Starting vasopressin earlier in septic shock did not change 28-day mortality

Design

Pragmatic cluster-randomised, cluster-crossover strategy trial (VASSPR)

Population

3,959 adults with septic shock on vasopressors at 13 hospitals in Idaho and Utah

Primary outcome

28-day mortality

Effect

31.8% vs 33.0% (adjusted OR 0.98, 95% CI 0.87 to 1.06)

VASSPR was a pragmatic cluster-randomised, cluster-crossover strategy trial at 13 hospitals in Idaho and Utah. Hospitals alternated monthly between a strategy recommending fixed-dose vasopressin once other vasopressors reached 0.1 micrograms per kg per minute of noradrenaline equivalent and one recommending it at 0.4. It included 3,959 adults with septic shock.

Among patients more likely to be managed differently (peak dose of 0.07 or more), 68.0% received vasopressin under the lower threshold and 42.7% under the higher one. Mortality at 28 days was 31.8% vs 33.0% (adjusted odds ratio 0.98, 95% CI 0.87 to 1.06; adjusted risk difference -0.4 percentage points, 95% CI -2.7 to 1.3). Kidney replacement therapy-free days were the same in both strategies.

The timing of the second vasopressor within this range did not matter for survival. This supports flexibility in practice rather than a fixed trigger.

• Vasopressin started at a lower background dose (0.1) did not lower 28-day mortality compared with a higher dose (0.4).
• Mortality was 31.8% vs 33.0%, with a confidence interval spanning no difference.
• Kidney replacement therapy-free days did not differ between strategies.
• Local protocols can reasonably choose either threshold on this evidence.
• The trial tested a hospital-level strategy, not individual bedside decisions.

Why it matters

It removes a common source of protocol argument: the exact dose at which a second vasopressor should join in.

Don't overread it

It tested two thresholds in a US setting and does not show whether vasopressin itself helps compared with none.

The statistics, in plain English

An adjusted odds ratio of 0.98 with an interval of 0.87 to 1.06 means the data are compatible with a small benefit, no difference or a small harm. A strategy trial compares policies, so only part of the patients in each arm actually received different treatment, which dilutes any effect.

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