Higher blood pressure targets in sepsis did not reduce mortality

Image: PD/CDC/Brower 

1. In patients with septic shock, maintaining a higher mean arterial pressure (MAP) target of 80 to 85 mmHg did not have an impact on 28- or 90-day mortality when compared with those maintained at 65 to 70 mmHg. 

2. There was no survival benefit in maintaining patients with a history of hypertension at a higher targeted MAP. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Current guidelines on the management of sepsis recommend using vasopressors to maintain a mean arterial pressure (MAP) of >65 mmHg. However, recent trials have demonstrated that a higher target MAP may benefit septic patients with a history of atherosclerosis or hypertension. In theory, a higher MAP may be required for hypertensive patients because of a rightward shift in their pressure-flow autoregulation to end-organs, but the clinical significance of maintaining a higher MAP in these patients remains controversial as there are also risks associated with aggressive use of vasopressors.

This multi-centre, open-label, randomized trial conducted in France assigned patients to two groups based on MAP target: low-target (65-70 mmHg) versus high-target (80-85 mmHg). There was no significant difference in the primary endpoint of mortality at day 28. Among patients with a history of chronic hypertension, fewer patients in the high-target group required initiation of renal-replacement therapy compared to those in the low-target group, although this did not have an impact on mortality.

For patients with a history of chronic hypertension, antihypertensive regimens and prior patient compliance with medications were not assessed; both of which limit the generalizability of this study. Furthermore, observed mortality in both groups was significantly lower than other similar sepsis trials, and so this study may have been underpowered. Nevertheless, these results raise an interesting point of how MAP targets in septic patients may differ in patients depending on comorbidities.

Click to read the study in NEJM

Click to read an accompanying editorial in NEJM

In-Depth [randomized controlled trial]: This study randomized 776 patients with septic shock to low- and high-target MAP groups maintained using vasopressors (norepinephrine or epinephrine). Baseline characteristics were well-matched for sepsis source, initial hemodynamics, type and dose of vasopressor used as well as prior comorbidities including a history hypertension. The primary outcome of mortality within 28 days was observed in 34.0% and 36.6% of the low- and high-target MAP groups, respectively (p=0.57). Patients in the high-target group received higher doses of vasopressors throughout the entire five-day titration period (p<0.001) and had a higher incidence of atrial fibrillation (low-target vs. high-target, 2.8% vs. 6.7%, p=0.02). When patients with chronic hypertension were analyzed as a subgroup, those randomized to high-target MAP had a lower incidence of doubling of plasma creatinine compared to those in the low-target group (low- vs. high-target, 52.0% vs. 38.9%, p=0.02) and subsequently, fewer patients in the high-target group required renal replacement therapy within the first week (low- vs. high-target, 42.2% vs. 31.7%, p=0.046).

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