Protocolized Reduction of Non-resuscitation Fluids vs Usual Care in Septic Shock

Protocolized Reduction of Non-resuscitation Fluids Versus Usual Care in Septic Shock Patients: A Multicentre Feasibility Trial

The objectives of this feasibility trial are to assess the efficacy and feasibility of methods and procedures of a protocol purposed to compare a reduction of administration of non-resuscitation fluids to usual care in patients with septic shock.

The clinical team caring for participants will not be blinded due to nature of the intervention. The participants, their family and health personnel responsible for outcome assessment at follow-up will be blinded to the allocation of the intervention. The steering group, author group, trial statistician, outcome assessors, prognosticators, statisticians, and the trial coordinating team will be blinded to group allocation.

Participants receive non-resuscitation fluids according to a pre-defined protocol starting within two hours of randomization. The intervention is continued for the duration of the ICU admission up to a maximum of 90 days.

Maintenance fluids are discontinued in participants with positive cumulative fluid balance who are not dehydrated Intravenous fluid and enteral water are given as needed to correct electrolyte disturbances Enteral nutrition with energy density of at least 2 kcal/ml is administered according to local practice Starting 72 hours after inclusion, glucose at a concentration of at least 20% and a maximal dose of 1g/kg/day may be used as nutrition if enteral feeding is not tolerated. Glucose at this dose or lower may be started earlier in patients with insulin dependent diabetes if enteral feeding is not tolerated and local protocol mandates this Parenteral nutrition is administered according to local protocol Intravenous medications are concentrated according to a predefined protocol Patients with neutral or negative cumulative fluid balance receive maintenance and other fluids such that total dose of fluids covers the daily need of water (about 1ml/kg/h)

Participants receive non-resuscitation fluids according to local routines, with the following stipulations: Maintenance fluids (crystalloids and/or glucose and/or enteral water) are given at a dose of 1 ml/kg/h unless local protocol states otherwise Glucose is used at maximal concentration of 10% unless local protocol states otherwise. Medications are concentrated according to local protocol

Fraction of randomised patients with sufficient data for the following clinical outcomes: all-cause mortality, days alive and free of mechanical ventilation, acute kidney injury, and ischemic events in the ICU (cerebral, cardiac, intestinal or limb ischemia)

Fraction of surviving randomized patients who were assessed by European Quality of Life-5 Dimensions 5- Level questionnaire (EQ5D-5L) and The Montreal Cognitive Assessment (MoCA)

Number of patients with one or more of the following complications in the ICU: cerebral, cardiac, intestinal or limb ischemia, or any acute kidney injury

from randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days

Acute kidney injury stages according to Kidney Disease Improving Global Outcomes [KDIGO] criteria, urea, and days alive and free of renal replacement therapy [RRT]

Daily highest dose of noradrenaline, daily lactate, and cardiovascular sequential organ failure assessment [SOFA] score

Number of patients with one or more ischemic events while in the ICU (cerebral, cardiac, intestinal or limb ischemia)

from randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days

Inclusion Criteria: Adult (≥ 18 years of age) Septic shock according to the Sepsis 3 criteria: suspected or confirmed infection AND infusion of vasopressor/inotrope to maintain mean arterial pressure of 65 mmHg or above despite adequate fluid resuscitation AND lactate of 2 mmol/L or above at any time following ICU admission when there was a simultaneous need for vasopressor/inotrope. Inclusion within 12 hours after ICU admission. Exclusion Criteria: Confirmed or suspected pregnancy

Beginning 9 months after publication of the main report of this trial individual de-identified data will be available for sharing with researchers who provide a methodologically sound proposal as judged by the steering committee. To gain access, data requestors will need to sign a data access agreement.