Sepsis - an ED perspective. Sepsis Alert & Biomarkers

Sammanfattning: Background: Sepsis, the life-threatening organ dysfunction due to dysregulated host response to an infection, is a medical emergency. Early diagnosis and treatment are important factors to prevent mortality and morbidity. However, sepsis can be diffuse and difficult to interpret. Therefore, it is important to define models for early identification applicable in the Emergency Department (ED), in order to meet the therapeutic goals of the Surviving Sepsis Campaign (SSC).Aim: To improve initial sepsis care at the ED by identifying biomarkers for risk stratification and by a region-wide implementation of the novel triage model Sepsis Alert. Methods: In the first study we retrospectively evaluated the implementation of the Sepsis Alert at the ED, SUS Malmö. The second study was a post-hoc analysis of the biomarker mid-regional proadrenomedullin (MR-proADM) ́s ability to guide antibiotic administration at the ED. In the third study, a prospective observational study, we investigated the biomarker proenkephalin A 119-159 (penKid) as a predictor of acute kidney injury, multi-organ failure (MOF) and mortality in unselected sepsis patients at the ED. The fourth study was a before-and-after multicenter study to assess whether the Sepsis Alert resulted in improved initial care of patients with severe infections at the ED. Results: We found that the implementation of Sepsis Alert led to shorter time to (appropriate) antibiotics, improvement of quality markers of sepsis care in accordance with SSC, and decreased length of hospital stay. Also, in a subgroup of 5/8 EDs, ICU care decreased after the intervention (Studies I & IV). In Study II, MR-proADM on arrival at the ED had the strongest association with the requirement for antibiotic administration, compared to other biomarkers. Also, ICU care and 28-day mortality was zero in patients with low concentrations of MR-proADM. In study III, penKid in unselected sepsis patients at the ED significantly predicted progression from renal-SOFA ≤ 1 to higher renal-SOFA scores, MOF, and mortality. Conclusions: The triage model Sepsis Alert improves sepsis care and is today an integrated part of the daily routine at the EDs in Skåne Region, and the experiences from this work are applied in the national mandatory guidelines “Personcentrerat och sammanhållet vårdförlopp för sepsis”. Moreover, the biomarker studied in this thesis may identify sepsis patients with good (low MR-proADM), and poor (high penKid) prognosis.