Septic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5-7 million patients worldwide develop sepsis with very high endotoxin activity in the blood and more than half die. The term endotoxic septic shock has been used for these patients but it is important to emphasize that endotoxin may be a factor in all forms of septic shock including non-bacterial etiologies like COVID-19 since translocation of bacterial products is a common feature of septic shock. A pattern of organ failure including hepatic dysfunction, acute kidney injury and various forms of endothelial dysfunction ranging from disseminated intravascular coagulation to thrombotic microangiopathy characterize endotoxic septic shock. However, while characteristic, the clinical phenotype is not unique to patients with high endotoxin, and the diagnosis relies on the measurement of endotoxin activity in addition to clinical assessment. Therapies for endotoxic septic shock are limited with immune modulating therapies under investigation and extracorporeal blood purification still controversial in many parts of the world. Weniger anzeigen

Medical language is in a constant state of evolution. Its grammar and vocabulary are not fixed by rigid rules. The interdisciplinary field of sepsis has become a meeting point for new insights arising from advances in systems biology, epidemiology, mechanistic understandings of disease process and antimicrobial interventions. This convergence has gained from our recent experience of SARS-CoV-2 infection and COVID-19 and possibilities inferred from emerging information technology. Biomedical descriptors have diverged along disciplinary lines creating an unfortunate disconnect between clinical and laboratory-based terminology. The resulting confusion between clinically determined sepsis and laboratory verified bloodstream infection raises practical questions that affect daily operational processes in the ward, clinic and laboratory. There is an urgent need to understand how the clinical sepsis pathway and corresponding clinical laboratory workflow can be better aligned as a single coherent entity. There is also an implicit need to understand how this process should produce actionable information in a timely and orderly manner, and identify residual obselete terminology that has crept into common usage. A widely accepted sepsis epistemology, ontology and heuristic will help us improve our clinical management of sepsis. Weniger anzeigen

The introduction of anakinra, baricitinib and tocilizumab into the treatment armamentarium of severe coronavirus disease 2019 (COVID-19) reinforced the concept of immunotherapy for bacterial sepsis. The current review investigates how the example of COVID-19 may be extrapolated to sepsis using a three-step approach. In the first step, the clinical evidence on how the immunotherapy of COVID-19 assisted viral clearance is presented. In a second step, the indications acquired from human and animal studies on the need to employ strategies with primary effective phagocytosis in sepsis are presented. In a final step, lessons learnt from COVID-19 immunotherapy are applied for sepsis. The end result is that sepsis immunotherapy should rely on the use of biomarkers which provide information on the activation of a specific prevailing mechanism in order to enable the selection of the appropriate drug. Weniger anzeigen

Background: Sepsis is associated with an increased risk of adverse cardiovascular events in a magnitude comparable to other major cardiovascular risk factors. Sepsis is one of the most common reasons for intensive care admission and survivors often have significant functional limitations following discharge. However, it is not clear to what extent chronic cardiovascular dysfunction might mediate these functional impairments, or how we might screen and manage these patients at risk of chronic cardiovascular disease. We conducted a scoping review to map existing evidence and identify research gaps relating to cardiovascular dysfunction following sepsis. Methods: We conducted a systematic search of MEDLINE, Embase and CINAHL databases using a concept, context, population (CoCoPop) framework. Studies examining cardiovascular outcomes or symptoms following an episode of sepsis in adults were included. Data were mapped based on the population assessed, cardiovascular outcomes examined, inclusion of objective measures of cardiac dysfunction such as biomarkers or cardiovascular imaging, or whether cardiovascular symptoms or patient-reported functional outcomes measures were recorded. Results: We identified 11 210 articles of which 70 were eligible for full text review and 28 were included in final analysis. Across our dataset, a wide range of incident cardiovascular outcomes were reported in the literature including incidence of congestive heart failure (13/28), arrhythmia (6/28), myocardial infarction (24/28) or cardiovascular death or all-cause mortality (20/28). Only 39% (11/28) of articles reported objective measures of cardiovascular function and only one article related cardiovascular function to functional impairment via patient-reported outcome measures. Conclusion: There are significant gaps in our understanding of cardiac dysfunction following sepsis . While the research highlights the strong association of sepsis with a variety of adverse cardiovascular outcomes, further prospective work is required to understand the mechanisms that mediate this phenomenon and how we can best identify and manage patients at risk. Weniger anzeigen

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock. Materials and methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.2 μg/kg/min after fluid optimization. The study was conducted in a mixed medical-surgical ICU over 12 months. Two blinded experts (a Dermatologist and a plastic surgeon) independently classified the skin type, validated the occurrence of mottling, and scored mottling in our patients. We recorded the demographics, hemodynamic variables, and mottling score and observed the incidence of mottling and its correlation with predictors of the severity of septic shock. We also compared CRT, arterial lactate, central venous oxygen saturation, and venoarterial PCO2 gap with occurrence of mottling in septic shock patients. Results: We included 108 patients with age 61 ± 16 years. Mean Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at enrolment were 10.3-21.9, respectively. Incidence of mottling was 20.3% (22/108). CRT >3 seconds was observed in 50.9% (55/108). Development of mottling was significantly associated with 90-day mortality; 20/22 (90.9%) patients died in the mottling group versus 58/86 (65.1%) in the non-mottling group (p = 0.028). Capillary refill time >3 seconds did not corelate with mortality; 40/55 (72.7%) Patients with CRT >3 seconds died versus 32/53 (60.4%) patients died in CRT ≤3 seconds group. Occurrence of mottling could predict mortality; positive predictive value of 90.9% which was comparable to positive predictive value of lactate levels >4 mmol/L, i.e., 94.1%. Conclusion: The incidence of mottling in septic shock is much less in patients of Indian ethnicity with brown skin color than in white-skinned population. Occurrence of mottling and not delayed CRT, is a better predictor of outcome in this setting. How to cite this article: Jog SA, Narasimhan VL, Rajhans PA, Akole PV, Pawar B, Bhurke B, et al. Mottling in Septic Shock: Ethnicity and Skin Color Matter. Indian J Crit Care Med 2023;27(12):902-909. Weniger anzeigen

Background: First medical contact for patients with sepsis often initiates in the prehospital setting, yet limited studies have explored the EMS sepsis recognition-mortality relationship. Racial and ethnic minority patients often have worse sepsis outcomes, yet the role of prehospital recognition in this inequity has not been explored. Our objective was to describe prehospital sepsis recognition and hospital mortality, with analysis by patient race and ethnicity. Methods: Using linked EMS and hospital records from the 2021 ESO Data Collaborative, we retrospectively analyzed 9-1-1 EMS transports for adult patients with emergency department ICD-10 sepsis diagnosis codes. EMS sepsis recognition was defined as a primary or secondary sepsis impression, use of an electronic health record specialty sepsis form, or a prehospital sepsis alert. We used multivariable logistic regression to assess the association between EMS sepsis recognition and hospital mortality, adjusting for age, sex, race and ethnicity, scene socioeconomic status, and documented clinical characteristics: altered mental status, hypotension, tachypnea, tachycardia, fever. We conducted a secondary analysis of patients who were positive for the quick sequential organ failure assessment (qSOFA) using first prehospital vital signs. Results: We analyzed 20,172 records for EMS-transported patients with diagnosed sepsis. Overall, 8% of patients were Black, 8% were Hispanic, and 72% were White. Prehospital sepsis recognition was 18%. Prehospital sepsis recognition was similar across racial and ethnic groups (Black: 17.2%, Hispanic: 17.4%, White: 18.1%) and adjusted odds of sepsis recognition did not differ between racial and ethnic groups. Overall mortality was 11% (2,186). Prehospital sepsis recognition was associated with a 18% reduction in adjusted odds of mortality (OR: 0.82, 95% CI: 0.70-0.94). Of patients who were qSOFA positive in the field (n = 2,168), EMS sepsis recognition was 32% and was similar across race and ethnicities. Adjusted odds of mortality were 0.68 (95% CI: 0.53-0.88) when sepsis was recognized in the prehospital setting. Conclusion: EMS identified sepsis in fewer than one in three patients even after limiting to those positive for qSOFA, without differences by race and ethnicity. EMS sepsis recognition was associated with reduced odds of mortality; however, Black patients remained at greater odds of death suggesting additional factors that warrant investigation. Weniger anzeigen

Background: Patients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock. Methods: Our study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018. We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics. Our primary outcome was 90-day mortality. Our secondary outcome was in-hospital mortality. Multiple logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection was used to assess associations. Findings: There were 13,932 patients with septic shock in our cohort. The mean age was 61 years (SD 16), 68% of the cohort identified as White (n = 9419), 28% identified as Black (n = 3936), 2% (n = 294) identified as Hispanic ethnicity, and 2% as other races not specified in the previous groups (n = 283). In our logistic regression model for 90-day mortality, patients identified as Black had 1.57 times the odds of mortality (95% CI 1.07-2.29, p = 0.02) compared to White patients. Other significant predictors included mechanical ventilation (OR 3.66, 95% CI 3.35-4.00, p < 0.01), liver disease (OR 1.75, 95% CI 1.59-1.93, p < 0.01), laboratory components of the Sequential Organ Failure Assessment score (OR 1.18, 95% CI 1.16-1.21, p < 0.01), lactate (OR 1.10, 95% CI 1.08-1.12, p < 0.01), congestive heart failure (OR 1.19, 95% CI 1.10-1.30, p < 0.01), human immunodeficiency virus (OR 1.35, 95% CI 1.04-1.75, p = 0.03), age (OR 1.04, 95% CI 1.04-1.04, p < 0.01), and the interaction between age and race (OR 0.99, 95% CI 0.99-1.00, p < 0.01). Among younger patients (<45 years), patients identified as Black accounted for a higher proportion of the deaths. Results were similar in the in-hospital mortality model. Interpretation: In this retrospective study of septic shock patients, we found that patients identified as Black had higher odds of mortality compared to patients identified as non-Hispanic White. Our findings suggest that the greatest disparities in mortality are among younger Black patients with septic shock. Funding: National Institutes of Health National Center for Advancing Translational Sciences (1KL2TR001429); National Institute of Health National Institute of General Medical Sciences (1K23GM144802). Weniger anzeigen

Sepsis is a clinical syndrome encompassing physiologic and biological abnormalities caused by a dysregulated host response to infection. Sepsis progression into septic shock is associated with a dramatic increase in mortality, hence the importance of early identification and treatment. Over the last two decades, the definition of sepsis has evolved to improve early sepsis recognition and screening, standardize the terms used to describe sepsis and highlight its association with organ dysfunction and higher mortality. The early 2000s witnessed the birth of early goal-directed therapy (EGDT), which showed a dramatic reduction in mortality leading to its wide adoption, and the surviving sepsis campaign (SSC), which has been instrumental in developing and updating sepsis guidelines over the last 20 years. Outside of early fluid resuscitation and antibiotic therapy, sepsis management has transitioned to a less aggressive approach over the last few years, shying away from routine mixed venous oxygen saturation and central venous pressure monitoring and excessive fluids resuscitation, inotropes use, and red blood cell transfusions. Peripheral vasopressor use was deemed safe and is rising, and resuscitation with balanced crystalloids and a restrictive fluid strategy was explored. This review will address some of sepsis management’s most important yet controversial components and summarize the available evidence from the last two decades. Keywords: colloids, corticosteroids, crystalloids, early goal-directed therapy, sepsis, septic shock, surviving sepsis campaign, vasopressors Weniger anzeigen

Platelet count is a key component of sepsis severity score. However, the predictive value of the platelet count at admission for mortality in sepsis remains unclear. We designed a retrospective observational study of patients with sepsis admitted to our hospital from January 2017 to September 2021 to explore the predictive value of platelet count at admission for mortality. A total of 290 patients with sepsis were included in this study. Multivariate logistic regression analysis was used to evaluate the risk factors for mortality and construct a predictive model with statistically significant factors. Compared with survivors, nonsurvivors tended to be much older and had significantly higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores (P < .001). The platelet count was significantly lower in the nonsurvivor group than in the survivor group (P < .001). Multivariate logistic regression analysis indicated that age (P = .003), platelet count (P < .001) and lactate level (P = .018) were independent risk factors for mortality in patients with sepsis. Finally, the area under the receiver operating characteristic curve of platelet count predicting mortality in sepsis was 0.763 (95% confidence interval, 0.709-0.817, P < .001), with a sensitivity of 55.6% and a specificity of 91.8%. In our study, platelet count at admission as a single biomarker showed good predictability for mortality in patients with sepsis. Weniger anzeigen