Prognostic factors associated with mortality in septic shock: a systematic review and meta-analysis

Septic shock is associated with high mortality rates ranging from 30% to 50%. In this systematic review and meta-analysis, we aimed to identify prognostic factors of early mortality in septic shock.

A systematic review and meta-analysis of prognostic factors associated with early mortality in septic shock was performed. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from database inception to Aug 13, 2025, were searched. All observational and randomised controlled trial studies that evaluated prognostic factors and early mortality (in-hospital or up to 31-days) in septic shock were included. Studies were excluded if they evaluated children or were post-mortem studies. Title and abstracts were reviewed by two independent reviewers. Summary data were extracted from published reports. The primary objective was to evaluate prognostic factors associated with mortality, reported as adjusted odds ratios (OR) using generic inverse variance method and random effects model and variables were significant if the p value was less than 0·05. This study was registered with Open Science Framework (OSF: 10.17605/OSF.IO/75H4G).

Of 6814 records identified by our search, 1420 articles were assessed for full-text review, of these, 95 studies of 4 831 379 patients were included. Of 95 included studies, 90 (95%) were observational studies and five (5%) were randomised controlled trials. In 4 831 379 patients, the mean age was 64 years, 58% of participants were male, 42% were female, and early hospital mortality occurred in 1 606 384 patients (33·2% [IQR 29·5-37·3]). Patient factors significantly associated with increased mortality included increasing age (adjusted OR 1·02 per 1 year [95% CI 1·01-1·02; I² =64%; moderate certainty), Black race (1·23 [1·21-1·25]; I² =0%; moderate certainty), hepatic cirrhosis (1·85 [1·64-2·08]; I² =0%; high certainty), malignancy (1·43 [1·09-1·88]; I² =91%; high certainty), and increased Charlson comorbidity index (1·22 per point [1·19-1·25]; I² =0%; high certainty). Presentation factors associated with increased mortality included acute kidney injury (1·88 [1·32-2·68]; I² =86%; high certainty) and higher severity-of-illness scores, including Acute Physiology and Chronic Health Evaluation II score (1·10 per point increase [1·08-1·12]; I² =60%; high certainty), Simplified Acute Physiology Score II (1·08 per point increase [1·06-1·09]; I² =0%; high certainty), and Sequential Organ Failure Assessment (1·21 per point increase [1·15-1·28]; I² =66%; high certainty). Treatment and biochemical factors associated with increased mortality included invasive mechanical ventilation (2·12 [1·00-4·51]; I² =86%; moderate certainty), norepinephrine use (3·60 [2·73-4·74]; I² =0%; high certainty), and elevated serum lactate (1·13 per 1 mmol/L [1·01-1·26]; I² =72%; high certainty).

This systematic review and meta-analysis identified prognostic factors associated with early mortality in septic shock. The identification of these prognostic factors could aid in clinical risk application, goals of care discussions, and identifying the subset of patients at highest and lowest risk of early mortality for patients with septic shock.

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