CLASSIC Trial

NEJM

June 17, 2022

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

What was the research question?

  • Does the use of restrictive fluid strategy reduce 90-day mortality in patients with septic shock compared to standard fluid strategy?


How did they do it?

  • An international, randomized trial at 31 centers in Denmark, Norway, Sweden, Switzerland, Italy, the Czech Republic, the United Kingdom, and Belgium.

  • 1554 patients with septic shock who received at least 1 liter of intravenous fluid within 12 hours of sepsis onset were randomized to receive restricted intravenous fluid (770 patients) or standard intravenous fluid therapy (784 patients).

  • In the restrictive fluid strategy, patients were allowed to get fluid for evidence of hypoperfusion, fluid loses, dehydration, or for daily intake of at least 1 liter. In the standard group, patients were given fluid as per the surviving sepsis campaign, for fluid loses, dehydration, or for maintenance based on a local protocol.

  • The primary outcome was 90-day mortality of any caused since randomization.


What did they find?

  • Median fluid was significantly lower in the restrictive group compared to the standard (1798 vs. 3811 ml).

  • 90-day mortality was not significantly in the restrictive group compared to the standard group (42.3% vs. 42.1%, adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P=0.96).

  • Serious adverse events in the ICU were not significantly different in the restrictive group compared to the standard (29.4% vs. 30.8%, adjusted absolute difference, −1.7 percentage points; 99% CI, −7.7 to 4.3).

  • At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups.


Are there any limitations?

  • No blinded.

  • Patients received some fluid before enrollment.

  • Some protocol violations occurred.

  • The assumed difference of 7% in the 90-day mortality may have been large to detect statistical difference.


What does it mean?

  • Restrictive fluid strategy did not reduce 90-day mortality in patients with septic shock compared to standard fluid strategy.

  • Continue to use standard fluid strategy as per 2016 surviving sepsis campaign waiting modification of guidelines.

CLASSIC Trial