Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Hospital, Clermont-Ferrand
About this trial
Sepsis is a dysregulated host response to infection that leads to life-threatening organ dysfunction and represents a major healthcare problem. Septic shock is the most severe form, characterized by increased capillary permeability and vasodilation, resulting in hypotension and tissue hypoxia. Early identification and treatment of tissue hypoperfusion are pivotal components of initial resuscitation to limit progression to multiple organ dysfunction and death. The 2021 Surviving Sepsis Guidelines recommend guiding initial resuscitation by targeting decreases in serum lactate levels in patients with elevated lactate. However, although elevated lactate levels may reflect tissue hypoxia, serum lactate is not a direct marker of tissue perfusion. Hyperlactatemia may be attributable to mechanisms other than tissue hypoperfusion, such as accelerated aerobic glycolysis driven by excessive β-adrenergic stimulation or impaired clearance (e.g., in liver failure).
The venous-to-arterial carbon dioxide partial pressure difference (CO₂ gap), which is inversely related to cardiac output, has been shown to reflect the adequacy of venous blood flow to remove CO₂ from tissues. The CO₂ gap is closely linked to microcirculatory blood flow during the early resuscitation phase of septic shock and may effectively identify persistent tissue hypoperfusion in shock states. A persistently high CO₂ gap during early resuscitation has been associated with significantly higher 28-day mortality and increased Sequential Organ Failure Assessment (SOFA) scores. Moreover, the CO₂ gap has been shown to respond to changes in cardiac output during inotrope infusion in patients with low blood flow, suggesting that its assessment could be useful for therapeutic adjustments. Therefore, there are compelling arguments to evaluate the usefulness of the CO₂ gap in guiding early resuscitation in patients with septic shock.
The investigators postulated that CO₂ gap-guided early resuscitation may be more effective in improving outcomes than lactate-guided resuscitation.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients aged 18 years or older AND
Acutely admitted to a study ICU AND
A suspected or documented site of infection or positive blood culture AND
Acute increase of at least 2 points in the Sequential Organ Failure Assessment (SOFA) score consequent to the infection AND
Disqualifiers
Septic shock for more than 12 hours at the time of screening
Primary cause of hypotension not due to sepsis (e.g., acute bleeding)
Decision not to resuscitate (or to limit full care) or not to intubate taken before obtaining consent
Death is deemed to be imminent or inevitable or patients with an underlying disease process with a life expectancy of less than 3 months
Trial design
Design model
Parallel
Treatments tested in this trial
CO2gap-guided resuscitation strategy
Procedure/SurgeryFor patients assigned to the interventional arm, adherence to the algorithm will complement clinical practices in the following areas: * Blood sampling for venous blood gas analysis. Blood samples will be taken from an existing central venous catheter; central venous access is common clinical practice in critically ill patients. * The use of dobutamine and blood transfusions in patients showing signs of oxygen deficiency (both will be carried out in accordance with the intended use and conditions of current practice).
Treatment groups
750 Participants
are divided into 2 treatment groupsGroup A: CO2gap-guided resuscitation strategyExperimental treatment 1 intervention
Group B: Lactate level-guided resuscitation strategyNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
The primary end point is all-cause mortality at 28 days after randomization
Time frame
Every day until Day 28Secondary outcomes
1
Key secondary endpoints
Duration of septic shock (i.e., vasopressor use) up to Day 28
Time frame
Every day until Day 282
Key secondary endpoints
All-cause mortality at Day 90
Time frame
Every day until Day 903
Secondary Efficacy Endpoints
Vasopressor-free and inotrope-free days up to Day 28
Time frame
Every day until Day 284
Secondary Efficacy Endpoints
Renal replacement therapy-free days (excluding patients on renal replacement therapy at time of randomization) up to Day 28
Time frame
Every day until Day 28Sponsors and contacts
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Source ClinicalTrials.gov