29 research outputs found
Designing intelligent anesthesia for a changing patient demographic: a consensus statement to provide guidance for specialist and non-specialist anesthetists written by members of and endorsed by the Society for Obesity and Bariatric Anaesthesia (SOBA)
No full textAdministration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion
No full textDrotrecogin alfa (Activated) in adults with septic shock
No full textThere have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock.In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697 patients with infection, systemic inflammation, and shock who were receiving fluids and vasopressors above a threshold dose for 4 hours to receive either DrotAA (at a dose of 24 μg per kilogram of body weight per hour) or placebo for 96 hours. The primary outcome was death from any cause 28 days after randomization.At 28 days, 223 of 846 patients (26.4%) in the DrotAA group and 202 of 834 (24.2%) in the placebo group had died (relative risk in the DrotAA group, 1.09; 95% confidence interval [CI], 0.92 to 1.28; P=0.31). At 90 days, 287 of 842 patients (34.1%) in the DrotAA group and 269 of 822 (32.7%) in the placebo group had died (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56). Among patients with severe protein C deficiency at baseline, 98 of 342 (28.7%) in the DrotAA group had died at 28 days, as compared with 102 of 331 (30.8%) in the placebo group (risk ratio, 0.93; 95% CI, 0.74 to 1.17; P=0.54). Similarly, rates of death at 28 and 90 days were not significantly different in other predefined subgroups, including patients at increased risk for death. Serious bleeding during the treatment period occurred in 10 patients in the DrotAA group and 8 in the placebo group (P=0.81).DrotAA did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock. (Funded by Eli Lilly; PROWESS-SHOCK ClinicalTrials.gov number, NCT00604214.)
Genetic mechanisms of critical illness in COVID-19.
No full textHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Individual and combined effects of chemical and mechanical power on postoperative pulmonary complications: a secondary analysis of the REPEAT study
No full textIntroduction: Intra-operative supplemental oxygen and mechanical ventilation expose the lungs to potentially injurious energy. This can be quantified as 'chemical power' and 'mechanical power', respectively. In this study, we sought to determine if intra-operative chemical and mechanical power, individually and/or in combination, are associated with postoperative pulmonary complications. Methods: Using an individual patient data analysis of three randomised clinical trials of intra-operative ventilation, we summarised intra-operative chemical and mechanical power using time-weighted averages. We evaluated the association between intra-operative chemical and mechanical power and a collapsed composite of postoperative pulmonary complications using multivariable logistic regression to estimate the odds ratios related to the effect of 1 J.min-1 increase in chemical or mechanical power with adjustment for demographic and intra-operative characteristics. We also included an interaction term to assess for potential synergistic effects of chemical and mechanical power on postoperative pulmonary complications. Results: Of 3837 patients recruited to three individual trials, 2492 with full datasets were included in the analysis. Intra-operative time-weighted average (SD) chemical power was 10.2 (3.9) J.min-1 and mechanical power was 10.5 (4.4) J.min-1. An increase of 1 J.min-1 in chemical power was associated with 8% higher odds of postoperative pulmonary complications (OR 1.08, 95%CI 1.05-1.10, p < 0.001), while the same increase in mechanical power raised odds by 5% (OR 1.05, 95%CI 1.02-1.08, p = 0.003). We did not find evidence of a significant interaction between chemical and mechanical power (p = 0.40), suggestive of an additive rather than synergistic effect on postoperative pulmonary complications. Discussion: Both chemical and mechanical power are independently associated with postoperative pulmonary complications. Further work is required to determine causality
Identification of Sleep Medicine and Anesthesia Core Topics for Anesthesia Residency: A Modified Delphi Technique Survey
No full textGenetic mechanisms of critical illness in COVID-19
No full textHost-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Perioperative management of obstructive sleep apnea in bariatric surgery: a consensus guideline
No full textBackground: The frequency of metabolic and bariatric surgery (MBS) is increasing worldwide, with over 500,000 cases performed every year. Obstructive sleep apnea (OSA) is present in 35%–94% of MBS patients. Nevertheless, consensus regarding the perioperative management of OSA in MBS patients is not established. Objectives: To provide consensus based guidelines utilizing current literature and, when in the absence of supporting clinical data, expert opinion by organizing a consensus meeting of experts from relevant specialties. Setting: The meeting was held in Amsterdam, the Netherlands. Methods: A panel of 15 international experts identified 75 questions covering preoperative screening, treatment, postoperative monitoring, anesthetic care and follow-up. Six researchers reviewed the literature systematically. During this meeting, the “Amsterdam Delphi Method” was utilized including controlled acquisition of feedback, aggregation of responses and iteration. Results: Recommendations or statements were provided for 58 questions. In the judgment of the experts, 17 questions provided no additional useful information and it was agreed to exclude them. With the exception of 3 recommendations (64%, 66%, and 66% respectively), consensus (>70%) was reached for 55 statements and recommendations. Several highlights: polysomnography is the gold standard for diagnosing OSA; continuous positive airway pressure is recommended for all patients with moderate and severe OSA; OSA patients should be continuously monitored with pulse oximetry in the early postoperative period; perioperative usage of sedatives and opioids should be minimized. Conclusion: This first international expert meeting provided 58 statements and recommendations for a clinical consensus guideline regarding the perioperative management of OSA patients undergoing MBS
Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project
No full textPurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection
Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project
No full textPurpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. © 2019, The Author(s)
