The Impact of Mechanical Energy Assessment on Mechanical Ventilation: A Comprehensive Review and Practical Application.

Mechanical ventilation (MV) provides basic organ support for patients who have acute hypoxemic respiratory failure, with acute respiratory distress syndrome as the most severe form. The use of excessive ventilation forces can exacerbate the lung condition and lead to ventilator-induced lung injury (VILI); mechanical energy (ME) or power can characterize such forces applied during MV. The ME metric combines all MV parameters affecting the respiratory system (ie, lungs, chest, and airways) into a single value. Besides evaluating the overall ME, this parameter can be also related to patient-specific characteristics, such as lung compliance or patient weight, which can further improve the value of ME for characterizing the aggressiveness of lung ventilation. High ME is associated with poor outcomes and could be used as a prognostic parameter and indicator of the risk of VILI. ME is rarely determined in everyday practice because the calculations are complicated and based on multiple equations. Although low ME does not conclusively prevent the possibility of VILI (eg, due to the lung inhomogeneity and preexisting damage), individualization of MV settings considering ME appears to improve outcomes. This article aims to review the roles of bedside assessment of mechanical power, its relevance in mechanical ventilation, and its associations with treatment outcomes. In addition, we discuss methods for ME determination, aiming to propose the most suitable method for bedside application of the ME concept in everyday practice.

Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

Anticoagulation Management during Extracorporeal Membrane Oxygenation-A Mini-Review.

Extracorporeal membrane oxygenation (ECMO) has been established as a life-saving technique for patients with the most severe forms of respiratory or cardiac failure. It can, however, be associated with severe complications. Anticoagulation therapy is required to prevent ECMO circuit thrombosis. It is, however, associated with an increased risk of hemocoagulation disorders. Thus, safe anticoagulation is a cornerstone of ECMO therapy. The most frequently used anticoagulant is unfractionated heparin, which can, however, cause significant adverse effects. Novel drugs (e.g., argatroban and bivalirudin) may be superior to heparin in the better predictability of their effects, functioning independently of antithrombin, inhibiting thrombin bound to fibrin, and eliminating heparin-induced thrombocytopenia. It is also necessary to keep in mind that hemocoagulation tests are not specific, and their results, used for setting up the dosage, can be biased by many factors. The knowledge of the advantages and disadvantages of particular drugs, limitations of particular tests, and individualization are cornerstones of prevention against critical events, such as life-threatening bleeding or acute oxygenator failure followed by life-threatening hypoxemia and hemodynamic deterioration. This paper describes the effects of anticoagulant drugs used in ECMO and their monitoring, highlighting specific conditions and factors that might influence coagulation and anticoagulation measurements.

Extracorporeal membrane oxygenation survival: External validation of current predictive scoring systems focusing on influenza A etiology.

Despite increasing clinical experience with extracorporeal membrane oxygenation (ECMO), its optimal indications remain unclear. Here, we externally evaluated all currently available ECMO survival-predicting scoring systems and the APACHE II score in subjects undergoing veno-venous ECMO (VV ECMO) support due to acute respiratory distress syndrome (ARDS) with influenza (IVA) and non-influenza (n-IVA) etiologies. Our aim was to find the best scoring system for influenza A ARDS ECMO success prediction. Retrospective data were analyzed to assess the abilities of the PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores to predict patient outcome. Patients treated with veno-venous ECMO support for ARDS were divided into two groups: IVA and n-IVA etiologies. Parameters collected within 24 hours before ECMO initiation were used to calculate PRESERVE, RESP, PRESET, ECMOnet, Roch, and APACHE II scores. Compared to the IVA group, the n-IVA group exhibited significantly higher ICU, 28-day, and 6-month mortality (P = .043, .034, and .047, respectively). Regarding ECMO support success predictions, the area under the receiver operating characteristic curve (AUC) was 0.62 for PRESERVE, 0.44 for RESP, 0.57 for PRESET, and 0.67 for ECMOnet, and 0.62 for Roch calculated for all subjects according to the original papers. In the IVA group, APACHE II had the best predictive value for ICU, hospital, 28-day, and 6-month mortality (AUC values of 0.73, 0.73, 0.70, and 0.73, respectively). In the n-IVA group, APACHE II was the best predictor of survival in the ICU and hospital (AUC 0.54 and 0.57, respectively). From all possible ECMO survival scoring systems, the APACHE II score had the best predictive value for VV ECMO subjects with ARDS caused by influenza A-related pneumonia with a cut-off value of about 32 points.

Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017.

IMPORTANCE: Infection is frequent among patients in the intensive care unit (ICU). Contemporary information about the types of infections, causative pathogens, and outcomes can aid the development of policies for prevention, diagnosis, treatment, and resource allocation and may assist in the design of interventional studies. OBJECTIVE: To provide information about the prevalence and outcomes of infection and the available resources in ICUs worldwide. DESIGN, SETTING, AND PARTICIPANTS: Observational 24-hour point prevalence study with longitudinal follow-up at 1150 centers in 88 countries. All adult patients (aged ≥18 years) treated at a participating ICU during a 24-hour period commencing at 08:00 on September 13, 2017, were included. The final follow-up date was November 13, 2017. EXPOSURES: Infection diagnosis and receipt of antibiotics. MAIN OUTCOMES AND MEASURES: Prevalence of infection and antibiotic exposure (cross-sectional design) and all-cause in-hospital mortality (longitudinal design). RESULTS: Among 15 202 included patients (mean age, 61.1 years [SD, 17.3 years]; 9181 were men [60.4%]), infection data were available for 15 165 (99.8%); 8135 (54%) had suspected or proven infection, including 1760 (22%) with ICU-acquired infection. A total of 10 640 patients (70%) received at least 1 antibiotic. The proportion of patients with suspected or proven infection ranged from 43% (141/328) in Australasia to 60% (1892/3150) in Asia and the Middle East. Among the 8135 patients with suspected or proven infection, 5259 (65%) had at least 1 positive microbiological culture; gram-negative microorganisms were identified in 67% of these patients (n = 3540), gram-positive microorganisms in 37% (n = 1946), and fungal microorganisms in 16% (n = 864). The in-hospital mortality rate was 30% (2404/7936) in patients with suspected or proven infection. In a multilevel analysis, ICU-acquired infection was independently associated with higher risk of mortality compared with community-acquired infection (odds ratio [OR], 1.32 [95% CI, 1.10-1.60]; P = .003). Among antibiotic-resistant microorganisms, infection with vancomycin-resistant Enterococcus (OR, 2.41 [95% CI, 1.43-4.06]; P = .001), Klebsiella resistant to ß-lactam antibiotics, including third-generation cephalosporins and carbapenems (OR, 1.29 [95% CI, 1.02-1.63]; P = .03), or carbapenem-resistant Acinetobacter species (OR, 1.40 [95% CI, 1.08-1.81]; P = .01) was independently associated with a higher risk of death vs infection with another microorganism. CONCLUSIONS AND RELEVANCE: In a worldwide sample of patients admitted to ICUs in September 2017, the prevalence of suspected or proven infection was high, with a substantial risk of in-hospital mortality.

Hypoxemia/hypoxia and new concepts of oxygen therapy in intensive care.

Oxygen is biologically vital element sustaining life. The tissue oxygen delivery is therefore precisely regulated. The degree of tissue oxygenation is estimated by measurement of oxygen blood level. The lack of oxygen on cellular and tissue level can lead to organ failure and life-threatening condition. Important adaptive processes are activated during the sublethal hypoxia with goal to preserve cellular and tissue functions. Inadequate effort to correct hypoxia can cause either disturbance of the adaptation or undesirable tissue hyperoxia. This fact is taken into account in two currently proposed concepts: (1) precise control of arterial oxemia and (2) permissive hypoxemia. Recent literature supports rather restrictive strategy of oxygen therapy in critical care.

