anesthesia and obstetrical anesthesia" [1], [2]."Evergreens" or "hot topics" with regard to anaesthesiological delivery room practice are presented and discussed regularly. The lectures often reveal the subtle change of the issues being debated much earlier than traditional textbook chapters do. This manuscript summarizes important findings from the last symposium held in 2016. Part I focuses on relevant causes for maternal morbidity and mortality as well as preventive measures, pregnancy in obese patients and sepsis in obstetric anaesthesia. Part II addresses established standards and new perspectives in the direct obstetric setting regarding epidural analgesia, post-dural puncture headache, anaesthesia and analgesia during and after caesarean section, haemodynamic monitoring during cesarean section and postpartum haemorrhage., Competing Interests: Interessenkonflikt: Prof. Dr. Thorsten Annecke erhält derzeit Forschungsunterstützung durch folgende Institutionen und Unternehmen: Centrum für Integrierte Onkologie Köln-Bonn, Bundesministerium für Wirtschaft und Energie, B. Braun Stiftung, Corpuls, Pulsion, Medtronic-Covidien, CytoSorbents, Dr. F. Köhler Chemie. Die anderen Autoren geben an, dass kein Interessenkonflikt vorliegt., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Blood potassium is the main prognostic biomarker used for triage in hypothermic cardiac arrest. The aim of this review was to assess the impact of hypothermia on blood potassium levels and compare the underlying pathophysiological theories., Methods: The Medline electronic database was searched via PubMed for articles published from January 1970 to December 2016. The search strategy included studies related to hypothermia and potassium levels. The relevant literature on clinical studies and experimental studies was reviewed by the authors., Results: Among the 50 studies included in the review, 39 (78%) reported a decrease in blood potassium levels upon hypothermia onset. Hypothermic hypokalaemia is linked to an intracellular shift rather than an actual net loss. The intracellular shift is caused by a variety of factors such as enhanced functioning of Na+K+ATPase, beta-adrenergic stimulation, pH and membrane stabilisation in deep hypothermia. In contrast, hypothermia can act as an aggravating factor in severe trauma with hyperkalaemia being an indicator of an irreversible state of cell death. An increase in the blood potassium level during hypothermia may result from a lack of enzyme functioning at cold temperatures and blocked active transport., Conclusion: Hypothermia causes an initial decrease of potassium levels; however, the final stage of hypothermic cardiac arrest can induce hyperkalaemia due to cell lysis and final depolarisation. Better understanding the physiopathology of potassium levels during accidental hypothermia could be critically important to better select patients who could benefit from aggressive resuscitation therapy such as extracorporeal cardiopulmonary resuscitation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Targeted temperature management (TTM) is widely used in critical care settings for conditions including hepatic encephalopathy, hypoxic ischemic encephalopathy, meningitis, myocardial infarction, paediatric cardiac arrest, spinal cord injury, traumatic brain injury, ischemic stroke and sepsis. Furthermore, TTM is a key treatment for patients after out-of-hospital cardiac-arrest (OHCA). However, the optimal cooling method, which is quick, safe and cost-effective still remains controversial. Since the oesophagus is adjacent to heart and aorta, fast heat-convection to the central blood-stream could be achieved with a minimally invasive oesophageal heat exchanger (OHE). To date, the optimal diameter of an OHE is still unknown. While larger diameters may cause thermal- or pressure-related tissue damage after long-term exposure to the oesophageal wall, smaller diameter (e.g., gastric tubes, up to 11mm) may not provide effective cooling rates. Thus, the objective of the study was to compare OHE-diameters of 11mm (OHE11) and 14.7mm (OHE14.7) and their effects on tissue and cooling capability., Methods: Pigs were randomized to OHE11 (N = 8) or OHE14.7 (N = 8). After cooling, pigs were maintained at 33°C for 1 hour. After 10h rewarming, oesophagi were analyzed by means of histopathology. The oesophagus of four animals from a separate study that underwent exactly the identical preparation and cooling protocol described above but received a maintenance period of 24h were used as histopathological controls., Results: Mean cooling rates were 2.8±0.4°C°C/h (OHE11) and 3.0±0.3°C °C/h (OHE14.7; p = 0.20). Occasional mild acute inflammatory transepithelial infiltrates were found in the cranial segment of the oesophagus in all groups including controls. Deviations from target temperature were 0.1±0.4°C (OHE11) and 0±0.1°C (OHE14.7; p = 0.91). Rewarming rates were 0.19±0.07°C °C/h (OHE11) and 0.20±0.05°C °C/h (OHE14.7; p = 0.75)., Conclusions: OHE with diameters of 11 mm and 14.7 mm achieve effective cooling rates for TTM and did not cause any relevant oesophageal tissue damage. Both OHE demonstrated acceptable deviations from target temperature and allowed for an intended rewarming rate (0.25°C/h).

