Abstract
Objectives
Risk stratification in patients with infection is usually based on the Sequential Organ Failure Assessment-Score (SOFA score). Our aim was to investigate whether the vasoactive peptide mid-regional pro-adrenomedullin (MR-proADM) improves the predictive value of the SOFA score for 30-day mortality in patients with acute infection presenting to the emergency department (ED).
Methods
This secondary analysis of the prospective observational TRIAGE study included 657 patients with infection. The SOFA score, MR-proADM, and traditional inflammation markers were all measured at time of admission. Associations of admission parameters and 30-day mortality were investigated by measures of logistic regression, discrimination analyses, net reclassification index (NRI), and integrated discrimination index (IDI).
Results
MR-proADM values were higher in non-survivors compared with survivors (4.5±3.5 nmol/L vs. 1.7 ± 1.8 nmol/L) with an adjusted odds ratio of 26.6 (95% CI 3.92 to 180.61, p=0.001) per 1 nmol/L increase in admission MR-proADM levels and an area under the receiver operator curve (AUC) of 0.86. While the SOFA score alone revealed an AUC of 0.81, adding MR-proADM further improved discrimination (AUC 0.87) and classification within predefined risk categories (NRI 0.075, p-value <0.05). An admission MR-proADM threshold of 1.75 nmol/L provided the best prognostic accuracy for 30-day mortality; with a sensitivity of 81% and a specificity of 75%, and a negative predictive value of 98%.
Conclusions
MR-proADM improved the mortality risk stratification in patients with infection presenting to the ED beyond SOFA score alone and may further improve initial therapeutic site-of-care decisions.
Trial registration
ClinicalTrials.gov NCT01768494. Registered January 15, 2013.
Funding source: Thermo Fisher Scientific
Award Identifier / Grant number: PP00P3_150531/1
Funding source: Schweizerische Akademie der Medizinischen Wissenschaften
Funding source: Forschungsrat of the Cantonal Hospital Aarau
Acknowledgments
This multidisciplinary and interprofessional trial was only possible in close collaboration of social services (Anja Keller, Regina Schmid), the nursing department (Susanne Schirlo, Petra Tobias), the central laboratory (Martha Kaeslin, Renate Hunziker), medical controlling (Juergen Froehlich, Thomas Holler, Christoph Reemts), IT (Roger Wohler, Kurt Amstad, Ralph Dahnke, Sabine Storost) of the Cantonal Hospital Aarau, Clinical Trial Unit (CTU), University Hospital Basel (Thomas Fabbro, Guido Stirnimann, Patrick Simon), the department of Health Economics of the University of Basel (Stefan Felder, Timo Tondelli), as well as all participating patients, nurses and physicians. The TRIAGE study group includes members from the University Department of Internal Medicine, Cantonal Hospital Aarau, Switzerland (Ulrich Buergi, MD, Petra Tobias, RN, Eva Grolimund, MD, Ursula Schild, RN, Zeljka Caldara, RN, Katharina Regez, RN, Martha Kaeslin, Ursina Minder, RN, Renate Hunziker, RN, Andriy Zhydkov, MD, Timo Kahles, MD, Krassen Nedeltchev, MD, Petra Schäfer-Keller, PhD) the Clinical Trial Unit University Hospital Basel (Stefanie von Felten, PhD), the Institute of Nursing Science, University of Basel, Switzerland (Sabina De Geest, PhD); the Department of Psychology, University of Berne (Pasqualina Perrig-Chiello, PhD). We thank Erica Holt for native English review.
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Research funding: Thermofisher provided an unrestricted research grant for the initial TRIAGE-study. PS was supported by the Swiss National Science Foundation (SNSF Professorship, PP00P3_150531/1). This TRIAGE study was supported by the Swiss Academy of Medical Sciences (Schweizerische Akademie der Medizinischen Wissenschaftlichen SAMW) and the Forschungsrat of the Cantonal Hospital of Aarau.
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Author contributions: EH, CG, MK and AM managed the data collection. EH, CG and PS performed the statistical analyses, and EH and CG drafted the manuscript. MK, AM, AK, BM and PS amended and commented on the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: PS and BM received research support paid to the institution from Thermofisher, bioMerieux, Roche Diagnostics, Nestle Health Science and Abbott Nutrition. AK received research support paid to the institution from Thermofisher. All other authors reported no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: As part of an observational quality control study, the Institutional Review Board of the Canton Aarau approved our protocol and waived the need for individual informed consent (EK-2012/059).
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Data availability: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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