In the emergency departments, shortened hospital stays and a reduced number of beds cause a large patient turnover.

For optimal treatment and observation of patients admitted to the emergency departments, a proper risk assessment is needed to ensure that the most ill patients are prioritized and are quickly examined and put under a more careful observation. Moreover, unnecessary admissions and the complications from these (functional decline, delirium, and iatrogenic infections) are avoided by identifying those patients who can be discharged.

So far, systematized triage systems are used for this risk assessment and to prioritize the order of patients to be treated.

A major proportion of patients admitted to emergency departments are elderly medical patients, including many multimorbid, weak, and frail patients often presenting unspecific symptoms.

Studies from various emergency departments located in the Copenhagen region, Denmark, among others the emergency departments at Hvidovre Hospital, Hillerød Hospital, and Frederiksberg Hospital, have shown that suPAR is associated with:

  • Age1,2
  • Severe and/or multiple comorbidities1,2
  • Length of hospital stay2
  • Admission to an intensive care unit2,3
  • Readmission within 30 and 90 days2
  • 48-hour, 30-day and 90-day mortality2

This means that in acute medical patients, suPAR measured on admission is higher in elderly patients, patients who end up being admitted for a long period, patients ending up in the intensive care unit, seriously or chronically ill patients, and multimorbid patients as well as patients who are readmitted or die within 30 as well as 90 days1–4.

Even taking into account other well-known prognostic factors, including sex, age, Charlson score, and CRP, suPAR still remains an independent predictor of readmission and mortality within 30 as well as 90 days2.

On the other hand, patients with a low suPAR level are at a lower risk of being readmitted or dying compared to others of the same age. Example:

  • The background 30- and 90-day mortality in patients below the age of 70 is 1.5% and 2.9%, respectively2.
  • In a patient below the age of 70 with a suPAR level of 0-3 ng/mL, the risk of dying within 30 and 90 days is 0.3% and 0.8%, respectively2.
  • By comparison, in a patient below the age of 70 with a suPAR level above 9 ng/mL the risk of dying within 30 and 90 days is 19.7% and 27.6%, respectively2.

Diagnoses

The suPAR level is elevated in emergency medical patients with:

  • cancer, diabetes, dementia, paralyses, cardiovascular diseases, chronic pulmonary diseases, peptic ulcer, hepatic diseases, rheumatic diseases, and renal/urinary tract diseases1,2,4.


 

Data from Hvidovre Hospital emergency department2.

Age: Median (25-75%) suPAR level:

  • 0-50 years: 2.3 ng/mL (1.8-3.0)
  • 50-70 years: 3.0 ng/mL (2.3-4.2)
  • >70 years: 4.4 ng/mL (3.2-6.1)

Length of hospital stay: Median suPAR level (25-75%):

  • 0 days: 2.6 ng/mL (1.9-3.6)
  • 2-4 days: 3.7 ng/mL (2.7-5.3)
  • >10 days: 5.1 ng/mL (3.6-7.5)

Admission to intensive care unit:

Median suPAR level (25-75%):

  • ÷ intensive care unit: 3.2 ng/mL (2.2-4.6)
  • + intensive care unit: 5.6 ng/mL (3.0-7.9)

Charlson score (number and severity of comorbidities):
Median suPAR level (25-75%):

  • No comorbidities: 2.9 ng/mL (2.1-4.2)
  • Charlson score = 1: 3.7 ng/mL (2.7-5.4)
  • Charlson score ≥ 4: 7.2 ng/mL (4.8-10.9)

Readmission: Median suPAR level (25-75%):

  • Neither readmission nor mortality within 30 days: 3.0 ng/mL (2.2-4.2)
  • Readmission within 30 days: 3.9 ng/mL (2.7-5.6)

Mortality (see Appendix 1):

Median suPAR level (25-75%):

  • Survived for 30 days: 3.1 ng/mL (2.2-4.5)
  • Died within 30 days: 6.8 ng/mL (4.7-9.9)
  • 30-day mortality AUC: 0.84 (95% CI: 0.81-0.86)

 

suPAR and clinical signs

suPAR is correlated with disease severity, but is suPAR correlated to the clinical signs? In a study published in Critical Care Medicine in 2018, the authors found that suPAR is correlated to the number of clinical signs (registered using the NEWS score) – however, many patients with none or 1 clinical sign had high suPAR (Figure 2) and these patients (as illustrated with the red box) had high risk of mortality5. Interestingly, suPAR was even stronger for those with none or few clinical signs compared to those presenting with multiple clinical signs, perhaps because these patients do not receive the same level of clinical attention5.

 

monograph1

Figure 2: suPAR levels according to NEWS score. N denotes the number of acute medical patients in each group. The red box illustrates that patients with 0-1 in NEWS score can have a high suPAR level5.

 

suPAR in a randomized controlled trial

An RCT including more than 16.000 acute medical patients showed that patients who had the suPAR level measured (suPAR group) were significantly more often discharged within 24 hours of admittance compared to patients without suPAR levels measured (control group). Furthermore, the mean length of hospital stay in the suPAR group was 6,5 hours shorter compared to control group (p<0.05).6

Although significantly more patients were discharged within 24 hours, there was no increased mortality among these patients. In those who were discharged with suPAR, 30-day mortality was 1,3% and in the control arm it was 1,8% (p=0.08). The suPAR AUC for 30-day mortality among the patients discharged within 24 hours was 0.92.7 Further analysis of the triage data showed that the Youden index was 5,9 ng/ml. Triaging patients down with suPAR below and up above the Youden index (5,9 ng/ml) resulted in 34% more patients triaged green
(Figure 3).

monograph3

Figure 3. Comparison on distribution of patients in triage groups between standard triage and triage with knowledge of suPAR. From Schultz et al, 2019.7

 

Clinical guidelines and cutoff values have been developed at Copenhagen University Hospital, Hvidovre in Denmark, where suPAR measurement was implemented as a clinical routine procedure in 2013 (Figure 4).

monograph4

Figure 4: Guideline used at Copenhagen University Hospital Hvidovre, Denmark.

 

1.Haupt, T. H. 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 16, R130 (2012).
2. Rasmussen, L. J. H. et al. Soluble urokinase plasminogen activator receptor (suPAR) in acute care: a strong marker of disease presence and severity, readmission and mortality. A retrospective cohort studyEmerg Med J. 2016 Nov;33(11):769-775
3. Raggam, R. B. et al. Soluble urokinase plasminogen activator receptor predicts mortality in patients with systemic inflammatory response syndrome. J. Intern. Med. 276, 651–8 (2014).
4. Nayak, R. K., Allingstrup, M., Phanareth, K. & Kofoed-enevoldsen, A. suPAR as a biomarker for risk of readmission and mortality in the acute medical setting. 62, 1–4 (2015).
5. Rasmussen LJH et al, Combining National Early Warning Score With Soluble Urokinase Plasminogen Activator Receptor (suPAR) Improves Risk Prediction in Acute Medical Patients: A Registry-Based Cohort Study. Crit Care Med. 2018 Dec;46(12):1961-1968
6. Schultz M at al. 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 Apr 11;27(1):43.Martin Schultz, Line J. H. Rasmussen, Thomas Høi-Hansen, et al., “Early Discharge from the
7. Schultz et al. Emergency Department Based on Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels: A TRIAGE III Substudy,” Disease Markers, vol. 2019, Article ID 3403549, 8 pages, 2019