Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.
BACKGROUND
Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting.


METHODS
We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin).


RESULTS
During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender.


CONCLUSIONS
Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes.


BACKGROUND
ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. schuetzph@gmail.com.|Medical Faculty of the University of Basel, Basel, Switzerland. schuetzph@gmail.com.
Philipp
P
Schuetz
Emergency Department, Groupe Hospitalier Pitié-Salpêtrière Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. pierre.hausfater@psl.aphp.fr.
Pierre
P
Hausfater
Department of critical care, Morton Plant Hospital, 300 Pinellas Street, Clearwater, FL, 33756, USA. alveoli.dna@gmail.com.
Devendra
D
Amin
Department of critical care, Morton Plant Hospital, 300 Pinellas Street, Clearwater, FL, 33756, USA. Adina.Amin@baycare.org.
Adina
A
Amin
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. sebastian.haubitz@gmail.com.
Sebastian
S
Haubitz
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. lukas.faessler@gmx.net.
Lukas
L
Faessler
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. kutz.alexander@gmail.com.
Alexander
A
Kutz
Department of Clinical Nursing Science, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. Antoinette.Conca@ksa.ch.
Antoinette
A
Conca
Department of Clinical Nursing Science, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. Barbara.Reutlinger@ksa.ch.
Barbara
B
Reutlinger
Emergency Department, Groupe Hospitalier Pitié-Salpêtrière Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. pauline.canavaggio@gmail.com.
Pauline
P
Canavaggio
Emergency Department, Groupe Hospitalier Pitié-Salpêtrière Assistance Publique-Hôpitaux de Paris (APHP), Paris, France. gabrielle_sauvin@hotmail.fr.
Gabrielle
G
Sauvin
Biochemistry Department, Hôpital Pitié-Salpêtrière and Univ-Paris Descartes, Paris, France. maguy.bernard@psl.aphp.fr.
Maguy
M
Bernard
Department of Laboratory Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. Andreas.Huber@ksa.ch.
Andreas
A
Huber
Division of General and Emergency Medicine, University Department of Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland. happy.mueller@unibas.ch.|Medical Faculty of the University of Basel, Basel, Switzerland. happy.mueller@unibas.ch.
Beat
B
Mueller
D053607:Adrenomedullin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D015331:Cohort Studies; D004636:Emergency Service, Hospital; D005260:Female; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D012306:Risk; D014218:Triage / Q000379:methods*
D015415:Biomarkers; C000606589:CALCA protein, human; D006020:Glycopeptides; D011498:Protein Precursors; C048197:copeptins; D053607:Adrenomedullin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide