The Multicentre Prospective Observational Study on the Management of Septic Shock

1.1. Septic shock Sepsis is currently defined as a life-threatening disease triggered by a dysregulated host response to infection. The most common sites of infection are pulmonary (40-60% of cases), abdominal (15-30%), genitourinary (15-30%), bloodstream, and skin or soft tissue, with significant geographic variation. A pathogen is identified in approximately 60-70% of cases. Multiple non-infectious inflammatory conditions, such as severe trauma, pancreatitis, severe vasculitis, or cardiac arrest associated with ischemia-reperfusion events, can present with pathophysiological abnormalities and presentations identical to those of purely infectious sepsis.

Sepsis represents a major global health problem. An estimated 49 million cases of sepsis and 11 million related deaths occur worldwide each year. The causes, incidence, and outcomes vary by geographic region and age. In addition to being a life-threatening condition, sepsis contributes to the development of other conditions, including cognitive impairment, functional impairment, and new or worsening chronic health problems.

In 2016, the Sepsis-3 group defined septic shock as "a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a higher risk of mortality than in sepsis alone. Patients with septic shock can be clinically identified by the need for vasopressor therapy to maintain a mean arterial pressure ≥ 65 mmHg and a serum lactate level > 2 mmol/L without hypovolaemia" [1]. Septic shock thus represents the most severe form of sepsis, with in-hospital mortality being 42% compared to 25-30% for sepsis without shock [5]. Mortality from septic shock decreased by approximately 35% and 50%, respectively, from 1990 to 2017 [3].

1.2. Management of septic shock Early and effective control of the source of infection is an absolute prerequisite for improving shock. Specific haemodynamic management is based on fluid supplementation of relative and absolute hypovolaemia. In the case of resistance to this fluid resuscitation, the administration of vasopressors counteracts venous and arterial vasoplegia. Failure to achieve the therapeutic targets set with this treatment may lead to the addition of corticosteroids and a second-line vasopressor. In parallel with this treatment, organ failures are compensated.

1.3. Unknown or poorly described clinical aspects The uncertainties regarding the routine clinical management of patients with septic shock, which this study will attempt to address, mainly concern the following elements.

1.3.1. Fluid therapy Type of fluids While guidelines recommend not to use synthetic colloids in sepsis, a debate continues regarding the benefit of preferring balanced crystalloid solution over isotonic saline. Even though the Surviving Sepsis Campaign (SSC) suggests the use of balanced solutions rather than isotonic saline, the effect of this strategy on prognosis remains debated [8]. The choices between these fluids are therefore probably heterogeneous in practice. While the use of albumin is suggested by the SSC for patients in whom large volumes of crystalloids have been administered [7], it is not certain that practitioners resort to it every time this indication arises.

Prediction of fluid responsiveness The SSC guidelines recommend the initial infusion of 30 mL/kg of fluid over the first 3 hours. However, these guidelines have been criticized for not taking into account individual factors that could influence this volume. More recent guidelines from the European Society of Intensive Care Medicine (ESICM), on the other hand, suggest individualizing the volume infused for initial resuscitation based on patient characteristics. Therefore, practices can be heterogeneous.

1.3.2. Time to initiate vasopressor treatment There are theoretical arguments and weak evidence in favour of an "early" initiation of noradrenaline during septic shock. This practice is not established, however, in the absence of recommendations. Practices are therefore very likely heterogeneous.

1.3.3. Second-line vasopressor While it is well established that norepinephrine is the standard first-line vasopressor for septic shock, it has been suspected that high doses of this vasopressor could in themselves have an adverse impact on patients. Vasopressin therefore appears to be a second-line vasopressor treatment, which could have an advantage over increasing norepinephrine doses when vasoplegia is resistant.

However, the question of a benefit of administering vasopressin as a second-line therapy remains open. This is suggested by the SSC guidelines when the norepinephrine dose (base) exceeds 0.25 or 0.5 µg/kg/min. This threshold, however, is not based on solid evidence. Thus, the timing of vasopressin initiation, if used at all, is currently debated, so practices vary.

The role of angiotensin II is even less well defined. The heterogeneity of practices regarding this vasopressor could be influenced in particular by the molecule's price, which could limit its use when resources are limited.

The benefit of administering methylene blue is also not clearly demonstrated, and this molecule is not currently included in consensus recommendations [14]. Here again, the use of this drug likely varies among centres and practitioners.

1.3.4. Corticosteroids Although it is well established that there is relative adrenal insufficiency during septic shock and that their administration restores the effectiveness of vasopressors, the effect of this administration on strong prognostic criteria remains heterogeneous according to the studies. In addition, the moment when corticosteroid supplementation should be started, and the indication of hydrocortisone is not precisely established. Practices are probably variable.

1.3.5. Methods used for haemodynamic monitoring of patients While blood pressure monitoring is performed for all patients in shock, the use of an arterial catheter for invasive monitoring likely varies depending on practices and available resources. Central venous pressure is also likely inconsistently measured, although the 2025 ESICM guidelines state that it should be measured in all patients in shock with a central venous arterial catheter.

Shock is defined by a reduction in tissue perfusion [20]. The means for clinical assessment are limited. Monitoring skin recoloration time provides effective management compared to monitoring arterial lactate levels in terms of prognosis. However, the frequency with which this index is measured likely varies. Finally, the recent ESICM 2025 guidelines on shock monitoring state that cardiac output should be monitored in patients in shock resistant to initial treatment. Whether this practice is adopted, the time at which monitoring is implemented, and the tools used for monitoring are most likely variable. Available resources probably play a role in this heterogeneity of practice.

1.4. Investigated issues Although there are published recommendations on the management of shock in general and septic shock in particular, it is unknown to what extent these recommendations are followed or achievable. One also lacks knowledge about the barriers to their implementation and the impact of heterogeneity in care on patient outcomes.

Our study aims to describe, in a large population of critically ill patients with septic shock, management procedures, the applicability of existing guidelines, and centre characteristics.

Inclusion criteria

• Age ≥18 years
• Hospitalization in intensive care unit
• Presence of septic shock, defined by the SEPSIS-3 criteria:

• Suspected or documented infection
• Acute elevation of the SOFA score ≥2 points
• Persistent hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation

Exclusion criteria

• Refusal to participate by the patient's relatives or the patient themselves.
• Patient already hospitalized in the ICU at the time of inclusion. It should be noted that prior inclusion in the study does not constitute an exclusion criterion.