Shock, Septic
Conditions
Brief summary
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.
Interventions
* 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)
OTHERUsual care
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
Sponsors
Region Skane
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in fluid administration | Within the first three days after inclusion (days 0-3) | Total difference in litres of administered fluids between groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with sufficient clinical outcome data | Within 90 days after inclusion | 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) |
| Proportion of participants assessed by EQ5D-5L and MoCA | 6 months after inclusion | 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) |
| Inclusion of eligible patients | During inclusion | Fraction of all eligible patients who were randomised and consented |
| Protocol violations | Within 90 days after inclusion | Fraction of patients experiencing at least one protocol violation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total volume of non-resuscitation fluids administered | Within the first three days (days 0-3) and within the first five days (days 0-5) after inclusion | Total volume of non-resuscitation fluids administered |
| Renal function | Within 90 days after inclusion | Acute kidney injury stages according to Kidney Disease Improving Global Outcomes \[KDIGO\] criteria, urea, and days alive and free of renal replacement therapy \[RRT\] |
| Gastrointestinal function | Within 90 days after inclusion | Days alive with full enteral nutrition |
| Total volume of resuscitation fluids administered | Within the first three days (days 0-3) and within the first five days (days 0-5) after inclusion | Total volume of resuscitation fluids administered |
| Mortality | 90 days after inclusion | All-cause mortality |
| Diuretics administered | Within the first five days (days 0-5) after inclusion | Daily dose and type of diuretics administered |
| Hemodynamic stability | Within the first five days (days 0-5) after inclusion | Daily highest dose of noradrenaline, daily lactate, and cardiovascular sequential organ failure assessment \[SOFA\] score |
| Ischemic events | from randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days | Number of patients with one or more ischemic events while in the ICU (cerebral, cardiac, intestinal or limb ischemia) |
| GOSE score | 6 months after inclusion | Glasgow Outcome Scale Extended (GOSE) score |
| Cumulative fluid balance | On day 3 and day 5 after inclusion | Cumulative fluid balance (excluding evaporation) |
| Complications in the ICU | from randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days | 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 |
| Days alive and free of mechanical ventilation | Within 90 days after inclusion | Days alive and free of mechanical ventilation |
| Cognitive function | 6 months after inclusion | Cognitive function measured using MoCA |
| Health-Related Quality of Life | 6 months after inclusion | Health-Related Quality of Life measured using the EQ5D-5L questionnaire |
Countries
Sweden
Outcome results
None listed