Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in high-risk patients undergoing major non-cardiac surgery (SPARSE)

Abstract

BackgroundPatients undergoing major surgery are often at risk of developing postoperative complications. We investigated whether the inflammatory biomarker suPAR can aid in identifying patients at high risk for postoperative complications, morbidity, and mortality.MethodsIn this prospective observational study (ClinicalTrials.gov identifier: NCT03851965), peripheral venous blood was collected from consecutive adult patients scheduled for major non-cardiac surgery with expected duration ≥2 hours under general anesthesia. Patients fulfilling the following inclusion criteria were included: age ≥18 years and American Society of Anesthesiologists’ physical status I to IV. Plasma suPAR levels were determined using the suPARnostic® quick triage lateral flow assay. The primary endpoint was post-operative complications defined as presence of any complication and/or admission to intensive care unit and/or mortality within the first 90 postoperative days.ResultsPreoperative suPAR had an OR of 1.50 (95%CI 1.24-1.82) for every ng/ml increase (AUC 0.82, 95%CI: 0.72-0.91). When including age, sex, ASA score, CRP, and grouped suPAR in multivariate analysis, patients with suPAR between 5.5 and 10 ng/ml had an OR of 12.7 (CI: 3.6-45.5) and patients with suPAR>10 ng/ml had an OR of 20.7 (CI: 4.5-95.4) compared to patients with suPAR≤5.5 ng/ml, respectively. ROC analysis including age, sex, CRP levels, and ASA score and had an AUC of 0.69 (95%CI: 0.58-0.80). When suPAR was added to this Model, the AUC increased to 0.84 (0.74-0.93) (p=0.009).ConclusionsPreoperative suPAR provided strong and independent predictive value on postoperative complications in high-risk patients undergoing major non-cardiac surgery.

Soluble Urokinase Receptor Levels Are Not Affected by the Systemic Inflammatory Response to Anesthesia and Operative Trauma

“…Of note, genetic links have been reported between suPAR-measured chronic inflammation and phenotypes, such as diabetes, obesity, and chronic kidney disease, with the predictive value of suPAR being present years before the development of disease [4, 6, 9]. In the surgical population, suPAR may not only reflect the preoperative state of immune activation, but may also be associated with postoperative organ damage and complications [9, 23]. Indeed, we observed higher suPAR levels in patients with an ASA IV compared to those with an ASA II or III score, suggesting that suPAR also reflects the underlying comorbidities or more advanced disease.…”

Association of preoperative plasma suPAR levels with intraoperative sublingual microvascular perfusion in patients undergoing major non-cardiac surgery

“…This analysis included 100 patients of a previous prospective observational study conducted in the University Hospital of Larisa, Larisa, Greece, from February 2019 to September 2020. 11 Ethical approval for this study was provided by the Ethical Committee of the university hospital of Larisa, Greece (IRB no. 60580).…”

“…The quantitative results are read within 20 minutes by an optical aLF Reader (Qiagen, Germany). 11 suPAR levels higher than 5.5 ng/ml were considered as a clinically important indicator of systemic inflammation. We chose the cut-off of 5.5 ng/ml as this has been previously used in a study of preoperative suPAR levels and post-operative complications and thus allows for comparison of previous findings.…”

“…22 As the chosen cut-off gave a rather large group above 5.5 ng/ml, we chose a second cut-off at 10 ng/ml. 11 There is no specific rationale for this second cut-off, except that suPAR in double digits is often referred to unusually high levels.…”

“…9 Not only suPAR is implicated in the inflammatory response of several diseases, but it was recently reported that individuals can be also genetically predisposed to higher or lower suPAR levels, which give suPAR a significant prognostic value in physiological or pathological conditions. 10 We have recently shown that the preoperative suPAR levels are highly predictive of postoperative complications in different types of surgical procedures or different risk groups, 11 but the reasons for this are unknown. Interestingly, the suPAR level has previously been demonstrated to be an independent predictor of coronary microvascular dysfunction in patients with non-obstructive coronary artery disease, with doubling of plasma suPAR being associated with about 30% decrease in coronary flow reserve and, eventually, with heart disease and worse long-term outcomes.…”