Soluble urokinase plasminogen activator receptor and lactate as prognostic biomarkers in patients presenting with non-specific chief complaints in the pre-hospital setting - the PRIUS-study

Robert Ivic, Jouni Nurmi, Lisa Kurland, Veronica Vicente, Veronica Lindström, Therese Djärv, Johanna Kaartinen, Maaret Castrén, Katarina Bohm, Robert Ivic, Jouni Nurmi, Lisa Kurland, Veronica Vicente, Veronica Lindström, Therese Djärv, Johanna Kaartinen, Maaret Castrén, Katarina Bohm

Abstract

Background: Emergency Medical Services (EMS) are faced daily with patients presenting with non-specific chief complaints (NSC). Patients presenting with NSCs often have normal vital signs. It has previously been established that NSCs may have a serious underlying condition that has yet to be identified. The aim of the current study was to determine if soluble urokinase plasminogen activator receptor (suPAR) and lactate could be used to identify serious conditions among patients presenting with NSCs to the EMS. The secondary aim was to describe the prognostic value for mortality in the group.

Method: A blinded prospective observational cohort study was conducted of patients brought to the ED by ambulance after calling the national emergency number 112 and who were assessed as having NSC by the EMS. Biomarkers were measured during index EMS assessment before transportation to the ED. Patients were followed via EMS and hospital electronic health records. Descriptive and logistic regression analyses were used.

Results: A total of 414 patients were included, with a median age of 82 years. A serious condition was present in 15.2% of the patients. Elevated suPAR above 3 ng/ml had a positive likelihood ratio (LR+) of 1.17 and a positive predictive value (PPV) of 17.3% as being predictive of a prevalent serious condition. Elevated suPAR above 9 ng/ml had LR+ 4.67 and a PPV of 16.7% as being predictive of 30-day mortality. Lactate was not significantly predictive.

Conclusion: Pre-hospital suPAR and lactate cannot differentiate serious conditions in need of urgent treatment and assessment in the ED among patients presenting with non-specific chief complaints. suPAR has shown to be predictive of 30-day mortality, which could add some value to the clinical assessment.

Trial registration: NCT03089359. Registered 20 March 2017, retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT03089359 .

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart over patients included in the study. *: Vital signs not within range. **: Missing laboratory test results of suPAR and/or lactate
Fig. 2
Fig. 2
A: ROC curve based on suPAR and lactate by prevalent serious condition. B: ROC curve based on suPAR and lactate by 30-day mortality

