Dissertation committee:
Ευάγγελος Γιαμαρέλλος-Μπουρμπούλης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Γεώργιος Δημόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ηρακλής Τσαγκάρης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αντώνιος Παπαδόπουλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Παρίσης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Έφη Πολυζωγοπούλου, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Σωτήριος Τσιόδρας, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Background. Sepsis guidelines suggest immediate start of resuscitation for patients with quick Sequential Organ Failure Assessment (qSOFA) 2 or 3. However, the interpretation of qSOFA 1 remains controversial. We investigated if measurements of soluble urokinase plasminogen activator receptor (suPAR) may improve risk detection when qSOFA is 1.
Methods. The study had two parts. At the first part, the combination of suPAR with qSOFA was analyzed in a prospective cohort for early risk detection. At the second part, the double-blind, randomized controlled trial (RCT) SUPERIOR evaluated the efficacy of the suPAR-guided medical intervention. SUPERIOR took place between November 2018 and December 2020. Multivariate stepwise Cox regression was used for the prospective cohort, while univariate and multivariate logistic regression were used for the RCT. Consecutive admissions at the emergency department (ED) with suspected infection, qSOFA 1 and suPAR≥12 ng/mL were allocated to single infusion of placebo or meropenem. The primary endpoint was early deterioration, defined as at least one-point increase of admission Sequential Organ Failure Assessment (SOFA) score the first 24 hours.
Results. Most of mortality risk was for patients with qSOFA 2 and 3. Taking the hazard ratio (HR) for death of patients with qSOFA=1 and suPAR<12 ng/mL as reference, the HR of qSOFA=1 and suPAR≥12ng/mL for 28-day mortality was 2.98 (95% CI 2.11-3.96).The prospective RCT was prematurely ended due to pandemia-related ED re-allocations, with 91 patients enrolled: 47 in the placebo and 44 in the meropenem arm. The primary endpoint was met in 40.4% (n= 19) and 15.9% (n= 7), respectively (difference 24.5% [5.9-40.8]; odds ratio 0.28 [0.10-0.76]). One post-hoc analysis showed significant median changes of SOFA score after 72 and 96 hours equal to 0 and -1 respectively.
Conclusions. Combining qSOFA 1 with the biomarker suPAR improves its prognostic performance for unfavorable outcome and may help decision for earlier treatment.
Keywords:
Sepsis, Infection, Biomarkers, Emergency Department, Antibiotics
