Effect of Extracerebral Contamination on Near-infrared Spectroscopy as Revealed during Organ Donation: A Prospective Observational Study in Brain-dead Organ Donors.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been utilized widely in anesthesia and intensive care to monitor regional cerebral oxygen saturation (rScO2). A normal oxygenation of extracerebral tissues may overlay and thereby mask cerebral desaturations, a phenomenon known as extracerebral contamination. The authors investigated the effect of a cessation of extracerebral tissue perfusion on rScO2 in patients with anoxic brains. METHODS: In a single-center, prospective, observational study, brain-dead adults undergoing organ donation were investigated. rScO2 was measured bifrontally using the INVOS 5100C/7100 as well as the ForeSight Elite system. To achieve an efficient conservation of organs and to prevent a redistribution of the perfusion fluid to other tissues, the aorta was clamped before organ perfusion. rScO2 was monitored until at least 40 min after aortic clamping. The primary outcome was the amount of extracerebral contamination as quantified by the absolute decrease in rScO2 after aortic clamping. Secondary outcomes were the absolute rScO2 values obtained before and after clamping. RESULTS: Twelve organ donors were included. Aortic clamping resulted in a significantly (P < 0.001) greater absolute decrease in rScO2 when comparing the INVOS (43.0 ± 9.5%) to the ForeSight (27.8 ± 7.1%) monitor. Before aortic clamping, near-normal rScO2 values were obtained by the INVOS (63.8 ± 6.2%) and the ForeSight monitor (67.7 ± 6.5%). The rScO2 significantly (P < 0.001) dropped to 20.8 ± 7.8% (INVOS) and 39.9 ± 8.1% (ForeSight) 30 min after clamping, i.e., a condition of a desaturation of both extracerebral and cerebral tissues. CONCLUSIONS: The abrupt end of extracerebral contamination, caused by aortic clamping, affected both NIRS monitors to a considerable extent. Both the INVOS and the ForeSight monitor were unable to detect severe cerebral hypoxia or anoxia under conditions of normal extracerebral oxygenation. While both NIRS monitors may guide measures to optimize arterial oxygen supply to the head, they should not be used with the intention to detect isolated cerebral desaturations.

The association between frailty and ageing: Results from an observational study including 9497 elderly patients.

BACKGROUND: Elderly surgical patients have a high risk of postoperative complications. However, patients exhibit considerable diversity in health and functional status; thus, identifying the fragile may be necessary when selecting surgical candidates. We aimed to compare the prevalence of frailty in patients ≥90 years with patients aged 80-89. Second, we assessed the association between frailty and all-cause 30-day mortality. METHODS: We performed a planned secondary analysis of the peri-interventional outcome study in the elderly (POSE), including 9497 patients (≥80 years) undergoing any surgical and nonsurgical procedures in 177 European centres from October 2017 to December 2018. The primary outcome assessment included frailty as a binary variable, and data were analysed using Fisher's exact test/Chi-squared test. The association between frailty and all-cause 30-day mortality was analysed using a multivariate logistic regression model adjusted for age, sex, surgical urgency, orthopaedic urgency, and surgical severity. RESULTS: In total, 999 of 9497 (10.5%) patients were 90 years or above. Among patients ≥90 years, 274 (27.4%) were frail compared to 1062 (12.5%) of patients aged 80-89 (odds ratio (OR): 2.6; 95% CI 2.3-3.1). Frailty was associated with increased 30-day mortality in both the unadjusted (crude OR 6.3; 5.1-7.7) and adjusted analysis (OR 4.5; 3.6-5.7). In the adjusted analysis, age ≥90 was not associated with 30-day mortality. CONCLUSION: We found a high frequency of frailty in patients aged 90 years or above compared with patients aged 80-89. In addition, frailty was associated with an increased risk of 30-day mortality. Surprisingly, age was not a significant risk factor in the adjusted mortality analysis.

Connected consciousness after tracheal intubation in young adults: an international multicentre cohort study.

BACKGROUND: Connected consciousness, assessed by response to command, occurs in at least 5% of general anaesthetic procedures and perhaps more often in young people. Our primary objective was to establish the incidence of connected consciousness after tracheal intubation in young people aged 18-40 yr. The secondary objectives were to assess the nature of these responses, identify relevant risk factors, and determine their relationship to postoperative outcomes. METHODS: This was an international, multicentre prospective cohort study using the isolated forearm technique to assess connected consciousness shortly after tracheal intubation. RESULTS: Of 344 enrolled subjects, 338 completed the study (mean age, 30 [standard deviation, 6.3] yr; 232 [69%] female). Responses after intubation occurred in 37/338 subjects (11%). Females (13%, 31/232) responded more often than males (6%, 6/106). In logistic regression, the risk of responsiveness was increased with female sex (odds ratio [ORadjusted]=2.7; 95% confidence interval [CI], 1.1-7.6; P=0.022) and was decreased with continuous anaesthesia before laryngoscopy (ORadjusted=0.43; 95% CI, 0.20-0.96; P=0.041). Responses were more likely to occur after a command to respond (and not to nonsense, 13 subjects) than after a nonsense statement (and not to command, four subjects, P=0.049). CONCLUSIONS: Connected consciousness occured after intubation in 11% of young adults, with females at increased risk. Continuous exposure to anaesthesia between induction of anaesthesia and tracheal intubation should be considered to reduce the incidence of connected consciousness. Further research is required to understand sex-related differences in the risk of connected consciousness.

Intra-operative blood transfusion in elderly patients on antithrombotic therapy.

BACKGROUND: Many elderly patients are receiving antithrombotics, which may increase intra-operative blood loss. We aimed to assess whether chronic antithrombotic therapy was associated with intra-operative transfusion of packed red blood cells in patients at least 80 years of age undergoing elective procedures. METHODS: We performed a secondary analysis of the prospective, observational European multicentre study entitled POSE (peri-interventional outcome study in the elderly) including 9497 surgical patients aged 80 years and older in 177 centres from October 2017 to December 2018. In this secondary analysis we included POSE patients who underwent elective procedures and with available data on chronic antithrombotic therapy. The primary outcome was intra-operative transfusion of packed red blood cells and results were analysed using multiple logistic regression model. We adjusted for the following predetermined explanatory variables: Age, sex, body mass index, American Society of Anaesthesiologists Physical Status Classification System, baseline haemoglobin concentration, disseminated cancer, and type and severity of surgery. RESULTS: A total of 7174 patients were included of whom 4073 (56.8%) were on antithrombotic therapy. Among patients on antithrombotic therapy 191 (4.7%) received intra-operative blood transfusion compared with 98 (3.2%) of patients not on chronic antithrombotic therapy (crude odds ratio: 1.51, 95% CI 1.18-1.94). Following multiple logistic regression analysis, the adjusted odds ratio was 0.98; 0.73-1.32. We found that chronic antithrombotic therapy was associated with intra-operative transfusion of packed red blood cells in elderly patients undergoing elective procedures in an unadjusted analysis, but not in a multivariate adjusted model.

High-Impact Actions to Reduce the Carbon Dioxide Footprint in an Ophthalmic Operation Room: A Narrative Review.

Germany's health care footprint accounts for 5.2% of the national emissions footprint which results in 0.71 tons of CO2 emission per capita. Thus, the health sector has a responsibility to take climate action. Surgery is a resource-intensive health care activity, requiring expensive equipment, sterilization procedures, advanced operative technologies, and obligatory life support systems. We spotlight the situation in a department of ophthalmology with frequent anesthesia services and highly standardized procedures. This narrative review discusses high-impact actions which result in a major reduction of the CO2 footprint according to the global road map for health care decarbonization, considering both the ophthalmic and anesthesiologic point of view.

Poor reporting quality of observational clinical studies comparing treatments of COVID-19 - a retrospective cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, the scientific world is in urgent need for new evidence on the treatment of COVID patients. The reporting quality is crucial for transparent scientific publication. Concerns of data integrity, methodology and transparency were raised. Here, we assessed the adherence of observational studies comparing treatments of COVID 19 to the STROBE checklist in 2020. METHODS: Design: We performed a retrospective, cross-sectional study. SETTING: We conducted a systematic literature search in the Medline database. This study was performed at the RWTH Aachen University Hospital, Department of Anaesthesiology Participants: We extracted all observational studies on the treatment of COVID-19 patients from the year 2020. MAIN OUTCOME MEASURES: The adherence of each publication to the STROBE checklist items was analysed. The journals' impact factor (IF), the country of origin, the kind of investigated treatment and the month of publication were assessed. RESULTS: We analysed 147 observational studies and found a mean adherence of 45.6% to the STROBE checklist items. The percentage adherence per publication correlated significantly with the journals' IF (point estimate for the difference between 1st and 4th quartile 11.07%, 95% CI 5.12 to 17.02, p < 0.001). U.S. American authors gained significantly higher adherence to the checklist than Chinese authors, mean difference 9.10% (SD 2.85%, p = 0.023). CONCLUSIONS: We conclude a poor reporting quality of observational studies on the treatment of COVID-19 throughout the year 2020. A considerable improvement is mandatory.

Association between benzodiazepine premedication and 30-day mortality rate: A propensity-score weighted analysis of the Peri-interventional Outcome Study in the Elderly (POSE).

BACKGROUND: Recent guidelines suggest that benzodiazepine premedication should be avoided in elderly patients, though with limited supporting evidence. OBJECTIVE: We conducted a secondary analysis of the POSE data to explore the association of premedication in patients aged 80 years or older with 30-day mortality. DESIGN: We used propensity score methods to perform a confounder-adjusted time-to-event analysis of the association between benzodiazepine premedication and 30-day mortality of the POSE study. SETTING: POSE was conducted as a European multicentre prospective cohort study. PATIENTS: Adults aged 80 years or older scheduled for surgical or nonsurgical intervention under anaesthesia. RESULTS: A total of 9497 patients were analysed. One thousand five hundred and twenty-one patients received benzodiazepine premedication, 7936 patients received no benzodiazepine premedication, 30 received clonidine and 10 had missing premedication data. Inverse propensity-score-weighted log-rank analysis did not provide unambiguous evidence for an association between benzodiazepine premedication and 30-day mortality; median [range] P = 0.048 [0.044 to 0.078], estimated 30-day mortality rates 3.21% and 4.45% in benzodiazepine-premedicated and nonbenzodiazepine-premedicated patients, respectively. Inverse propensity-score-weighted Cox regression resulted in a hazard ratio of 0.71 (95% CI 0.49 to 1.04), pointing at a possible reduction of 30-day mortality in the benzodiazepine premedication group. Sensitivity analyses, which constituted subgroup, matched-pairs, and subclassification analyses, resulted in similar findings. CONCLUSION: This secondary analysis of the POSE data did not find evidence for an unambiguous association between benzodiazepine premedication and 30-day mortality. Point estimates indicated a reduction of 30-day mortality in benzodiazepine-premedicated patients. The results presented here might be affected by unmeasured confounding factors, which could be addressed in a randomised trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03152734.

Postoperative delirium is an independent factor influencing the length of stay of elderly patients in the intensive care unit and in hospital.

PURPOSE: Postoperative delirium (POD) is an often unrecognized adverse event in older people after surgery. The aim of this subgroup analysis of the PRe-Operative Prediction of postoperative DElirium by appropriate SCreening (PROPDESC) trial in patients aged 70 years and older was to identify preoperative risk factors and the impact of POD on length of stay (LOS) in intensive care unit (ICU) and hospital. METHODS: Of the total 1097 patients recruited at a German university hospital (from September 2018 to October 2019) in the PROPDESC prospective observational study, 588 patients aged 70 years and older (mean age 77.2 ± 4.7 years) were included for subgroup analysis. The primary endpoint POD was considered positive if one of the following tests were positive on any of the five postoperative visit days: Confusion Assessment Method for ICU (CAM-ICU), Confusion Assessment Method (CAM), 4'A's (4AT) and Delirium Observation Scale (DOS). Trained doctoral students carried out these visitations and additionally the nursing staff were interviewed for completion of the DOS. To evaluate the independent effect of POD on LOS in ICU and in hospital, a multi-variable linear regression analysis was performed. RESULTS: The POD incidence was 25.9%. The results of our model showed POD as an independent predictor for a prolonged LOS in ICU (36%; 95% CI 4-78%; < 0.001) and in hospital (22%; 95% CI 4-43%; < 0.001). CONCLUSION: POD has an independent impact on LOS in ICU and in hospital. Based on the effect of POD for the elderly, a standardized risk screening is required. TRAIL REGISTRATION: German Registry for Clinical Studies: DRKS00015715.

Risk assessment of perioperative neurocognitive disorders, where are we now?

PURPOSE OF REVIEW: Perioperative neurocognitive disorders (PNDs) are among the most frequent complications after surgery and are associated with considerable morbidity and mortality. We analysed the recent literature regarding risk assessment of PND. RECENT FINDINGS: Certain genetic variants of the cholinergic receptor muscarinic 2 and 4, as well as a marked degree of frailty but not the kind of anaesthesia (general or spinal) are associated with the risk to develop postoperative delirium (POD). Models predict POD with a discriminative power, for example, area under the receiver operating characteristics curve between 0.52 and 0.94. SUMMARY: Advanced age as well as preexisting cognitive, functional and sensory deficits remain to be the main risk factors for the development of PND. Therefore, aged patients should be routinely examined for both preexisting and new developing deficits, as recommended in international guidelines. Appropriate tests should have a high discrimination rate, be feasible to be administered by staff that do not require excessive training, and only take a short time to be practical for a busy outpatient clinic. Models to predict PND, should be validated appropriately (and externally if possible) and should not contain a too large number of predictors to prevent overfitting of models.

Sustainable work in anaesthesiology and intensive care medicine.

The climate crisis is omnipresent and one of the most pressing challenges of the 21st century. In the position paper "Ecological sustainability in anaesthesiology and intensive care medicine", the Professional Association of German Anesthesiologists (BDA) and the German Society for Anesthesiology and Intensive Care Medicine (DGAI) made specific recommendations which contribute to a consistent and sustainable reduction in CO2 emissions. This article highlights the aspects of the position paper which the authors believe can be easily implemented in clinical practice and have a major effect on reducing CO2 emissions. The recommendations focus on the topics of medication, medical products, waste management, mobility, energy management, research and teaching with practical examples and results from the Green Team (Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn) and from the toolkit of the DGAI/BDA. Ways are shown to limit inhalation anesthetic-caused CO2-emissions, to reduce drug waste, to change single-use for reusable materials and to develop sustainable waste concepts.

Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study.

BACKGROUND: Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors. METHODS: The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success. RESULTS: Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported-an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non-rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (adjusted odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (adjusted odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (adjusted odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001). CONCLUSIONS: The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19.

Characterization of Transverse Aortic Constriction in Mice Based on the Specific Recruitment of Leukocytes to the Hypertrophic Myocardium and the Aorta Ascendens.

Transverse aortic constriction (TAC) is a model that mimics pressure overload-induced left ventricular (LV) hypertrophy in mice. Alterations in immune cell functionality can promote cardiac and vascular remodeling. In the present study, we characterized the time course in innate immune cell dynamics in response to TAC in the different tissues of mice. It was determined whether TAC induces a characteristic leukocyte-driven immune response in the myocardium, aorta ascendens and descendens, spleen, blood, and draining lymph nodes supported by cytokine-driven chemotaxis in mice at 3, 6, and 21 days following surgery. We used complex flow cytometry staining combinations to characterize the various innate immune cell subsets and a multiplex array to determine cytokine concentrations in the serum. The results of the current study indicated that leukocytes accumulate in the myocardium and aorta ascendens in response to TAC. The leukocyte dynamics in the myocardium were dominated by the Ly6Clow macrophages with an early accumulation, whereas the response in the aorta ascendens was characterized by a long-lasting proinflammatory phenotype driven by Ly6Chigh macrophages, neutrophils, and activated DCs. In contrast to the high-pressure environment of the aorta ascendens, the tissue of the aorta descendens did not react to TAC with any leukocyte increase. The levels of proinflammatory cytokines in the blood were elevated in response to TAC, indicating a systemic reaction. Moreover, our findings strongly suggest that cardiac macrophages could origin from splenic pools and reach the site of the inflammation via the blood. Based on the current findings, it can be concluded that the high-pressure conditions in the aorta ascendens cause a characteristic immune response, dominated by the accumulation of leukocytes and the activation of DCs that varies in comparison to the immune cell dynamics in the myocardium and the aorta descendens.

Postoperative delirium after cardiac surgery of elderly patients as an independent risk factor for prolonged length of stay in intensive care unit and in hospital.

BACKGROUND: Postoperative delirium (POD) is a relevant and underdiagnosed complication after cardiac surgery that is associated with increased intensive care unit (ICU) and hospital length of stay (LOS). The aim of this subgroup study was to compare the frequency of tested POD versus the coded International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis of POD and to evaluate the influence of POD on LOS in ICU and hospital. METHODS: 254 elective cardiac surgery patients (mean age, 70.5 ± 6.4 years) at the University Hospital Bonn between September 2018 and October 2019 were evaluated. The endpoint tested POD was considered positive, if one of the tests Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method (CAM), 4 'A's Test (4AT) or Delirium Observation Scale (DOS) was positive on one day. RESULTS: POD occurred in 127 patients (50.0%). LOS in ICU and hospital were significantly different based on presence (ICU 165.0 ± 362.7 h; Hospital 26.5 ± 26.1 days) or absence (ICU 64.5 ± 79.4 h; Hospital 14.6 ± 6.7 days) of POD (p < 0.001). The multiple linear regression showed POD as an independent predictor for a prolonged LOS in ICU (48%; 95%CI 31-67%) and in hospital (64%; 95%CI 27-110%) (p < 0.001). The frequency of POD in the study participants that was coded with the ICD F05.0 and F05.8 by hospital staff was considerably lower than tests revealed by the study personnel. CONCLUSION: Approximately 50% of elderly patients who underwent cardiac surgery developed POD, which is associated with an increased ICU and hospital LOS. Furthermore, POD is highly underdiagnosed in clinical routine.

Extended neuromonitoring in aortic arch surgery : A case series.

BACKGROUND: Aortic arch repair for aortic dissection is still associated with a high mortality rate. Providing adequate means of neuromonitoring to guide cerebral hemodynamics is advantageous, especially during selective anterior cerebral perfusion (SACP). OBJECTIVE: We aimed to investigate an easy multimodal neuromonitoring set-up consisting of processed electroencephalography (EEG), near infrared spectroscopy (NIRS), and transcranial doppler sonography (TCD). MATERIAL AND METHODS: We collected intraoperative data from six patients undergoing surgery for aortic dissection. In addition to standard hemodynamic monitoring, patients underwent continuous bilateral NIRS, processed EEG with bispectral index (BIS), and intermittent transcranial doppler sonography of the medial cerebral artery (MCA) with a standard B­mode ultrasound device. Doppler measurements were taken bilaterally before cardiopulmonary bypass (CPB), during CPB, and during SACP at regular intervals. RESULTS: Of the patients four survived without neurological deficits while two suffered fatal outcomes. Of the survivors two suffered from transient postoperative delirium. Multimodal monitoring led to a change in CPB flow or cannula repositioning in three patients. Left-sided mean flow velocities of the MCA decreased during SACP, as did BIS values. CONCLUSION: Monitoring consisting of BIS, NIRS, and TCD may have an impact on hemodynamic management in aortic arch operations.

Noble gases and neuroprotection: summary of current evidence.

PURPOSE OF REVIEW: To summarize the current data on neuroprotection derived by noble gas treatment focusing on xenon and argon. RECENT FINDINGS: Both xenon and argon have demonstrated neuroprotective properties in an array of disease models. However, current data for argon after traumatic brain injury (TBI) is conflicting. Recent human data is only available for xenon showing some beneficial aspects (fewer adverse events) but no effect on outcomes, such as incidence of postoperative delirium. SUMMARY: Promising results are available for neuroprotection derived by noble gas treatment. Results for xenon are more consistent than those for argon. The mechanism of action of xenon (noncompetitive NMDA-receptor inhibition) is also better understood compared with that of argon. The evidence for argon's neuroprotective actions (particularly after TBI) remains uncertain.

[Perioperative Medicine in Visceral Surgery in the Elderly Patient from an Anaesthesiological Perspective]. / Perioperative Medizin in der Viszeralchirurgie beim alten Patienten aus anästhesiologischer Perspektive.

Demographic change is leading to an increasing number of old patients both in our society and in hospitals. With increasing age, not only the number of pre-existing conditions increases, but also the postoperative complication rate and mortality. Ultimately, however, it is not age that is decisive, but the condition of the patient and his or her capacity to face the physical and mental challenges of a surgical procedure. Frail patients are particularly at risk of complications, and an essential strategy - known as prehabilitation - is to put them in a better state pre-operatively through physical and mental training, as well as nutritional counselling. Delirium is one of the most frequent postoperative complications. Measures such as refraining from premedication with benzodiazepines, measuring the depth of anaesthesia, refraining from long-acting opioids, performing fast-track surgery, and providing glasses/hearing aids quickly postoperatively can reduce the risk of delirium. Close interdisciplinary consultation between surgeons, anaesthetists, geriatricians and physiotherapists is essential to coordinate the perioperative procedure and reduce the perioperative risk for elderly patients.

[Evaluation of the Effectiveness of a Standard Operating Procedure (SOP) for the Perioperative Management of Colorectal Surgery]. / Evaluation der Effektivität einer Standard Operating Procedure (SOP) zur perioperativen Therapie bei kolorektalen Operationen.

INTRODUCTION: In recent years, perioperative care of patients after colorectal surgery has been increasingly standardised according to the fast-track concept and is accepted as a structured method of care to reduce perioperative complications. Indeed, initial studies have indicated that there is a long-term favourable effect on the oncological outcome, if the adherence to the individual measures is at least 70%. Even though there is unambiguous evidence for the efficacy of the modern perioperative treatment concept, it is often difficult to comply with the protocol during normal clinical work, particularly in Germany. The objective of this study was to record the rate of compliance before and after the introduction of the SOP and to evaluate its efficacy. METHODS: We performed a retrospective analysis of the patient data after all elective colorectal surgery in the Bonn University Hospital from 2017 to 2020. 153 patients were operated on before the implementation of the SOP in January 2019 (group I); the remaining 153 patients were operated on after the implementation of the SOP and received appropriate care (group II). Compliance to the protocol was analysed for both the individual key interventions and the overall concept. RESULTS: There was significant improvement in the compliance for both the individual measures (prehabilitation group I: 5.9%, group II: 42.5%, p < 0.001; preparation of the intestine I: 16.5%, II: 73.9%, p < 0.001; intraoperative volume management I: 14,00 ml/kg BW/h, II: 9.12 ml/kg BW/h, p < 0.001, BW: body weight; minimally invasive surgical technique I: 53.6%, II: 73.9%, p < 0.001; etc.) and for the overall perioperative treatment concept (I: 39%, II: 54%, p = 0.02). However, we fell far short of compliance of at least 70%. Nevertheless, patient autonomy was achieved earlier after introduction of the SOP (I: day 15, II: day 9, p < 0.001) and the postoperative hospital stay was shortened (I: 14 [6 - 99] days, II 11 [4 - 64] days; p = 0.007). CONCLUSION: Although the implementation of the SOP led to significant improvements, further optimisation is required to attain the recommended protocol compliance of 70%. Measures within the hospital could include foundation of an interdisciplinary fast-track team and a specialised nurse as the connecting link between the patients, nursing and physicians. On the other hand, implementation throughout Germany can only be achieved by more influential actions. One possible support would be the S3 guideline on perioperative management of gastrointestinal tumours, which is under development. This could, for example, be used to support argumentation with funding providers.

Inhaled Argon Impedes Hepatic Regeneration after Ischemia/Reperfusion Injury in Rats.

Organoprotective effects of noble gases are subject of current research. One important field of interest is the effect of noble gases on hepatic regenerative capacity. For the noble gas argon, promising studies demonstrated remarkable experimental effects in neuronal and renal cells. The aim of this study was to investigate the effects of argon on the regenerative capacity of the liver after ischemia/reperfusion injury (IRI). Male, Sprague-Dawley rats underwent hepatic IRI by clamping of the hepatic artery. Expression of hepatoproliferative genes (HGF, IL-1ß, IL-6, TNF), cell cycle markers (BrdU, TUNEL, Ki-67), and liver enzymes (ALT, AST, Bilirubin, LDH) were assessed 3, 36, and 96 h after IRI. Expression of IL-1ß and IL-6 was significantly higher after argon inhalation after 36 h (IL-1ß 5.0 vs. 8.7 fold, p = 0.001; IL-6 9.6 vs. 19.1 fold, p = 0.05). Ki-67 was higher in the control group compared to the argon group after 36 h (214.0 vs. 38.7 positive cells/1000 hepatocytes, p = 0.045). Serum levels of AST and ALT did not differ significantly between groups. Our data indicate that argon inhalation has detrimental effects on liver regeneration after IRI as measured by elevated levels of the proinflammatory cytokines IL-1ß and IL-6 after 36 h. In line with these results, Ki-67 is decreased in the argon group, indicating a negative effect on liver regeneration in argon inhalation.

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride.

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs-nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)-might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.

Post-stroke treatment with argon attenuated brain injury, reduced brain inflammation and enhanced M2 microglia/macrophage polarization: a randomized controlled animal study.

BACKGROUND: In recent years, argon has been shown to exert neuroprotective effects in an array of models. However, the mechanisms by which argon exerts its neuroprotective characteristics remain unclear. Accumulating evidence imply that argon may exert neuroprotective effects via modulating the activation and polarization of microglia/macrophages after ischemic stroke. In the present study, we analyzed the underlying neuroprotective effects of delayed argon application until 7 days after reperfusion and explored the potential mechanisms. METHODS: Twenty-one male Wistar rats underwent transient middle cerebral artery occlusion or sham surgery randomly for 2 h using the endoluminal thread model. Three hours after transient middle cerebral artery occlusion induction and 1 h after reperfusion, animals received either 50% vol Argon/50% vol O2 or 50% vol N2/50% vol O2 for 1 h. The primary outcome was the 6-point neuroscore from 24 h to d7 after reperfusion. Histological analyses including infarct volume, survival of neurons (NeuN) at the ischemic boundary zone, white matter integrity (Luxol Fast Blue), microglia/macrophage activation (Iba1), and polarization (Iba1/Arginase1 double staining) on d7 were conducted as well. Sample size calculation was performed using nQuery Advisor + nTerim 4.0. Independent t test, one-way ANOVA and repeated measures ANOVA were performed, respectively, for statistical analysis (SPSS 23.0). RESULTS: The 6-point neuroscore from 24 h to d7 after reperfusion showed that tMCAO Ar group displayed significantly improved neurological performance compared to tMCAO N2 group (p = 0.026). The relative numbers of NeuN-positive cells in the ROIs of tMCAO Ar group significantly increased compared to tMCAO N2 group (p = 0.010 for cortex and p = 0.011 for subcortex). Argon significantly suppressed the microglia/macrophage activation as revealed by Iba1 staining (p = 0.0076) and promoted the M2 microglia/macrophage polarization as revealed by Iba1/Arginase 1 double staining (p = 0.000095). CONCLUSIONS: Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion significantly alleviated neurological deficit within the first week and preserved the neurons at the ischemic boundary zone 7 days after stroke. Moreover, argon reduced the excessive microglia/macrophage activation and promoted the switch of microglia/macrophage polarization towards the anti-inflammatory M2 phenotype. Studies making efforts to further elucidate the protective mechanisms and to benefit the translational application are of great value.