Abstract
BACKGROUND: Sepsis-associated encephalopathy (SAE) may be worsened by early systemic insults. We aimed to investigate the association of early systemic insults with outcomes of critically ill patients with severe SAE. METHODS: We performed a retrospective analysis using data from the French OUTCOMEREA prospective multicenter database. We included patients hospitalized in intensive care unit (ICU) for at least 48 h with severe SAE (defined by a score on the Glasgow Coma Scale (GCS) ≤ 13 and severe sepsis or septic shock (SEPSIS 2.0 criteria)) requiring invasive ventilation and who had no primary brain injury. We analyzed early systemic insults (abnormal glycemia (< 3 mmol/L or ≥ 11 mmol/L), hypotension (diastolic blood pressure ≤ 50 mmHg), temperature abnormalities (< 36 °C or ≥ 38.3 °C), anemia (hematocrit < 21%), dysnatremia (< 135 mmol/L or ≥ 145 mmol/L), oxygenation abnormalities (PaO(2) < 60 or > 200 mmHg), carbon dioxide abnormalities (< 35 mmHg or ≥ 45 mmHg), and the impact of their correction at day 3 on day-28 mortality and awakening, defined as a recovery of GCS > 13. RESULTS: We included 995 patients with severe SAE, of whom 883 (89%) exhibited at least one early systemic insult that persisted through day 3. Compared to non-survivors, survivors had significantly less early systemic insults (hypoglycemia, hypotension, hypothermia, and anemia) within the first 48 h of ICU admission. The absence of correction of the following systemic insults at day 3 was independently associated with mortality: blood pressure (adjusted hazard ratio (aHR) = 1.77, 95% confidence interval (CI) 1.34-2.34), oxygenation (aHR = 1.78, 95% CI 1.20-2.63), temperature (aHR = 1.46, 95% CI 1.12-1.91) and glycemia (aHR = 1.41, 95% CI 1.10-1.80). Persistent abnormal blood pressure, temperature and glycemia at day 3 were associated with decreased chances of awakening. CONCLUSIONS: In patients with severe SAE, the persistence of systemic insults within the first three days of ICU admission is associated with increased mortality and decreased chances of awakening.