Herwig Gerlach

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.

The last two to three years provided several “big steps” regarding our understanding and management of sepsis. The increasing insight into pathomechanisms of post-infectious defense led to some new models of host response. Besides hyper-, hypo-, and anti-inflammation as the traditional approaches to sepsis pathophysiology, tolerance and resilience were described as natural ways that organisms react to microbes. In parallel, huge data analyses confirmed these research insights with a new way to define sepsis and septic shock (called “Sepsis-3”), which led to discussions within the scientific community. In addition to these advances in understanding and defining the disease, follow-up protocols of the initial “sepsis bundles” from the Surviving Sepsis Campaign were created; some of them were part of quality management studies by clinicians, and some were in the form of mandatory procedures. As a result, new “bundles” were initiated with the goal of enabling standardized management of sepsis and septic shock, especially in the very early phase. This short commentary provides a brief overview of these two major fields as recent hallmarks of sepsis research.

Traumatic events like critical illness and intensive care are threats to life and bodily integrity and pose a risk factor for posttraumatic stress disorder (PTSD). PTSD affects the quality of life and morbidity and may increase health-care costs. Limited access to specialist care results in PTSD patients being treated in primary care settings. Narrative exposure therapy (NET) is based on the principles of cognitive behavioral therapy and has shown positive effects when delivered by health-care professionals other than psychologists. The primary aims of the PICTURE trial (from “PTSD after ICU survival”) are to investigate the effectiveness and applicability of NET adapted for primary care with case management in adults diagnosed with PTSD after intensive care. This is an investigator-initiated, multi-center, primary care-based, randomized controlled two-arm parallel group, observer-blinded superiority trial conducted throughout Germany. In total, 340 adult patients with a total score of at least 20 points on the posttraumatic diagnostic scale (PDS-5) 3 months after receiving intensive care treatment will be equally randomized to two groups: NET combined with case management and improved treatment as usual (iTAU). All primary care physicians (PCPs) involved will be instructed in the diagnosis and treatment of PTSD according to current German guidelines. PCPs in the iTAU group will deliver usual care during three consultations. In the experimental group, PCPs will additionally be trained to deliver an adapted version of NET (three sessions) supported by phone-based case management by a medical assistant. At 6 and 12 months after randomization, structured blinded telephone interviews will assess patient-reported outcomes. The primary composite endpoint is the absolute change from baseline at month 6 in PTSD symptom severity measured by the PDS-5 total score, which also incorporates the death of any study patients. Secondary outcomes cover the domains depression, anxiety, disability, health-related quality-of-life, and cost-effectiveness. The principal analysis is by intention to treat. If the superiority of the experimental intervention over usual care can be demonstrated, the combination of brief NET and case management could be a treatment option to relieve PTSD-related symptoms and to improve primary care after intensive care. ClinicalTrials.gov, NCT03315390 . Registered on 10 October 2017. German Clinical Trials Register, DRKS00012589 . Registered on 17 October 2017.

The increasing insight into pathomechanisms of dysregulated host response in several inflammatory diseases led to the implementation of the term “cytokine storm” in the literature more than 20 years ago. Direct toxic effects as well as indirect immunomodulatory mechanisms during cytokine storm have been described and were the basis for the rationale to use several substances and devices in life-threatening infections and hyperinflammatory states. Clinical trials have been performed, most of them in the form of minor, investigator-initiated protocols; major clinical trials focused mostly on sepsis and septic shock. The following review tries to summarize the background, pathophysiology, and results of clinical investigations that had implications for the development of therapeutic strategies and international guidelines for the management of hyperinflammation during syndromes of cytokine storm in adult patients, predominantly in septic shock.

This article reminds us that, in hematologic malignancies, use of modern approaches like infusion of “chimeric antigen receptor” (CAR) T cells may lead to severe toxicities such as cytokine release syndrome (CRS). The authors underline that the clinical course is often similar to septic hyperinflammation with subsequent multiple organ dysfunction syndrome (MODS), thus requiring interventions as used for cytokine storm in infections. The authors propose guidelines for such treatment. This Recommendation is of an article referenced in an F1000 Faculty Review also written by Herwig Gerlach.

Perioperative hemodynamic optimisation improves postoperative outcome for patients undergoing high-risk surgery (HRS). In this prospective randomized multicentre study we studied the effects of an individualized, goal-directed fluid management based on continuous stroke volume variation (SVV) and stroke volume (SV) monitoring on postoperative outcomes. 64 patients undergoing HRS were randomized either to a control group (CON, n = 32) or a goal-directed group (GDT, n = 32). In GDT, SVV and SV were continuously monitored (FloTrac/Vigileo) and patients were brought to and maintained on the plateau of the Frank-Starling curve (SVV P < 0.05) and SVV decreased in GDT (from 9.0 to 8.0 %, P < 0.05) but not in CON. The number of postoperative wound infections was lower in GDT (0 vs. 7, P < 0.01). Although not statistically significant, the proportion of patients with at least one complication (46 vs. 62 %), the number of postoperative complications per patient (0.65 vs. 1.40), the maximum sofa score (5.9 vs. 7.2), and the cumulative TISS score (69 vs. 83) tended to be lower. This multicentre study shows that fluid management based on a SVV and SV optimisation protocol is feasible and decreases postoperative wound infections. Our findings also suggest that a goal-directed strategy might decrease postoperative organ dysfunction.