Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor

Evangelos J Giamarellos-Bourboulis, Anna Norrby-Teglund, Vassiliki Mylona, Athina Savva, Iraklis Tsangaris, Ioanna Dimopoulou, Maria Mouktaroudi, Maria Raftogiannis, Marianna Georgitsi, Anna Linnér, George Adamis, Anastasia Antonopoulou, Efterpi Apostolidou, Michael Chrisofos, Chrisostomos Katsenos, Ioannis Koutelidakis, Katerina Kotzampassi, George Koratzanis, Marina Koupetori, Ioannis Kritselis, Korina Lymberopoulou, Konstantinos Mandragos, Androniki Marioli, Jonas Sundén-Cullberg, Anna Mega, Athanassios Prekates, Christina Routsi, Charalambos Gogos, Carl-Johan Treutiger, Apostolos Armaganidis, George Dimopoulos, Evangelos J Giamarellos-Bourboulis, Anna Norrby-Teglund, Vassiliki Mylona, Athina Savva, Iraklis Tsangaris, Ioanna Dimopoulou, Maria Mouktaroudi, Maria Raftogiannis, Marianna Georgitsi, Anna Linnér, George Adamis, Anastasia Antonopoulou, Efterpi Apostolidou, Michael Chrisofos, Chrisostomos Katsenos, Ioannis Koutelidakis, Katerina Kotzampassi, George Koratzanis, Marina Koupetori, Ioannis Kritselis, Korina Lymberopoulou, Konstantinos Mandragos, Androniki Marioli, Jonas Sundén-Cullberg, Anna Mega, Athanassios Prekates, Christina Routsi, Charalambos Gogos, Carl-Johan Treutiger, Apostolos Armaganidis, George Dimopoulos

Abstract

Introduction: Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed.

Methods: A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden.

Results: Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥ 17 and suPAR ≥ 12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥ 12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥ 17 and suPAR ≥ 12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort.

Conclusions: A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.

Figures

Figure 1
Figure 1
Flowchart of enrolment of the Greek study cohort.
Figure 2
Figure 2
Serum suPAR levels among 315 survivors and 52 non-survivors from sepsis over the course of 10 days. Circles denote outliers, and asterisks above boxplots denote extremes. aP < 0.0001 between survivors and non-survivors at the indicated day of sampling. suPAR, soluble urokinase plasminogen activator receptor.
Figure 3
Figure 3
Receiver operator curve (ROC) analyses of APACHE II score, serum suPAR, and their combination to define unfavorable outcome in a study cohort of 1,914 Greek patients. Areas under curve (AUCs) and 95% confidence intervals are shown. APACHE II, Acute Physiology and Chronic Health Evaluation II; suPAR, soluble urokinase plasminogen activator receptor.
Figure 4
Figure 4
Kaplan-Meier estimates of survival of patients enrolled in the study cohort stratified into four strata of severity by APACHE II score and serum suPAR. Every curve differed significantly from the others. Log-rank tests of comparisons are stratum (i) versus stratum (ii) 43.93 (P < 0.0001), stratum (ii) versus stratum (iii) 33.72 (P < 0.0001), and stratum (iii) versus stratum (iv) 14.43 (P < 0.0001). APACHE II, Acute Physiology and Chronic Health Evaluation II; suPAR, soluble urokinase plasminogen activator receptor.

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