Restriction of Intravenous Fluid in ICU Patients with Septic Shock

Abstract

BACKGROUNDIntravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODSIn this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTSWe enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (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. CONCLUSIONSAmong adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.

Surviving Sepsis Campaign Guidelines 2021: highlights for the practicing clinician

“…The subsequent publication of the CLASSIC (Conservative vs Liberal Fluid Therapy in Septic Shock) trial, which compared restrictive vs standard IV fluid therapy in patients with septic shock, did not show a difference between these 2 approaches in patient mortality or adverse events up to 90 days. 26 This suggests that either approach remains reasonable and the panel's suggestion to give fluids only in patients with signs of hypoperfusion continues to be a prudent approach to ongoing fluid therapy. Future trials may provide more evidence on the optimal dose of fluids and timing of vasopressor initiation in septic patients.…”

Restrictive fluid therapy and high-dose vitamin C in sepsis

“…Usual care treatment consists of antibiotics, infection source control, fluid resuscitation and vasopressors, with the aim of reducing the microbial burden and supporting organ function 3 . The recent Conservative versus Liberal Approach to Fluid Therapy in Septic Shock (CLASSIC) 4 and Lessening Organ Dysfunction with Vitamin C (LOVIT) 5 trials provide incremental evidence on fluid volume for resuscitation and treatment with high-dose intravenous vitamin C, respectively, in patients with sepsis (Table 1 ).…”

“…The recent Conservative versus Liberal Approach to Fluid Therapy in Septic Shock (CLASSIC) 4 and Lessening Organ Dysfunction with Vitamin C (LOVIT) 5 trials provide incremental evidence on fluid volume for resuscitation and treatment with high-dose intravenous vitamin C, respectively, in patients with sepsis (Table 1 ).…”

“…Fluid therapy is a cornerstone of the management of severe sepsis; however, insufficient evidence exists to guide recommendations on the appropriate volume for managing haemodynamic instability after initial resuscitation 3 . Liberal fluid therapy is common, despite concerns about the potentially harmful effects of high fluid volumes 4 . For example, in the Australian Resuscitation In Sepsis Evaluation (ARISE) trial, which included 1,600 adults with septic shock, patients in the usual care group received an average of >80 ml/kg of intravenous fluid in the first 72 h after enrollment 6 .…”

“…The CLASSIC trial is a European, parallel-group, open-label randomized study that compared a restrictive versus standard fluid therapy regimen in 1,550 adults with septic shock 4 . The primary outcome was 90-day mortality and the secondary outcomes included serious adverse events, defined as a composite of ischaemic events and acute kidney injury (AKI).…”