References

    1. van Bokhoven MA, Koch H, van der Weijden T, Dinant GJ. Special methodological challenges when studying the diagnosis of unexplained complaints in primary care. J Clin Epidemiol. 2008;61(4):318–322. doi: 10.1016/j.jclinepi.2007.05.008.
    1. Samaras N, Chevalley T, Samaras D, Gold G. Older patients in the emergency department: a review. Ann Emerg Med. 2010;56(3):261–269. doi: 10.1016/j.annemergmed.2010.04.015.
    1. Aminzadeh F, Dalziel WB. Older adults in the emergency department: a systematic review of patterns of use, adverse outcomes, and effectiveness of interventions. Ann Emerg Med. 2002;39(3):238–247. doi: 10.1067/mem.2002.121523.
    1. Djärv T, Castrén M, Mårtenson L, Kurland L. Decreased general condition in the emergency department: high in-hospital mortality and a broad range of discharge diagnoses. Eur J Emerg Med. 2015;22(4):241–6. 10.1097/MEJ.0000000000000164.
    1. Castren M, et al. Non-specific complaints in the ambulance; predisposing structural factors. BMC Emerg Med. 2015;15(1):8. doi: 10.1186/s12873-015-0034-5.
    1. Ivic R, Kurland L, Vicente V, Castrén M, Bohm K. Serious conditions among patients with non-specific chief complaints in the pre-hospital setting: a retrospective cohort study. Scand J Trauma Resusc Emerg Med. 2020;28(1):74. doi: 10.1186/s13049-020-00767-0.
    1. Vanpee D, et al. Epidemiological profile of geriatric patients admitted to the emergency department of a university hospital localized in a rural area. Eur J Emerg Med. 2001;8(4):301–304. doi: 10.1097/00063110-200112000-00010.
    1. Nemec M, Koller MT, Nickel CH, Maile S, Winterhalder C, Karrer C, Laifer G, Bingisser R. Patients presenting to the emergency department with non-specific complaints: the Basel non-specific complaints (BANC) study. Acad Emerg Med. 2010;17(3):284–292. doi: 10.1111/j.1553-2712.2009.00658.x.
    1. Rutschmann, O.T., Chevalley T., Zumwald C., Luthy C., Vermeulen B., Sarasin F.P., Pitfalls in the emergency department triage of frail elderly patients without specific complaints. Swiss Med Wkly, 2005. 135(9–10): p. 145–150, DOI: 2005/09/smw-10888.
    1. Safwenberg U, Terent A, Lind L. The emergency department presenting complaint as predictor of in-hospital fatality. Eur J Emerg Med. 2007;14(6):324–331. doi: 10.1097/MEJ.0b013e32827b14dd.
    1. Ivic R, Kurland L, Vicente V, Castrén M, Bohm K. Serious conditions among patients with non-specific chief complaints in the pre-hospital setting: a retrospective cohort study. Scand J Trauma Resusc Emerg Med. 2020;28(1):74. 10.1186/s13049-020-00767-0.
    1. Martin-Loeches I, et al. Determinants of time to death in hospital in critically ill patients around the world. Intensive Care Med. 2016;42(9):1454–1460. doi: 10.1007/s00134-016-4479-0.
    1. Thuno M, Macho B, Eugen-Olsen J. suPAR: the molecular crystal ball. Dis Markers. 2009;27(3):157–172. doi: 10.1155/2009/504294.
    1. Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med. 2012;38(9):1418–1428. doi: 10.1007/s00134-012-2613-1.
    1. Borne Y, et al. Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation. Eur J Heart Fail. 2014;16(4):377–383. doi: 10.1002/ejhf.49.
    1. Casagranda I, Vendramin C, Callegari T, Vidali M, Calabresi A, Ferrandu G, Cervellin G, Cavazza M, Lippi G, Zanotti I, Negro S, Rocchetti A, Arfini C. Usefulness of suPAR in the risk stratification of patients with sepsis admitted to the emergency department. Intern Emerg Med. 2015;10(6):725–730. doi: 10.1007/s11739-015-1268-7.
    1. Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med. 2012;10(1):2. doi: 10.1186/1741-7015-10-2.
    1. Eugen-Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, Langkilde A, Petersen J, Pielak T, Møller LN, Jeppesen J, Lyngbaek S, Fenger M, Olsen MH, Hildebrandt PR, Borch-Johnsen K, Jørgensen T, Haugaard SB. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med. 2010;268(3):296–308. doi: 10.1111/j.1365-2796.2010.02252.x.
    1. Gustafsson A, Ljunggren L, Bodelsson M, Berkestedt I. The prognostic value of suPAR compared to other inflammatory markers in patients with severe Sepsis. Biomark Insights. 2012;7:39–44. doi: 10.4137/BMI.S9460.
