Veno-arterial Carbon Dioxide Partial Pressure Difference (CO2gap) for Early Resuscitation of Septic Shock

Condition(s) studied

Investigational drug(s) / intervention(s)

CO2gap-guided resuscitation strategy: For 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).

Study summary

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

Primary outcome measure(s)

• The primary end point is all-cause mortality at 28 days after randomization — Every day until Day 28

Trial sites (28)

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