A protocol based on hypotension probability indicator vs. standard care to prevent intraoperative hypotension during supratentorial brain surgery: a prospective randomized pilot trial.

BACKGROUND: To test the hypothesis that Hypotension probability indicator (HPI) driven hemodynamic protocol use may decrease the exposition to hypotension (mean arterial pressure below 65 mmHg) during supratentorial intracranial procedures. METHODS: Patients undergoing supratentorial tumor resection under general anesthesia (ASA 1-3) were included into this randomized single center-controlled pilot trial. Patients in the control group (COV, N.=20) were managed based on the institutional standard to avoid hypotension. Patients in the intervention (INT, N.=20) group were managed using a protocol triggered by the HPI above 85 based on the stroke volume variation, dynamic elastance, and cardiac index parameters. The number of patients experiencing hypotension (mean arterial pressure below 65 mmHg) during the whole procedure and anesthesia maintenance phase was the primary outcome variable. The number of hypotensive periods, time spent in hypotension, and hypotension dose served as secondary outcome variables. Other clinically relevant parameters and postsurgical outcomes were screened. RESULTS: The number of patients who never experienced hypotension was significantly lower in the INT group during the anesthesia maintenance phase (10 (50%) vs. 16 (80%); P=0.049). In several other hemodynamic outcomes, a distinct numerical, but statistically non-significant trend towards lower hypotension exposition was observed. There were no significant differences in clinically relevant parameters. CONCLUSIONS: In this pilot trial, the HPI-based protocol decreased the incidence of hypotension during the anesthesia maintenance but non-significant trends among secondary outcomes were also documented. Larger trials are needed to confirm our findings.

Individualizing Fluid Management in Patients with Acute Respiratory Distress Syndrome and with Reduced Lung Tissue Due to Surgery-A Narrative Review.

Fluids are the cornerstone of therapy in all critically ill patients. During the last decades, we have made many steps to get fluid therapy personalized and based on individual needs. In patients with lung involvement-acute respiratory distress syndrome-finding the right amount of fluids after lung surgery may be extremely important because lung tissue is one of the most vulnerable to fluid accumulation. In the current narrative review, we focus on the actual perspectives of fluid therapy with the aim of showing the possibilities to tailor the treatment to a patient's individual needs using fluid responsiveness parameters and other therapeutic modalities.

SepsEast Registry indicates high mortality associated with COVID-19 caused acute respiratory failure in Central-Eastern European intensive care units.

The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.

Effect of dexamethasone in patients with ARDS and COVID-19 (REMED trial)-study protocol for a prospective, multi-centre, open-label, parallel-group, randomized controlled trial.

BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.

Effect of dexamethasone in patients with ARDS and COVID-19 - prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Concrete and cement composites used for radioactive waste deposition.

This review article presents the current state-of-knowledge of the use of cementitious materials for radioactive waste disposal. An overview of radwaste management processes with respect to the classification of the waste type is given. The application of cementitious materials for waste disposal is divided into two main lines: i) as a matrix for direct immobilization of treated waste form; and ii) as an engineered barrier of secondary protection in the form of concrete or grout. In the first part the immobilization mechanisms of the waste by cement hydration products is briefly described and an up-to date knowledge about the performance of different cementitious materials is given, including both traditional cements and alternative binder systems. The advantages, disadvantages as well as gaps in the base of information in relation to individual materials are stated. The following part of the article is aimed at description of multi-barrier systems for intermediate level waste repositories. It provides examples of proposed concepts by countries with advanced waste management programmes. In the paper summary, the good knowledge of the material durability due to its vast experience from civil engineering is highlighted however with the urge for specific approach during design and construction of a repository in terms of stringent safety requirements.

Comparison of absolute fluid restriction versus relative volume redistribution strategy in low central venous pressure anesthesia in liver resection surgery: a randomized controlled trial.

BACKGROUNDː Lowering central venous pressure (CVP) can decrease blood loss during liver resection and it is associated with improved outcomes. Multiple CVP reducing maneuvers have been described, but direct comparison of their effectiveness and safety has never been performed. METHODSː Patients undergoing resections of two or more liver segments were equally randomized to absolute fluid restriction (AR, N.=17) or relative volume redistribution group (RR, N.=17). The ease of reaching low CVP, blood loss, morbidity and mortality were assessed. Besides, the effect of Pringle maneuver and utility of stroke volume variation (SVV) were analyzed. RESULTSː Both methods of CVP reduction were equally effective (0.7±0.9 vs. 0.9±1.0 protocolized steps in the AR and RR group; P=0.356) and safe (no difference in observed blood loss, intraoperative hemodynamic parameters, lactate levels, morbidity and mortality). Patients in the AR group received smaller amount of fluids in the pre-resection period (120 (100-150) vs. 600 (500-700) mL; P<0.001), and had slightly longer hospital stay (10 [8-14] vs. 8 [7-11]; P=0.045). Low CVP was predicted by SVV>10% with 81.4% sensitivity and 77.1% specificity. Reduced blood loss and transfusion rate was observed when Pringle maneuver was used. CONCLUSIONSː In our study, absolute fluid restriction and relative volume redistribution seemed to be equally effective and safe methods of lowering CVP in patients undergoing liver resection. According to our data high SVV might be considered as a low CVP replacement. Pringle maneuver reduced blood loss and transfusion requirement.

Comparison of the accuracy of hemoglobin point of care testing using HemoCue and GEM Premier 3000 with automated hematology analyzer in emergency room.

The laboratory analysis provides accurate, but time consuming hemoglobin level estimation especially in the emergency setting. The reliability of time-sparing point of care devices (POCT) remains uncertain. We tested two POCT devices accuracy (HemoCue®201+ and Gem®Premier™3000) in routine emergency department workflow. Blood samples taken from patients admitted to the emergency department were analyzed for hemoglobin concentration using a laboratory reference Beckman Coulter LH 750 (HBLAB), the HemoCue (HBHC) and the Gem Premier 3000 (HBGEM). Pairwise comparison for each device and HbLAB was performed using correlation and the Bland-Altman methods. The reliability of transfusion decision was assessed using three-zone error grid. A total of 292 measurements were performed in 99 patients. Mean hemoglobin level were 115 ± 33, 110 ± 28 and 111 ± 30 g/l for HbHC, HbGEM and HbLAB respectively. A significant correlation was observed for both devices: HbHC versus HbLAB (r2 = 0.93, p < 0.001) and HBGEM versus HBLAB (r2 = 0.86, p < 0.001). The Bland-Altman method revealed bias of -3.7 g/l (limits of agreement -20.9 to 13.5) for HBHC and HBLAB and 2.5 g/l (-18.6 to 23.5) for HBGEM and HBLAB, which significantly differed between POCT devices (p < 0.001). Using the error grid methodology: 94 or 91 % of values (HbHC and HbGEM) fell in the zone of acceptable difference (A), whereas 0 and 1 % (HbHC and HbGEM) were unacceptable (zone C). The absolute accuracy of tested POCT devices was low though reaching a high level of correlation with laboratory measurement. The results of the Morey´s error grid were unfavorable for both POCT devices.

Viscoelastic Methods of Blood Clotting Assessment - A Multidisciplinary Review.

Viscoelastic methods (VEM) made available the bedside assessment of blood clotting. Unlike standard laboratory tests, the results are based on the whole blood coagulation and are available in real time at a much faster turnaround time. In combination with our new knowledge about pathophysiology of the trauma-induced coagulopathy, the goal-oriented treatment protocols have been recently proposed for the initial management of bleeding in trauma victims. Additionally, the utility of viscoelastic monitoring devices has been proved even outside this setting in cardiosurgical patients or those undergoing liver transplantation. Many other situations were described in literature showing the potential use of bedside analysis of coagulation for the management of bleeding or critically ill patients. In the near future, we may expect further improvement in current bedside diagnostic tools enabling not only the assessment of secondary hemostasis but also the platelet aggregation. More sensitive assays for new anticoagulants are underway. Aim of this review is to offer the reader a multidisciplinary overview of VEM and their potential use in anesthesiology and critical care.

Fluid management guided by a continuous non-invasive arterial pressure device is associated with decreased postoperative morbidity after total knee and hip replacement.

BACKGROUND: The use of goal directed fluid protocols in intermediate risk patients undergoing hip or knee replacement was studied in few trials using invasive monitoring. For this reason we have implemented two different fluid management protocols, both based on a novel totally non-invasive arterial pressure monitoring device and compared them to the standard (no-protocol) treatment applied before the transition in our academic institution. METHODS: Three treatment groups were compared in this prospective study: the observational (CONTROL, N = 40) group before adoption of fluid protocols and two randomized groups after the transition to protocol fluid management with the use of the continuous non-invasive blood pressure monitoring (CNAP®) device. In the PRESSURE group (N = 40) standard variables were used for restrictive fluid therapy. Goal directed fluid therapy using pulse pressure variation was used in the GDFT arm (N = 40). The influence on the rate of postoperative complications, on the hospital length of stay and other parameters was assessed. RESULTS: Both protocols were associated with decreased fluid administration and maintained hemodynamic stability. Reduced rate of postoperative infection and organ complications (22 (55 %) vs. 33 (83 %) patients; p = 0.016; relative risk 0.67 (0.49-0.91)) was observed in the GDFT group compared to CONTROL. Lower number of patients receiving transfusion (4 (10 %) in GDFT vs. 17 (43 %) in CONTROL; p = 0.005) might contribute to this observation. No significant differences were observed in other end-points. CONCLUSION: In our study, the use of the fluid protocol based on pulse pressure variation assessed using continuous non-invasive arterial pressure measurement seems to be associated with a reduction in postoperative complications and transfusion needs as compared to standard no-protocol treatment. TRIAL REGISTRATION: ACTRN12612001014842.

Continuous non-invasive monitoring improves blood pressure stability in upright position: randomized controlled trial.

Intermittent blood pressure (BP) monitoring is the standard-of-care during low and intermediate risk anaesthesia, yet it could lead to delayed recognition of BP fluctuations. Perioperative hypotension is known to be associated with postoperative complications. Continuous, non-invasive methods for BP monitoring have been developed recently. We have tested a novel non-invasive, continuous monitor (using the volume clamp method) to assist with maintaining BP in safe ranges for patients undergoing surgery in a beach chair position. Forty adult patients undergoing thyroid gland surgery in an upright position were included in this prospective randomised controlled trial. Patients were equally allocated to the group with continuous monitoring of BP using the CNAP® Monitor and to the control group managed using an intermittent oscillometric BP cuff. The absolute and proportional time spent outside the range of ±20% of the target BP along with other hemodynamic and clinical parameters were evaluated. The continuous monitoring decreased the anaesthesia time spent below -20% pressure range [absolute: 12 min (4-20) vs. 27 min (16-34); p=0.001; relative to procedure length: 14% (7-20) vs. 33.5% (17.5-53); p=0.003]. No significant differences were observed in postoperative morbidity or in hospital length of stay. Continuous non-invasive BP monitoring via the CNAP® Monitor allows for better BP management in patients undergoing surgery in a beach chair position. In our randomised trial the time spent in hypotension was significantly shorter using continuous monitoring.

Cost analysis of the stroke volume variation guided perioperative hemodynamic optimization - an economic evaluation of the SVVOPT trial results.

BACKGROUND: Perioperative goal directed therapy (GDT) can substantially improve the outcomes of high risk surgical patients as shown by many clinical studies. However, the approach needs initial investment and can increase the already very high staff workload. These economic imperatives may be at least partly responsible for weak adherence to the GDT concept. A few models are available for the evaluation of GDT cost-effectiveness, but studies of real economic data based on a recent clinical trial are lacking. In order to address this we have performed a retrospective analysis of the data from the "Intraoperative fluid optimization using stroke volume variation in high risk surgical patients" trial (ISRCTN95085011). METHODS: The health-care payers perspective was used in order to evaluate the perioperative hemodynamic optimization costs. Hospital invoices from all patients included in the trial were extracted. A direct comparison between the study (GDT, N = 60) and control (N = 60) groups was performed. A cost tree was constructed and major cost drivers evaluated. RESULTS: The trial showed a significant improvement in clinical outcomes for GDT treated patients. The mean cost per patient were lower in the GDT group 2877 ± 2336€ vs. 3371 ± 3238€ in controls, but without reaching a statistical significance (p = 0.596). The mean cost of all items except for intraoperative monitoring and infusions were lower for GDT than control but due to the high variability they all failed to reach statistical significance. Those costs associated with clinical care (68 ± 177€ vs. 212 ± 593€; p = 0.023) and ward stay costs (213 ± 108€ vs. 349 ± 467€; p = 0.082) were the most important differences in favour of the GDT group. CONCLUSIONS: Intraoperative fluid optimization with the use of stroke volume variation and Vigileo/FloTrac system showed not only a substantial improvement of morbidity, but was associated with an economic benefit. The cost-savings observed in the overall costs of postoperative care trend to offset the investment needed to run the GDT strategy and intraoperative monitoring. TRIAL REGISTRATION: ISRCTN95085011.

Respiratory induced dynamic variations of stroke volume and its surrogates as predictors of fluid responsiveness: applicability in the early stages of specific critical states.

Respiratory induced dynamic variations of stroke volume and its surrogates are very sensitive and specific predictors of fluid responsiveness, but their use as targets for volume management can be limited. In a recent study, limiting factors were present in 53 % of surgical patients with inserted arterial line. In the intensive care unit (ICU) population the frequency is presumably higher, but the real prevalence is unknown. Our goal was to study the feasibility of dynamic variations guided initial volume resuscitation in specific critical states. We have performed a 5 year retrospective evaluation of patients admitted with diagnosis sepsis, polytrauma, after high risk surgery or cardiac arrest. Occurrence of major (sedation, mandatory ventilation and tidal volume, open chest and arrhythmias) and minor limiting factors (PEEP level, use of vasopressors and presence of arterial catheter) was screened within the first 24 h after admission. In the study period 1296 patients were hospitalized in our ICU with severe sepsis (n = 242), polytrauma (n = 561), after high risk surgery (n = 351) or cardiac arrest (n = 141). From these patients 549 (42.4 %) fulfilled all major criteria for applicability of dynamic variations. In our evaluation only limited number of patients admitted for polytrauma (51 %), sepsis (37 %), after cardiac arrest (39 %) or surgical procedure (33 %) fulfil all the major criteria for use of dynamic variations at the ICU admission. The prevalence was similar in patients with shock. Occurrence of minor factors can pose further bias in evaluation of these patients. General use of dynamic variations guided protocols for initial resuscitations seems not universally applicable.