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Although there are published guidelines for the management of shock in general and septic shock in particular, the extent to which these guidelines are adhered to or achievable is unknown. Our study aims to describe, in a large population of critical care patients, the management procedures for septic shock, the applicability of existing guidelines, and the characteristics of the centres.
The primary objective is to assess current clinical practices for the treatment and monitoring of patients with septic shock.
The secondary objectives are to investigate the association of current clinical practices for the treatment and monitoring with 28-day all-cause mortality, to assess the association of current clinical practices for the treatment and monitoring with other outcomes, including 90-day all-cause mortality, ICU length of stay, days without renal replacement therapy, days without vasopressors support and days without invasive mechanical ventilation, to assess the factors that influence the disparity of practices, among the severity of the patients, the country, the availability of drugs and devices and to measure the relative frequency of balanced fluid and isotonic saline administration.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| septic shock patients | Any patients ≥18 years, hospitalization in intensive care unit with a suspected or documented infection and requiring vasopressors |
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| Measure | Description | Time Frame |
|---|---|---|
| clinical practices for the treatment and monitoring of patients with septic shock | To assess current clinical practices for the treatment and monitoring, including sequence of their use, of patients with septic shock | up to day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| association of clinical practices for the treatment with 28-day all-cause mortality | To investigate the association of current clinical practices for the treatment and monitoring with 28-day all-cause mortality. | up to day 90 |
| association of clinical practices for the hemodynamic monitoring with 28-day all-cause mortality |
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Inclusion Criteria:
Age ≥18 years
Hospitalization in intensive care unit
Presence of septic shock, defined by the SEPSIS-3 criteria:
Exclusion Criteria:
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Patients ≥18 years, hospitalization in intensive care unit with a septic shock
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xavier Monnet, MD, PhD | Contact | +33 (0)1 45 21 35 39 | xavier.monnet@aphp.fr | |
| Christopher Lai, MD, PhD | Contact | +33(0)680821557 | christopher.lai@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Xavier Monnet, MD, PhD | AP-HP, Service de médecine intensive-réanimation, Hôpital de Bicêtre, DMU 4 CORREVE, Inserm UMR S_999, FHU SEPSIS, CARMAS, Université Paris-Saclay, 78 rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France. | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35472583 | Result | Lakbar I, Munoz M, Pauly V, Orleans V, Fabre C, Fond G, Vincent JL, Boyer L, Leone M. Septic shock: incidence, mortality and hospital readmission rates in French intensive care units from 2014 to 2018. Anaesth Crit Care Pain Med. 2022 Jun;41(3):101082. doi: 10.1016/j.accpm.2022.101082. Epub 2022 Apr 25. | |
| 31151462 | Result |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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To investigate the association of current clinical practices for the hemodynamic monitoring with 28-day all-cause mortality. |
| up to day 90 |
| association of clinical practices for the treatment and monitoring with 90-day all-cause mortality | To investigate the association of current clinical practices for the treatment and monitoring with 90-day all-cause mortality | day 90 |
| association of clinical practices for the treatment and monitoring with days without renal replacement therapy | To investigate the association of current clinical practices for the treatment and monitoring with days without renal replacement therapy | day 90 |
| association of clinical practices for the treatment and monitoring with days without vasopressor support | To investigate the association of current clinical practices for the treatment and monitoring with days without vasopressor support | day 90 |
| association of clinical practices for the treatment and monitoring with days without invasive mechanical ventilation | To investigate the association of current clinical practices for the treatment and monitoring with days without invasive mechanical ventilation | day 90 |
| Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019 May 31;23(1):196. doi: 10.1186/s13054-019-2478-6. |
| 30772908 | Result | Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Cavalcanti AB, Bakker J, Hernandez G, Alegria L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavez N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, Gonzalez H, Arancibia JM, Munoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Munoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpan B, Fasce F, Luengo C, Medel N, Cortes C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, Gonzalez MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudin A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, Garcia F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garces P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Perez V, Delgado G, Lopez A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderon A, Paredes G, Barberan JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernan Portilla A, Davila H, Mora JA, Calderon LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071. |
| 41236566 | Result | Monnet X, Messina A, Greco M, Bakker J, Aissaoui N, Cecconi M, Coppalini G, De Backer D, Edul VK, Evans L, Hernandez G, Hunsicker O, Ince C, Kaufmann T, Levy B, Malbrain MLNG, Mebazaa A, Myatra SN, Ostermann M, Pinsky MR, Saugel B, Savi M, Singer M, Teboul JL, Vieillard-Baron A, Vincent JL, Chew MS. ESICM guidelines on circulatory shock and hemodynamic monitoring 2025. Intensive Care Med. 2025 Nov;51(11):1971-2012. doi: 10.1007/s00134-025-08137-z. Epub 2025 Nov 14. |
| 40470636 | Result | Annane D, Briegel J, Granton D, Bellissant E, Bollaert PE, Keh D, Kupfer Y, Pirracchio R, Rochwerg B. Corticosteroids for treating sepsis in children and adults. Cochrane Database Syst Rev. 2025 Jun 5;6(6):CD002243. doi: 10.1002/14651858.CD002243.pub5. |
| 19186278 | Result | Maxime V, Lesur O, Annane D. Adrenal insufficiency in septic shock. Clin Chest Med. 2009 Mar;30(1):17-27, vii. doi: 10.1016/j.ccm.2008.10.003. |
| 39965613 | Result | Bauer SR, Wieruszewski PM, Bissell Turpin BD, Dugar S, Sacha GL, Sato R, Siuba MT, Schleicher M, Vachharajani V, Falck-Ytter Y, Morgan RL. ADJUNCTIVE VASOPRESSORS AND SHORT-TERM MORTALITY IN ADULTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS. Shock. 2025 May 1;63(5):668-676. doi: 10.1097/SHK.0000000000002558. Epub 2025 Feb 7. |
| 40611266 | Result | Jozwiak M, Cousin VL, De Backer D, Malbrain MLNG, Monnet X, Messina A, Chew MS; Cardiovascular Dynamics section of the European Society of Intensive Care Medicine. Vasopressin use across shock states: international insights from an international ESICM-endorsed survey: the PRESS Survey. Crit Care. 2025 Jul 3;29(1):273. doi: 10.1186/s13054-025-05505-5. |
| 37479058 | Result | Sacha GL, Bauer SR. Optimizing Vasopressin Use and Initiation Timing in Septic Shock: A Narrative Review. Chest. 2023 Nov;164(5):1216-1227. doi: 10.1016/j.chest.2023.07.009. Epub 2023 Jul 20. |
| 36788938 | Result | Jozwiak M. Alternatives to norepinephrine in septic shock: Which agents and when? J Intensive Med. 2022 Jun 12;2(4):223-232. doi: 10.1016/j.jointm.2022.05.001. eCollection 2022 Oct. |
| 28425079 | Result | Auchet T, Regnier MA, Girerd N, Levy B. Outcome of patients with septic shock and high-dose vasopressor therapy. Ann Intensive Care. 2017 Dec;7(1):43. doi: 10.1186/s13613-017-0261-x. Epub 2017 Apr 20. |
| 40329359 | Result | Shi R, Braik R, Monnet X, Gu WJ, Ospina-Tascon G, Permpikul C, Djebbour M, Soumare A, Agaleridis V, Lai C. Early norepinephrine for patients with septic shock: an updated systematic review and meta-analysis with trial sequential analysis. Crit Care. 2025 May 6;29(1):182. doi: 10.1186/s13054-025-05400-z. |
| 37608327 | Result | Monnet X, Lai C, Ospina-Tascon G, De Backer D. Evidence for a personalized early start of norepinephrine in septic shock. Crit Care. 2023 Aug 22;27(1):322. doi: 10.1186/s13054-023-04593-5. |
| 40163133 | Result | Mekontso Dessap A, AlShamsi F, Belletti A, De Backer D, Delaney A, Moller MH, Gendreau S, Hernandez G, Machado FR, Mer M, Monge Garcia MI, Myatra SN, Peng Z, Perner A, Pinsky MR, Sharif S, Teboul JL, Vieillard-Baron A, Alhazzani W; European Society of Intensive Care Medicine. European Society of Intensive Care Medicine (ESICM) 2025 clinical practice guideline on fluid therapy in adult critically ill patients: part 2-the volume of resuscitation fluids. Intensive Care Med. 2025 Mar;51(3):461-477. doi: 10.1007/s00134-025-07840-1. Epub 2025 Mar 31. |
| 34789298 | Result | Vincent JL, Singer M, Einav S, Moreno R, Wendon J, Teboul JL, Bakker J, Hernandez G, Annane D, de Man AME, Monnet X, Ranieri VM, Hamzaoui O, Takala J, Juffermans N, Chiche JD, Myatra SN, De Backer D. Equilibrating SSC guidelines with individualized care. Crit Care. 2021 Nov 17;25(1):397. doi: 10.1186/s13054-021-03813-0. No abstract available. |
| 40540789 | Result | Long J, Chen Z, Luo X, Zhen L, Chi X. Fluid resuscitation management in patients with sepsis and septic shock: a network meta-analysis. Am J Emerg Med. 2025 Oct;96:80-90. doi: 10.1016/j.ajem.2025.06.001. Epub 2025 Jun 4. |
| 34643578 | Result | Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Joost Wiersinga W, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Yataco AC, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Executive Summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):1974-1982. doi: 10.1097/CCM.0000000000005357. No abstract available. |
| 29079487 | Result | Winters ME, Sherwin R, Vilke GM, Wardi G. What is the Preferred Resuscitation Fluid for Patients with Severe Sepsis and Septic Shock? J Emerg Med. 2017 Dec;53(6):928-939. doi: 10.1016/j.jemermed.2017.08.093. Epub 2017 Oct 25. |
| 26903336 | Result | Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289. |
| 29297082 | Result | Prescott HC, Angus DC. Enhancing Recovery From Sepsis: A Review. JAMA. 2018 Jan 2;319(1):62-75. doi: 10.1001/jama.2017.17687. |
| 31954465 | Result | Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7. |
| 39774315 | Result | Meyer NJ, Prescott HC. Sepsis and Septic Shock. N Engl J Med. 2024 Dec 5;391(22):2133-2146. doi: 10.1056/NEJMra2403213. No abstract available. |
| 26903338 | Result | Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |