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Management of Sepsis and Septic Shock

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 33742

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Special Issue Editors

Prof. Dr. Markus A. Weigand

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Guest Editor

Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
Interests: sepsis; septic shock; severe infection; hemodynamic management; inflammation; immunology
Special Issues, Collections and Topics in MDPI journals

Dr. Armin Kalenka

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Guest Editor

District Hospital Bergstrasse, Department of Anaesthesiology and Intensive Care Medicine, Heppenheim, Germany
Interests: sepsis; septic shock; ARDS; mechanical ventilation; ECMO

Special Issue Information

Dear Colleagues,

In today's understanding, sepsis is primarily a pathology of the immune system, triggered by an underlying infection but perpetuated by the host’s response itself. Outcomes in sepsis have greatly improved overall, probably because of an enhanced focus on early diagnosis and fluid resuscitation, and other improvements in supportive care for critically ill patients. These improvements include lung-protective ventilation, a more judicious use of blood products, and strategies to reduce nosocomial infections as well as the rapid delivery of effective antibiotics.

In this Special Issue, we invite researchers and clinicians to submit their work, including original clinical research studies, meta-analyses and systematic reviews that will provide additional knowledge regarding the management of sepsis and septic shock.

Prof. Dr. Markus A. Weigand
Dr. Armin Kalenka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

sepsis;
septic shock;
inflammation;
infection;
bacteremia;
critically ill patients;
host’s response;
multiple organ dysfunction syndrome;
organ failure.

Published Papers (10 papers)

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Research

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14 pages, 701 KiB

Open AccessArticle

Diagnostic Performance of Procalcitonin for the Early Identification of Sepsis in Patients with Elevated qSOFA Score at Emergency Admission

by Myrto Bolanaki, Martin Möckel, Johannes Winning, Michael Bauer, Konrad Reinhart, Angelika Stacke, Peter Hajdu and Anna Slagman

J. Clin. Med. 2021, 10(17), 3869; https://doi.org/10.3390/jcm10173869 - 28 Aug 2021

Cited by 6 | Viewed by 2168

Abstract

Infectious biomarkers such as procalcitonin (PCT) can help overcome the lack of sensitivity of the quick Sequential Organ Failure Assessment (qSOFA) score for early identification of sepsis in emergency departments (EDs) and thus might be beneficial as point-of-care biomarkers in EDs. Our primary aim was to investigate the diagnostic performance of PCT for the early identification of septic patients and patients likely to develop sepsis within 96 h of admission to an ED among a prospectively selected patient population with elevated qSOFA score. In a large multi-centre prospective cohort study, we included all adult patients (n = 742) with a qSOFA score of at least 1 who presented to the ED. PCT levels were measured upon admission. Of the study population 27.3% (n = 202) were diagnosed with sepsis within the first 96 h. The area under the curve for PCT for the identification of septic patients in EDs was 0.86 (95% confidence interval (CI): 0.83–0.89). The resultant sensitivity for PCT at a cut-off of 0.5 µg/L was 63.4% (95% CI: 56.3–70.0). Furthermore, specificity was 89.2% (95% CI: 86.3–91.7), the positive predictive value was 68.8% (95% CI: 62.9–74.2), and the negative predictive value was 86.7% (95% CI: 84.4–88.7). The early measurement of PCT in a patient population with elevated qSOFA score served as an effective tool for the early identification of sepsis in ED patients. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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12 pages, 781 KiB

Open AccessArticle

Extracellular Water to Total Body Water Ratio in Septic Shock Patients Receiving Protocol-Driven Resuscitation Bundle Therapy

by Bora Chae, Yo Sep Shin, Seok-In Hong, Sang Min Kim, Youn-Jung Kim, Seung Mok Ryoo and Won Young Kim

