Embracing a New Evidence-Based Thought Paradigm of Sepsis.

ABSTRACT: In 1991, sepsis was first defined by the Society of Critical Care Medicine as the systemic inflammatory response syndrome, in the presence of infection. Systemic inflammatory response syndrome is an adaptive host response to infection, as well as to other insults like trauma and stress. Research pertaining to sepsis was guided by this adaptive definition for 25 years. After established guidelines for sepsis management were challenged in 2014, sepsis was redefined in 2016 as a dysregulated host response to infection. However, there still remains no consensus on which immunologic or metabolic mechanisms have become dysregulated. We sought to examine sepsis literature published after the 2016 consensus definition and compare it to the original systemic inflammatory response syndrome paradigm proposed in 1991. The purpose of this intensive analysis was to recommend a new sepsis archetype, with consideration to dysregulated immunologic and metabolic mechanisms that have recently been identified in sepsis. Nurses and other clinicians must shift their thought paradigm toward an evidence-based dysregulated model, in order to improve on sepsis recognition and management.

The Toxic Stress of Racism and Its Relationship to Frailty.

Significant morbidity and mortality from COVID-19-related illnesses have been observed among people of color within the United States. While theories involving healthcare inequity and political division have emerged to explain this observation, the role of chronic stress and inflammation is also being explored. Toxic stress is experienced disproportionately by race, ethnicity, and socioeconomic status and increases frailty and vulnerability to diseases such as COVID-19. C-reactive protein (CRP) is a biomarker associated with the inflammatory response that is typically elevated due to exposure to acute or chronic traumatic stress, as well as COVID-19. This study explored the relationship between CRP and Hispanic/non-Hispanic ethnicity among adults hospitalized with COVID-19 via a secondary analysis of retrospective electronic health record (EHR) data collected from a community healthcare system in Southern California. A total of 1,744 cases representing hospitalized adults with COVID-19 were reviewed. Data were extracted from the EHR to reflect demographics, medical diagnoses, medications, CRP, and comorbidity burden. Frequencies, percentages, and measures of central tendency were assessed to understand the distribution of data. Associations were conducted using Pearson's r and the chi-square test of independence. Differences between groups were examined via independent samples t-tests. The sample was 52% Hispanic, 56% male, and the mean age was 62 years (SD = 16.1). The mean age of Hispanic cases was younger than non-Hispanic cases (p < .001, η = 0.289). Serum CRP was significantly higher in the Hispanic cases, with a high degree of association (p < .001, η = 0.472). In addition, higher CRP levels were significantly associated with the need for mechanical ventilation (p < .001, φc = 0.216). No significant relationships were found between CRP and age, body mass index (BMI), or comorbidity burden. Findings challenge the assumption that the disproportionate morbidity and mortality suffered by the Hispanic population due to COVID-19 was due to age, BMI, or comorbidities such as metabolic syndrome or heart disease. CRP in the Hispanic population should be further investigated to understand its relationship to chronic stress, frailty, and risk for COVID-19 in this population.

Clinical metabolic monitoring to inform metabolic dysregulation in sepsis.

OBJECTIVE: The objective of this study was to offer further evidence of the utility of metabolic monitoring in early recognition of sepsis. Metabolic derangement in sepsis is of increasing interest. Sepsis was redefined as a dysregulated host response to infection, and studies have since emerged advising that disrupted metabolic pathways in sepsis may interfere with the host's ability to convert oxygen to useable energy. Indirect calorimetry (IC) is a metabolic monitoring technology that measures oxygen consumption (V02) and resting energy expenditure (REE). IC offers clinically important, specific information in terms of patient's metabolic state and has been shown to differentiate patients with sepsis from those without. Additionally, IC is more specific than predictive equations used as the established standard for clinical nutrition. RESEARCH METHODS AND PROCEDURES: Data for this retrospective descriptive study were obtained from chart review of records of critically ill patients who received metabolic monitoring while under the care of the nutrition support team. Data were retrieved from January through March of 2020. The cases included were from January 2018 through January 2020. Variables included key demographics, sepsis diagnosis and specific metabolic variables of cellular respiration and energy expenditure. RESULTS: For this all-male sample (N = 56), mean age was 56 years (±17.5). Significant differences were noted in V02 between the two groups of cases (sepsis and non-sepsis); (p = .026, Cohen's d = 0.618); and REE (p = .032, Cohen's d = 0.607). A strong association was found between V02 and sepsis (Eta 0.981). REE as measured by IC was statistically more specific than predictive equation (p < .001, Cohen's d = 0.527). CONCLUSIONS: VO2 and REE were significantly altered in subjects with sepsis in this study, demonstrating that IC may be a useful tool in identifying sepsis. This study was based on an earlier pilot which yielded similar results. Indirect calorimetry can be easily performed clinically, offering specific metabolic information that can be helpful in the determination of a diagnosis of sepsis. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution to this manuscript. The study design, analysis of retrospective data, and manuscript preparation were completed entirely by the authors. IMPLICATIONS FOR CLINICIANS: Sepsis remains one of the number one killers of hospitalized patients globally Current means of identifying sepsis remain overly sensitive and under-specific, making recognition of sepsis challenging for Emergency Clinicians Metabolic monitoring can be done easily in the clinical setting by nurses and respiratory therapists. Metabolic monitoring has the capability of offering further information specific to the identification of sepsis, and to further understanding of the altered metabolic phenotype of patients with sepsis.

Mitochondrial Dysregulation in Sepsis: A Literature Review.

BACKGROUND: Until 2016, the condition Sepsis was widely understood to be the systemic immune response syndrome in the presence or suspicion of an infectious source. Systemic immune response syndrome, an adaptive response, has been repeatedly demonstrated to lack specificity for sepsis. The current definition of sepsis describes a dysregulated host response to infection, yet the dysregulated nature of the response has yet to be defined. Successful recognition and management of sepsis are critically dependent on understanding and operationalizing the definition of sepsis. OBJECTIVE: The authors sought to review the current literature on sepsis and its relationship to oxygen downregulation within the mitochondria along the electron transport chain. METHODS: Articles retrieved from databases PubMed and CINAHL, pertaining to human cells, post 2001, in English, original experimental, quasi-experimental, or cohort design. Articles were selected and retrieved by the first author and synthesized by both authors. RESULTS: The 10 articles included in the review were all bench science cellular studies. They demonstrated consistent, statistically significant differences when investigating mitochondrial oxygen downregulation in sepsis versus control, offering strong, statistically significant support for the hypothesis of mitochondrial dysregulation in the septic host. CONCLUSIONS: The evidence makes a compelling case for mitochondrial dysregulation to inform the current definition of sepsis as a dysregulated host response. As the evidence points to a linear, progressive time/exposure-dependent disruption in oxygen downregulation in sepsis at the cellular level, it lends credence to the recommendations for early intervention and its relationship with survivability. Time is not on the side of the individual with sepsis.