Higher mean arterial pressure targets increased mortality in septic shock patients with chronic hypertension (RR 1.22, 95% CI 1.05-1.41) compared to standard targets.
Do higher mean arterial pressure targets reduce mortality in patients with septic shock?
Higher MAP targets in septic shock do not improve overall mortality and may increase mortality in patients with chronic hypertension, demonstrating that study-level meta-regressions can suffer from ecological fallacy.
Absolute Event Rate: 0% vs 0%
Introduction: Optimal mean arterial pressure (MAP) targets in septic shock remain controversial, with prior study-level meta-regression suggesting that chronic hypertension modifies treatment effects. However, ecological associations may not reflect individual-level causation. We investigated whether study-level hypertension prevalence predicts treatment effects and compared this to within-study hypertension subgroup analyses. Methods: We conducted a systematic review and meta-analysis following the PRISMA 2020 guideline through multiple literature databases up to October 8, 2025. We included randomized controlled trials (RCTs) comparing higher versus standard MAP targets in septic shock that reported mortality outcomes. We performed random-effects meta-analysis and univariable meta-regression testing six study-level covariates, and pooled within-study hypertension subgroup data using inverse-variance methods. Results: Six RCTs enrolling 4,060 patients were included. Overall mortality showed no significant difference between higher versus standard MAP targets (random-effects risk ratio RR 1.03, 95% confidence interval CI 0.90-1.17, P-value = 0.72, I² = 22.5%). Study-level meta-regression found no significant effect modification by hypertension prevalence or other covariates (all P-values > 0.05) in this six-study subset. However, within-study hypertension subgroup analysis (two trials, 1,405 patients) revealed higher MAP targets increased mortality in hypertensive patients (pooled RR 1.22, 95% CI 1.05-1.41, P-value = 0.009), demonstrating ecological fallacy where aggregate associations contradicted individual-level effects. Conclusions: Our performed study-level meta-regression demonstrated unreliable evidence for effect modification. Within-study hypertension subgroup data suggest higher MAP targets may harm rather than benefit hypertensive patients, contradicting ecological inferences and highlighting the necessity of individual patient data meta-analyses in further, better-sampled studies.
Alshahrani et al. (Sun,) reported a other. Higher mean arterial pressure targets increased mortality in septic shock patients with chronic hypertension (RR 1.22, 95% CI 1.05-1.41) compared to standard targets.