RELIEF

Population

• Patients at increased risk of complications while undergoing major abdominal surgery.

Intervention

Restrictive intravenous-fluid regimen during and up to 24 hours after surgery (median intake 3.7 liters among 1490 patients; IQR 2.9-4.9).

Comparator

Liberal intravenous-fluid regimen during and up to 24 hours after surgery (median intake 6.1 liters among 1493 patients; IQR 5.0-7.4).

Key results

• Disability-free survival at 1 year was 81.9% with restrictive fluids vs 82.3% with liberal fluids; hazard ratio for death or disability 1.05 (95% CI 0.88-1.24; P=0.61).
• Among patients with reported intake, median intravenous fluid during and up to 24 hours after surgery was 3.7 liters in 1490 restrictive-group patients vs 6.1 liters in 1493 liberal-group patients (P<0.001).
• Acute kidney injury, a key secondary outcome, was 8.6% with restrictive fluids vs 5.0% with liberal fluids (P<0.001).
• Surgical-site infection (16.5% vs 13.6%; P=0.02) and renal-replacement therapy (0.9% vs 0.3%; P=0.048) were higher with restriction, but those differences were not significant after adjustment for multiple testing. Septic complications or death were 21.8% vs 19.8% (P=0.19).

Harms

• Acute kidney injury was higher with the restrictive regimen (8.6% vs 5.0%; P<0.001).
• Surgical-site infection and renal-replacement therapy were higher with restriction on unadjusted testing, but those differences were not significant after adjustment for multiple testing.

Practice impact

• Do not use a restrictive perioperative fluid strategy to improve 1-year disability-free survival after major abdominal surgery.
• Watch kidney injury when fluids are tightly restricted; RELIEF associated restriction with more acute kidney injury.

Applicability

• Most applicable to patients at increased risk of complications during major abdominal surgery who can be managed with either a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery.

Limitations

• Fluid intake was reported for 1490 patients in the restrictive group and 1493 in the liberal group, not for all 3000 randomized patients.
• Surgical-site infection and renal-replacement therapy differences were not significant after adjustment for multiple testing.
• The trial compared two named fluid strategies; it does not define an optimal milliliter-by-milliliter target for every case.

Common misinterpretations

• RELIEF is not a win for restriction. The primary outcome did not differ, and acute kidney injury was higher with the restrictive regimen.
• Higher unadjusted rates of surgical-site infection and renal-replacement therapy with restriction should not be treated as confirmed effects after the multiple-testing adjustment.