SEPSISPAM Trial Summary
Primary Findings
The SEPSISPAM trial demonstrated that targeting a higher mean arterial pressure (MAP) of 80-85 mmHg compared to the standard 65-70 mmHg in patients with septic shock did not result in significant differences in mortality at either 28 or 90 days. 1
Study Design and Population
The SEPSISPAM trial was a randomized controlled trial examining high versus low MAP goals in patients with septic shock undergoing resuscitation 1. The trial enrolled 776 mechanically ventilated and sedated patients with septic shock across multiple centers 2.
Key Outcomes
Mortality
- No significant difference in 28-day mortality between high-target (80-85 mmHg) and low-target (65-70 mmHg) MAP groups 1
- No significant difference in 90-day mortality between groups 1
Subgroup Analysis: Chronic Hypertension
- Patients with a history of chronic hypertension showed potential benefit from higher MAP targets, particularly in reducing acute kidney injury 3
- Among chronic hypertensive patients with pre-ICU exposure to angiotensin II receptor blockers, the high MAP target group had significantly less severe acute kidney injury (adjusted OR 0.24,95% CI 0.09-0.66, p=0.006) 3
- 297 chronic hypertensive patients were analyzed in this post-hoc analysis 3
Neurological Effects
- Patients in the high-target MAP group (80-85 mmHg) demonstrated significantly higher arousal levels compared to the low-target group (65-70 mmHg) 2
- Maximal Richmond Agitation and Sedation Scale (RASS) scores were significantly higher in the high-target group at days 2,4, and 5, despite similar cumulative sedative drug doses 2
- This suggests improved cerebral perfusion with higher MAP targets 2
Clinical Implications
General Septic Shock Population
- The standard MAP target of 65 mmHg remains appropriate for most patients with septic shock, as higher targets do not improve overall mortality 1
- This finding has been incorporated into major sepsis guidelines, including the 2016 Surviving Sepsis Campaign guidelines 1
Special Populations Requiring Consideration
- Patients with chronic hypertension, particularly those on angiotensin II receptor blockers, may benefit from higher MAP targets (80-85 mmHg) to reduce acute kidney injury risk 3
- Patients requiring improved arousal and cerebral perfusion may benefit from higher MAP targets 2
Integration with Current Guidelines
The SEPSISPAM trial results directly influenced the 2016 Surviving Sepsis Campaign guidelines, which recommend a MAP goal of ≥65 mmHg during initial resuscitation 1. The trial provided evidence that routine targeting of higher MAP does not improve outcomes in unselected populations 1, though individualization based on chronic hypertension history remains a consideration 3.