    1. Haupt TH, Kallemose T, Ladelund S, Rasmussen LJ, Thorball CW, Andersen O, Pisinger C, Eugen-Olsen J. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population. Biomark Insights. 2014;9:91–100. doi: 10.4137/BMI.S19876.
    1. Koch A, Tacke F. Why high suPAR is not super--diagnostic, prognostic and potential pathogenic properties of a novel biomarker in the ICU. Crit Care. 2011;15(6):1020. doi: 10.1186/cc10577.
    1. Koch A, Tacke F. Risk stratification and triage in the emergency department: has this become 'suPAR' easy? J Intern Med. 2012;272(3):243–246. doi: 10.1111/j.1365-2796.2012.02568.x.
    1. Chenevier-Gobeaux C, Lemarechal H, Doumenc B, Peschanski N, Claessens YE, Borderie D, Ray P. Prognostic value of soluble urokinase plasminogen activator receptor in patients presenting to the emergency department with chest pain suggestive of acute coronary syndrome. Clin Biochem. 2021;92:19–24. doi: 10.1016/j.clinbiochem.2021.02.009.
    1. Lafon T, et al. Prognostic performance of endothelial biomarkers to early predict clinical deterioration of patients with suspected bacterial infection and sepsis admitted to the emergency department. Ann Intensive Care. 2020;10(1):113. doi: 10.1186/s13613-020-00729-w.
    1. Stauning MA, Altintas I, Kallemose T, Eugen-Olsen J, Lindstrøm MB, Rasmussen LJH, et al. Soluble Urokinase plasminogen activator receptor as a decision marker for early discharge of patients with COVID-19 symptoms in the emergency department. J Emerg Med. 2021. 10.1016/j.jemermed.2021.03.012.
    1. Di Mauro FM, Schoeffler GL. Point of care measurement of lactate. Top Companion Anim Med. 2016;31(1):35–43. doi: 10.1053/j.tcam.2016.05.004.
    1. Bakker J, Coffernils M, Leon M, Gris P, Vincent JL. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest. 1991;99(4):956–962. doi: 10.1378/chest.99.4.956.
    1. Jansen TC, van Bommel J, Mulder PG, Rommes JH, Schieveld SJM, Bakker J. The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study. Crit Care. 2008;12(6):R160. doi: 10.1186/cc7159.
    1. van Beest PA, Mulder PJ, Oetomo SB, van den Broek B, Kuiper MA, Spronk PE. Measurement of lactate in a prehospital setting is related to outcome. Eur J Emerg Med. 2009;16(6):318–322. doi: 10.1097/MEJ.0b013e32832dbe54.
    1. Vårdgivarguiden. CAKnet. [cited 2015 19 jan]; Available from: .
    1. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. doi: 10.1016/0021-9681(87)90171-8.
    1. Schultz M, Rasmussen LJH, Kallemose T, Kjøller E, Lind MN, Ravn L, Lange T, Køber L, Rasmussen LS, Eugen-Olsen J, Iversen K. Availability of suPAR in emergency departments may improve risk stratification: a secondary analysis of the TRIAGE III trial. Scand J Trauma Resusc Emerg Med. 2019;27(1):43. doi: 10.1186/s13049-019-0621-7.
    1. Rasmussen, L.J., et al. suPAR Monograph. 2019 2019 2020-11-27]; Available from: .
    1. Karakoumis J, Nickel CH, Kirsch M, Rohacek M, Geigy N, Müller B, Ackermann S, Bingisser R. Emergency presentations with nonspecific complaints-the burden of morbidity and the Spectrum of underlying disease: nonspecific complaints and underlying disease. Medicine (Baltimore) 2015;94(26):e840. doi: 10.1097/MD.0000000000000840.
    1. Nickel CH, Messmer AS, Geigy N, Misch F, Mueller B, Dusemund F, Hertel S, Hartmann O, Giersdorf S, Bingisser R. Stress markers predict mortality in patients with nonspecific complaints presenting to the emergency department and may be a useful risk stratification tool to support disposition planning. Acad Emerg Med. 2013;20(7):670–679. doi: 10.1111/acem.12172.
    1. Haupt TH, et al. Plasma suPAR levels are associated with mortality, admission time, and Charlson comorbidity index in the acutely admitted medical patient: a prospective observational study. Crit Care. 2012;16(4):R130. doi: 10.1186/cc11434.
    1. Uusitalo-Seppala R, et al. Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study. J Intern Med. 2012;272(3):247–256. doi: 10.1111/j.1365-2796.2012.02569.x.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj