SEPSISPAM Trial

What was the research question?

• In patient with septic shock, does a higher mean arterial pressure improve mortality compared to a lower mean arterial pressure?

How did they do it?

• Multicenter, open label, randomized trial in 29 centers in France

• 776 patients with septic shock were randomly assigned to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group).

• The primary end point was mortality at day 28.

What did they find?

• 28-day mortality was not significantly different between the high-target group compared to low-target group (36.6% vs. 34%; P=0.57).

• No significant difference in mortality at 90 days with 43.8% compared to 42.3% respectively (P=0.74).

• Serious adverse events did not differ significantly between the two groups (19.1% vs. 17.8%; P=0.64). However, new onset age fibrillation was higher in the high-target group compared to the low-target group (6.7% vs. 2.8%, P=0.02).

• In patients with chronic hypertension (n=340), renal replacement therapy was required at lower frequency in the high-target group compared to low target group (31.7% vs. 42.2%, p=0.046, NNT 9.5), but no difference in mortality.

Are there any limitations?

• The study is underpowered with a higher risk of type II error due to a lower mortality than predicted.

• Slow recruitment process which may limit the external validity of the trial.

• There is a compliance bias in favor of the null hypothesis as 16.5% of patients in the high-target group versus 10.3% (P=0.01) in the low-target failed to achieve the target bold pressure.

What does it mean?

• No difference in 28- or 90-day mortality in patients with septic shock and a mean arterial pressure of 80-85 mm Hg compared to 65-70 mm Hg.

• For the majority of septic shock patients, we target MAP of 65-70 mm Hg and may choose a higher target of 80-85 mm Hg in patients with history of chronic hypertension.