Association between time to target mean arterial pressure and 90-day mortality in septic shock: a post hoc analysis of the OPTPRESS trial.

BACKGROUND: In septic shock resuscitation, maintaining a mean arterial pressure (MAP) of at least 65 mmHg is recommended; however, the clinical relevance of the time required to achieve target MAP remains unclear. We evaluated the association between time to target MAP (TTT-MAP) and clinical outcomes in septic shock.

METHODS: This post hoc secondary analysis used data from the OPTPRESS randomized controlled trial. TTT-MAP was defined as the time from randomization to first attainment of the randomized-arm lower-bound MAP target (80 mmHg in the high-target arm; 65 mmHg in the low-target arm) and categorized as <1 h, 1-3 h, 3-6 h, 6-12 h, ≥12 h, and unreached. The primary outcome was 90-day all-cause mortality. The primary analysis used doubly robust estimation. Secondary analyses included continuous TTT-MAP modeling, Cox proportional hazards models, and assessments of hypotension burden and vasopressor exposure.

RESULTS: Among 516 patients enrolled in OPTPRESS, 476 were included in the complete-case cohort. In the primary six-category analysis, compared with TTT-MAP <1 h, the delayed-attainment category (≥12 h) was associated with higher 90-day mortality (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.11-1.98; p = 0.008), whereas 1-3 h, 3-6 h, and 6-12 h were not. In the continuous analysis restricted to patients who achieved target MAP within 24 h, TTT-MAP was not significantly associated with 90-day mortality per 1-h increase (aOR 1.025, 95% CI 0.972-1.082; p = 0.362). In Cox models, prolonged TTT-MAP (≥12 h or unreached) was associated with increased 90-day mortality versus early attainment (<12 h and reached) (adjusted hazard ratio [aHR] 3.24, 95% CI 2.19-4.80; p < 0.001).

CONCLUSION: In this secondary analysis of the OPTPRESS trial, delayed attainment of the randomized lower-bound MAP target was associated with higher 90-day mortality. However, because TTT-MAP reflects time to first target attainment rather than the hypotension burden itself, these findings should not be interpreted as defining a clinically acceptable duration of hypotension or a threshold effect.