Introduction: Current sepsis guidelines recommend antimicrobial treatment (AT) within one hour after onset of sepsis-related organ dysfunction (OD) and surgical source control within 12 hours. The objective of this study was to explore the association between initial infection management according to sepsis treatment recommendations and patient outcome. Methods: In a prospective observational multi-center cohort study in 44 German ICUs, we studied 1,011 patients with severe sepsis or septic shock regarding times to AT, source control, and adequacy of AT. Primary outcome was 28-day mortality. Results: Median time to AT was 2.1 (IQR 0.8 – 6.0) hours and 3 hours (-0.1 – 13.7) to surgical source control. Only 370 (36.6%) patients received AT within one hour after OD in compliance with recommendation. Among 422 patients receiving surgical or interventional source control, those who received source control later than 6 hours after onset of OD had a significantly higher 28-day mortality than patients with earlier source control (42.9% versus 26.7%, P <0.001). Time to AT was significantly longer in ICU and hospital non-survivors; no linear relationship was found between time to AT and 28-day mortality. Regardless of timing, 28-day mortality rate was lower in patients with adequate than non-adequate AT (30.3% versus 40.9%, P < 0.001). Conclusions: A delay in source control beyond 6 hours may have a major impact on patient mortality. Adequate AT is associated with improved patient outcome but compliance with guideline recommendation requires improvement. There was only indirect evidence about the impact of timing of AT on sepsis mortality.

Background: Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates. Methods: We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia. Results: With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever. Conclusions: Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011.

Background: General anesthesia may cause atelectasis and deterioration in oxygenation in obese patients. The authors hypothesized that individualized positive end-expiratory pressure (PEEP) improves intraoperative oxygenation and ventilation distribution compared to fixed PEEP. Methods: This secondary analysis included all obese patients recruited at University Hospital of Leipzig from the multicenter Protective Intraoperative Ventilation with Higher versus Lower Levels of Positive End-Expiratory Pressure in Obese Patients (PROBESE) trial (n = 42) and likewise all obese patients from a local single-center trial (n = 54). Inclusion criteria for both trials were elective laparoscopic abdominal surgery, body mass index greater than or equal to 35 kg/m², and Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score greater than or equal to 26. Patients were randomized to PEEP of 4 cm H₂O (n = 19) or a recruitment maneuver followed by PEEP of 12 cm H₂O (n = 21) in the PROBESE study. In the single-center study, they were randomized to PEEP of 5 cm H₂O (n = 25) or a recruitment maneuver followed by individualized PEEP (n = 25) determined by electrical impedance tomography. Primary endpoint was Pao ₂/inspiratory oxygen fraction before extubation and secondary endpoints included intraoperative tidal volume distribution to dependent lung and driving pressure. Results: Ninety patients were evaluated in three groups after combining the two lower PEEP groups. Median individualized PEEP was 18 (interquartile range, 16 to 22; range, 10 to 26) cm H₂O. Pao ₂/inspiratory oxygen fraction before extubation was 515 (individual PEEP), 370 (fixed PEEP of 12 cm H₂O), and 305 (fixed PEEP of 4 to 5 cm H₂O) mmHg (difference to individualized PEEP, 145; 95% CI, 91 to 200; P < 0.001 for fixed PEEP of 12 cm H₂O and 210; 95% CI, 164 to 257; P < 0.001 for fixed PEEP of 4 to 5 cm H₂O). Intraoperative tidal volume in the dependent lung areas was 43.9% (individualized PEEP), 25.9% (fixed PEEP of 12 cm H₂O) and 26.8% (fixed PEEP of 4 to 5 cm H₂O) (difference to individualized PEEP: 18.0%; 95% CI, 8.0 to 20.7; P < 0.001 for fixed PEEP of 12 cm H₂O and 17.1%; 95% CI, 10.0 to 20.6; P < 0.001 for fixed PEEP of 4 to 5 cm H₂O). Mean intraoperative driving pressure was 9.8 cm H₂O (individualized PEEP), 14.4 cm H₂O (fixed PEEP of 12 cm H₂O), and 18.8 cm H₂O (fixed PEEP of 4 to 5 cm H₂O), P < 0.001. Conclusions: This secondary analysis of obese patients undergoing laparoscopic surgery found better oxygenation, lower driving pressures, and redistribution of ventilation toward dependent lung areas measured by electrical impedance tomography using individualized PEEP. The impact on patient outcome remains unclear. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New:

In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs. This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality. Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival. The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany. The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807 ) on May 1, 2017.

Purpose To investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI). Methods Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality. Results 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80–1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0–2.2] days in the BDG group and 4.4 (IQR 2.0–9.1, p < 0.01) days in the control group. Conclusions Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.