Anaesthetic efficacy and postinduction hypotension with remimazolam compared with propofol: a multicentre randomised controlled trial.

Remimazolam, a short-acting benzodiazepine, may be used for induction and maintenance of total intravenous anaesthesia, but its role in the management of patients with multiple comorbidities remains unclear. In this phase 3 randomised controlled trial, we compared the anaesthetic efficacy and the incidence of postinduction hypotension during total intravenous anaesthesia with remimazolam vs. propofol. A total of 365 patients (ASA physical status 3 or 4) scheduled for elective surgery were assigned randomly to receive total intravenous anaesthesia with remimazolam (n = 270) or propofol (n = 95). Primary outcome was anaesthetic effect, quantified as the percentage of time with Narcotrend® Index values ≤ 60, during surgery (skin incision to last skin suture), with a non-inferiority margin of -10%. Secondary outcome was the incidence of postinduction hypotensive events. Mean (SD) percentage of time with Narcotrend Index values ≤ 60 during surgery across all patients receiving remimazolam (93% (20.7)) was non-inferior to propofol (99% (4.2)), mean difference (97.5%CI) -6.28% (-8.89-infinite); p = 0.003. Mean (SD) number of postinduction hypotension events was 62 (38.1) and 71 (41.1) for patients allocated to the remimazolam and propofol groups, respectively; p = 0.015. Noradrenaline administration events (requirement for a bolus and/or infusion) were also lower in patients allocated to remimazolam compared with propofol (14 (13.5) vs. 20 (14.6), respectively; p < 0.001). In conclusion, in patients who were ASA physical status 3 or 4, the anaesthetic effect of remimazolam was non-inferior to propofol.

Burnout and its determinants among anaesthesia care providers in Switzerland: a multicentre cross-sectional study.

The escalating epidemic of burnout in healthcare professionals affects provider well-being, patient care and sustainability of healthcare systems. The objective of this study was to determine the prevalence of burnout among anaesthesia care providers (consultants, trainees or nurse anaesthetists) in Switzerland and identify risk factors to develop strategies for prevention. This multicentre cross-sectional study was conducted at 22 anaesthesia departments in the German-speaking part of Switzerland, using an online questionnaire. Burnout assessment was performed using the Maslach Burnout Inventory. Additionally, the questionnaire included questions on workplace and personal risk factors. Of 1630 anaesthesia care providers contacted, 688 (42%) completed the survey. Among respondents who specified their work positions (n = 676), 52% (149/287) of nurses and 59% (229/389) of physicians were at high risk of burnout; and 9% (26/287) of nurses and 18% (70/389) of physicians met the criteria for burnout syndrome. Logistic regression analysis found significant associations between burnout and perceived lack of support at work among physicians (odds ratio (95%CI) 2.66 (1.40-5.24), p = 0.004); being a trainee in the 1st and 2nd year of training (2.91 (1.14-7.41), p = 0.024); being a trainee with > 5 years of experience (2.78 (1.08-6.98), p = 0.031); and male gender among nurses (4.13 (1.62-11.2), p = 0.004) and physicians (2.32 (1.22-4.47), p = 0.011). Work-related errors due to high workload or fatigue were reported by 65% (444/688) and consideration of leaving the profession due to working conditions was expressed by 46% (319/688) of respondents. Anaesthetic care providers in German-speaking Switzerland experience a considerable prevalence of burnout, influenced mainly by workplace factors.

Iron Deficiency and Incident Infections among Community-Dwelling Adults Age 70 Years and Older: Results from the DO-HEALTH Study.

OBJECTIVES: To assess if baseline iron deficiency, with or without anemia, is associated with incident infections over 3 years among community-dwelling older adults. DESIGN: Prospective secondary analysis of DO-HEALTH, a 3-year randomized, double-blind controlled trial. SETTING AND PARTICIPANTS: 2157 community-dwelling adults age 70+ from 5 European countries with good cognitive function and mobility and no major health events in the 5 years prior to enrollment Measurements: Incident infections, their severity and type were recorded every 3 months throughout the 3-year follow-up. Iron deficiency was defined as soluble transferrin receptor (sTfR) levels > 28.1 nmol/l and anemia as hemoglobin levels < 120 g/l for women and 130 g/l for men. We applied negative binomial mixed effects regression models with random effects for countries, and controlling for treatment allocation, age, sex, body mass index, polypharmacy, number of comorbidities, smoking status, living situation, alcohol intake, frailty status, and physical activity levels. A pre-defined stratified analysis was performed to explore if the associations between iron deficiency and infections were consistent by baseline anemia status. RESULTS: In total, 2141 participants were included in the analyses (mean age 74.9 years, 61.5% of women, 26.8% with iron deficiency). Across all participants, baseline iron deficiency was not associated with incident overall infections, but was associated with a 63% greater rate of incident severe infections requiring hospitalization (incidence rate ratio [IRR] 1.63, 95% Confidence Interval [CI] 1.11-2.41, p=0.01). This association was more pronounced among the 2000 participants who did not have anemia at baseline (IRR=1.80, 95% CI 1.20-2.69, p=0.005). CONCLUSION: Based on this prospective study among generally healthy European community-dwelling older adults, iron deficiency was not associated with the incidence rate of overall infections but may increase the incidence of severe infections. Intervention studies are needed to prove the causality of this observation.

The Haemostasis Traffic Light, a user-centred coagulation management tool for acute bleeding situations: a simulation-based randomised dual-centre trial.

The Haemostasis Traffic Light is a cognitive aid with a user-centred design to enhance and simplify situation awareness and decision-making during peri-operative bleeding. Its structure helps to prioritise therapeutic interventions according to the pathophysiology and the severity of the bleeding. This investigator-initiated, randomised, prospective, international, dual-centre study aimed to validate the Haemostasis Traffic Light by adapting it to the local coagulation protocols of two university hospitals. Between 9 January and 12 May 2020, we recruited 84 participants at the University Hospital Zurich, Switzerland, and the Italian Hospital of Buenos Aires, Argentina. Each centre included 21 resident and 21 staff anaesthetists. Participants were randomly allocated to either the text-based algorithm or the Haemostasis Traffic Light. All participants managed six bleeding scenarios using the same algorithm. In simulated bleeding scenarios, the design of the Haemostasis Traffic Light algorithm enabled more correctly solved cases, OR (95%CI) 7.23 (3.82-13.68), p < 0.001, and faster therapeutic decisions, HR (95%CI) 1.97 (1.18-3.29, p = 0.010). In addition, the tool improved therapeutic confidence, OR (95%CI) 4.31 (1.67-11.11, p = 0.003), and reduced perceived work-load coefficient (95%CI) -6.1 (-10.98 to -1.22), p = 0.020). This study provides empirical evidence for the importance of user-centred design in the development of haemostatic management protocols.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

Efficacy of quadruple treatment on different types of pre-operative anaemia: secondary analysis of a randomised controlled trial.

In patients with pre-operative anaemia undergoing cardiac surgery, combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12 and oral folic acid reduces allogeneic blood product transfusions. It is unclear if certain types of anaemia particularly benefit from this treatment. We performed a post-hoc analysis of anaemic patients from a randomised trial on the 'Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery'. We used linear regression analyses to examine the efficacy of a combination anaemia treatment compared with placebo on the following deficiencies, each representing a part of the combination treatment: ferritin and transferrin saturation; endogenous erythropoietin; holotranscobalamine; and folic acid in erythrocytes. Efficacy was defined as change in reticulocyte count from baseline to the first, third and fifth postoperative days and represented erythropoietic activity in the immediate peri-operative recovery phase. In all 253 anaemic patients, iron deficiency was the most common cause of anaemia. Treatment significantly increased reticulocyte count in all regression analyses on postoperative days 1, 3 and 5 (all p < 0.001). Baseline ferritin and endogenous erythropoietin were negatively associated with change in reticulocyte count on postoperative day 5, with an unstandardised regression coefficient B of -0.08 (95%CI -0.14 to -0.02) and -0.14 (95%CI -0.23 to -0.06), respectively. Quadruple anaemia treatment was effective regardless of the cause of anaemia and its effect manifested early in the peri-operative recovery phase. The more pronounced a deficiency was, the stronger the subsequent boost to erythropoiesis may have been.

Improving decision making through presentation of viscoelastic tests as a 3D animated blood clot: the Visual Clot.