J. Clin. Med. 2021, 10(13), 2917; https://doi.org/10.3390/jcm10132917 - 29 Jun 2021

Cited by 2 | Viewed by 1786

Abstract

(1) Bio-electrical impedance analysis (BIA) is a rapid, simple, and noninvasive tool for evaluating the metabolic status and for assessing volume status in critically ill patients. Little is known, however, the prognostic value of body composition analysis in septic shock patients. This study assessed the association between parameters by body composition analysis and mortality in patients with septic shock in the emergency department (ED). (2) Data were prospectively collected on adult patients with septic shock who underwent protocol-driven resuscitation bundle therapy between December 2019 and January 2021. The primary outcome was 30-day mortality. (3) The study included 261 patients, the average ratio of extracellular water (ECW) to total body water (TBW) was significantly higher in non-survivors than in survivors (0.414 vs. 0.401, p < 0.001). Multivariate analysis showed that ECW/TBW ≥ 0.41 (odds ratio (OR), 4.62; 95% confidence interval (CI), 2.31–9.26, p < 0.001), altered mental status (OR, 2.88; 95% CI, 1.28–6.46, p = 0.010), and lactate level (OR, 1.24; 95% CI, 1.12–1.37, p < 0.001) were significantly associated with 30-day mortality in patients with septic shock. (4) ECW/TBW ≥ 0.41 may be associated with 30-day mortality in patients with septic shock receiving protocol-driven resuscitation bundle therapy in the ED. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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9 pages, 932 KiB

Open AccessArticle

Presepsin in the Rapid Response System for Cancer Patients: A Retrospective Analysis

by Min-Jung Lee, Won-Ho Han, June-Young Chun, Sun-Young Kim and Jee-Hee Kim

J. Clin. Med. 2021, 10(10), 2153; https://doi.org/10.3390/jcm10102153 - 16 May 2021

Cited by 2 | Viewed by 1761

Abstract

Introduction: Early diagnosis of sepsis is paramount to effective management. The present study aimed to compare the prognostic accuracy of presepsin levels and other biomarkers in the assessment of septic shock and mortality risk in cancer patients. Materials and methods: A total of 74 cancer patients were evaluated for presepsin, lactic acid, C-reactive protein (CRP) levels, and white blood cell count (WBC). Specificity and sensitivity values for septic shock and death were compared between four biomarkers in all patients and those with and without acute kidney injury (AKI). Results: A total of 27 and 29 patients experienced septic shock and died, respectively. The area under the curve (AUC) and sensitivity and specificity estimated for presepsin levels for septic shock were 60%, 74%, and 51%, respectively. The corresponding values for mortality were 62%, 72%, and 49%, respectively. In patients without AKI, AUC of presepsin levels for septic shock and death were 62% and 65%, respectively; in those with AKI, these values were 44% and 58%, respectively. Presepsin levels showed higher sensitivity and specificity values than WBC and higher specificity than CRP but were similar to those of lactic acid levels. Conclusions: Presepsin levels are similar to lactic acid levels in the assessment of septic shock and mortality risk in cancer patients. In patients with AKI, presepsin levels should be considered carefully. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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11 pages, 770 KiB

Open AccessArticle

Characteristics of Critically Ill Patients with COVID-19 Compared to Patients with Influenza—A Single Center Experience

by Frank Herbstreit, Marvin Overbeck, Marc Moritz Berger, Annabell Skarabis, Thorsten Brenner and Karsten Schmidt

J. Clin. Med. 2021, 10(10), 2056; https://doi.org/10.3390/jcm10102056 - 11 May 2021

Cited by 8 | Viewed by 2020

Abstract

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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9 pages, 475 KiB

Open AccessArticle

Using Machine Learning to Predict Invasive Bacterial Infections in Young Febrile Infants Visiting the Emergency Department

by I-Min Chiu, Chi-Yung Cheng, Wun-Huei Zeng, Ying-Hsien Huang and Chun-Hung Richard Lin

J. Clin. Med. 2021, 10(9), 1875; https://doi.org/10.3390/jcm10091875 - 26 Apr 2021

Cited by 5 | Viewed by 2310

Abstract

Background: The aim of this study was to develop and evaluate a machine learning (ML) model to predict invasive bacterial infections (IBIs) in young febrile infants visiting the emergency department (ED). Methods: This retrospective study was conducted in the EDs of three medical centers across Taiwan from 2011 to 2018. We included patients age in 0–60 days who were visiting the ED with clinical symptoms of fever. We developed three different ML algorithms, including logistic regression (LR), supportive vector machine (SVM), and extreme gradient boosting (XGboost), comparing their performance at predicting IBIs to a previous validated score system (IBI score). Results: During the study period, 4211 patients were included, where 126 (3.1%) had IBI. A total of eight, five, and seven features were used in the LR, SVM, and XGboost through the feature selection process, respectively. The ML models can achieve a better AUROC value when predicting IBIs in young infants compared with the IBI score (LR: 0.85 vs. SVM: 0.84 vs. XGBoost: 0.85 vs. IBI score: 0.70, p-value < 0.001). Using a cost sensitive learning algorithm, all ML models showed better specificity in predicting IBIs at a 90% sensitivity level compared to an IBI score > 2 (LR: 0.59 vs. SVM: 0.60 vs. XGBoost: 0.57 vs. IBI score >2: 0.43, p-value < 0.001). Conclusions: All ML models developed in this study outperformed the traditional scoring system in stratifying low-risk febrile infants after the standardized sensitivity level. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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12 pages, 1253 KiB

Open AccessArticle

Vasoactive-Inotropic Score as an Early Predictor of Mortality in Adult Patients with Sepsis

by Juhyun Song, Hanjin Cho, Dae Won Park, Sungwoo Moon, Joo Yeong Kim, Sejoong Ahn, Seong-geun Lee and Jonghak Park

J. Clin. Med. 2021, 10(3), 495; https://doi.org/10.3390/jcm10030495 - 31 Jan 2021

Cited by 13 | Viewed by 2773

Abstract

Vasoactive and inotropic medications are essential for sepsis management; however, the association between the maximum Vasoactive-Inotropic score (VISmax) and clinical outcomes is unknown in adult patients with sepsis. We investigated the VISmax as a predictor for mortality among such patients in the emergency department (ED) and compared its prognostic value with that of the sequential organ failure assessment (SOFA) score. This single-center retrospective study included 910 patients diagnosed with sepsis between January 2016 and March 2020. We calculated the VISmax using the highest doses of vasopressors and inotropes administered during the first 6 h on ED admission and categorized it as 0–5, 6–15, 16–30, 31–45, and >45 points. The primary outcome was 30-day mortality. VISmax for 30-day mortality was significantly higher in non-survivors than in survivors. The mortality rates in the five VISmax groups were 17.2%, 20.8%, 33.3%, 54.6%, and 70.0%, respectively. The optimal cut-off value of VISmax to predict 30-day mortality was 31. VISmax had better prognostic value than the cardiovascular component of the SOFA score and initial lactate levels. VISmax was comparable to the APACHE II score in predicting 30-day mortality. Multivariable analysis showed that VISmax 16–30, 31–45, and >45 were independent risk factors for 30-day mortality. VISmax in ED could help clinicians to identify sepsis patients with poor prognosis. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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12 pages, 796 KiB

Open AccessArticle

Pre-Hospital Lactatemia Predicts 30-Day Mortality in Patients with Septic Shock—Preliminary Results from the LAPHSUS Study

by Romain Jouffroy, Teddy Léguillier, Basile Gilbert, Jean Pierre Tourtier, Emmanuel Bloch-Laine, Patrick Ecollan, Vincent Bounes, Josiane Boularan, Papa Gueye-Ngalgou, Valérie Nivet-Antoine, Jean-Louis Beaudeux and Benoit Vivien

J. Clin. Med. 2020, 9(10), 3290; https://doi.org/10.3390/jcm9103290 - 14 Oct 2020

Cited by 7 | Viewed by 2386

Abstract

Background: Assessment of disease severity in patients with septic shock (SS) is crucial in determining optimal level of care. In both pre- and in-hospital settings, the clinical picture alone is not sufficient for assessing disease severity and outcomes. Because blood lactate level is included in the clinical criteria of SS it should be considered to improve the assessment of its severity. This study aims to investigate the relationship between pre-hospital blood lactate level and 30-day mortality in patients with SS. Methods: From 15 April 2017 to 15 April 2019, patients with SS requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were prospectively included in the LAPHSUS study, an observational, non-randomized controlled study. Pre-hospital blood lactate levels were measured at the time of first contact between the patients and the MICU. Results: Among the 183 patients with septic shock requiring action by the MICU drawn at random from LAPHSUS study patients, six (3%) were lost to follow-up on the 30th day and thus 177 (97%) were analyzed for blood lactate levels (mean age 70 ± 14 years). Pulmonary, urinary and digestive infections were probably the cause of the SS in respectively 58%, 21% and 11% of the cases. The 30-day overall mortality was 32%. Mean pre-hospital lactatemia was significantly different between patients who died and those who survived (respectively 7.1 ± 4.0 mmol/L vs. 5.9 ± 3.5 mmol/L, p < 10⁻³). Using Cox regression analysis adjusted for potential confounders we showed that a pre-hospital blood lactate level ≥ 4 mmol/L significantly predicted 30-day mortality in patients with SS (adjusted hazard ratio = 2.37, 95%CI (1.01–5.57), p = 0.04). Conclusion: In this study, we showed that pre-hospital lactatemia predicts 30-day mortality in patients with septic shock handled by the MICU. Further studies will be needed to evaluate if pre-hospital lactatemia alone or combined with clinical scores could affect the triage decision-making process for those patients. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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Review

