Septic Shock
Conditions
Keywords
Septic shock, Fluid resuscitation
Brief summary
Background: Recent studies have questioned the safety of current fluid resuscitation strategies in patients with septic shock as prospective and observational data suggesting that the resulting fluid overload is associated with mortality. Two strategies have evolved to prevent or minimize fluid overload: restrictive fluid administration or active removal of accumulated fluid. While several small trials show benefits with a restrictive fluid administration regimen, active protocolized de-resuscitation was scarcely evaluated. The combination of both strategies yet warrants systematic evaluation. Aim: This study aims to assess the efficacy and feasibility of an early active de-resuscitation protocol in patients with septic shock. We hypothesize that the application of a structured early de-resuscitation protocol versus standard of care will lead to less fluid overload at day three after ICU admission. Study Intervention: Patients admitted to the ICU with confirmed or suspected septic shock (Sepsis-3 definition) will be randomized (1:1) to either the intervention or standard of care. In the intervention arm, patients are managed according to the REDUCE fluid management protocol during resuscitation and de-resuscitation.
Interventions
OTHERFluid management according to the REDUCE Fluid Protocol
Fluid management according to the protocol will be guided by pre-defined clinical signs for impaired perfusion and fluid overload.
OTHERStandard of care
Fluid resuscitation and de-resuscitation will be managed according to the standard of care
Sponsors
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors will be blinded to the treatment allocation.
Intervention model description
Patients will be randomized to receive either fluid resuscitation/de-resuscitation according to the REDUCE protocol or standard of care.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients admitted to ICU with the diagnosis of septic shock as defined according to the Sepsis-3 criteria (suspected or confirmed infection AND vasopressor/inotrope ongoing to maintain MAP ≥ 65 mmHg AND Lactate ≥ 2 mmol/l in the last 6 hours
Exclusion criteria
* Age \<18 years * Septic shock for more than 12 hours at the time of screening * Acute burn injury \>/= 10% of the body surface area * Known pregnancy or lactating women * Consent not obtainable due to national legislation * Patients on chronic dialysis * Patients that are known to be allergic to furosemide or metolazone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patient with a negative fluid balance on day 3 | Up to day 3 after ICU admission | Proportion of patients with a negative cumulative fluid balance on day 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with fluid overload at day 3 and ICU discharge | From hospital admission to the end of ICU stay, on average after 7 days | Fluid overload as defined as ((input-output)/admission weight)\*100 |
| Feasibility of the REDUCE fluid protocol | From randomisation until the end of ICU stay, on average after 7 days | Number of REDUCE fluid protocol violations |
| Incidence of ischemic events and severe AKI | Ischemic events and AKI: From randomisation until the end of ICU stay (on average after 7 days), and at day 30; electrolyte and acid-base/medication associated safety endpoints: during ICU stay (on average 7 days) | Number of patients with:ischaemic events, severe AKI (AKIN stage 2 or more); respectively episodes of: severe hypernatremia (sodium \>/= 155mmol/l), severe hypokalemia (\< 3.0 mmol/l), severe metabolic alkalosis (pH \>/= 7.55, bicarbonate \>/= 35 mmol/l), anaphylactic reaction to diuretic drug |
| Ventilator-free days at day 30 | Up to 30 days after randomisation | Ventilator free days up to day 30 |
| Vasopressor-free days at day 30 | Up to 30 days after randomisation | Vasopressor free days up to day 30 |
| Renal replacement therapy | Up to 90 days after randomisation | Need for and time on renal replacement therapy |
| Number of patients with need for renal replacement at 90days | Up to 90 days after randomisation | Number of patients with on-going need for renal replacement at 90days |
| All-cause mortality | Up to 90 days after randomisation | At 30days and 90 days after randomization |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORAnna S Messmer, MD
Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
Outcome results
None listed