Steroid, ascorbic acid, and thiamine in adults with sepsis and septic shock: a systematic review and component network meta-analysis

To assess the effect from individual component in combinations of steroid, ascorbic acid, and thiamine on outcomes in adults with sepsis and septic shock with component network meta-analysis (NMA). We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials from 1980 to March 2021 for randomized controlled trials (RCT) that studied the use of glucocorticoid, fludrocortisone, ascorbic acid, and thiamine in patients with sepsis and septic shock. Citations screening, study selection, data extraction, and risk of bias assessment were independently performed by two authors. The primary outcome was short-term mortality. Secondary outcomes were longer-term mortality, time to resolution of shock and duration of mechanical ventilation. Thirty-three RCTs including 9898 patients presented on short-term mortality. In additive component NMA, patients on ascorbic acid alone (RR 0.74, 95% CI 0.57-0.97) or the combination of glucocorticoid and fludrocortisone (RR 0.89, 95% CI 0.80-0.99) had lower short-term mortality, but only the latter was associated with improved long-term mortality (RR 0.89, 95% CI 0.82-0.98). The use of glucocorticoid or the combination of glucocorticoid, ascorbic acid and thiamine hastened resolution of shock. Component NMA showed glucocorticoid (MD - 0.96, 95% CI - 1.61 to - 0.30) but not ascorbic acid or thiamine shortened the time to resolution of shock. Glucocorticoid shortened the duration of mechanical ventilation (MD - 1.48, 95% CI - 2.43 to - 0.52). In adults with sepsis and septic shock, the combination of glucocorticoid and fludrocortisone improved short-term and longer-term mortality. Glucocorticoid shortened the time to resolution of shock and duration of mechanical ventilation. There was no strong evidence supporting the routine use of thiamine and ascorbic acid, but they were associated with minimal adverse effects.