Decompression of the chest is a life-saving invasive procedure for tension pneumothorax, trauma-associated cardiopulmonary resuscitation or massive haematopneumothorax that every emergency physician or intensivist must master. Particularly in the preclinical setting, indication must be restricted to urgent cases, but in these cases chest decompression must be executed without delay, even in subpar circumstances. The methods available are needle decompression or thoracentesis via mini-thoracotomy with or without insertion of a chest tube in the midclavicular line of the 2nd/3rd intercostal space (Monaldi-position) or in the anterior to mid-axillary line of the 4th/5th intercostal space (Bülau-position). Needle decompression is quick and does not require much material, but should be regarded as a temporary measure. Due to insufficient length of the usual 14-gauge intravenous catheters, the pleural cavity cannot be reached in a considerable percentage of patients. In the case of mini-thoracotomy, one must be cautious not to penetrate the chest inferior of the mammillary level, to employ blunt dissection techniques, to clearly identify the pleural space with a finger and not to use a trocar. In extremely urgent cases opening the pleural membrane by thoracostomy without inserting a chest tube is sufficient in mechanically ventilated patients. Complications are common and mainly include ectopic positions, which can jeopardise effectiveness of the procedure, sometimes fatal injuries to adjacent intrathoracic or - in case of too inferior placement - intraabdominal organs as well as haemorrhage or infections. By respecting the basic rules for safe chest decompression many of these complications should be avoidable.

Background: On-pump cardiac surgery triggers a significant postoperative systemic inflammatory response, sometimes resulting in multiple-organ dysfunction associated with poor clinical outcome. Extracorporeal cytokine elimination with a novel haemoadsorption (HA) device (CytoSorb®) promises to attenuate inflammatory response. This study primarily assesses the efficacy of intraoperative HA during cardiopulmonary bypass (CPB) to reduce the proinflammatory cytokine burden during and after on-pump cardiac surgery, and secondarily, we aim to evaluate effects on postoperative organ dysfunction and outcomes in patients at high risk., Methods/design: This will be a single-centre randomised, two-arm, patient-blinded trial of intraoperative HA in patients undergoing on-pump cardiac surgery. Subjects will be allocated to receive either CPB with intraoperative HA or standard CPB without HA. The primary outcome is the difference in mean interleukin 6 (IL-6) serum levels between the two study groups on admission to the intensive care unit. A total number of 40 subjects was calculated as necessary to detect a clinically relevant 30 % reduction in postoperative IL-6 levels. Secondary objectives evaluate effects of HA on markers of inflammation up to 48 hours postoperatively, damage to the endothelial glycocalyx and effects on clinical scores and parameters of postoperative organ dysfunction and outcomes., Discussion: In this pilot trial we try to assess whether intraoperative HA with CytoSorb® can relevantly reduce postoperative IL-6 levels in patients undergoing on-pump cardiac surgery. Differences in secondary outcome variables between the study groups may give rise to further studies and may lead to a better understanding of the mechanisms of haemoadsorption., Trial Registration: German Clinical Trials Register number DRKS00007928 (Date of registration 3 Aug 2015).

