Early hyperbaric oxygen therapy is associated with favorable outcome in patients with iatrogenic cerebral arterial gas embolism: systematic review and individual patient data meta-analysis of observational studies.

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) caused by invasive medical procedures may be treated with hyperbaric oxygen therapy (HBOT). Previous studies suggested that initiation of HBOT within 6-8 h is associated with higher probability of favorable outcome, when compared to time-to-HBOT beyond 8 h. We performed a group level and individual patient level meta-analysis of observational studies, to evaluate the relationship between time-to-HBOT and outcome after iatrogenic CAGE. METHODS: We systematically searched for studies reporting on time-to-HBOT and outcome in patients with iatrogenic CAGE. On group level, we meta-analyzed the differences between median time-to-HBOT in patients with favorable versus unfavorable outcome. On individual patient level, we analyzed the relationship between time-to-HBOT and probability of favorable outcome in a generalized linear mixed effects model. RESULTS: Group level meta-analysis (ten studies, 263 patients) shows that patients with favorable outcome were treated with HBOT 2.4 h (95% CI 0.6-9.7) earlier than patients with unfavorable outcome. The generalized linear mixed effects model (eight studies, 126 patients) shows a significant relationship between time-to-HBOT and probability of favorable outcome (p = 0.013) that remains significant after correcting for severity of manifestations (p = 0.041). Probability of favorable outcome decreases from approximately 65% when HBOT is started immediately, to 30% when HBOT is delayed for 15 h. CONCLUSIONS: Increased time-to-HBOT is associated with decreased probability of favorable outcome in iatrogenic CAGE. This suggests that early initiation of HBOT in iatrogenic CAGE is of vital importance.

Comparison of Postoperative Neurocognitive Function in Older Adult Patients with and without Diabetes Mellitus.

INTRODUCTION: Delayed neurocognitive recovery (DNR; neurocognitive disorder up to 30 days postoperative) and postoperative neurocognitive disorders (POCD; neurocognitive disorder 1-12 months postoperative) occur frequently after surgery, with diabetes mellitus (DM) suggested to contribute to this. This was a single-center prospective cohort study. The main aim of this study was to investigate the role of DM and preoperative hemoglobin A1c (HbA1c) in the development of POCDs after noncardiac surgery. METHODS: Older adult patients ≥65 years of age scheduled for elective surgery were recruited. The Modified Telephone Interview for Cognitive Status questionnaire (TICS-M), a test of global cognitive functioning, was administered to determine cognition. Preoperative, 30-day postoperative, and 6-month postoperative cognition were compared for patients with and without DM. Cognitive decline was subdivided into mild (1 to 2 standard deviations below controls) and major (≥2 standard deviations below controls) DNR or POCD. Preoperative HbA1c levels were correlated with TICS-M scores. RESULTS: We analyzed 102 patients [median (IQR [range]) age 72.0 (5 [68-74])]), who were divided into patients with DM (80 patients [78%]) and patients without DM (22 patients [22%]). Baseline cognitive function was similar for both groups. Repeated measures ANOVA showed that mean DM patient TICS-M scores decreased 30 days postoperative (F(2, 200) = 4.0, p = 0.02), with subsequent recovery 6-month postoperative, compared to stable TICS-M scores in non-DM patients. There were significantly more DM patients with DNR than non-DM patients (n = 11 [50%] vs. n = 14 [17.5%]; p = 0.031). There were no between-group differences in mild or major POCD. Higher preoperative HbA1c levels were significantly correlated with decreased 30-day Δcognition scores (F(1, 54) = 9.4, p = 0.003) with an R2 of 0.149 (ß -0.45, 95% confidence interval: -0.735 to -0.154). CONCLUSIONS: Older adult patients with DM undergoing surgery have an increased risk of DNR compared to older adult non-DM patients, but no increased risk of POCD. In DM patients, higher preoperative HbA1c levels were associated with an increased risk of DNR.

International Survey on Perioperative Management of Patients With Infective Endocarditis.

