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.

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.

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.

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.

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.

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.

Dabigatran anticoagulation and Stanford type A aortic dissection: lethal coincidence: Case report with literature review.

BACKGROUND: Novel oral anticoagulants are now encountered in patients needing emergency surgery. Knowledge and treatment options are limited. METHODS AND RESULT: We present the case of a 76-year-old patient who suffered from an acute Stanford type A aortic dissection, needing emergency surgical aortic repair. He was anticoagulated with dabigatran due to past atrial fibrillation. Despite haemodiafiltration, surgical revision and massive transfusion of packed red blood cells, fresh frozen plasma, platelets, coagulation factors, and recombinant factor VIIa, the patient died from intractable bleeding with sustained therapeutic levels of dabigatran. CONCLUSION: After reviewing the literature, we summarize the limited treatment options and show possible approaches for patients treated with dabigatran needing emergency surgery.

Patient blood management in Europe.

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed 'patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.

Adaptation in anaesthesia team coordination in response to a simulated critical event and its relationship to clinical performance.

BACKGROUND: Recent studies in anaesthesia and intensive care indicate that a team's ability to adapt its coordination activities to changing situational demands is crucial for effective teamwork and thus, safe patient care. This study addresses the relationship between adaptation of team coordination and markers of clinical performance in response to a critical event, particularly regarding which types of coordination activities are used and which team member engages in those coordination activities. METHODS: Video recordings of 15 two-person anaesthesia teams (anaesthesia trainee plus anaesthesia nurse) performing a simulated induction of general anaesthesia were coded, using a structured observation system for coordination activities. The simulation involved a critical event-asystole during laryngoscopy. Clinical performance was assessed using two separate reaction times related to the critical event. RESULTS: Analyses of variance revealed a significant effect of the critical event on team coordination: after the occurrence of the asystole, team members adapted their coordination activities by spending more time on information management-a specific type of coordination activity (F(1,28)=15.17, P=0.001). No significant effect was found for task management. The increase in information management was related to faster decisions regarding how to respond to the critical event, but only for trainees and not for nurses. CONCLUSIONS: Our findings support the claim that adaptation of coordination activities is related to improved team performance in healthcare. Moreover, adaptation and its relationship to team performance were found to vary with regard to type of coordination activities and team member.

Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma.

BACKGROUND: Indications, efficacy, and safety of plasma products are highly debated. We compared the concentrations of haemostatic proteins and cytokines in solvent/detergent-treated plasma (SDP) and fresh-frozen plasma (FFP). METHODS: Concentrations of the following parameters were measured in 25 SDP and FFP samples: fibrinogen (FBG), factor (F) II, F V, F VII, F VIII, F IX, F X, F XIII, von Willebrand factor (vWF), D-Dimers, ADAMTS-13 protease, tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, and IL-10. RESULTS: Mean FBG concentrations in SDP and FFP were similar, but in FFP, the range was larger than in SDP (P<0.01). Mean F II, F VII, F VIII, F IX, and F XIII levels did not differ significantly. Higher concentrations of F V (P<0.01), F X (P<0.05), vWF (P<0.01), and ADAMTS-13 (P<0.01) were found in FFP. With the exception of F VIII and F IX, the range of concentrations for all of these factors was smaller (P<0.05) in SDP than in FFP. Concentrations of TNF-α, IL-8, and IL-10 (all P<0.01) were higher in FFP than in SDP, again with a higher variability and thus larger ranges (P<0.01). CONCLUSIONS: Coagulation factor content is similar for SDP and FFP, with notable exceptions of less F V, vWF, and ADAMTS-13 in SDP. Cytokine concentrations (TNFα, IL-8, and IL-10) were significantly higher in FFP. The clinical relevance of these findings needs to be established in outcome studies.

High-frequency jet ventilation for minimizing breathing-related liver motion during percutaneous radiofrequency ablation of multiple hepatic tumours.

Movements of the liver caused by spontaneous breathing (during sedation or local anaesthesia) or by ventilation during anaesthesia are a source of concern in CT-guided procedures because of the limited spatial and contrast resolution of unenhanced imaging, artifacts caused by the probes and the relatively low temporal resolution of the fluoroscopy mode. During CT-guided radiofrequency ablation (RFA), it is essential that the lesion can be visualized optimally and that the ablation probe is positioned accurately to avoid non-target injuries. We therefore used high-frequency jet ventilation and general anaesthesia to minimize ventilation-related liver movement and provide optimal conditions for a patient undergoing RFA of hepatic metastases. The technical and anaesthetic considerations are discussed, and a specific limitation of transcutaneous PCO(2) measurement during activation of the ablation is reported for the first time.

The volatile anaesthetic sevoflurane attenuates lipopolysaccharide-induced injury in alveolar macrophages.

Acute lung injury (ALI) is a well-defined inflammation whereby alveolar macrophages play a crucial role as effector cells. As shown previously in numerous experimental approaches, volatile anaesthetics might reduce the degree of injury in pre- or post-conditioning set-ups. Therefore, we were interested to evaluate the effect of the application of the volatile anaesthetic sevoflurane on alveolar macrophages regarding the expression of inflammatory mediators upon lipopolysaccharide (LPS) stimulation in vitro. Alveolar macrophages were stimulated with LPS. Two hours later, cells were exposed additionally to air (control) or to sevoflurane-containing air for 4, 6, 8, 12 or 24 h. Tumour necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage-inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1) proteins were determined and chemotaxis assays were performed. To evaluate possible cellular signalling pathways phosphorylation of the kinases extracellular-regulated kinase (ERK) and Akt was assessed. In the early phase of sevoflurane post-conditioning expression of TNF-alpha, CINC-1, MIP-2 and MCP-1 was attenuated, leading to a diminished chemotaxis reaction for neutrophils. Phosphorylation of ERK seems to be a possible cellular mechanism in the sevoflurane-induced protection in vitro. Pharmacological post-conditioning of alveolar macrophages with sevoflurane immunmodulates the inflammatory response upon stimulation with endotoxin. This might be a possible option for a therapeutical approach in ALI.

Postconditioning with a volatile anaesthetic in alveolar epithelial cells in vitro.

Acute lung injury is a common complication in critically ill patients. The present study examined possible immunomodulating effects of the volatile anaesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro. Sevoflurane was applied after the onset of injury, simulating a "postconditioning" scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4-h co-exposure to a CO(2)/air mixture with sevoflurane 2.2 volume %; control cells were exposed to the CO(2)/air mixture only. Cytokine-induced neutrophil chemoattractant-1, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, as well as the potential protective mediators inducible nitric oxide synthase (iNOS)2 and heat shock protein (HSP)-32, were analysed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed. A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32. The data presented in the current study provide strong evidence that anaesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of acute lung injury.