Hypothermia is a severe, unpleasant side effect during general anesthesia. Thus, temperature surveillance is a prerequisite in general anesthesia settings during experimental surgeries. The gold standard to measure the core body temperature (Tcore) is placement of a Swan-Ganz catheter in the pulmonary artery, which is a highly invasive procedure. Therefore, Tcore is commonly examined in the urine bladder and rectum. However, these procedures are known for their inaccuracy and delayed record of temperatures. Zero-heat-flux (ZHF) thermometry is an alternative, non-invasive method quantifying Tcore in human patients by applying a thermosensoric patch to the lateral forehead. Since the porcine cranial anatomy is different to the human's, the optimal location of the patch remains unclear to date. The aim was to compare three different patch locations of ZHF thermometry in a porcine hypothermia model. Hypothermia (33.0 °C Tcore) was conducted in 11 anesthetized female pigs (26-30 kg). Tcore was measured continuously by an invasive Swan-Ganz catheter in the pulmonary artery (Tpulm). A ZHF thermometry device was mounted on three different defined locations. The smallest average difference between Tpulm and TZHF during stable temperatures was 0.21 ± 0.16 °C at location A, where the patch was placed directly behind the eye. Also during rapidly changing temperatures location A showed the smallest bias with 0.48 ± 0.29 °C. Location A provided the most reliable data for Tcore. Therefore, the ZHF thermometry patch should be placed directly behind the left temporal corner of the eye to provide a non-invasive method for accurate measurement of Tcore in pigs.

Introduction: It is well established that obesity-related hormones can have modulatory effects associated with the immune response. Ghrelin, a hormone mainly derived from endocrine cells of the gastric mucosa, regulates appetite, energy expenditure and body weight counteracting leptin, a hormone mainly derived from adipocytes. Additionally, receptors of both have been detected on immune cells and demonstrated an immune regulatory function during sepsis., Methods: In the present study, the effect of peripheral ghrelin administration on early immune response and survival was investigated with lean mice and mice with diet-induced obesity using cecal ligation and puncture to induce sepsis., Results: In the obese group, we found that ghrelin treatment improved survival, ameliorated hypothermia, and increased hyperleptinemia as compared to the lean controls. We also observed that ghrelin treatment divergently regulated serum IL-1ß and TNF-α concentrations in both lean and obese septic mice. Ghrelin treatment initially decreased but later resulted in increased bacteriaemia in lean mice while having no impact upon obese mice. Similarly, ghrelin treatment increased early neutrophil oxidative burst while causing a decrease 48 hours after sepsis inducement., Conclusion: In conclusion, as the immune response to sepsis temporally changes, ghrelin treatment differentially mediates this response. Specifically, we observed that ghrelin conferred protective effects during the early phase of sepsis, but during the later phase deteriorated immune response and outcome. These adverse effects were more pronounced upon lean mice as compared to obese mice.

Background: We report on the design and implementation of a study protocol entitled Acupuncture randomised trial for post anaesthetic recovery and postoperative pain - a pilot study (ACUARP) designed to investigate the effectiveness of acupuncture therapy performed in the perioperative period on post anaesthetic recovery and postoperative pain., Methods/design: The study is designed as a randomised controlled pilot trial with three arms and partial double blinding. We will compare (a) press needle acupuncture, (b) no treatment and (c) press plaster acupressure in a standardised anaesthetic setting. Seventy-five patients scheduled for laparoscopic surgery to the uterus or ovaries will be allocated randomly to one of the three trial arms. The total observation period will begin one day before surgery and end on the second postoperative day. Twelve press needles and press plasters are to be administered preoperatively at seven acupuncture points. The primary outcome measure will be time from extubation to 'ready for discharge' from the post anaesthesia care unit (in minutes). The 'ready for discharge' end point will be assessed using three different scores: the Aldrete score, the Post Anaesthetic Discharge Scoring System and an In-House score. Secondary outcome measures will comprise pre-, intra- and postoperative variables (which are anxiety, pain, nausea and vomiting, concomitant medication)., Discussion: The results of this study will provide information on whether acupuncture may improve patient post anaesthetic recovery. Comparing acupuncture with acupressure will provide insight into potential therapeutic differences between invasive and non-invasive acupuncture techniques., Trial Registration: NCT01816386 (First received: 28 October 2012).

Background: Obesity is a growing health problem and associated with immune dysfunction. Sepsis is defined as systemic inflammatory response syndrome that occurs during infection. Excessive inflammation combined with immune dysfunction can lead to multiorgan damage and death., Methods: The authors investigated the influence of a class 1 obesity (body mass index between 30 and 34.9) on immune function and outcome in sepsis and the role of leptin on the immune response. The authors used a long-term high-fat-diet feeding model (12 weeks) on C57Bl/6 mice (n = 100) and controls on standard diet (n = 140) followed by a polymicrobial sepsis induced by cecal ligation and puncture., Results: The authors show that class 1 obesity is connected to significant higher serum leptin levels (data are mean ± SEM) (5.7 ± 1.2 vs. 2.7 ± 0.2 ng/ml; n = 5; P = 0.033) and improved innate immune response followed by significant better survival rate in sepsis (71.4%, n = 10 vs. 10%, n = 14; P < 0.0001). Additional sepsis-induced increases in leptin levels stabilize body temperature and are associated with a controlled immune response in a time-dependent and protective manner. Furthermore, leptin treatment of normal-weight septic mice with relative hypoleptinemia (n = 35) also significantly stabilizes body temperature, improves cellular immune response, and reduces proinflammatory cytokine response resulting in improved survival (30%; n = 10)., Conclusions: Relative hyperleptinemia of class 1 obesity or induced by treatment is protective in sepsis. Leptin seems to play a regulatory role in the immune system in sepsis, and treatment of relative hypoleptinemia could offer a new way of an individual sepsis therapy.

Introduction: Sepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome., Methods: In this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting., Results: Platelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r = -0.867; P < 0.0001), SOFA (r = -0.857; P <0.0001), and SAPS II score (r = -0.839; P < 0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P < 0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P < 0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis., Conclusion: In this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome.

Introduction: Vascular leakage after ischemia-reperfusion (IR) is largely attributed to the destruction of the endothelial barrier and its associated negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes. Therefore, we compared sevoflurane with propofol with regard to the protection of the glycocalyx and the release of negatively charged substances in vivo., Methods: After surgical preparation under midazolam-fentanyl, nine pigs each received either propofol or sevoflurane. Ischemia of 90 min was induced by a balloon catheter in the thoracic aorta. After 120 min of reperfusion, the anesthetics were changed back to midazolam-fentanyl. Five animals, each without aortic occlusion, served as time controls. Blood electrolyte parameters were measured, from which the strong ion gap (SIG) was calculated. Serum heparan sulfate concentrations and immunohistology served as a marker of glycocalyx destruction., Results: Immediately after reperfusion, SIG increased significantly only in the propofol group (+6.7 mEq/l versus baseline; p < .05), remaining stable in sevoflurane and both time-controlled groups. Initially, heparan sulfate concentration increased comparably in both experimental groups, but after 120 min, it became stable in sevoflurane-anesthetized animals, while increasing further in the propofol group (p < .05)., Conclusions: Unmeasured anions, predictive of negative outcome in previous studies, did not increase significantly in sevoflurane-anesthetized animals. Additionally, there was less heparan sulfate shedding over time, signaling less destruction of the glycocalyx. Therefore, in this in-vivo situation, sevoflurane proves to be superior to propofol in protecting the endothelium from IR injury.

Background: Adhesion of polymorphonuclear neutrophils and platelets to the vessel wall contributes to generating ischemia-reperfusion injury. Endothelial adhesion molecules are harbored within the glycocalyx, which covers every healthy vascular endothelium but is deteriorated by ischemia-reperfusion. Pretreating the heart with volatile anesthetics reduces myocardial infarct size and protects against ischemia-reperfusion injury. The authors analyzed a possible protective effect of sevoflurane on the glycocalyx and implications for postischemic cell adhesion., Methods: Isolated guinea pig hearts were perfused with crystalloid buffer and subjected to 20 min of global warm ischemia and 10 min of reperfusion. An intracoronary bolus of 3 x 10(6) polymorphonuclear neutrophilic leukocytes or 1 x 10(9) platelets of human origin was applied after reperfusion, either with or without pretreating with 0.5 or 1 minimal alveolar concentration sevoflurane. The number of sequestered cells was calculated from the difference between coronary input and output. Coronary effluent was collected throughout reperfusion to measure shedding of the glycocalyx., Results: Ischemia-reperfusion induced a significant increase in median (interquartile range) adhesion versus control nonischemic hearts of both leukocytes (38.9 (36.3-42.9) vs. 14.5 (13.1-16.0)%) and platelets (25.0 (22.5-27.1) vs. 9.4 (8.4-10.7)%). Shedding was evidenced by eightfold increases in washout of syndecan-1 and heparan sulfate versus basal. Sevoflurane reduced cell adhesion to near basal at 1 minimal alveolar concentration (leukocytes: 21.2% (19.2-23.9%), platelets: 11.5% (10.4-12.0%). Shedding measurements and electron microscopy demonstrated that sevoflurane-treated hearts retained much of their 200 nm-thick glycocalyx., Conclusions: Sevoflurane reduces glycocalyx shedding in the postischemic coronary bed, maintaining the natural cover for endothelial adhesion molecules and, thus, reducing cell adhesion. This may explain beneficial outcomes linked to clinical use of volatile anesthetics after ischemia-reperfusion.

Amniotic fluid embolism (AFE) is a rare, but often catastrophic, complication of pregnancy and associated with severe coagulopathy. We present an algorithm-based approach in managing coagulopathy and hemorrhage in a fatal case of histopathologically proven AFE. Thrombelastometry was used for rapid evaluation of the coagulation status. Stop of extensive hyperfibrinolysis with tranexamic acid, stabilization of initial clot formation with high-dose fibrinogen and platelet transfusions, and use of prothrombin complex concentrate together with a 1: 1 transfusion regimen of red packed cells and fresh frozen plasma was successful to control diffuse bleeding and restore clot firmness after hysterectomy. Stable clotting situation was maintained despite further clinical deterioration and development of multiple organ failure in this patient.

Objective: This study was performed to investigate the effect of vasopressor therapy on systolic pressure variation (SPV) and pulse pressure variation (PPV) compared to experimentally measured left ventricular stroke volume variation (SVV)., Design and Setting: Prospective study in a university laboratory., Subjects: Twelve anesthetized and mechanically ventilated pigs., Interventions: Increase in mean arterial pressure (by 100%) using phenylephrine and decrease (by 38%) using adenosine., Measurements and Results: SPV and PPV were calculated and compared to SVV derived from aortic blood flow measurements. SPV was significantly affected by changes in arterial pressure [4.6% (1.5) vs. 6.3% (2.1), p < 0.05, increased vs. decreased arterial pressure], whereas PPV did not change during modifications of arterial pressure. During baseline conditions and decreased afterload, correlation with SVV was good both for SPV (r =0.892 and r = 0.859, respectively) and for PPV (r = 0.870 and r = 0.871, respectively) (all p < 0.001). Correlation with SVV was only moderate during increased arterial pressure (r = 0.683 for SPV and r = 0.732 for PPV, p < 0.05)., Conclusion: For guiding fluid therapy in patients under vasopressor support, PPV seems superior to SPV.

Therapy for severe myocardial ischemia/reperfusion sometimes necessitates intermittent positive pressure ventilation, which may impair left ventricular function by reduction of ventricular loading. It is unknown today whether positive airway pressure also affects contractile force after myocardial ischemia/reperfusion. The authors tested whether positive end-expiratory pressure (PEEP) impairs myocardial contractility in acute ischemic heart failure. In 11 anesthetized mechanically ventilated pigs (28 +/- 3 kg), cardiac output (CO, aortic flow probe), load-independent parameters of left ventricular contractility (conductance method: preload recruitable stroke work [PRSW] and end-systolic elastance [E(es)]) and preload (end-diastolic volume [EDV] conductance) were assessed before and after myocardial ischemia and reperfusion (left anterior descending artery occlusion, 60 min). Data were taken during PEEP 0, 5, and 10 cm H2O. Before myocardial ischemia, both PEEP 5 and 10 cm H2O reduced CO (P < 0.05) because of a reduction of EDV (P < 0.05, PEEP 10 cm H2O). The PRSW remained unchanged (not significant [NS]) and E(es) increased (P < 0.05, PEEP 10 cm H2O). After myocardial ischemia/reperfusion, CO and PRSW, but not E(es) (NS), deteriorated markedly. At the same time, PEEP 10 cm H2O reduced CO (P < 0.05) and, slightly, EDV (NS). Now, both PRSW (P < 0.05, PEEP 5 cm H2O) and E(es) (P < 0.05, PEEP 10 cm H2O) improved upon ventilation with PEEP. In our model, the administration of PEEP impaired global left ventricular function before and after myocardial ischemia/reperfusion. The observed impairment is not attributable to compromised contractility.

Background: The warm ischemic period of lungs harvested from a non-heart-beating donor (NHBD) results in an increased ischemia-reperfusion injury after transplantation. The intravenous application of nitroglycerin (NTG), a nitric oxide (NO) donor, proved to be beneficial during reperfusion of lung grafts from heart-beating donors. The objective of the present study was to investigate the effect of nitroglycerin on ischemia-reperfusion injury after transplantation of long-term preserved NHBD-lungs., Methods: Sixteen pigs (body weight, 20-30 kg) underwent left lung transplantation. In the control group (n=5), lungs were flushed (Perfadex, 60 mL/kg) and harvested immediately after cardiac arrest. In the NHBD group (n=5) and the NHBD-NTG group (n=6), lungs were flushed 90 min (warm ischemia) after cardiac arrest. After a total ischemia time of 19 hr, lungs were reperfused and graft function was observed for 5 hr. Recipient animals in the NHBD-NTG group received 2 microg/kg/min of NTG administered intravenously during the observation period starting 5 min before reperfusion. Tissue specimens and bronchoalveolar lavage fluid (BALF) were obtained at the end of the observation period., Results: Compared with the control group, pulmonary gas exchange was significantly impaired in the NHBD group, whereas graft function in the NHBD-NTG group did not change. Leukocyte fraction and protein concentration in the BALF and histologic alteration of the NHBD-NTG group were not different from controls., Conclusions: Continuous infusion of NTG in the early reperfusion period improves pulmonary graft function of NHBD lungs after long-term preservation. The administration of an NO donor during reperfusion may favor the use of NHBD lungs to alleviate the critical organ shortage in lung transplantation.

Several studies have shown that warm ischemia before short-term preservation of pulmonary grafts from non-heart-beating donors (NHBD) induced morphological changes, but still provided a good pulmonary graft function. The aim of this study was to investigate morphological and metabolic changes of NHBD lungs after long-term preservation. Left lung allotransplantation was performed on 12 native-bred pigs. In the NHBD group, lungs were subjected to 90 min of warm ischemia before harvesting, whereas lungs in the HBD group were harvested immediately after cardiac arrest. After a total ischemic period of 19 h, lungs were reperfused and pulmonary gas exchange was assessed. Bronchoalveolar lavage (BAL) and tissue specimen for wet-to-dry weight (W/D) ratio, histologic examination, and measurement of high-energy phosphates were taken 5 h after reperfusion. All parameters were compared with a sham-operated control group. Five hours after reperfusion, mean paO2 and paCO2 were 288 +/- 52 and 48 +/- 0.8 mmHg, respectively, during isolated ventilation of the pulmonary graft with 100% oxygen in the NHBD group. W/D ratio and high-energy phosphates of the pulmonary graft did not differ between our study groups. Histologic examination showed significant morphological changes in the HBD and NHBD group, but alterations were more pronounced in the NHBD group. The percentage of neutrophils, total protein content, and potassium concentration were significantly elevated in the BAL fluid of the NHBD group. Despite the observed aggravation of cellular injury after long-term preservation, NHBD lungs still performed a good pulmonary graft function.

Background: Critical organ shortage in lung transplantation could be attenuated by the use of non-heart-beating donor (NHBD) lungs. In addition, prolonged ischemic tolerance of the organs would contribute to the alleviation of organ shortage. The aim of this study was to investigate pulmonary graft function of NHBD lungs after long-term hypothermic storage., Methods: Twelve native-bred pigs (bodyweight 20 to 30 kg) underwent left lung allotransplantation. In the heart-beating donor (HBD) group, lungs were harvested immediately after cardiac arrest. In the NHBD group, lungs were subjected to a warm ischemic period of 90 minutes before harvesting. After a total ischemic time of 19 hours, pulmonary grafts in both groups were reperfused and pulmonary graft function was assessed. All values were compared with a sham-operated control group., Results: Pulmonary graft function in the HBD group was excellent. In the NHBD group, pulmonary gas exchange was impaired, but still provided good graft function compared with the excellent graft function in the HBD group. Pulmonary vascular resistance was even lower in the NHBD group. In the NHBD group, calculated intrapulmonary shunt fraction (Qs/Qt) was significantly increased compared with the sham-group. Histologic alteration and wet-to-dry ratio did not differ significantly between the HBD and NHBD group., Conclusions: We conclude that NHBD lungs (90 minutes of warm ischemic time) have the potential to alleviate organ shortage in lung transplantation even after an extended total ischemic time.