Daily Sepsis Research Analysis

BACKGROUND: Inflammatory cytokines play a pivotal role in septic shock, driving tissue injury and circulatory failure. Hemoadsorption has been proposed as an extracorporeal strategy that removes inflammatory mediators. Patient selection and treatment timing may be integral to clinical benefit. OBJECTIVES: To determine whether adjunctive hemoadsorption with the HA-330 cytokine adsorber reduces 28-day mortality in patients with septic shock requiring high-dose vasopressors, compared with standard treatment alone. METHODS: This multicenter, randomized controlled trial enrolled patients with septic shock requiring norepinephrine ≥ 0.2 mcg/kg/min at two tertiary care centers in Thailand. Participants were assigned 1:1 to standard treatment alone (ST group) or standard treatment with two 3-hour sessions of hemoadsorption using HA-330 (HA group). The primary outcome was 28-day mortality. The trial was terminated early at the second pre-planned interim analysis due to slow recruitment and funding constraints before reaching the planned sample size of 206 participants. RESULTS: A total of 128 participants were enrolled; 65 were assigned to the ST group and 63 to the HA group. The median age was 67 years, and baseline characteristics were largely comparable between groups. By day 28, 38 of 65 (58%) participants in the ST group and 28 of 63 (44%) in the HA group had died (relative risk, 0.76; 95% CI, 0.54-1.07; P = 0.16; hazard ratio, 0.68; 95% CI, 0.44-1.07; P = 0.09). No significant differences were observed in organ support-free days, shock reversal, vasopressor doses, or inflammatory markers. In a post-hoc Cox model adjusted for IL-6 (log-transformed) and VIS at hour 0, the hazard ratio for 28-day mortality was 0.62 (95% CI, 0.39-0.97; P = 0.037). No serious adverse events were reported in either group. CONCLUSIONS: In this randomized trial which was terminated early, adjunctive hemoadsorption with HA-330 in patients with septic shock requiring high-dose vasopressors did not statistically reduce 28-day mortality. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05136183); registered November 29, 2021.

IMPORTANCE: Guidelines suggest administering at least 30 mL/kg of initial fluid to patients with sepsis-induced hypoperfusion. However, there is uncertainty regarding the benefits of fluid resuscitation in patients with severe cardiac or kidney comorbidities or intermediate elevation of lactate level (18.0-36.0 mg/dL). OBJECTIVE: To evaluate the association of 30 mL/kg or more of fluid administered within 6 hours of hospital arrival with 30-day mortality across key target populations with community-onset sepsis. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults hospitalized for community-onset sepsis in 67 hospitals in the Michigan Hospital Medicine Safety Consortium (discharge dates from December 2021 to January 2025) who had an indication for fluid resuscitation (ie, hypotension or lactate level of 18.0 mg/dL or greater) within 3 hours of hospital arrival. Data were analyzed from November 26, 2024, to November 16, 2025. EXPOSURE: Receipt of at least 30 mL/kg vs less than 30 mL/kg fluid in the first 6 hours after hospital arrival. Fluid volume included all crystalloid fluid and blood products. MAIN OUTCOMES AND MEASURES: Association between administration of 30 mL/kg or more of fluid within 6 hours of hospital arrival and 30-day mortality using weighted regression models adjusted for patient characteristics. Target populations were defined by (1) fluid indication: hypoperfusion (hypotension or lactate level >36.0 mg/dL) vs intermediate lactate elevation (18.0-36.0 mg/dL) and (2) presence of severe comorbidities that might increase risk of fluid overload (left ventricular ejection fraction <40%, severe-to-critical aortic stenosis, or end-stage kidney disease). Secondary analyses used adjusted logistic regression models with restricted cubic spline terms to evaluate associations of fluid volume administered with mortality. RESULTS: Among 43 321 patients hospitalized for community-onset sepsis, 25 481 (58.8%) had an indication for fluid resuscitation and were included in the study (median age, 71 years [IQR, 61-80 years]; 50.5% male; 37.0% with body mass index >30.0, calculated as weight in kilograms divided by height in meters squared). A total of 12 943 (50.8%) had hypoperfusion without severe comorbidities; 1741 (6.8%), hypoperfusion with severe comorbidities; 9974 (39.1%), intermediate lactate elevation without severe comorbidities; and 823 (3.2%), intermediate lactate elevation with severe comorbidities. Administration of 30 mL/kg or more of fluid vs less than 30 mL/kg was associated with lower adjusted 30-day mortality rates in patients with hypoperfusion without severe comorbidities (26.0% [95% CI, 24.9%-27.2%] vs 30.4% [95% CI, 28.8%-32.0%]; adjusted absolute difference [diff], -4.4 percentage points [pp] [95% CI, -6.1 to -2.7 pp]) and intermediate lactate elevation without severe comorbidities (12.0% [95% CI, 10.6%-13.5%] vs 13.9% [95% CI, 12.9%-14.8%]; diff, -1.8 pp [95% CI, -3.6 to -0.1 pp]). For patients with hypoperfusion and severe cardiac or kidney comorbidities, the association between 30-day adjusted mortality and receiving 30 mL/kg or more of fluid vs less than 30 mL/kg was not statistically significant (34.7% [95% CI, 30.8%-38.6%] vs 38.8% [95% CI, 35.8%-41.8%]; diff, -4.1 pp [95% CI, -9.0 to 0.8 pp]), although spline models indicated decreasing mortality with fluid resuscitation of 30 mL/kg or more of fluid. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with community-onset sepsis, initial administration of 30 mL/kg or more of fluid was associated with lower 30-day mortality among patients who had either hypoperfusion or intermediate lactate elevation without severe cardiac or kidney comorbidities. The findings suggest that broader application of at least 30 mL/kg of initial fluid resuscitation for sepsis in patients with hypoperfusion and cardiac or kidney comorbidities or intermediate lactate elevation may reduce sepsis-related mortality.

BACKGROUND: Calprotectin, a neutrophil activation marker, is a promising diagnostic biomarker for infection and sepsis, but its usefulness in the emergency department (ED) is unclear. The aim of this study was to investigate the diagnostic value of calprotectin for sepsis and the source of infection in the ED. METHODS: A total of 583 prospectively included patients presenting with suspected sepsis to the ED of a university hospital in southern Sweden were analyzed. Calprotectin was measured in plasma samples obtained at admission. RESULTS: Mean age was 69 years and 49% were female. Calprotectin discriminated between sepsis and noninfectious systemic inflammatory response syndrome with an area under the curve (AUC) of 0.63, but was not an independent predictor in multivariable analysis including C-reactive protein (CRP). The Modified Early Warning Score did not show any discriminatory ability. Calprotectin and CRP discriminated between lower respiratory tract infection and (1) upper respiratory tract infection, (2) urinary tract infection, and (3) other sources of infection. Addition of calprotectin to CRP significantly increased the AUC for lower versus upper respiratory tract infection and lower respiratory tract infection versus urinary tract infection. Calprotectin was an independent predictor for all outcomes while CRP was only an independent predictor of lower versus upper respiratory tract infection. CONCLUSIONS: Calprotectin may improve differentiation of lower respiratory tract infections from upper respiratory tract infections and urinary tract infections in patients presenting to the ED with sepsis. Further research is needed to clarify if calprotectin adds diagnostic value to standard clinical assessment.