In severely ill patients low concentrations of the corticosteroid binding globulin are typically found; the aim of this study was to quantify directly free bioactive cortisol concentrations in the sera of postoperative cardiosurgical patients. Serum samples of 12 consecutive patients undergoing aortocoronary bypass surgery taken preoperatively and on the postoperative days 1 to 4 were analyzed. Total serum cortisol was quantified using liquid chromatography-tandem mass spectrometry with an on-line sample extraction system and tri-deuterated cortisol as the internal standard, and free serum cortisol was measured after over-night equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately two-fold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203-293 nmol/l); first postoperative day, 512 nmol/l (IQR 410-611 nmol/l)), median dialyzable free cortisol concentration was almost seven-fold increased (preoperatively, 14.2 nmol/l (IOR 10.9-20.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3-134 nmol/l)). On the fourth postoperative day, median free cortisol was still significantly increased compared to baseline sampling (p < 0.05), whereas median total cortisol was not. A median of 5.7% (IQR 5.4-7.0%) of total cortisol was found as free cortisol on the preoperative day, 21.2% (IQR 18.9-23.5%) on the first postoperative day and 10.5% (IQR 9.8-14.0%) on the fourth postoperative day. It is concluded that during the postoperative period the free-to-bound ratio of cortisol is highly variable and that during the acute phase response direct quantification of free bioactive cortisol concentrations seems to be biologically more appropriate than the measurement of total cortisol concentrations.
The 11th revision of the International Classification of Diseases (ICD-11) will come into effect in January 2022. Among other things, The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS‑3 definition) will be implemented in it. This defines sepsis as a "life-threatening organ dysfunction caused by a dysregulated host response to infection". The aim of the present secondary analysis of a survey on the topic of "sepsis-induced coagulopathy" was to evaluate whether the SEPSIS‑3 definition, 4 years after its international introduction, has arrived in everyday clinical practice of intensive care units (ICU) run by anesthesiologists in Germany and thus the requirements for its use of the ICD-11 are given.Between October 2019 and May 2020, we carried out a nationwide survey among German medical directors of ICUs. In a separate block of questions we asked about the definition of sepsis used in daily practice. In addition, we asked whether the quick-sequential (sepsis-related) organ failure assessment (qSOFA) score is used in screening for sepsis in the hospital to which to the participating ICU belongs.A total of 50 medical directors from anesthesiological ICUs took part in the survey. In total, the ICUs evaluated stated that they had around 14% of the high-care beds registered in Germany. The SEPSIS‑3 definition is integrated into everyday clinical practice at 78.9% of the university hospitals and 84.0% of the participating teaching hospitals. In contrast, the qSOFA screening test is only used by 26.3% of the participating university hospitals, but at least 52% of the teaching hospitals and 80% of the other hospitals.The data show that both SEPSIS‑3 and qSOFA have become part of everyday clinical practice in German hospitals. The cautious use of qSOFA at university hospitals with simultaneous broad acceptance of the SEPSIS‑3 definition can be interpreted as an indication that the search for a suitable screening test for sepsis has not yet been completed.HINTERGRUND: Im Januar 2022 wird die 11. Revision der International Classification of Diseases (ICD-11) in Kraft treten. Unter anderem wird darin die SEPSIS-3-Definition implementiert sein, in der Sepsis als „lebensbedrohliche Organdysfunktion, hervorgerufen durch eine fehlregulierte Wirtsantwort auf eine Infektion“ definiert wird. Ziel der vorliegenden Sekundärauswertung einer Umfrage zum Thema „Sepsis-induzierte Koagulopathie“ war es zu evaluieren, ob die SEPSIS-3-Definition (engl. The Third International Consensus Definitions for Sepsis and Septic Shock) 4 Jahre nach ihrer internationalen Einführung im klinischen Alltag anästhesiologisch geführter Intensivstationen in Deutschland angekommen ist und so die Voraussetzungen für die Verwendung des ICD-11 gegeben sind.Im Rahmen einer deutschlandweiten Umfrage unter ärztlichen Leitern von Intensivstationen, die zwischen Oktober 2019 und Mai 2020 durchgeführt wurde, wurde in einem gesonderten Fragenblock nach der verwendeten Sepsisdefinition gefragt. Zusätzlich wurde gefragt, ob der quick-Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) Score zum Screening auf Sepsis in dem Krankenhaus, zu dem die teilnehmende Intensivstation gehört, verwendet wird.Insgesamt nahmen 50 ärztliche Leiter von anästhesiologisch geführten Intensivbereichen an der Umfrage teil. In Summe gaben die ausgewerteten Intensivstationen an, etwa 14,0 % der in Deutschland registrierten High-Care-Betten zu führen. An 78,9 % der Universitätsklinika und 84,0 % der teilnehmenden Lehrkrankenhäuser ist die SEPSIS-3-Definition im klinischen Alltag integriert. Im Gegensatz dazu wird der Screening-Test „qSOFA“ nur von 26,3 % der teilnehmenden Universitätsklinika, aber immerhin von 52,0 % der Lehrkrankenhäuser und 80,0 % der „sonstigen“ Krankenhäuser verwendet.Unsere Daten zeigen, dass sowohl SEPSIS‑3 als auch qSOFA im klinischen Alltag deutscher Krankenhäuser angekommen sind. Die zurückhaltende Verwendung des qSOFA an Universitätsklinika bei gleichzeitiger breiter Akzeptanz der SEPSIS-3-Definition kann als Indiz interpretiert werden, dass die Suche nach einem geeigneten Screeningtest für Sepsis noch nicht abgeschlossen ist.
Background Sepsis may be complicated by impaired corticosteroid production. Giving corticosteroids may benefit patients. Objectives To examine the effects of corticosteroids on death at one month in sepsis. Search methods We searched CENTRAL (The Cochrane Library Issue 3, 2009), MEDLINE (October 2009), EMBASE (October 2009), LILACS (October 2009), reference lists of articles, and also contacted trial authors. Selection criteria We included randomized and quasi‐randomized controlled trials of corticosteroids versus placebo or supportive treatment in severe sepsis and septic shock. Data collection and analysis All review authors agreed the eligibility of trials. One review author extracted data, which was checked by the other review authors and the primary author of the paper whenever possible. We obtained some missing data from the trial authors. We assessed the methodological quality of the trials. Main results We identified 25 trials, of which 20 (17 randomized and three quasi‐randomized trials) could be pooled in a meta‐analysis. Corticosteroids did not change 28‐day mortality (20 trials, n = 2138, relative risk (RR) 0.87, 95% confidence interval (CI) 0.74 to 1.01; random‐effects model). There was significant heterogeneity that was partly related to the dosing strategy. Treatment with a long course of low dose corticosteroids significantly reduced 28‐day mortality (RR 0.84, 95% CI 0.72 to 0.97; P = 0.02), increased the proportion of shock reversal by day seven (six trials, n = 965, RR 1.35, 95% CI 1.16 to 1.57; random‐effects model) and day 28 (six trials, n = 952, RR 1.12, 95% CI 1.02 to 1.23), reduced the sepsis‐related organ failure assessment (SOFA) score by day seven (five trials, n = 916, RR ‐1.47, (95% CI ‐2.01 to ‐0.92), and survivors' length of stay in the intensive care unit (eight trials, n= 622, RR ‐4.49, 95% CI ‐7.04 to ‐1.94), without inducing gastroduodenal bleeding (13 trials, n = 1594, RR 11.12, 95% CI 0.81 to 1.53), superinfection (14 trials, n = 1917, RR 1.01, 95% CI 0.82 to 1.25), or neuromuscular weakness (three trials, n = 811, RR 0.63, 95% CI 0.12 to 3.35). Corticosteroid increased the risk of hyperglycaemia (nine trials, n = 1434, RR 1.16, 95% 1.07 to 1.25) and hypernatraemia (three trials, n= 805, RR 1.61, 95% CI 1.26 to 2.06). Authors' conclusions Overall, corticosteroids did not change mortality in severe sepsis and septic shock. A long course of low dose corticosteroids reduced 28‐day mortality without inducing major complications; metabolic disorders were increased.
Objective To assess the effects of corticosteroids on mortality in patients with severe sepsis and septic shock. Data sources Randomised and quasi-randomised trials of corticosteroids versus placebo (or supportive treatment alone) retrieved from the Cochrane infectious diseases group9s trials register, the Cochrane central register of controlled trials, Medline, Embase, and LILACS. Review method Two pairs of reviewers agreed on eligibility of trials. One reviewer entered data on to the computer and four reviewers checked them. We obtained some missing data from authors of trials and assessed methodological quality of trials. Results 16/23 trials (n = 2063) were selected. Corticosteroids did not change 28 day mortality (15 trials, n = 2022; relative risk 0.92, 95% confidence interval 0.75 to 1.14) or hospital mortality (13 trials, n = 1418; 0.89, 0.71 to 1.11). There was significant heterogeneity. Subgroup analysis on long courses (≥ 5 days) with low dose (≤ 300 mg hydrocortisone or equivalent) corticosteroids showed no more heterogeneity. The relative risk for mortality was 0.80 at 28 days (five trials, n = 465; 0.67 to 0.95) and 0.83 at hospital discharge (five trials, n = 465, 0.71 to 0.97). Use of corticosteroids reduced mortality in intensive care units (four trials, n = 425, 0.83, 0.70 to 0.97), increased shock reversal at 7 days (four trials, n = 425; 1.60, 1.27 to 2.03) and 28 days (four trials, n = 425, 1.26, 1.04 to 1.52) without inducing side effects. Conclusions For all trials, regardless of duration of treatment and dose, use of corticosteroids did not significantly affect mortality. With long courses of low doses of corticosteroids, however, mortality at 28 days and hospital morality was reduced.