Point-of-care viscoelastic coagulation tests are used increasingly and enable physicians to run precise whole blood coagulation diagnostics. However, the somewhat complicated and abstract presentation of results may hinder these advantages. For this reason, we developed the Visual Clot as an alternative mode of presentation for thrombelastometric data. An algorithm takes existing parameters from rotational thromboelastometry and creates a visual representation in the form of an animated blood clot named 'Visual Clot'. In a prospective international dual-centre study, 60 physicians were presented with rotational thromboelastometry results in the standard way or as a Visual Clot. They were then asked to make therapeutic decisions based on pathological findings. Overall proportion of correct therapeutic decisions was median (IQR [range] 100 (83-100 [39-100]) % for Visual Clot vs. 44 (25-50 [0-83]) % for standard rotational thromboelastometry presentation of results, p < 0.001. Mixed regression models yielded a mean OR (95%CI) 22.1 (13.4-36.5), p < 0.001 for correct decisions with the Visual Clot compared with standard rotational thromboelastometry, with an 18.7 (16.4-21.1), p < 0.001 second decrease in decision time. Perceived cognitive work-load was lower, and participants rated their diagnostic confidence to be higher with the Visual Clot, both p < 0.001. Although correct interpretation of standard rotational thromboelastometry results depended on previous rotational thromboelastometry knowledge and experience, Visual Clot interpretation did not. The Visual Clot improved rotational thromboelastometry-based therapeutic decisions, as pathologies can be recognised more rapidly and accurately. These findings underline the significance of an alternative additional visualisation technique that simplifies the interpretation of abstract standard data.

Automated tracheal intubation in an airway manikin using a robotic endoscope: a proof of concept study.

Robotic endoscope-automated via laryngeal imaging for tracheal intubation (REALITI) has been developed to enable automated tracheal intubation. This proof-of-concept study using a convenience sample of participants, comprised of trained anaesthetists and lay participants with no medical training, assessed the performance of a robotic device for the insertion of a tracheal tube into a manikin. A prototype robotic endoscope device was inserted into the trachea of an airway manikin by seven anaesthetists and seven participants with no medical training. Each individual performed six device insertions into the trachea in manual mode and six in automated mode. The anaesthetists succeeded with 40/42 (95%) manual insertions (median (IQR [range]) 17 (12-26 [4-132]) s) and 40/42 (95%) automated insertions (15 (13-18 [7-25]) s). The non-trained participants succeeded in 41/42 (98%) manual insertions (median (IQR [range]) 18 (13-21 [8-133]) s) and 42/42 (100%) automated insertions (16 (13-23 [10-58])] s). The duration of insertion did not differ between groups. An effect of increasing experience was observed in both groups in manual mode. A Likert scale for 'ease of use' (0 = very difficult to 10 = very easy) showed similar results within the two groups; the mean (SD) was 5.9 (2.1) for the anaesthetists and 6.9 (1.3) for the non-trained participants. We have successfully performed the first automated tracheal device insertion in a manikin with comparable results in a convenience sample of anaesthetists and lay participants with no medical training.

Impact of a Patient Blood Management monitoring and feedback programme on allogeneic blood transfusions and related costs.

A Patient Blood Management programme was established at the University Hospital of Zurich, along with a monitoring and feedback programme, at the beginning of 2014 with a first analysis reported in 2015. Our study aimed to investigate the further impact of this Patient Blood Management monitoring and feedback programme on transfusion requirements and related costs. We included adult patients discharged between 2012 and 2017. A total of 213,882 patients underwent analysis: 66,659 patients in the baseline period (2012-2013); 35,309 patients in the year after the introduction of the Patient Blood Management monitoring and feedback programme (2014) and 111,914 patients in the continued sustainability period (2015-2017). The introduction of the Patient Blood Management monitoring and feedback programme reduced allogeneic blood product transfusions by 35%, from 825 units per 1000 hospital discharges in 2012 to 536 units in 2017. The most sustained effect was an approximately 40% reduction in red blood cell transfusions, from 535 per 1000 discharges to 319 units. Fewer patients were transfused in the periods after the introduction of the Patient Blood Management monitoring and feedback programme (6251 (9.4%) vs. 2932 (8.3%) vs. 8196 (7.3%); p < 0.001). Compared with 2012, the yearly OR for being exposed to any blood transfusion declined steadily after the introduction of the Patient Blood Management monitoring and feedback programme to 0.64 (95%CI 0.61-0.68; p < 0.001) in 2017. For patients requiring extracorporeal membrane oxygenation, transfusion requirements were also sustainably reduced. This reduction in allogeneic blood transfusions led to savings of 12,713,754 Swiss francs (£ 9,497,000 sterling; EUR 11,100,000; US$ 12,440,000) in blood product acquisition costs over 4 years. In-hospital mortality was not affected by the programme. The Patient Blood Management monitoring and feedback programme sustainably reduced transfusion requirements and related costs, without affecting in-hospital mortality.

Using an animated patient avatar to improve perception of vital sign information by anaesthesia professionals.

BACKGROUND: Maintaining situation awareness of monitored patients can be challenging because care providers must continually read and integrate multiple waveforms and numerical vital sign values into a mental model of the patient's situation. We developed and evaluated a technology designed to improve perception of vital sign information by presenting patient status as an animated patient avatar. METHODS: After step-wise improvement of the avatar, anaesthesia professionals from two hospitals participated in a comparative study of conventional monitoring. Participants observed identical monitoring scenarios via the two technologies for brief time intervals and afterwards recalled patient status. RESULTS: Overall, 150 anaesthesia professionals participated in the validation process and 32 participated in the comparative study, completing 128 scenarios, which allowed for 64 direct comparisons. The avatar's inter-rater reliability was high, with Fleiss' kappa of 0.98 (95% confidence interval 0.96-0.99, P<0.001). With the avatar, participants recalled almost twice as many vital signs correctly as with conventional monitoring (9 vs 5, P<0.001). Perceived confidence was improved (2=certain vs 1=uncertain, P<0.001) and perceived workload lowered (task load index 60 vs 76, P<0.001). Participants obtained these results only after watching an educational video explaining the avatar and suggesting quick learnability and potential for real-life usability. CONCLUSIONS: This study provides empirical evidence that an animated avatar offers the opportunity to transmit vital sign information significantly more quickly than conventional monitoring and with improved confidence and reduced cognitive effort. This could help care providers gain situation awareness more efficiently.

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) µg.ml-1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.

What is the evidence for platelet transfusion in perioperative settings?

BACKGROUND AND OBJECTIVES: Platelet transfusions are widely administered to restore perioperative haemostasis in haemorrhagic patients; however, the role of platelet transfusion is not well understood and administration is often based on empiric data. This review aims to explore consensus regarding platelet transfusion trigger, dose and how the haemostatic efficacy of platelet transfusion was assessed for the treatment of perioperative bleeding. MATERIALS AND METHODS: A literature search was carried out using MEDLINE (PubMed) on 28 February 2017, to identify publications reporting the effect of platelet transfusion in relation to triggers, dose and assessment of haemostatic efficacy in bleeding patients in a perioperative setting. RESULTS: Eight publications were identified across a variety of settings, covering both prophylactic and therapeutic platelet transfusion in adult patients; the majority of the reports were in cardiac surgery. A high degree of variability was observed in the published studies, with only 50% of articles specifying a trigger for platelet transfusion. The most commonly used trigger was platelet count (25% of publications), with no consensus identified regarding the platelet count values used as triggers. Doses reported per transfusion varied from 1 to 12 units, and outcome measures were mixed, although the majority of publications (63%) assessed the requirement for transfusion with other blood products. CONCLUSION: The lack of consensus in published studies hinders our ability to draw conclusions regarding platelet transfusion and highlights the need for further studies to assess the appropriate dose and triggers for use in perioperative patients.

Change of transfusion and treatment paradigm in major trauma patients.

Trauma promotes trauma-induced coagulopathy, which requires urgent treatment with fixed-ratio transfusions of red blood cells, fresh frozen plasma and platelet concentrates, or goal-directed administration of coagulation factors based on viscoelastic testing. This retrospective observational study compared two time periods before (2005-2007) and after (2012-2014) the implementation of changes in trauma management protocols which included: use of goal-directed coagulation management; admission of patients to designated trauma centres; whole-body computed tomography scanning on admission; damage control surgery; permissive hypotension; restrictive fluid resuscitation; and administration of tranexamic acid. The incidence of massive transfusion (≥ 10 units of red blood cells from emergency department arrival until intensive care unit admission) was compared with the predicted incidence according to the trauma associated severe haemorrhage score. All adult (≥ 16 years) trauma patients primarily admitted to the University Hospital Zürich with an injury severity score ≥ 16 were included. In 2005-2007, the observed and trauma associated severe haemorrhage score that predicted the incidence of massive transfusion were identical, whereas in 2012-2014 the observed incidence was less than half that predicted (3.7% vs. 7.5%). Compared to 2005-2007, the proportion of patients transfused with red blood cells and fresh frozen plasma was significantly lower in 2012-2014 in both the emergency department (43% vs. 17%; 31% vs. 6%, respectively), and after 24 h (53% vs. 27%; 37% vs. 16%, respectively). The use of tranexamic acid and coagulation factor XIII also increased significantly in the 2012-2014 time period. Implementation of a revised trauma management strategy, which included goal-directed coagulation management, was associated with a reduced incidence of massive transfusion and a reduction in the transfusion of red blood cells and fresh frozen plasma.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response.

Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe(2+)) to ferric Hb(Fe(3+)), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria.