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.

Pre-operative gastric ultrasound in patients at risk of pulmonary aspiration: a prospective observational cohort study.

Point-of-care gastric sonography offers an objective approach to assessing individual pulmonary aspiration risk before induction of general anaesthesia. We aimed to evaluate the potential impact of routine pre-operative gastric ultrasound on peri-operative management in a cohort of adult patients undergoing elective or emergency surgery at a single centre. According to pre-operative gastric ultrasound results, patients were classified as low risk (empty, gastric fluid volume ≤ 1.5 ml.kg-1 body weight) or high risk (solid, mixed or gastric fluid volume > 1.5 ml.kg-1 body weight) of aspiration. After sonography, examiners were asked to indicate changes in aspiration risk management (none; more conservative; more liberal) to their pre-defined anaesthetic plan and to adapt it if patient safety was at risk. We included 2003 patients, 1246 (62%) of which underwent elective and 757 (38%) emergency surgery. Among patients who underwent elective surgery, 1046/1246 (84%) had a low-risk and 178/1246 (14%) a high-risk stomach, with this being 587/757 (78%) vs. 158/757 (21%) among patients undergoing emergency surgery, respectively. Routine pre-operative gastric sonography enabled changes in anaesthetic management in 379/2003 (19%) of patients, with these being a more liberal approach in 303/2003 (15%). In patients undergoing elective surgery, pre-operative gastric sonography would have allowed a more liberal approach in 170/1246 (14%) and made a more conservative approach indicated in 52/1246 (4%), whereas in patients undergoing emergency surgery, 133/757 (18%) would have been managed more liberally and 24/757 (3%) more conservatively. We showed that pre-operative gastric ultrasound helps to identify high- and low-risk situations in patients at risk of aspiration and adds useful information to peri-operative management. Our data suggest that routine use of pre-operative gastric ultrasound may improve individualised care and potentially impact patient safety.

[Principles of perioperative coagulation management]. / Prinzipien des perioperativen Gerinnungsmanagements.

The coagulation system is a complex network of interacting proteins and cells with extensive sensitivity, amplification and control pathways. The system represents a delicate balance between procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes, e.g. bleeding and thrombosis, occur immediately when this balance is no longer in equilibrium. A correct understanding of the complex coagulation pathophysiology in the perioperative setting is essential for an effective treatment. In a bleeding patient, patient's history, clinical findings, routine and advanced laboratory coagulation testing as well as point-of-care coagulation monitoring help to reliably and readily identify the underlying coagulation disorder. Modern coagulation management is proactive, individualized, balanced and follows clearly defined algorithms. Coagulopathic bleeding can be successfully controlled with specific interventions in the coagulation system.

[Principles of perioperative coagulation management]. / Prinzipien des perioperativen Gerinnungsmanagements.

The coagulation system is a complex network of interacting proteins and cells with extensive sensitivity, amplification and control pathways. The system represents a delicate balance between procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes, e.g. bleeding and thrombosis, occur immediately when this balance is no longer in equilibrium. A correct understanding of the complex coagulation pathophysiology in the perioperative setting is essential for an effective treatment. In a bleeding patient, patient's history, clinical findings, routine and advanced laboratory coagulation testing as well as point-of-care coagulation monitoring help to reliably and readily identify the underlying coagulation disorder. Modern coagulation management is proactive, individualized, balanced and follows clearly defined algorithms. Coagulopathic bleeding can be successfully controlled with specific interventions in the coagulation system.

Thrombelastography in the surgical patient.

Coagulopathy in surgical patients is an important factor in triggering major perioperative complications, i.e., intra- or postoperative bleeding and thrombo-embolic events associated with an increased mortality and morbidity. Different methods exist to assess the coagulation status of patients before, during and after surgery. Routine coagulation tests have long been considered to be the clinical standard. However, these tests have considerable limitations. Information regarding the kinetics of clot formation, clot strength, interaction of the coagulation components, platelet function and fibrinolysis is not available. Moreover, there is an important delay in obtaining test results. In contrast, thrombelastography and thrombelastometry, which both measure the visco-elastic properties of whole blood, allow the dynamic assessment of a developing clot, from fibrin formation to clot strengthening and clot lysis. Both techniques are increasingly being used in daily clinical practice in order to detect perioperative coagulopathy and to guide predominantly pro-coagulant therapy in different settings. This article provides an overview of both techniques, thrombelastography (TEG) and thrombelastometry (ROTEM), and their field of perioperative application considering of recently published data.

Successful rotational thromboelastometry-guided treatment of traumatic haemorrhage, hyperfibrinolysis and coagulopathy.

Transfusion of allogeneic blood products is associated with increased morbidity and mortality. Therefore, strategies for reducing transfusion of these products during trauma management are valuable. We report a case of severe blunt abdominal trauma, successfully treated with antifibrinolytic medication and fibrinogen concentrate. Rotational thromboelastometry (ROTEM) was used to identify hyperfibrinolysis and afibrinogenaemia. In order to achieve haemostasis, over a 3-h period, the patient received a total of 1 g of tranexamic acid, 7 U of packed red blood cells, 16 g of fibrinogen concentrate (Haemocomplettan P), 3500 ml of colloids and 5500 ml of lactated Ringer's solution. Together with surgical measures, this treatment stopped the bleeding and stabilised the patient. There was no transfusion of either fresh-frozen plasma or platelets. The limited need for allogeneic blood products is of particular interest, and clinical studies of the approach used here appear to be warranted.

Hypoxia attenuates effector-target cell interaction in the airway and pulmonary vascular compartment.

Leucocyte infiltration is known to play an important role in hypoxia-induced tissue damage. However, little information is available about hypoxia and interaction of effector (neutrophils) with target cells (alveolar epithelial cells, AEC; rat pulmonary artery endothelial cells, RPAEC). The goal of this study was to elucidate hypoxia-induced changes of effector-target cell interaction. AEC and RPAEC were exposed to 5% oxygen for 2-6 h. Intercellular adhesion molecule-1 (ICAM-1) expression was determined and cell adherence as well as cytotoxicity assays were performed. Nitric oxide and heat shock protein 70 (HSP70) production was assessed in target cells. Under hypoxic conditions enhanced ICAM-1 production was found in both cell types. This resulted in an increase of adherent neutrophils to AEC and RPAEC. The death rate of hypoxia-exposed target cells decreased significantly in comparison to control cells. Nitric oxide (NO) concentration was enhanced, as was production of HSP70 in AEC. Blocking NO production in target cells resulted in increased cytotoxicity in AEC and RPAEC. This study shows for the first time that target cells are more resistant to effector cells under hypoxia, suggesting hypoxia-induced cell protection. An underlying mechanism for this phenomenon might be the protective effect of increased levels of NO in target cells.

Effects of heparin, haemodilution and aprotinin on kaolin-based activated clotting time: in vitro comparison of two different point of care devices.

BACKGROUND: During cardiopulmonary bypass (CPB), measurement of kaolin-based activated clotting time (kACT) is a standard practice in monitoring heparin-induced anticoagulation. Despite the fact that the kACT test from the Sonoclot Analyzer (SkACT) has been commercially available for several years, no published data on the performance of SkACT are available. Thus, the aim of this in vitro study was to compare SkACT with an established kACT from Hemochron (HkACT). METHODS: Blood was withdrawn from 25 patients before elective cardiac surgery. SkACT and HkACT were measured in duplicate after in vitro administration of heparin (0, 1, 2 and 3 U/ml), calcium-free lactated Ringer's solution (25% and 50% haemodilution) and aprotinin (200 kIU/ml). RESULTS: A total of 600 duplicate kACT measurements were obtained from 25 cardiac surgery patients. Overall, mean bias +/- SD between SkACT and HkACT was 7 +/- 70 s (1.3% +/- 14.1%). Administration of heparin, haemodilution and aprotinin induced a comparable effect on both activated clotting time (ACT) tests. Mean bias ranged from -4 +/- 39 s (-1.7% +/- 12.9%) to 4 +/- 78 s (3.2% +/- 15.6%) for heparinzed blood samples after haemodilution or aprotinin application and increased after combined aprotinin administration and haemodilution. After haemodilution and administration of aprotinin, both ACT tests were less reliable for values >480 s in heparinized blood samples. CONCLUSION: Accuracy and performance of SkACT and HkACT were comparable after in vitro administration of heparin, aprotinin and haemodilution. Both ACT tests were considerably affected by aprotinin and haemodilution.

Volumetric assessment of left heart preload by thermodilution: comparing the PiCCO-VoLEF system with transoesophageal echocardiography.

The new Volumetric Ejection Fraction monitoring system (VoLEF), when combined with the Pulse Contour Cardiac Output monitoring system (PiCCO) system, allows measurement of left and right heart end-diastolic volumes by thermodilution. The aim of this study was to evaluate whether the left heart end-diastolic volume index determined by the VoLEF system (LHEDI) better reflects left ventricular end-diastolic area index (LVEDAI) measured by transoesophageal echocardiography than does global end-diastolic volume index (GEDI) measured by the PiCCO system alone. Following induction of anaesthesia, PiCCO, VoLEF and transoesophageal echocardiography measurements were performed before and after a fluid challenge in 20 patients scheduled for elective cardiac surgery. Both left ventricular end-diastolic area index and global end-diastolic volume index, but not left heart end-diastolic volume index, significantly increased after fluid administration. Mean bias +/- 2 SD for DeltaLHEDI-DeltaLVEDAI was -2.2 +/- 32.0% and for DeltaGEDI-DeltaLVEDAI -0.6 +/- 16.8%. In contrast to global end-diastolic volume index, the use of left heart end-diastolic volume index determined by the VoLEF system cannot be recommended as an estimate of left ventricular preload.

[Preoperative fasting times: patients' perspective]. / Präoperative Nüchternzeiten: Sicht der Patienten.

BACKGROUND: In order to improve perioperative subjective quality of care it seems desirable to shorten preoperative fasting times as much as possible within acceptable safety limits. These efforts should result in a measurable reduction of preoperative thirst and hunger as well as in improvements of patient well-being. It is unknown to what extent preoperative patient comfort is limited by thirst and hunger from a patient point of view. The purpose of this study was to determine the impact of a traditional fasting regimen on preoperative patient discomfort. PATIENTS AND METHODS: We conducted a survey on preoperative thirst and hunger in 412 adult American Society of Anesthesiologists ASA I and II patients scheduled for minor elective surgery. RESULTS: Of the patients 33% complained of moderate to strong thirst, whereas 19% had moderate to strong hunger, 47% of the participants would have liked to have been able to drink and 72% would have appreciated a light breakfast before surgery. Mean preoperative fasting times were 12.8+/-3.4 h for fluids and 15.5+/-4.4 h for solids. "Thirst" was named by 3.3% and "hunger" by 0.8% of patients as the most important factor for preoperative discomfort but "long wait" (8.5%), "tenseness" (6.5%) and "anxiety" (4.8%) were the most frequently named factors. Answers were independent of the duration of preoperative fasting. CONCLUSION: Patient comfort is compromised by traditional fasting rules and liberalization of these policies is desired by patients. However, efforts to reduce preoperative anxiety and tenseness might have an additional, important potential to improve perioperative quality of care from a patient's perspective.

Hypoxia aggravates lipopolysaccharide-induced lung injury.

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-alpha and macrophage inflammatory protein-1beta, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.

[Patients' needs and expectations regarding anaesthesia. A survey on the pre-anaesthetic visit of patients and anaesthesiologists]. / Welche Bedürfnisse und Erwartungen haben Patienten an die Anästhesie? Eine Umfrage bei Patienten und Anästhesisten zur Prämedikationsvisite.

BACKGROUND: This prospective survey aimed at elucidating the patients' expectations and needs regarding the pre-anaesthetic visit and the forthcoming anaesthesia. The same questionnaire was answered by both patients and anaesthesiologists. METHODS: A total of 200 ASA I-III patients were interviewed prior to the preoperative anaesthetic visit. The questionnaire consisted of the topics preoperative affective situation, information and self-estimation of anaesthesia knowledge, expectations regarding the pre-anaesthetic visit/anaesthesia and extent of information concerning the perioperative course including risk and possible complications. The same questionnaire was presented to 35 certified anaesthesiologists with the request to estimate the patients' answers. Answers were rated using a Likert-scale, a comparison of patients' and anaesthesiologists' replies was performed. RESULTS: For all 5 topics considerable differences between patients' answers and anaesthesiologists' rating were found (e.g. for the assessment of the affective situation, the relevance of family physicians as information source, the desired anaesthetic technique or the extent of anaesthesia-related risk information). No differences were observed for the importance of an anaesthesiologist as information source and fear reduction by the pre-anaesthetic visit. CONCLUSIONS: Anaesthesiologists tend to misinterpret many patients' expectations and attitudes. The results demonstrate the potential for quality improvement of the pre-anaesthetic visit.