OBJECTIVES: To estimate the current practice in the perioperative management of patients undergoing cardiac surgery due to infective endocarditis. DESIGN: A prospective, open, 24-item, web-based cross-sectional survey. SETTING: Online survey endorsed by the European Association of Cardiothoracic Anesthesiology and Intensive Care (EACTAIC). PARTICIPANTS: Members of the EACTAIC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 156 responses from 44 countries were received, with a completion rate of 99%. The response rate was 16.6%. Most respondents (76%) practiced cardiac anesthesia in European hospitals, and most respondents stated that a multidisciplinary endocarditis team was not established at their center, that cardiac anesthesiologists appeared to be involved infrequently in those teams (36%), and that they were not involved in decision-making on indication and timing of surgery (88%). In contrast, the cardiac anesthesiologist performed intraoperative antibiotic therapy (62%) and intraoperative transesophageal echocardiography (90%). Furthermore, there was a relative heterogeneity concerning perioperative monitoring, as well as for coagulation and transfusion management. CONCLUSIONS: This international survey evaluated current practice among cardiac anesthesiologists in the perioperative management of patients with infective endocarditis and the anesthesiologist's role in multidisciplinary decision-making. Heterogeneity in treatment approaches was identified, indicating relevant knowledge gaps that should encourage further clinical research to optimize treatment and postoperative outcomes in this specific population.

Initiatives to detect and prevent death from perioperative deterioration.

PURPOSE OF REVIEW: This study indicates that there are differences between hospitals in detection, as well as in adequate management of postsurgical complications, a phenomenon that is described as 'failure-to-rescue'.In this review, recent initiatives to reduce failure-to-rescue in the perioperative period are described. RECENT FINDINGS: Use of cognitive aids, emergency manuals, family participation as well as remote monitoring systems are measures to reduce failure-to-rescue situations. Postoperative visit of an anaesthesiologist on the ward was not shown to improve outcome, but there is still room for improvement of postoperative care. SUMMARY: Improving the complete emergency chain, including monitoring, recognition and response in the afferent limb, as well as diagnostic and treatment in the efferent limb, should lead to reduced failure-to-rescue situations in the perioperative period.

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway.

AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. METHODS: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. RESULTS: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. CONCLUSIONS/INTERPRETATION: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities.

Anesthesia Considerations in Infective Endocarditis.

The management of infective endocarditis is complex and inherently requires multidisciplinary cooperation. About half of all patients diagnosed with infective endocarditis will meet the criteria to undergo cardiac surgery, which regularly takes place in urgent or emergency settings. The pathophysiology and clinical presentation of infective endocarditis make it a unique disorder within cardiac surgery that warrants a thorough understanding of specific characteristics in the perioperative period. This includes, among others, echocardiography, coagulation, bleeding management, or treatment of organ dysfunction. In this narrative review article, the authors summarize the current knowledge on infective endocarditis relevant for the clinical anesthesiologist in perioperative management of respective patients. Furthermore, the authors advocate for the anesthesiologist to become a structural member of the endocarditis team.

Adaptive threshold-based alarm strategies for continuous vital signs monitoring.

Continuous vital signs monitoring in post-surgical ward patients may support early detection of clinical deterioration, but novel alarm approaches are required to ensure timely notification of abnormalities and prevent alarm-fatigue. The current study explored the performance of classical and various adaptive threshold-based alarm strategies to warn for vital sign abnormalities observed during development of an adverse event. A classical threshold-based alarm strategy used for continuous vital signs monitoring in surgical ward patients was evaluated retrospectively. Next, (combinations of) six methods to adapt alarm thresholds to personal or situational factors were simulated in the same dataset. Alarm performance was assessed using the overall alarm rate and sensitivity to detect adverse events. Using a wireless patch-based monitoring system, 3999 h of vital signs data was obtained in 39 patients. The clinically used classical alarm system produced 0.49 alarms/patient/day, and alarms were generated for 11 out of 18 observed adverse events. Each of the tested adaptive strategies either increased sensitivity to detect adverse events or reduced overall alarm rate. Combining specific strategies improved overall performance most and resulted in earlier presentation of alarms in case of adverse events. Strategies that adapt vital sign alarm thresholds to personal or situational factors may improve early detection of adverse events or reduce alarm rates as compared to classical alarm strategies. Accordingly, further investigation of the potential of adaptive alarms for continuous vital signs monitoring in ward patients is warranted.

Anesthetic considerations for endovascular treatment in stroke therapy.

PURPOSE OF REVIEW: The introduction of clot removement by endovascular treatment (EVT) in 2015 has improved the clinical outcome of patients with acute ischemic stroke (AIS) due to a large vessel occlusion (LVO). Anesthetic strategies during EVT vary widely between hospitals, with some departments employing local anesthesia (LA), others performing conscious sedation (CS) or general anesthesia (GA). The optimal anesthetic strategy remains debated. This review will describe the effects of anesthetic strategy on clinical and radiological outcomes and hemodynamic parameters in patients with AIS undergoing EVT. RECENT FINDINGS: Small single-center randomized controlled trails (RCTs) found either no difference or favored GA, while large observational cohort studies favored CS or LA. RCTs using LA as separate comparator arm are still lacking and a meta-analysis of observational studies failed to show differences in functional outcome between LA vs. other anesthetic strategies. Advantages of LA were shorter door-to-groin time in patients and less intraprocedural hypotension, which are both variables that are known to impact functional outcome. SUMMARY: The optimal anesthetic approach in patients undergoing EVT for stroke therapy is still unclear, but based on logistics and peri-procedural hemodynamics, LA may be the optimal choice. Multicenter RCTs are warranted comparing LA, CS and GS with strict blood pressure targets and use of the same anesthetic agents to minimize confounding variables.

Novel Anti-inflammatory Effects of Canagliflozin Involving Hexokinase II in Lipopolysaccharide-Stimulated Human Coronary Artery Endothelial Cells.

PURPOSE: Vascular inflammation and disturbed metabolism are observed in heart failure and type 2 diabetes mellitus. Glycolytic enzyme hexokinase II (HKII) is upregulated by inflammation. We hypothesized that SGLT2 inhibitors Canagliflozin (Cana), Empagliflozin (Empa) or Dapagliflozin (Dapa) reduces inflammation via HKII in endothelial cells, and that HKII-dependent inflammation is determined by ERK1/2, NF-κB. and/or AMPK activity in lipopolysaccharide (LPS)-stimulated human coronary artery endothelial cells (HCAECs). METHODS: HCAECs were pre-incubated with 3 µM or 10 µM Cana, 1 µM, 3 µM or 10 µM Empa or 0.5 µM, 3 µM or 10 µM Dapa (16 h) and subjected to 3 h LPS (1 µg/mL). HKII was silenced via siRNA transfection. Interleukin-6 (IL-6) release was measured by ELISA. Protein levels of HK I and II, ERK1/2, AMPK and NF-κB were detected using infra-red western blot. RESULTS: LPS increased IL-6 release and ERK1/2 phosphorylation; Cana prevented these pro-inflammatory responses (IL-6: pg/ml, control 46 ± 2, LPS 280 ± 154 p < 0.01 vs. control, LPS + Cana 96 ± 40, p < 0.05 vs. LPS). Cana reduced HKII expression (HKII/GAPDH, control 0.91 ± 0.16, Cana 0.71 ± 0.13 p < 0.05 vs. control, LPS 1.02 ± 0.25, LPS + Cana 0.82 ± 0.24 p < 0.05 vs. LPS). Empa and Dapa were without effect on IL-6 release and HKII expression in the model used. Knockdown of HKII by 37% resulted caused partial loss of Cana-mediated IL-6 reduction (pg/ml, control 35 ± 5, LPS 188 ± 115 p < 0.05 vs. control, LPS + Cana 124 ± 75) and ERK1/2 activation by LPS. In LPS-stimulated HCAECs, Cana, but not Empa or Dapa, activated AMPK. AMPK activator A769662 reduced IL-6 release. CONCLUSION: Cana conveys anti-inflammatory actions in LPS-treated HCAECs through 1) reductions in HKII and ERK1/2 phosphorylation and 2) AMPK activation. These data suggest a novel anti-inflammatory mechanism of Cana through HKII.

Comparison of adequacy of anaesthesia monitoring with standard clinical practice monitoring during routine general anaesthesia: An international, multicentre, single-blinded randomised controlled trial.

BACKGROUND: Previous studies have suggested that monitoring the levels of both hypnosis and antinociception could reduce periods of inadequate anaesthesia. However, the evidence regarding associated benefits of this monitoring is still limited. OBJECTIVE: The primary objective of this study was to confirm that guidance of anaesthesia by depth of hypnosis and antinociception monitoring decreases the number of inadequate anaesthesia events in comparison with standard clinical practice. DESIGN: A multicentre, single-blinded, randomised controlled trial. SETTING: The study was conducted in four European University hospitals in four different countries between December 2013 and November 2016. PATIENTS: The study population consisted of a total of 494 adult patients undergoing elective surgery requiring tracheal intubation. INTERVENTIONS: The patients were allocated to one of two groups. The first group was treated using Entropy for depth of hypnosis and surgical pleth index to determine depth of antinociception (adequacy of anaesthesia group; AoA group). The second group was monitored using standard monitoring alone (control group). Anaesthesia was conducted with target-controlled infusions of propofol and remifentanil. MAIN OUTCOME MEASURES: The primary outcome of the study was the number of total unwanted events for example signs of inadequately light or unintentionally deep anaesthesia. RESULTS: Evidence of inadequate anaesthesia had an incidence of around 0.7 events per patient in both groups with no difference between groups (P = 0.519). In the AoA group, the overall consumption of propofol was significantly reduced (6.9 vs. 7.5 mg kg h, P = 0.008) in comparison with the control group. The consumption of remifentanil was equal in both groups. The times to emergence [8.0 vs. 9.6 min (P = 0.005)] and full recovery in the postanaesthesia care unit (P = 0.043) were significantly shorter in the AoA group. No differences were seen in postoperative pain scores or in the use of analgesics. CONCLUSION: In the current study, the guidance of total intravenous anaesthesia by Entropy and surgical pleth index in comparison with standard monitoring alone was not able to validate reduction of unwanted anaesthesia events. However, there was a reduction in the use of propofol, and shorter times for emergence and time spent in the postanaesthesia care unit. TRIAL REGISTRATION: at ClinicalTrials.gov NCT01928875.

Pharmacological Conditioning of the Heart: An Update on Experimental Developments and Clinical Implications.

The aim of pharmacological conditioning is to protect the heart against myocardial ischemia-reperfusion (I/R) injury and its consequences. There is extensive literature that reports a multitude of different cardioprotective signaling molecules and mechanisms in diverse experimental protocols. Several pharmacological agents have been evaluated in terms of myocardial I/R injury. While results from experimental studies are immensely encouraging, translation into the clinical setting remains unsatisfactory. This narrative review wants to focus on two aspects: (1) give a comprehensive update on new developments of pharmacological conditioning in the experimental setting concentrating on recent literature of the last two years and (2) briefly summarize clinical evidence of these cardioprotective substances in the perioperative setting highlighting their clinical implications. By directly opposing each pharmacological agent regarding its recent experimental knowledge and most important available clinical data, a clear overview is given demonstrating the remaining gap between basic research and clinical practice. Finally, future perspectives are given on how we might overcome the limited translatability in the field of pharmacological conditioning.

Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species.

SGLT-2i's exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i's empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) exert an anti-oxidative effect and alleviate cyclic stretch-induced endothelial permeability in human coronary artery endothelial cells (HCAECs). HCAECs were pre-incubated with one of the SGLT-2i's (1 µM EMPA, 1 µM DAPA and 3 µM CANA) for 2 h, followed by 10% stretch for 24 h. HCAECs exposed to 5% stretch were considered as control. Involvement of ROS was measured using N-acetyl-l-cysteine (NAC). The sodium-hydrogen exchanger 1 (NHE1) and NADPH oxidases (NOXs) were inhibited by cariporide, or GKT136901, respectively. Cell permeability and ROS were investigated by fluorescence intensity imaging. Cell permeability and ROS production were increased by 10% stretch; EMPA, DAPA and CANA decreased this effect significantly. Cariporide and GKT136901 inhibited stretch-induced ROS production but neither of them further reduced ROS production when combined with EMPA. SGLT-2i's improve the barrier dysfunction of HCAECs under enhanced stretch and this effect might be mediated through scavenging of ROS. Anti-oxidative effect of SGLT-2i's might be partially mediated by inhibition of NHE1 and NOXs.

Liraglutide for perioperative management of hyperglycaemia in cardiac surgery patients: a multicentre randomized superiority trial.

AIMS: Most cardiac surgery patients, with or without diabetes, develop perioperative hyperglycaemia, for which intravenous insulin is the only therapeutic option. This is labour-intensive and carries a risk of hypoglycaemia. We hypothesized that preoperative administration of the glucagon-like peptide-1 receptor agonist liraglutide reduces the number of patients requiring insulin for glycaemic control during cardiac surgery. MATERIALS AND METHODS: In this randomized, blinded, placebo-controlled, parallel-group, balanced (1:1), multicentre randomized, superiority trial, adult patients undergoing cardiac surgery in four Dutch tertiary hospitals were randomized to receive 0.6 mg subcutaneous liraglutide on the evening before surgery and 1.2 mg after induction of anaesthesia or matching placebo. Blood glucose was measured hourly and controlled using an insulin-bolus algorithm. The primary outcome was insulin administration for blood glucose >8.0 mmol/L in the operating theatre. Research pharmacists used centralized, stratified, variable-block, randomization software. Patients, care providers and study personnel were blinded to treatment allocation. RESULTS: Between June 2017 and August 2018, 278 patients were randomized to liraglutide (139) or placebo (139). All patients receiving at least one study drug injection were included in the intention-to-treat analyses (129 in the liraglutide group, 132 in the placebo group). In the liraglutide group, 55 (43%) patients required additional insulin compared with 80 (61%) in the placebo group and absolute difference 18% (95% confidence interval 5.9-30.0, P = 0.003). Dose and number of insulin injections and mean blood glucose were all significantly lower in the liraglutide group. We observed no difference in the incidence of hypoglycaemia, nausea and vomiting, mortality or postoperative complications. CONCLUSIONS: Preoperative liraglutide, compared with placebo, reduces insulin requirements while improving perioperative glycaemic control during cardiac surgery.

Perioperative Cardioprotection: Clinical Implications.

Perioperative cardioprotection aims to minimize the consequences of myocardial ischemia-reperfusion injury. In isolated tissue and animal experiments, several treatments have been identified providing cardioprotection. Some of these strategies have been confirmed in clinical proof-of-concept studies. However, the final translation of cardioprotective strategies to really improve clinical outcome has been disappointing: large randomized controlled clinical trials mostly revealed inconclusive, neutral, or negative results. This review provides an overview of the currently available evidence regarding clinical implications of perioperative cardioprotective therapies from an anesthesiological perspective, highlighting nonpharmacological as well as pharmacological strategies. We discuss reasons why translation of promising experimental results into clinical practice and outcome improvement is hampered by potential confounders and suggest future perspectives to overcome these limitations.

The effectiveness of a low-dose esketamine versus an alfentanil adjunct to propofol sedation during endoscopic retrograde cholangiopancreatography: A randomised controlled multicentre trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most complex gastrointestinal endoscopic procedures. Currently, it is still unclear which sedation regimen best facilitates an ERCP. The N-methyl-D-aspartate receptor antagonist esketamine has anaesthetic, analgesic and sympathomimetic properties and is known to cause less cardiorespiratory depression than other sedatives. It could therefore be an ideal adjunct to propofol for deep sedation. OBJECTIVE: To assess the effectiveness of esketamine versus alfentanil as an adjunct to propofol target-controlled infusion (TCI) for deep sedation during ambulant ERCP. DESIGN: A randomised controlled multicentre study. SETTING: Endoscopic intervention suite at an academic and general hospital in the Netherlands. PARTICIPANTS: Adult, American Society of Anesthesiologists Physical Status I to III patients scheduled to undergo ERCP. INTERVENTION: Consecutive patients were randomly assigned to receive sedation for an ERCP with propofol TCI and alfentanil (group A) or with propofol TCI and esketamine (group E). MAIN OUTCOME MEASURES: The primary outcome was effectiveness of the sedation regimen expressed as the total dose of propofol - as a surrogate parameter - necessary to perform ERCP in a satisfactory manner for endoscopist and patients. Secondary outcomes were recovery time, patients' and endoscopists' satisfaction with sedation, side effects (e.g. psychotomimetic effects, nausea and vomiting) and the number of respiratory and cardiovascular adverse events. RESULTS: Data from 162 patients were analysed. The total dose of propofol required was significantly lower in group E (n=83) (8.3 mg kg h) than in group A (n=79) (10.5 mg kg h) (P < 0.001). There were no significant differences in recovery time, patients' and endoscopists' satisfaction, side effects, psychotomimetic effects and the number of sedation-related adverse events. CONCLUSION: Low-dose esketamine reduces the total amount of propofol necessary for sedation during ERCP in American Society of Anesthesiologists I and II patients without affecting recovery time, satisfaction of patients and endoscopists, side effects and respiratory or cardiovascular adverse events, when compared with alfentanil. TRIAL REGISTRATION: The Netherlands Trial Register (NTR5486).

Ten years of the Helsinki Declaration on patient safety in anaesthesiology: An expert opinion on peri-operative safety aspects.

: Patient safety is an activity to mitigate preventable patient harm that may occur during the delivery of medical care. The European Board of Anaesthesiology (EBA)/European Union of Medical Specialists had previously published safety recommendations on minimal monitoring and postanaesthesia care, but with the growing public and professional interest it was decided to produce a much more encompassing document. The EBA and the European Society of Anaesthesiology (ESA) published a consensus on what needs to be done/achieved for improvement of peri-operative patient safety. During the Euroanaesthesia meeting in Helsinki/Finland in 2010, this vision was presented to anaesthesiologists, patients, industry and others involved in health care as the 'Helsinki Declaration on Patient Safety in Anaesthesiology'. In May/June 2020, ESA and EBA are celebrating the 10th anniversary of the Helsinki Declaration on Patient Safety in Anaesthesiology; a good opportunity to look back and forward evaluating what was achieved in the recent 10 years, and what needs to be done in the upcoming years. The Patient Safety and Quality Committee (PSQC) of ESA invited experts in their fields to contribute, and these experts addressed their topic in different ways; there are classical, narrative reviews, more systematic reviews, political statements, personal opinions and also original data presentation. With this publication we hope to further stimulate implementation of the Helsinki Declaration on Patient Safety in Anaesthesiology, as well as initiating relevant research in the future.

Insights into postoperative respiration by using continuous wireless monitoring of respiratory rate on the postoperative ward: a cohort study.

Change of respiratory rate (RespR) is the most powerful predictor of clinical deterioration. Brady- (RespR ≤ 8) and tachypnea (RespR ≥ 31) are associated with serious adverse events. Simultaneously, RespR is the least accurately measured vital parameter. We investigated the feasibility of continuously measuring RespR on the ward using wireless monitoring equipment, without impeding mobilization. Continuous monitoring of vital parameters using a wireless SensiumVitals® patch was installed and RespR was measured every 2 mins. We defined feasibility of adequate RespR monitoring if the system reports valid RespR measurements in at least 50% of time-points in more than 80% of patients during day- and night-time, respectively. Data from 119 patients were analysed. The patch detected in 171,151 of 227,587 measurements valid data for RespR (75.2%). During postoperative day and night four, the system still registered 68% and 78% valid measurements, respectively. 88% of the patients had more than 67% of valid RespR measurements. The RespR's most frequently measured were 13-15; median RespR was 15 (mean 16, 25th- and 75th percentile 13 and 19). No serious complications or side effects were observed. We successfully measured electronically RespR on a surgical ward in postoperative patients continuously for up to 4 days post-operatively using a wireless monitoring system. While previous studies mentioned a digit preference of 18-22 for RespR, the most frequently measured RespR were 13-16. However, in the present study we did not validate the measurements against a reference method. Rather, we attempted to demonstrate the feasibility of achieving continuous wireless measurement in patients on surgical postoperative wards. As the technology used is based on impedance pneumography, obstructive apnoea might have been missed, namely in those patients receiving opioids post-operatively.

Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor α-Stimulated Human Coronary Arterial Endothelial Cells.

BACKGROUND/AIMS: Heart failure is characterized by chronic low-grade vascular inflammation, which in itself can lead to endothelial dysfunction. Clinical trials showed reductions in heart failure-related hospitalizations of type 2 diabetic patients using sodium glucose co-transporter 2 inhibitors (SGLT2i's). Whether and how SGLT2i's directly affect the endothelium under inflammatory conditions is not completely understood. The aim of the study was to investigate whether the SGLT2i Empagliflozin (EMPA) and Dapagliflozin (DAPA) reduce tumor necrosis factor α (TNFα) induced endothelial inflammation in vitro. METHODS: Human coronary arterial endothelial cells (HCAECs) and human umbilical vein endothelial cells (HUVECs) were (pre-)incubated with 1 µM EMPA or DAPA and subsequently exposed to 10 ng/ml TNFα. ROS and NO were measured using live cell imaging. Target proteins were either determined by infrared western blotting or fluorescence activated cell sorting (FACS). The connection between Cav-1 and eNOS was determined by co-immunoprecipitation. RESULTS: Nitric oxide (NO) bioavailability was reduced by TNFα and both EMPA and DAPA restored NO levels in TNFα-stimulated HCAECs. Intracellular ROS was increased by TNFα, and this increase was completely abolished by EMPA and DAPA in HCAECs by means of live cell imaging. eNOS signaling was significantly disturbed after 24 h when cells were exposed to TNFα for 24h, yet the presence of both SGLT2is did not prevent this disruption. TNFα-induced enhanced permeability at t=24h was unaffected in HUVECs by EMPA. Similarly, adhesion molecule expression (VCAM-1 and ICAM-1) was elevated after 4h TNFα (1.5-5.5 fold increase of VCAM-1 and 4-12 fold increase of ICAM-1) but were unaffected by EMPA and DAPA in both cell types. Although we detected expression of SGLT2 protein levels, the fact that we could not silence this expression by means of siRNA and the mRNA levels of SGLT2 were not detectable in HCAECs, suggests aspecificity or our SGLT2 antibody and absence of SGLT2 in our cells. CONCLUSION: These data suggest that EMPA and DAPA rather restore NO bioavailability by inhibiting ROS generation than by affecting eNOS expression or signaling, barrier function and adhesion molecules expression in TNFα-induced endothelial cells. Furthermore, the observed effects cannot be ascribed to the inhibition of SGLT2 in endothelial cells.

Plasma from Volunteers Breathing Helium Reduces Hypoxia-Induced Cell Damage in Human Endothelial Cells-Mechanisms of Remote Protection Against Hypoxia by Helium.

PURPOSE: Remote ischemic preconditioning protects peripheral organs against prolonged ischemia/reperfusion injury via circulating protective factors. Preconditioning with helium protected healthy volunteers against postischemic endothelial dysfunction. We investigated whether plasma from helium-treated volunteers can protect human umbilical vein endothelial cells (HUVECs) against hypoxia in vitro through release of circulating of factors. METHODS: Healthy male volunteers inhaled heliox (79% helium, 21% oxygen) or air for 30 min. Plasma was collected at baseline, directly after inhalation, 6 h and 24 h after start of the experiment. HUVECs were incubated with either 5% or 10% of the plasma for 1 or 2 h and subjected to enzymatically induced hypoxia. Cell damage was measured by LDH content. Furthermore, caveolin 1 (Cav-1), hypoxia-inducible factor (HIF1α), extracellular signal-regulated kinase (ERK)1/2, signal transducer and activator of transcription (STAT3) and endothelial nitric oxide synthase (eNOS) were determined. RESULTS: Prehypoxic exposure to 10% plasma obtained 6 h after helium inhalation decreased hypoxia-induced cell damage in HUVEC. Cav-1 knockdown in HUVEC abolished this effect. CONCLUSIONS: Plasma of healthy volunteers breathing helium protects HUVEC against hypoxic cell damage, possibly involving circulating Cav-1.