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13 pages, 627 KiB

Open AccessReview

Sepsis and the Human Microbiome. Just Another Kind of Organ Failure? A Review

by Kevin M. Tourelle, Sebastien Boutin, Markus A. Weigand and Felix C. F. Schmitt

J. Clin. Med. 2021, 10(21), 4831; https://doi.org/10.3390/jcm10214831 - 21 Oct 2021

Cited by 7 | Viewed by 4099

Abstract

Next-generation sequencing (NGS) has been further optimised during the last years and has given us new insights into the human microbiome. The 16S rDNA sequencing, especially, is a cheap, fast, and reliable method that can reveal significantly more microorganisms compared to culture-based diagnostics. It might be a useful method for patients suffering from severe sepsis and at risk of organ failure because early detection and differentiation between healthy and harmful microorganisms are essential for effective therapy. In particular, the gut and lung microbiome in critically ill patients have been probed by NGS. For this review, an iterative approach was used. Current data suggest that an altered microbiome with a decreased alpha-diversity compared to healthy individuals could negatively influence the individual patient’s outcome. In the future, NGS may not only contribute to the diagnosis of complications. Patients at risk could also be identified before surgery or even during their stay in an intensive care unit. Unfortunately, there is still a lack of knowledge to make precise statements about what constitutes a healthy microbiome, which patients exactly have an increased perioperative risk, and what could be a possible therapy to strengthen the microbiome. This work is an iterative review that presents the current state of knowledge in this field. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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18 pages, 1586 KiB

Open AccessReview

Metabolic Alterations in Sepsis

by Weronika Wasyluk and Agnieszka Zwolak

J. Clin. Med. 2021, 10(11), 2412; https://doi.org/10.3390/jcm10112412 - 29 May 2021

Cited by 63 | Viewed by 8102

Abstract

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. Contrary to the older definitions, the current one not only focuses on inflammation, but points to systemic disturbances in homeostasis, including metabolism. Sepsis leads to sepsis-induced dysfunction and mitochondrial damage, which is suggested as a major cause of cell metabolism disorders in these patients. The changes affect the metabolism of all macronutrients. The metabolism of all macronutrients is altered. A characteristic change in carbohydrate metabolism is the intensification of glycolysis, which in combination with the failure of entering pyruvate to the tricarboxylic acid cycle increases the formation of lactate. Sepsis also affects lipid metabolism—lipolysis in adipose tissue is upregulated, which leads to an increase in the level of fatty acids and triglycerides in the blood. At the same time, their use is disturbed, which may result in the accumulation of lipids and their toxic metabolites. Changes in the metabolism of ketone bodies and amino acids have also been described. Metabolic disorders in sepsis are an important area of research, both for their potential role as a target for future therapies (metabolic resuscitation) and for optimizing the current treatment, such as clinical nutrition. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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14 pages, 1028 KiB

Open AccessReview

Sepsis as a Pan-Endocrine Illness—Endocrine Disorders in Septic Patients

by Weronika Wasyluk, Martyna Wasyluk and Agnieszka Zwolak

J. Clin. Med. 2021, 10(10), 2075; https://doi.org/10.3390/jcm10102075 - 12 May 2021

Cited by 19 | Viewed by 4977

Abstract

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic–pituitary–adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic–pituitary–thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic–pituitary–gonadal axis, the reduction in testosterone concentration in men and the stress-induced “hypothalamic amenorrhea” in women have been described. Catecholamine and β-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the “dysregulated host response to infection”. They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value. Full article

(This article belongs to the Special Issue Management of Sepsis and Septic Shock)

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