Restrictive versus Liberal fluids in Septic shock

Tine S. Meyhoff, Peter B. Hjortrup et el(Classic Trial Group-Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care) published study in NEJM comparing restrictive vs standard fluid therapy in septic shock.


This was an international, stratified, parallel-group, open-label, randomized clinical trial in 31 ICUs in Denmark, Norway, Sweden, Switzerland, Italy, the Czech Republic, the United Kingdom, and Belgium. 


1554 patients, 18 years of age or older  who were in the ICU and had septic shock, which was defined as suspected or confirmed infection, a plasma lactate level of 2 mmol per liter (18 mg per deciliter) or higher, receipt of ongoing infusion of a vasopressor or inotropic agent, and receipt of at least 1 liter of intravenous fluids. 

Patients received a median of 3 liters of intravenous fluid before they underwent randomization and were enrolled within 3 hours after admission to the ICU.


The restrictive-fluid group received intravenous crystalloid fluids in small boluses (250 or 500 ml) that could only be given to treat severe hypoperfusion, as defined by lactate levels, mean arterial pressure, mottling, or urine output; to replace documented fluid losses; or to correct dehydration and electrolyte deficiency if the enteral route was contraindicated. The standard-fluid group had no limits on the volume of fluids that could be administered, but management recommendations were based on the 2016 Surviving Sepsis Campaign guidelines. 


The median between-group difference in the volume of intravenous fluids administered was approximately 2 liters. The authors found no significant difference in mortality at 90 days in the total population (the primary outcome), in any of the prespecified secondary outcomes (including renal function) or in the prespecified subgroups, or in the occurrence of ischemic events.


A highly restrictive fluid-management strategy is safe. Even Standard regimen used in this trial was itself restrictive based on 2016 surviving sepsis guidelines, in comparison to older liberal fluid strategies.

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