Purpose sepsis has broad implications for both clinical care and interventional trial design. However, reasons for death in sepsis remain poorly understood. We sought to characterize reasons for in-hospital mortality in a population of patients with sepsis or septic shock. Materials and methods We performed a retrospective review of patients admitted to the intensive care unit with sepsis or septic shock who died during their index admission. Reasons for death were classified into 6 categories determined a priori by group consensus. Interrater reliability was calculated and Fleiss κ reported. The associations between selected patient characteristics (eg, serum lactate) and reason for death were also assessed. Results One hundred fifteen patients were included. Refractory shock (40%) and comorbid withdrawal of care (44%) were the most common reasons for death. Overall interrater agreement was substantial (κ = 0.61, P < .01). Lactate was higher in patients who died because of refractory shock as compared with those who died for other reasons (4.7 vs 2.8 mmol/L, P < .01). Conclusion In this retrospective cohort, refractory shock and comorbid withdrawal of care were the most common reasons for death. Following prospective validation, the classification methodology presented here may be useful in the design/interpretation of trials in sepsis.

Aim We hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. We also assessed the association between microcirculatory dysfunction and inflammatory markers in the post-cardiac arrest state. Methods We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield Microscopy. Microcirculatory flow was assessed using the Microcirculation flow index (MFI) at 6 and 24 hours in the cardiac arrest patients, and within 6 hours of Emergency Department admission in the sepsis and control patients. Results We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual microcirculatory blood flow was significantly impaired in post-cardiac arrest patients at 6 hours (MFI 2.6 [IQR: 2 - 2.9]) and 24 hours (2.7 [IQR: 2.3 - 2.9]) compared to controls (3.0 [IQR: 2.9 - 3.0]; p < 0.01 and 0.02, respectively). After adjustment for initial APACHE II score, post-cardiac arrest patients had significantly lower MFI at 6-hours compared to sepsis patients (p < 0.03). In the post-cardiac arrest group, patients with good neurologic outcome had better microcirculatory blood flow as compared to patients with poor neurologic outcome (2.9 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 1.9 – 2.8]; p < 0.03). There was a trend toward higher median MFI at 24 hours in survivors vs. non-survivors (2.8 [IQR: 2.4 – 3.0] vs. 2.6 [IQR: 2.1-2.8] respectively; p < 0.09). We found a negative correlation between MFI-6 and vascular endothelial growth factor (VEGF) (r= −0.49, P= 0.038). However, after Bonferroni adjustment for multiple comparisons, this correlation was statistically non-significant. Conclusion Microcirculatory dysfunction occurs early in post-cardiac arrest patients. Better microcirculatory function at 24 hours may be associated with good neurologic outcome.