Calprotectin and Calgranulin C as Biomarkers of Pancreatic Tumors: Baseline Levels and Level Changes after Surgery.

Pancreatic tumors and their surgical resection are associated with significant morbidity and mortality, and the biomarkers currently used for these conditions have limited sensitivity and specificity. Because calprotectin and calgranulin C serum levels have been demonstrated to be potential biomarkers of certain cancers and complications of major surgery, the levels of both proteins were tested in the current study in patients with benign and malignant pancreatic tumors that were surgically removed. The baseline serum levels and kinetics of calprotectin and calgranulin C during the 7-day postoperative period were evaluated with immunoassays in 98 adult patients who underwent pancreatic surgery. The baseline serum levels of calprotectin and calgranulin C in patients with malignant (n = 84) and benign tumors (n = 14) were significantly higher (p < 0.01) when compared to those in the healthy controls (n = 26). The serum levels of both proteins were also significantly (p < 0.05) higher in patients with benign tumors than in those with malignant tumors. After surgery, the serum levels of calprotectin and calgranulin C were significantly (p < 0.01) higher than their baseline values, and this elevation persisted throughout the seven days of the follow-up period. Interestingly, starting on day 1 of the postoperative period, the serum levels of both proteins were significantly (p < 0.05) higher in the 37 patients who developed postoperative pancreatic fistulas (POPFs) than in the patients who had uneventful recoveries (n = 61). Moreover, the serum levels of calprotectin and calgranulin C demonstrated a significant predictive value for the development of POPF; the predictive values of these two proteins were better than those of the serum level of C-reactive protein and the white blood cell count. Taken together, the results of this study suggest that calprotectin and calgranulin C serum levels are potential biomarkers for pancreatic tumors, surgical injury to the pancreatic tissue and the development of POPFs.

Anorectal dysfunction after laparoscopic low anterior rectal resection for rectal cancer with and without radiotherapy (manometry study).

BACKGROUND AND OBJECTIVES: The aim was to evaluate the impact of radiotherapy (RT) on anorectal function of patients with low rectal cancer undergoing low anterior resection (LAR). METHODS: Prospective clinical cohort study conducted to assess the functional outcome by means of high-resolution anorectal manometry and LARS score. RESULTS: In total, 65 patients were enrolled in the study (27 patients underwent LAR without RT, 38 patients underwent RT and LAR). There were no statistically significant differences between study subgroups regarding demographic and clinical data; postoperative morbidity was significantly higher in irradiated patients. One year after the surgery, mean LARS score was significantly higher in patients who underwent RT and surgery. Major LARS was detected in 37.0% of irradiated patients and in 14.8% of patients after surgery alone. Anorectal manometry revealed significantly lower resting pressures in patients after RT and LAR; the squeeze pressures were similar. Rectal compliance and all volumes describing rectal sensitivity (first sensation, urge to defecate, and discomfort volume) were significantly lower in irradiated patients. CONCLUSIONS: RT significantly deteriorates the functional outcome of patients after LAR. Manometry revealed internal sphincter dysfunction, reduced capacity, and compliance of neorectum, which seem to have a significant correlation with LARS presence/seriousness.

Selected Biomarkers Correlate with the Origin and Severity of Sepsis.

The microbial etiology and source of sepsis influence the inflammatory response. Therefore, the plasma levels of cytokines (IL-6, IL-8, and IL-10), chemokines (CCL2/MCP-1, MIP-1ß), heparin-binding protein (HBP), soluble CD14 (sCD14), and cortisol were analyzed in blood from septic patients obtained during the first 96 hours of intensive care unit hospitalization. The etiology was established in 56 out of a total of 62 patients enrolled in the study. Plasma concentrations of MCP-1, sCD14, IL-6, and IL-10 were significantly higher in patients with community-acquired pneumonia (CAP; n = 10) and infective endocarditis (IE; n = 11) compared to those with bacterial meningitis (BM; n = 18). Next, cortisol levels were higher in IE patients than in those with BM and CAP, and at one time point, cortisol was also higher in patients with gram-negative sepsis when compared to those with gram-positive infections. Furthermore, cortisol and MCP-1 levels correlated positively with the daily measured SOFA score. In addition, HBP levels were significantly higher in patients with IE than in those with BM. Our findings suggest that MCP-1, sCD14, IL-6, IL-10, cortisol, and HBP are modulated by the source of sepsis and that elevated MCP-1 and cortisol plasma levels are associated with sepsis-induced organ dysfunction.

Exogenous surfactant as a bridge to prolonged "total lung rest" in severely injured patient during extracorporeal membrane oxygenation.

We report a case of a 20-year-old male patient suffering from motorcycle accident complicated by rapid development of severe refractory hypoxemia and hypercapnia due to serious bilateral lung contusions and lacerations. Positive pressure mechanical ventilation induced pressure-dependent massive air leak from disrupted pulmonary tissue. Simultaneous implementation of veno-venous extracorporeal membrane oxygenation together with surfactant application allowed prolonged disconnection of patient from mechanical ventilation ("total lung rest" mode). Despite considerable areas of nonaerated tissue on computed tomography prior to the disconnection from mechanical ventilation, almost total functional recovery of lungs was eventually achieved.

Hypotension after induction of general anesthesia: occurrence, risk factors, and therapy. A prospective multicentre observational study.

BACKGROUND: Hypotension after induction of general anesthesia (GAIH) is common in anesthesiology practice and can impact outcomes. METHODS: In this prospective multicenter, cross-sectional, observational study, the hypotension was defined as a decrease in mean arterial pressure of > 30% compared to the first measurement in the operation theatre before general anesthesia (GA) induction. Blood pressure was measured immediately at the time of endotracheal intubation (TETI), at five (T5) and 10 (T10) minutes after. All subjects aged > 18 years undergoing elective non-cardiac surgery under GA were included. The goals were description of GAIH occurrence, the association of GAIH with selected comorbidities, chronic medications, and anesthetics with GAIH, and the type and efficacy of interventions used to correct hypotension. RESULTS: Data from 661 subjects, whose GA was induced with propofol and sufentanil, were analyzed. In 36.5% of subjects, GAIH was observed at ≥ 1 of the assessed time points. GAIH was present in 2.9% subjects at all time points. The probability of GAIH is raising with age, degree of hypertension at time of arrival to theatre and presence of diabetes. The type of volatile anesthetic was not associated with the occurrence of GAIH. The overall efficiency of interventions to correct hypotension was 94.4%. Bolus fluids were the most often used intervention and was 96.4% effective. CONCLUSION: GAIH rate depends on age, degree of blood pressure decompensation prior the surgery, and presence of diabetes mellitus type II.

Tissue ischemia microdialysis assessments following severe traumatic haemorrhagic shock: lactate/pyruvate ratio as a new resuscitation end point?

BACKGROUND: Intensive care of severe trauma patients focuses on the treatment of haemorrhagic shock. Tissues should be perfused sufficiently with blood and with sufficient oxygen content to ensure adequate tissue oxygen delivery. Tissue metabolism can be monitored by microdialysis, and the lactate/pyruvate ratio (LPR) may be used as a tissue ischemia marker. The aim of this study was to determine the adequate cardiac output and haemoglobin levels that avoid tissue ischemia. METHODS: Adult patients with serious traumatic haemorrhagic shock were enrolled in this prospective observational study. The primary observed parameters included haemoglobin, cardiac output, central venous saturation, arterial lactate and the tissue lactate/pyruvate ratio. RESULTS: Forty-eight patients were analysed. The average age of the patients was 39.8 ± 16.7, and the average ISS was 43.4 ± 12.2. Hb < 70 g/l was associated with pathologic arterial lactate, ScvO2 and LPR. Tissue ischemia (i.e., LPR over 25) developed when CI ≤ 3.2 l/min/m(2) and Hb between 70 and 90 g/l were observed. Severe tissue ischemia events were recorded when the Hb dropped below 70 g/l and CI was 3.2-4.8 l/min/m(2). CI ≥ 4.8 l/min/m(2) was not found to be connected with tissue ischemia, even when Hb ≤ 70 g/l. CONCLUSION: LPR could be a useful marker to manage traumatic haemorrhagic shock therapies. In initial traumatic haemorrhagic shock treatments, it may be better to maintain CI ≥ 3.2 l/min/m(2) and Hb ≥ 70 g/l to avoid tissue ischemia. LPR could also be a useful transfusion trigger when it may demonstrate ischemia onset due to low local DO2 and early reveal low/no tissue perfusion.

[Is obesity an adverse prognostic factor for pulmonary manifestations of influenza? Lesson from complicated disease course H1N1]. / Je závazná obezita nepríznivým prognostickým faktorem u chripkového zánetu plic? Poucení z komplikujícího prubehu onemocnení H1N1.

Influenza viruses cause annual epidemics that occur at different times in both the northern and southern hemisphere. In cases of seasonal influenza these are usually mild forms of the disease, which rarely lead to death of the patient. Vulnerable groups include the elderly, the young or those with comorbidities, where the virus affects tens of thousands of victims around the world. Occasionally, however, large epidemics appear caused by a dangerous variant of a new virus, which is usually characterized by high contagiousness and pathogenicity (virulence). Consequently, it is often accompanied by a complicated disease course and associated with high mortality. In 2009, a viral pandemic disease marked pH1N1 2009 Influenza A appeared. Even though the initial predictions were far worse, the course of influenza caused by this virus was often complicated by acute respiratory failure in the form of acute respiratory distress syndrome (ARDS). This formed part of the wider multiple organ failure syndrome (MODS). This type of virus often infects younger age groups and is more contagious compared to the seasonal flu. In order to illustrate the complicated forms of viral infections pH1N1 2009 Influenza A we present three case studies which demonstrate complicated pulmonary manifestation, which take the primary form of ARDS.

Long-Term Outcomes of Extracorporeal Life Support in Respiratory Failure.

Although extracorporeal life support is an expensive method with serious risks of complications, it is nowadays a well-established and generally accepted method of organ support. In patients with severe respiratory failure, when conventional mechanical ventilation cannot ensure adequate blood gas exchange, veno-venous extracorporeal membrane oxygenation (ECMO) is the method of choice. An improvement in oxygenation or normalization of acid-base balance by itself does not necessarily mean an improvement in the outcome but allows us to prevent potential negative effects of mechanical ventilation, which can be considered a crucial part of complex care leading potentially to an improvement in the outcome. The disconnection from ECMO or discharge from the intensive care unit should not be viewed as the main goal, and the long-term outcome of the ECMO-surviving patients should also be considered. Approximately three-quarters of patients survive the veno-venous ECMO, but various (both physical and psychological) health problems may persist. Despite these, a large proportion of these patients are eventually able to return to everyday life with relatively little limitation of respiratory function. In this review, we summarize the available knowledge on long-term mortality and quality of life of ECMO patients with respiratory failure.

Methylene blue: a controversial diagnostic acid and medication?

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.

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.

Elevated jugular venous oxygen saturation after cardiac arrest.

BACKGROUND: We performed a retrospective analysis of our earlier study on cerebral oxygenation monitoring by jugular venous oximetry (SjvO2) in patients of out-of-hospital cardiac arrest (OHCA). The study was focused on high SjvO2 values (≥75%) and their association with neurological outcomes and serum neuron-specific enolase (NSE) concentration. METHOD: Forty OHCA patients were divided into (i) high (Group I), (ii) normal (Group II), and (iii) low (Group III) SjvO2, with the mean SjvO2 ≥ 75%, 55-74% and <55% respectively. The neurological outcome was evaluated using the Cerebral Performance Category scale (CPC) on the 90th day after cardiac arrest (post-CA). NSE concentration was determined after ICU admission and then at 24, 48, and 72 hours (h) post-CA. RESULTS: High mean SjvO2 occurred in 67% of patients, while no patients had low mean SjvO2. The unfavourable outcome was significantly more common in Group I than Group II (74% versus 23%, p < 0.01). Group I patients had significantly higher median NSE than Group II at 48 and 72 h post-CA. A positive correlation was found between SjvO2 and PaCO2. Each 1 kPa increase in CO2 led to an increase of SjvO2 by 2.2 %+/-0.66 (p < 0.01) in group I and by 5.7%+/-1.36 (p < 0.0001) in group II. There was no correlation between SjvO2 and MAP or SjvO2 and PaO2. CONCLUSION: High mean SjvO2 are often associated with unfavourable outcomes and high NSE at 48 and 72 hours post-CA. Not only low but also high SjvO2 values may require therapeutic intervention.

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.

Patient-controlled epidural analgesia versus conventional epidural analgesia after total hip replacement - a randomized trial.

AIMS: Patient-controlled analgesia (PCA) is usually considered a better option for pain management compared to conventional analgesia. The beneficial effect of PCA has been assessed in a number of studies; however, the results are inconsistent. The goal of this study was to compare of patient-controlled epidural analgesia (PCEA) to conventional epidural analgesia after total hip replacement (THR). METHODS: This prospective study was performed at the Department of Anesthesia and Intensive Care Medicine at a tertiary university hospital. After THR, patients were admitted to the intensive care unit (ICU) and randomized to one of two groups (PCEA and non-PCEA). Postoperative pain in the PCEA group was treated using a standardized protocol, while the analgesia in the non-PCEA group was based on physician prescription according to the patient's clinical condition. The total consumption of analgesics, patients' satisfaction, pain intensity, and analgesia-related complications were recorded for 24 h after surgery. RESULTS: The final sample consisted of 111 patients (PCEA group, n=55 and non-PCEA group, n=56). The PCEA group had significantly lower total consumption of analgesic mixtures (0.9±0.3 and 1.3±0.4 mL/kg per day, P<0.001).There was greater patient satisfaction (P<0.001) in the PCEA group. The mean pain intensity over 24 hours postoperatively was similar for both groups (P=0.14). There was no significant difference in rate of analgesia-related complications between the groups (hypotension, P=0.14; bradypnea, P=0.11). CONCLUSION: Compared to conventional epidural analgesia based on physician prescription, PCEA led to less total analgesic consumption and greater patient satisfaction after THR.

Calprotectin and calgranulin C serum levels in bacterial sepsis.

The aim of this study was to evaluate the serum levels of calprotectin and calgranulin C and routine biomarkers in patients with bacterial sepsis (BS). The initial serum concentrations of calprotectin and calgranulin C were significantly higher in patients with BS (n = 66) than in those with viral infections (n = 24) and the healthy controls (n = 26); the level of calprotectin was found to be the best predictor of BS, followed by the neutrophil-lymphocyte count ratio (NLCR) and the level of procalcitonin (PCT). The white blood cell (WBC) count and the NLCR rapidly returned to normal levels, whereas PCT levels normalized later and the increased levels of calprotectin, calgranulin C, and C-reactive protein persisted until the end of follow-up. Our results suggest that the serum levels of calprotectin are a reliable biomarker of BS and that the WBC count and the NLCR are rapid predictors of the efficacy of antimicrobial therapy.