Brief 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.

Conditions

• Sepsis - to Reduce Mortality in the Intensive Care Unit
• Septic Shock

Intervention / Treatment

• Procedure: CO2gap-guided resuscitation strategy

Primary Outcome Measures

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

Countries

France

Locations and Investigators

• CHu Angers, Angers, France (Not yet recruiting)
  • Sigismond Lasocki (Principal Investigator)
• CH Aurillac, Aurillac, France (Not yet recruiting)
  • Emanuele TURBIL (Principal Investigator)
• CH de la Côte Basque, Bayonne, France (Recruiting)
  • Hadrien ROZE (Principal Investigator)
• CHU Bordeaux Hôpital Haut Lévèque, Bordeaux, France (Recruiting)
  • Antoine DEWITTE (Principal Investigator)
• CHU Bordeaux Pellegrin Hospital, Bordeaux, France (Recruiting)
  • Matthieu BIAIS (Principal Investigator)
• CHU Clermont-Ferrand Estaing, Clermont-Ferrand, France (Recruiting)
  • Lise Laclautre
  • Emmanuel FUTIER (Principal Investigator)
• CHU Clermont-Ferrand Gabriel Montpied, Clermont-Ferrand, France (Recruiting)
  • Lise Laclautre
  • Thomas GODET (Principal Investigator)
• CHU Dijon, Dijon, France (Recruiting)
  • Grégoire GUINOT (Principal Investigator)
• CHU Grenoble, Grenoble, France (Not yet recruiting)
  • Marie Christine HERAULT (Principal Investigator)
• CH Le puy en Velay, Le Puy-en-Velay, France (Recruiting)
  • Rémi ESPENEL (Principal Investigator)
• HCL - Lyon Sud, Lyon, France (Not yet recruiting)
  • Romain FORT (Principal Investigator)
• HCL Hôpital Edouard Herriot, Lyon, France (Not yet recruiting)
  • Anne Claire LUKASZEWICZ (Principal Investigator)
• AP HM Hôpital la Timone, Marseille, France (Recruiting)
  • Pierre SIMEONE (Principal Investigator)
• CHU Montpellier, Montpellier, France (Recruiting)
  • Samir JABER (Principal Investigator)
• Clinique Saint Jean Sud de France, Montpellier, France (Recruiting)
  • Yassir AARAB (Principal Investigator)
• CH Moulins-Yzeure, Moulins, France (Not yet recruiting)
  • Pierre-antoine PIOCHE (Principal Investigator)
• CHU Nantes, Nantes, France (Recruiting)
  • Paul ROOZE (Principal Investigator)
• CHU Nîmes, Nîmes, France (Not yet recruiting)
  • Claire Roger (Principal Investigator)
• APHP Beaujon, Paris, France (Recruiting)
  • Emmanuel WEISS (Principal Investigator)
• APHP Bicêtre, Paris, France (Recruiting)
  • Benjamin BERGIS (Principal Investigator)
• APHP La pitié Salpêtrière - Anesthésie et soin intensif, Paris, France (Recruiting)
  • Fanny VARDON (Principal Investigator)
• APHP Lariboisière, Paris, France (Recruiting)
  • Maxime COUTROT (Principal Investigator)
• CHU la pitié slapêtrière - Anesthésie Réanimation, Paris, France (Recruiting)
  • Constantin Jean Michel (Principal Investigator)
• CHU Poitiers, Poitiers, France (Recruiting)
  • Quentin SAINT GENIS (Principal Investigator)
• CHU Rennes, Rennes, France (Recruiting)
  • Yoann LAUNEY (Principal Investigator)
• CHRU Strasbourg - Service d'anesthésie-Réanimation médicale, Strasbourg, France (Recruiting)
  • Olivier COLLANGE (Principal Investigator)
• CHU Strasbourg Service d'Anesthésie-Réanimation chirurgicale, Strasbourg, France (Recruiting)
  • Julien POTTERCHER (Principal Investigator)
• Chu Toulouse, Toulouse, France (Recruiting)
  • Fanny VARDON (Principal Investigator)
• CH Vichy, Vichy, France (Not yet recruiting)
  • Loic DOPEUX (Principal Investigator)