This systematic review included 11 studies involving 18,362 adults with septic shock or sepsis-induced hypotension, comparing earlier versus later vasopressor initiation relative to fluid loading. The two multicentre randomized trials were neutral for their primary patient-centred endpoints, with moderate-certainty evidence, despite 1.1–2.1 L separation in 24-hour fluid volume. Observational mortality findings were discordant and rated very low certainty, with reports of lower mortality, higher mortality, and no association. Definitions of early initiation ranged from 25 minutes to three hours, and exposure heterogeneity prevented meta-analysis.
Randomized evidence did not demonstrate improvement in primary patient-centred outcomes despite differences in fluid exposure. Conflicting observational mortality findings do not establish a benefit from earlier vasopressor initiation.
Study limitation: Variable timing anchors and inconsistent definitions of completed fluid resuscitation limit comparability across studies.
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