Sepsis in the ICU-II

Sepsis in the Intensive Care Unit-II

Sepsis-induced cardiac dysfunction (SIMD) is a well-known phenomenon yet its diagnosis remains elusive with no accepted definition, or defining pathophysiological mechanism associated with this disease. Systolic dysfunction occurs in 20-70% of patients, and may be severe, yet does not appear to have any prognostic value for mortality. Diastolic function has also been variably described and seems to be related to short-term mortality. However, the contribution of left ventricular systolic and diastolic dysfunction to mortality in sepsis are still far from clear, with uncertain contribution from previous cardiovascular disease, vasopressor and inotropic drugs and mechanical ventilation. Another poorly investigated area is right ventricular dysfunction. Cor pulmonale occurs in up to 25% of patients with septic shock, and is invariably related to pulmonary haemodynamics and mechanical ventilation, yet very little is known about how this affects prognosis. Finally, although the outcome of disease is a function of multiple parameters, septic cardiomyopathy is most frequently characterized based on individual echocardiographic parameters, without considering their interactions or placing them in the context of biomarkers and clinically available haemodynamic data. Available relevant studies are often monocentric, and many fail to consider the various confounders that influence the clinical outcome in sepsis. Therefore, the diagnostic and prognostic value of combinations of clinical, biochemical and haemodynamic variables remains to be established.

Accordingly, the purpose of this study is to identify biomarkers and echocardiographic and haemodynamic signatures characteristic of specific outcomes in SIMD to support the diagnosis and prognosis in SIMD. Specific aims are:

1. To determine the association between left ventricular systolic and diastolic dysfunction, and adverse outcome in SIMD;
2. To determine the association between right ventricular systolic and diastolic dysfunction, and adverse outcome in SIMD;
3. To determine the association between novel biomarkers and adverse outcome in SIMD;
4. To determine the combined value of biomarker, echocardiographic, and haemodynamic variables for predicting adverse outcomes in SIMD;
5. To explore if there are different phenotypes of SIMD using unsupervised machine learning algorithms, and whether they are associated with adverse outcomes.

50 patients will be enrolled in a feasibility study to evaluate the logistical setup for acute echocardiography and biobanking facilities. A further 280 patients will be enrolled with inclusion from peripheral centers once feasibility is confirmed.

Note 15 Mar 2026: typing mistake noted in prior text, the sample size was originally for 330 patients (i.e. 50 + 280), not 350 (50 + 300) patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis; Septic Shock; Cardiomyopathies; Organ Failure, Multiple
• Intervention / Treatment: Other: Exposure is septic shock (defined according to Sepsis-III) and standard treatment according to departmental protocols.

Detailed Description

UPDATE 26 Feb 2022:

A pilot project was completedafter recruitment of 50 patients confirming the feasibility of data collection, study logistics, biomarker assay set-up and frequency of outcomes. Cancellation of non-COVID related research in 2020&2021 has caused significant delays. Recruitment of patients will continue during 2022&2023. At the time of writing 70 patients have been recruited across 4 centres.

UPDATE 15 Mar 2026:

At the steering committee meeting on 12 August 2024, the principal investigator presented population characteristics of the first 49 patients in the feasibility phase and compared them with the subsequent 231 recruited patients. The two cohorts were similar in age and sex, but the later cohort had higher median SAPS II scores, greater use of organ support, and higher ICU and 30-day mortality. Discussions with recruiting sites indicated that the COVID-19 pandemic had substantially changed the case-mix of ICU admissions; nursing staff shortages and bed closures led to admission of more severely ill patients, particularly at the major recruiting site. The steering committee concluded that there was no need to deviate from the original protocol but recommended recruitment of an additional 49 patients to reduce potential heterogeneity in the underlying population. The total target sample size was therefore set at 379 patients. The expanded sample size was approved by the Swedish Ethical Review Authority on 7 Feb 2025.

• Study Type: Observational
• Enrollment (Actual): 379

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • CHU Dijon-Bourgogne
  • Paris, France, 75015
    • CHU Georges Pompidou
• Sweden
  • Jönköping, Sweden, 55305
    • Ryhov Sjukhus Jönköping
  • Linköping, Sweden, 58185
    • Dept of Anaesthesia and Intensive Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All consecutive patients admitted to participating ICUs with a presumptive diagnosis of septic shock will be screened for eligibility. Patients fulfilling the Sepsis-III criteria for septic shock will included. Study inclusion must occur within 12h of ICU admission.

Description

Inclusion Criteria:

• Adult patients admitted to ICU and fulfilling the Sepsis-III criteria for septic shock

Exclusion Criteria:

• No informed consent
• Acute coronary syndromes

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adult patients with septic shock; All adult (>=18 yo) patients admitted to participating ICUs with septic shock defined according to the Sepsis III criteria. Purely observation study with no intervention. Patients are exposed to septic shock and treatment according to standard departmental protocols at each centre.	Other: Exposure is septic shock (defined according to Sepsis-III) and standard treatment according to departmental protocols.; Collection of data, biomarker and echocardiography analysis will be centralized and blinded. Assessment of endpoints will be blinded.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial injury	increased hsTnT	any time during ICU stay within the study period, up to 10 days
Organ failure free days	Organ failure	30 days of study inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 day mortality	Short term mortality	30 days after study inclusion
365 day mortality	Long term mortality	365 days after study inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcomes	Vasopressor inotropic score	during ICU stay, up to 10 days
Exploratory outcomes	Days free of mechanical ventilation	30 days of study inclusion
Exploratory outcomes	ML-derived haemodynamic phenotypes	during ICU stay, up to 10 days

Collaborators and Investigators

• Sponsor: Linkoeping University
• Collaborators: Centre Hospitalier Universitaire Dijon; Bicetre Hospital; European Georges Pompidou Hospital; Ryhov County Hospital
• Investigators: Study Chair: Michelle Chew, MBBS, PhD, Linkoeping University Hospital; Principal Investigator: Bernard Cholley, MD, PhD, CHU George Pompidou; Principal Investigator: Belaid Bouhemad, MD, PhD, CHU Dijon; Principal Investigator: Fredrik Hammarsköjld, MD, PhD, Ryhov Hospital, Jönköping; Principal Investigator: Xavier Monnet, MD, PhD, Hôpital Bicêtre

Publications and helpful links

General Publications

• Blixt PJ, Nguyen M, Cholley B, Hammarskjold F, Toiron A, Bouhemad B, Lee S, De Geer L, Andersson H, Aneq MA, Engvall J, Chew MS. Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock. Ann Intensive Care. 2024 Jan 18;14(1):12. doi: 10.1186/s13613-023-01235-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): February 11, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 21, 2020
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Cardiomyopathies; Shock, Septic; Multiple Organ Failure
• Other Study ID Numbers: SICU-II

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No