By Betty Tran, MD, MSc

Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago

Dr. Tran reports no financial relationships relevant to this field of study.

SYNOPSIS: In this multicenter, retrospective study, acute neurologic dysfunction was the organ dysfunction most strongly associated with short- and long-term mortality in patients surviving a sepsis hospitalization.

SOURCE: Schuler A, Wulf DA, Lu Y, et al. The impact of acute organ dysfunction on long-term survival in sepsis. Crit Care Med 2018;46:843-849.

Based on the most recent Sepsis-3 definitions, sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.1 Organ dysfunction is measured by an increase in the Sequential Organ Failure Assessment (SOFA) score; even a modest increase in SOFA score is associated with in-hospital mortality in excess of 10%.1 However, given the heterogeneity in sepsis presentations, it is not clear if different organ dysfunction is associated with different outcomes. In this retrospective study of randomly selected patients admitted for sepsis through the ED at 21 Kaiser Permanente Northern California hospitals, Schuler et al aimed to study the effect of each of six different types of acute, sepsis-related organ failure (hepatic, renal, coagulation, neurologic, cardiac, respiratory) on long-term mortality. Acute organ dysfunction was quantified using the SOFA score, with modification for selected organ systems to include other clinically relevant data and recorded as a maximum at 48 hours and over the course of hospitalization. Outcomes included hospital mortality and post-sepsis mortality only in patients who were discharged alive. Care was taken to adjust for concomitant organ dysfunction in patients who could be experiencing multiple organ dysfunction. Several sensitivity analyses were performed, including a propensity score model to adjust for presepsis/hospital risk factors that could predispose patients to specific organ dysfunctions.

Overall, 30,163 septic patients were evaluated, with a median follow-up time for survivors of 797 days (interquartile range, 384-1,219 days). Overall hospital mortality was 9.4%, one-year mortality was 31.7%, two-year mortality was 44.0%, and three-year mortality was 59.7%. The most prevalent organ dysfunction was cardiac (62.4%), with the least common liver (16.5%). The organ dysfunctions most strongly associated with hospital mortality were neurologic (odds ratio [OR], 1.86; P < 0.001), respiratory (OR, 1.43; P < 0.001), and cardiac (OR, 1.31; P < 0.001).

Acute neurologic dysfunction was the organ dysfunction most strongly associated with increased long-term mortality (for each 1-point increase in SOFA subscore, OR, 1.18; 95% CI, 1.15-1.20; P < 0.001). This finding remained consistent in all sensitivity analyses, including adjustment for other concomitant organ dysfunction, as well as propensity score models accounting for presepsis conditions that influenced acute organ dysfunction more than any other condition.

COMMENTARY

This study adds to the growing body of research focused on long-term patient outcomes and sequelae after a hospitalization for sepsis. We know that acute neurologic dysfunction occurs commonly in septic patients,2 and that it is associated with adverse outcomes;3 hence its incorporation into the quick SOFA score aimed to identify patients at increased risk for poor outcomes due to infection. Although these findings will need to be validated in other studies, Schuler et al suggested that acute sepsis-related neurologic dysfunction is the organ dysfunction that most strongly correlates to short- and long-term mortality.

Strengths of this study included long-term follow-up for a large cohort, detailed adjustment for confounding factors (such as illness severity and concomitant other organ dysfunction), and a sensitivity analyses. The sensitivity analysis included a robust propensity score model that accounted for more than 3,000 diagnosis codes. These codes identified presepsis clinical conditions with clinical face validity that carried the highest likelihood of development of acute organ dysfunction, which allows for one to isolate the effect of sepsis hospitalization rather than chronic organ dysfunction. Whether this is a true causative relationship is unclear based on the retrospective nature of this study. However, this finding may carry implications for sepsis-related in-hospital and discharge prognoses to inform patients’ families/surrogates, as well as provide insight for future investigations into the mechanisms by which sepsis affects long-term survival.

REFERENCES

  1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-810.
  2. Shankar-Hari M, Rubenfeld GD. Understanding long-term outcomes following sepsis: Implications and challenges. Curr Infect Dis Rep 2016;18:37.
  3. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of clinical criteria for sepsis. For the Third International Consensus Definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:762-774.