Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4+, CD8+ T cells; CD25+ CD127- regulatory T cells; CD14+ monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8+ cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4+ T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.

Intraoperative hypotension is associated with acute kidney injury (AKI). Clinicians thus frequently use vasopressors, such as norepinephrine, to maintain blood pressure. However, vasopressors themselves might promote AKI. We sought to determine whether both intraoperative hypotension and cumulative intraoperative norepinephrine dose are independently associated with postoperative AKI in patients undergoing noncardiac surgery. This was a retrospective cohort analysis of 38 338 adult male and female patients who had noncardiac surgery. The primary outcome was AKI within the first 7 postoperative days. We performed adjusted multivariable logistic regression analysis to determine whether intraoperative hypotension (quantified as area under a mean arterial pressure [MAP] of 65 mm Hg) and cumulative intraoperative norepinephrine dose were independently associated with AKI. The median (25th percentile, 75th percentile) area under a MAP of 65 mm Hg was 0.09 (0.02, 0.22) mm Hg∗day in patients with AKI and 0.05 (0.01, 0.14) mm Hg∗day in patients without AKI (P<0.001). The cumulative intraoperative norepinephrine dose was 1.92 (0.00, 13.09) μg kg^-1 in patients with AKI and 0.00 (0.00, 0.00) μg kg^-1 in patients without AKI (P<0.001). Both the area under a MAP of 65 mm Hg (odds ratio 1.55 [95% confidence interval 1.17-2.02] per mm Hg∗day; P=0.002) and the cumulative intraoperative norepinephrine dose (odds ratio 1.02 [95% confidence interval 1.01-1.02] per μg kg^-1; P<0.001) were independently associated with AKI. Both intraoperative hypotension and cumulative intraoperative norepinephrine dose were independently associated with postoperative AKI in patients undergoing noncardiac surgery. Pending results of trials testing whether these relationships are causal, it seems prudent to avoid both profound hypotension and high norepinephrine doses in adults undergoing noncardiac surgery.

Background: It is crucial to rapidly identify sepsis so that adequate treatment may be initiated. Accordingly, the Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) scores are used to evaluate intensive care unit (ICU) and non-ICU patients, respectively. As demand for ICU beds rises, the intermediate care unit (IMCU) carries greater importance as a bridge between the ICU and the regular ward. This study aimed to examine the ability of SOFA and qSOFA scores to predict suspected infection and mortality in IMCU patients. Methods: Retrospective data analysis included 13,780 surgical patients treated at the IMCU, ICU, or both between January 01, 2012, and September 30, 2018. Patients were screened for suspected infection (i.e., the commencement of broad-spectrum antibiotics) and then evaluated for the SOFA score, qSOFA score, and the 1992 defined systemic inflammatory response syndrome (SIRS) criteria. Results: Suspected infection was detected in 1306 (18.3%) of IMCU, 1365 (35.5%) of ICU, and 1734 (62.0%) of IMCU/ICU encounters. Overall, 458 (3.3%) patients died (IMCU 45 [0.6%]; ICU 250 [6.5%]; IMCU/ICU 163 [5.8%]). All investigated scores failed to predict suspected infection independently of the analyzed subgroup. Regarding mortality prediction, the qSOFA score performed sufficiently within the IMCU cohort (AUCROC SIRS 0.72 [0.71–0.72]; SOFA 0.52 [0.51–0.53]; qSOFA 0.82 [0.79–0.84]), while the SOFA score was predictive in patients of the IMCU/ICU cohort (AUCROC SIRS 0.54 [0.53–0.54]; SOFA 0.73 [0.70–0.77]; qSOFA 0.59 [0.58–0.59]). Conclusions: None of the assessed scores was sufficiently able to predict suspected infection in surgical ICU or IMCU patients. While the qSOFA score is appropriate for mortality prediction in IMCU patients, SOFA score prediction quality is increased in critically ill patients.

It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. NCT03021525.

An abdominal inflammatory focus is the second most often source of sepsis with a high risk of death in surgical intensive care units. By establishing evidence-based bundled strategies the surviving sepsis campaign provided an optimized rapid and continuous treatment of these emergency patients. Hereby the hospital mortality decreased from 35 to 30 %. Sepsis treatment is based on three major therapeutic elements: surgical treatment (source control), antiinfective treatment, and supportive care. The international guidelines of the surviving sepsis campaign were updated recently and recommend rapid diagnosis of the infection and source control within the first 12 h after the diagnosis (grade 1c). Interestingly this recommendation is mainly based on studies on soft tissue infections. In this retrospective analysis 76 septic patients with an intraabdominal inflammatory focus were included. All patients underwent surgery at different time-points after diagnosis. With 80 % patients of the early intervention group had an improved overall survival (vs. 73 % in the late intervention group). Literature on the time dependency of early source control is rare and in part contradicting. Results of this pilot study reveal that immediate surgical intervention might be of advantage for septic emergency patients. Further multi-center approaches will be necessary to evaluate, whether the TTI has any impact on the outcome of septic patients with intestinal perforation.

The term “Alarm fatigue” is commonly used to describe the effect which a high number of alarms can have on caregivers: Frequent alarms, many of which are avoidable, can lead to inadequate responses, severely impacting patient safety. In the first step of a long-term effort to address this problem, both the direct and indirect impact of alarms, as well as possible causes of unnecessary alarms were focused. Models of these causes and impacts were developed using a scoping review which included guided interviews with experts from medical informatics, clinicians and medical device manufacturers. These models can provide the methodical grounds for the definition of targeted interventions and the assessment of their effects.