Multicenter Observational Study of the Development of Progressive Organ Dysfunction and Therapeutic Interventions in Normotensive Sepsis Patients in the Emergency Department

Abstract

Objectives: Progressive organ dysfunction is the leading cause of sepsis-associated mortality; however, its incidence and management are incompletely understood. Sepsis patients with moderately impaired perfusion (serum lactate 2.0 to 3.9 mmol/L) who are not in hemodynamic shock ("preshock" sepsis patients) may be at increased risk for progressive organ dysfunction and increased mortality. The objectives of this study were to: 1) quantify the occurrence of progressive organ dysfunction among preshock sepsis patients, 2) examine if there were baseline differences in demographic and physiologic parameters between preshock sepsis patients who experienced progressive organ dysfunction and those who did not, and 3) examine if intravenous (IV) fluid administered in the emergency department (ED) differed between these two groups of patients.Methods: This was a prospective, observational study in four urban EDs targeting the preshock sepsis population, defined as adults (18 years or older) with suspected infection, serum lactate between 2.0 and 3.9 mmol/L, and without hypotension (systolic blood pressure [sBP] < 90 mm Hg or mean arterial pressure [MAP] < 70 mm Hg) or requiring mechanical ventilation at ED presentation. The primary composite outcome was progressive organ dysfunction, defined as a rise in the Sequential Organ Failure Assessment (SOFA) score of ! 1, vasopressor use, mechanical ventilation use within 72 hours after ED presentation, or in-hospital death. The secondary outcomes were any intensive care unit (ICU) admission, and total ICU and hospital lengths of stay (LOS).Results: Among 94 preshock sepsis patients, the primary composite outcome occurred in 24 of 94 (26%). In patients with the primary outcome, 22 of 24 (92%) experienced a rise in SOFA score of ! 1, five of 24 (21%) received vasopressor agents, and seven of 24 (30%) required mechanical ventilation. There were no baseline demographic or physiologic parameter differences between patients who met the primary outcome versus those who did not, while patients with the primary outcome had a higher average SOFA score at admission (2.4 vs. 1.3, p = 0.011) and at all subsequent time points. Median IV fluid volume administered to all preshock sepsis patients during their ED stay was 1,225 mL (interquartile range [IQR] = 712 to 2,000 mL) and did not differ significantly between patients with (1,150 mL, IQR = 469 to 2,000 mL) or without (1,250 mL, IQR = 750 to 2,000 mL) the primary outcome (p = 0.73). Patients with progressive organ dysfunction or death were more likely to be admitted to an ICU (50% vs. 20%, p < 0.01) and have an increased median hospital LOS (6 days vs. 3 days, p = 0.005), compared to those without progressive organ dysfunction.

Predictors of Patients Who Present to the Emergency Department With Sepsis and Progress to Septic Shock Between 4 and 48 Hours of Emergency Department Arrival*

“…In addition, Kennedy et al (4) found a nonsignificant trend of increased bands more than 5% in patients with sepsis requiring transfer to the ICU within 4 hours, and in our study, we found that bandemia (> 10%) was associated with progression from sepsis to septic shock (3,17). Arnold et al (18) found only the initial level of organ dysfunction as measured by a modified Sequential Organ Failure Assessment score was associated with progressive organ dysfunction in a multicenter cohort of preshock sepsis patients. Gender, initial individual physiologic variables including serum lactate, and comorbidities were not associated with progressive organ dysfunction (3).…”

Fluid Volume, Lactate Values, and Mortality in Sepsis Patients with Intermediate Lactate Values

“…A handful of smaller studies evaluated patients with sepsis with intermediate lactate values and reported similar findings (15,16,18,(28)(29)(30). In our large, modern cohort, we confirm that rising index lactate values were associated with increased mortality.…”

“…We believe that this is an important consideration that should be addressed by future prospective study. Finally, this study did not address clinical changes after index lactate values (e.g., incident hypotension or organ failure) that might have altered lactate values or fluid administration practice independently of our observed variables (14,18,29,41).…”

Predictive monitoring for sepsis and necrotizing enterocolitis to prevent shock

“…Depending on the number of SIRS criteria and the thresholds for laboratory values such as serum lactate, these systems have a wide range of sensitivity and false positives [45,46]. Implementation of these early warning systems in various hospital settings has led to improved outcomes, including decreased time to antibiotic administration [47] and less progression to multi-organ failure [48]. For infants and children, the Pediatric Early Warning System (PEWS) was developed as a tool for bedside caregivers to assess cardiorespiratory and neurologic deterioration but its impact on sepsis-related outcomes has not been tested [49].…”