title: Biomarker-guided personalised emergency medicine for all - hope for another hype?
abstract: Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.
authors.affiliation: Medical University Clinic of the Medical Faculty University of Basel, Kantonsspital Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.affiliation: Dept. of Internal Medicine, University Hospital "Inselspital" Bern, Switzerland.
authors.forename: Drahomir
authors.initials: D
authors.lastname: Aujesky
authors.affiliation: Dept. of Cardiology, Dept. of Internal Medicine, University Hospital Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.affiliation: Medical University Clinic of the Medical Faculty University of Basel, Kantonsspital Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
mesh_terms: D053607:Adrenomedullin / Q000097:blood; D000465:Algorithms; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D004635:Emergency Medicine; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006331:Heart Diseases / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D057285:Precision Medicine / Q000379:methods*; D011498:Protein Precursors / Q000097:blood; D012140:Respiratory Tract Diseases / Q000097:blood / Q000175:diagnosis*; D013557:Switzerland; D014218:Triage; D014336:Troponin / Q000097:blood
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D005338:Fibrin Fibrinogen Degradation Products; D011498:Protein Precursors; D014336:Troponin; C036309:fibrin fragment D; C088633:proadrenomedullin; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide