Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Summary

Across 11 studies (6,661 patients), there was no overall mortality benefit to very early vasopressor initiation; however, initiation within 1–3 hours after septic shock diagnosis was associated with reduced short-term mortality in subgroup analyses. Considerable heterogeneity underscores the need for standardized definitions and protocols.

Key Findings

• No overall short-term mortality difference between very early and later vasopressor initiation in pooled analysis (OR 0.66; 95% CI 0.36–1.19; I² 82%).
• Subgroup with initiation 1–3 hours after diagnosis showed lower mortality (OR 0.70; 95% CI 0.60–0.82; I² 0%).
• Using septic shock diagnosis as time zero also favored earlier initiation (OR 0.64; 95% CI 0.48–0.85; I² 39%).

Clinical Implications

Consider initiating vasopressors within 1–3 hours of septic shock diagnosis when feasible, while ensuring adequate volume assessment; avoid assuming benefit from “extremely early” initiation without context. Institutions should standardize time-zero definitions and protocols.

Limitations

• High heterogeneity across studies and variable definitions of 'early' initiation.
• Mixture of RCTs and quasi-experimental/observational designs may introduce confounding.

Future Directions

Conduct standardized, protocolized RCTs defining time zero uniformly and comparing initiation windows (e.g., ≤1 h vs 1–3 h vs >3 h) with patient-centered outcomes.