Sepsis, Critical Illness, and Perioperative Optimization – Maria Cronhjort’s Research Group

Our research group conducts translational research focused on the care of critically ill patients and those undergoing surgery, with the goal of improving clinical outcomes. Our projects include the international intensive care platform study INCEPT on thrombosis prophylaxis and albumin use, the development of biomarkers for necrotizing soft-tissue infections, early detection and treatment of sepsis, new therapies for post-ICU syndrome, and initiatives to strengthen patient involvement.

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Sepsis, Critical Illness, and Perioperative Optimization

The research group conducts translational research on the care of critically ill and surgical patients, with a particular focus on sepsis, intensive care, and perioperative optimization. Projects include early detection and treatment of sepsis, restrictive fluid management, and the development of diagnostic biomarkers for necrotizing soft tissue infections. The group also leads international platform studies, such as INCEPT, where dosing of thrombosis prophylaxis and use of albumin in shock are investigated. Other research areas include Post‑Intensive Care Syndrome (PICS), cardiac dysfunction in critically ill patients, and perspectives of elderly patients undergoing colorectal surgery. The research spans from clinical trials to the development of new methods and tools, aiming to improve outcomes, enhance patient involvement, and support families. In addition, the group actively involves patients and the public in the research process to strengthen the relevance and implementation of its results.

Read about our projects

Projects

Sepsis – Early Detection and Treatment

Sepsis is a common and life‑threatening condition, responsible for approximately 20% of global mortality. Its true incidence in Sweden remains insufficiently characterized, as only a minority of patients receive an accurate diagnostic code. Evidence also suggests that women receive antibiotics later than men and that sex‑specific biological differences may influence disease trajectories. At Södersjukhuset, we have established a multidisciplinary research group and developed an automated tool for identifying patients with suspected sepsis, independent of clinical diagnostic coding. The tool has been validated and the results published. Within this project, we map the incidence of sepsis in the Stockholm region, analyze associations between treatment delay, sex differences, and mortality, and investigate sex‑specific differences in symptom onset, sepsis bundle adherence, and clinical outcomes. Maria Cronhjort serves as the principal supervisor for Mikael Hallengren and co‑supervisor for Cristian Duré in this project.

Restrictive Fluid Management

Observational studies have demonstrated an association between fluid overload and increased mortality. Several randomized trials conducted in low‑income settings have indicated reduced mortality with restrictive fluid strategies. To clarify the effect in high‑resource environments, we conducted the CLASSIC trial—the first randomized clinical trial evaluating restrictive fluid management with access to full intensive care support.

In this European multicenter study, 1,554 patients with septic shock were randomized to restrictive or standard fluid therapy. The primary outcome was 90‑day mortality; one‑year survival and health‑related quality of life were also assessed.

Maria Cronhjort leads two mechanistic sub‑studies investigating pathophysiological processes related to vascular integrity and cardiac dysfunction. We analyze biomarkers of endothelial and myocardial injury, including glycocalyx markers that may help identify patients at risk of increased vascular leakage and fluid‑related complications. The overarching aim is to enable individualized fluid therapy.

Jens Christensen is the PhD student working on this project

INCEPT Platform Trial for Adult ICU Patients

Maria Cronhjort is the national coordinator for the INCEPT research platform. The platform employs adaptive trial designs and Bayesian statistical methods, enabling rapid response during, for example, future pandemics. The first two domains on the platform evaluate dosing strategies for thromboprophylaxis and the use of albumin in patients with shock.

Thromboprophylaxis Dosing

Despite routine use of thromboprophylaxis, the incidence of venous thromboembolism remains high (4–10%) in critically ill patients. Dosing practices vary substantially across intensive care units. We randomize patients to low, intermediate, or weight‑based doses of low‑molecular‑weight heparin. A planned substudy will analyze anti‑FXa levels under the different dosing strategies. Maria Cronhjort supervises Sandra Jonmarker,who is the national study coordinator for the thromboprophylaxis domain.

Albumin

In a previous substudy within the CLASSIC project, we identified substantial practice variation in the use of albumin in the management of critically ill patients. We are now planning a randomized trial comparing treatment with or without albumin for resuscitation and substitution during ICU stay.

The Older Patient’s Perspective on Colorectal Surgery

Colorectal cancer (CRC) is the third most common cancer in Sweden. Advanced age and comorbidities at diagnosis must be considered when offering aggressive treatments such as radiotherapy, chemotherapy, or surgery. We aim to determine whether we appropriately select older individuals for operative management.

We study patients aged over 80 who undergo surgery or decline surgical treatment. The project includes both qualitative and quantitative assessments of patient perspectives and health‑related quality of life. Maria Cronhjort is the principal supervisor for Elisabeth Andersson, who conducts this project in collaboration with colorectal surgeon Deborah Saraste.

Thrombomodulin for the Diagnosis of Necrotizing Soft Tissue Infection (NSTI)

Rapid diagnosis is essential in NSTI, and surgical exploration is required for confirmation. Because suspected NSTI necessitates immediate operative evaluation, many patients undergo unnecessary surgery. In collaboration with Professor Anna Norrby‑Teglund and Dr. Laura Medina, we investigate thrombomodulin as a tool for improved early diagnosis, as it has recently been identified as a robust biomarker of necrosis in later stages of the disease. We are conducting an observational study measuring thrombomodulin levels in patients presenting with suspected NSTI at the emergency departments of Danderyds Hospital, Södersjukhuset, and Karolinska University Hospital (BioSTER).

Restrictive Fluid Management in Sepsis

This year, we are conducting a cohort study (NEAT) investigating time to norepinephrine initiation in patients with sepsis and hypotension presenting to the emergency departments at Danderyds Hospital, S:t Göran, Skövde, and Södersjukhuset.

Mikael Hallengren is the PhD student in this project.

Post‑Intensive Care Syndrome

More than half of intensive care survivors develop new physical, cognitive, or psychological impairments during the first year following their ICU stay. This condition is known as Post‑Intensive Care Syndrome (PICS). The intensive care unit at Danderyds Hospital participates in a regional observational study validating a screening tool for PICS. We lead a substudy examining sex differences in muscle weakness as a predictor of 90‑day mortality.

ISAC: Improved Survivorship After Critical Illness

Within the CRIC network, we are preparing a large multicenter trial evaluating the effect of mutual peer‑support interventions for relatives of intensive care patients.
Agnes Laurin is the PhD student associated with this project.

Cardiac Dysfunction in Critically Ill Patients

Cardiac involvement is common in critical illness, yet the long‑term consequences remain poorly understood. The intensive care unit at Danderyds Hospital participates in a national observational study (NCT05860504) in which echocardiography is performed on patients with multiorgan failure during their ICU stay. We investigate the association between cardiac dysfunction and mortality and lead a substudy using novel echocardiographic methods to diagnose right ventricular failure. This project is conducted in collaboration with Jonatan Oras at the Sahlgrenska Academy.

Patient and Public Involvement

Together with Associate Professor Anna Schandl at Södersjukhuset, we have established a group of former ICU patients and family members from Danderyds Hospital and Södersjukhuset. This group contributes to the planning of future studies and facilitates the implementation of research findings.

Publications

All publications from group members

Staff and contact

Group leader

All members of the group