Impact and Progression of Organ Dysfunction in Patients with Necrotizing Soft Tissue Infections; A multicenter study

Eileen Bulger, University of Washington; Addison May, Vanderbilt University; Sharon Henry, University of Maryland; Adrian Maung, Yale University; Kevin Foster, Maricopa Integrated Health Systems; David Evans, The Ohio State University; Andrew Bernanrd, University of Kentucky; Jacob Quick, University of Missouri; Stephen Cohn, University of Texas; Therese Duane, JPS Health Network; Robert Sawyer, University of Virginia HSC; Irit Segalovich, Atox Bio Ltd; Gregory Maislin, Biomedical Statistical Consulting; David Smith, City of Hope; Leslie Kobayashi, University of California, San Diego; Wayne Dankner, Atox Bio Ltd; Anat Shirvan, Atox Bio Ltd

Necrotizing soft tissue infections (NSTI) represent a rare but devastating disease for which the systemic manifestations have been poorly characterized. In an effort to define an optimal endpoint for clinical trials, the objective of this study was to establish the pattern of organ dysfunction over time  and determine the relationship between organ dysfunction and clinical outcome.

We hypothesized that organ dysfunction on admission and failure of resolution of organ dysfunction would both be associated with poor outcome.

This was a multicenter, retrospective study of NSTI patients presenting to 12 US academic medical centers in 2013. Patients with a surgical diagnosis of NSTI without prior debridement were included. Organ dysfunction was assessed using the modified SOFA score (mSOFA: excluding liver) on admission and on hospital days 1,2,3,7,10 and 14. The presence of organ dysfunction on admission and resolution of organ dysfunction were correlated with ICU-free days (of 28 days), ventilator-free days, number of debridements and mortality.

198 patients were enrolled, 62% male, mean age 51yrs, 40% monomicrobial. The mean mSOFA score on admission was 2.4 ± 3.0 with 49% presenting with mSOFA ≥ 2.0 and 35% with mSOFA ≥ 3. Patients demonstrated worsening of the mSOFA score over the first 24hrs followed by gradual resolution (figure). A mSOFA ≥ 2 at admission was associated with a significant decrease in ventilator-free days (mean 26.9 vs 21.4 days, p< 0.001), and ICU free days (24.1 vs 16.6, p< 0.001), more debridements (mean 1.9 vs 2.4, p=0.01) and higher mortality (2% vs 13.3%, p=0.006). The persistence of organ dysfunction (mSOFA > 1) among survivors at day 14 was also associated with fewer ICU free days (17.8 vs 23.6, p<0.001) and ventilator free days (23.6 vs 27, p=0.001).

Early development of systemic organ dysfunction in patients with NSTI is associated with higher morbidity and mortality. Failure of resolution of organ dysfunction by d14 is also associated with poor outcome. mSOFA score may be a useful marker for patient selection for inclusion in interventional trials and the resolution of organ dysfunction by d14 may be an important clinical endpoint.