New insights in sepsis epidemiology and long-term consequences of critical illness

Sepsis and critical illness are global health challenges and impact both short- and long-term outcomes for patients. This thesis investigates different aspects of sepsis and critical illness, in a short- and long-term perspective.

Study I analyzes in a retrospective single-center observational setting, the risk of developing post-injury sepsis in intensive care admitted trauma patients. The incidence of sepsis after trauma was high and associated with 30-day mortality. Several risk factors were independently associated with post-injury sepsis. Post- injury sepsis patients had also a more complicated clinical course. The study emphasizes the need for early awareness and personalized care for trauma patients who developed post-injury sepsis.

Study II analyzes in a nationwide case-control study outcomes and risk factors for intensive care patients with community-acquired sepsis. Sepsis survivors had substantial excess mortality compared to controls. Elevated mortality was also notable in the subgroup analysis of cases without somatic comorbidity at admission. Risk factors for developing sepsis were low socioeconomic status, psychiatric illness, substance abuse, metastatic malignancy, renal disease, liver disease, and congestive heart failure. The findings underscore the impact of sepsis on short-term outcomes and highlight who is at risk.

Study III was a nationwide cohort design investigating long-term outcomes after community-acquired sepsis. Exploring sepsis patients, we found they had a high morbidity burden before admission, followed by a distinct rise in the post- discharge phase. Patients with sepsis had a sustained excess mortality up until three years. Furthermore, for one-year survivors, sepsis remained associated with increased mortality during the period one to three years after admission. These findings address the multifaceted health challenges of sepsis survivors beyond their initial acute illness.

Study IV examined prolonged high-potency benzodiazepine use after intensive care. We identified that 4% of benzodiazepine-naïve patients continued long- term use post-discharge. Key risk factors included older age, female sex, and pre-existing psychiatric and somatic conditions. Prolonged benzodiazepine use was linked to increased mortality. The findings call for careful monitoring of medication use in intensive care survivors to prevent dependency and adverse long-term outcomes.

List of scientific papers

This thesis is based on the following papers, which will be referred to by Roman numerals as indicated below:

I. Post-injury Sepsis-Associations with Risk Factors, Impact on Clinical Course, and Mortality: A Retrospective Observational Study

Jesper Eriksson*, Ann-Charlotte Lindström*, Elisabeth Hellgren, Ola Friman, Emma Larsson, Mikael Eriksson, Anders Oldner *Shared first authorship

Critical Care Explorations, 2021 Aug 2;3(8):e0495. https://doi.org/10.1097/cce.0000000000000495

Il. Nationwide case-control study of risk factors and outcomes for community-acquired sepsis

Ann-Charlotte Lindström, Mikael Eriksson, Johan Mårtensson, Anders Oldner, Emma Larsson

Scientific Reports, 2021 Jul 23;11(1):15118. https://doi.org/10.1038/s41598-021-94558-x

III. The impact of critical community-acquired sepsis on long-term mortality and morbidity-a nationwide cohort study

Ann-Charlotte Lindström*, Jesper Eriksson*, Mikael Eriksson, Johan Mårtensson, Emma Larsson ** , Anders Oldner ** *Equal author contribution, ** Equal author contribution

[Submitted]

IV. Onset of prolonged high-potency benzodiazepine use among ICU survivors: a nationwide cohort study

Ann-Charlotte Lindström, Erik von Oelreich, Jesper Eriksson, Mikael Eriksson, Johan Mårtensson, Emma Larsson, Anders Oldner

Critical Care Explorations, 2024 Jul 8;6(7):e1124. https://doi.org/10.1097/cce.0000000000001124