Biomarkers in critically ill patients

We investigated whether biomarkers could (1) improve early diagnosis of sepsis (2) predict prognosis in patients with pneumonia and aneurysmal subarachnoid hemorrhage, (3) predict prognosis and investigate the association with obesity in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia, and (4) whether biomarkers can be used to guide the duration of antibiotic treatment in patients with sepsis. Biomarkers for diagnosis in sepsis In chapter 2 we focused on the diagnostic accuracy of procalcitonin (PCT) and C-reactive protein (CRP) to predict proven infection, according to the Centers of Disease Control (CDC) criteria in critically ill fulfilling the Sepsis-3 criteria. We showed that PCT and CRP were not able to distinguish proven sepsis from non-proven sepsis in Sepsis-3 criteria-positive ICU patients. Biomarkers for prognosis in critically ill patients In chapter 3 we aimed to investigate the prognostic value of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial peptide (MR-proANP) at baseline compared with the Acute Physiological and Chronic Health Evaluation (APACHE) IV model and Sequential Organ failure Assessment (SOFA) score to predict 28-day mortality in critically ill patients with proven pneumonia. Secondary aim was the prediction of 28-day mortality by biomarker clearance. Baseline MR-proADM and MR-proANP were not significant predictors for 28-day mortality. Patients with low MR-proADM and MR-proANP clearance were significant predictors for 28-day mortality (hazard ratio (HR) 2.38, 95% CI 1.21 – 4.70, p 0.013 and HR 2.27, 95% CI 1.16 – 4.46, p 0.017). In chapter 4 we assessed the ability of baseline C-terminal pro-arginine Vasopressin (CT-proAVP) to predict disease outcome, mortality and delayed cerebral ischemia (DCI) in critically ill patients with an aneurysmal subarachnoid hemorrhage (aSAH) compared with the World Federation of Neurological Surgeons (WFNS) score and APACHE IV. CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for one-year poor functional outcome (odds ratio (OR) 8.04, 95% CI 2.97 - 21.75, p < 0.001). CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and one-year mortality (OR 9.31, 95% CI 1.55 – 56.07, p 0.015 and OR 5.15, 95% CI 1.48 – 17.93, p 0.010). CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI (p 0.061). Biomarkers in critically ill patients with SARS-CoV-2 pneumonia In chapter 5 we assessed the ability of MR-proADM and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. MR-proADM ≥ 1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12 – 14.84, p < 0.001 and HR 3.72, 95% CI 1.71 – 8.08, p 0.001). In chapter 6 we investigated whether obesity is associated with differences in MR-proADM and CT-proET-1 in critically ill patients with SARS-CoV-2 pneumonia. There were no significant differences in concentrations MR-proADM, CT-proET-1 at baseline and the next six days between patients with and without obesity. Clinical therapeutic applicability of biomarkers Chapter 7 described the Stop Antibiotics on guidance of Procalcitonin Study (SAPS) in which the biomarker PCT was tested as a guide to tailor the duration of antibiotic treatment in critically ill patients with a presumed infection / sepsis in 15 ICUs in the Netherlands. The SAPS-trial revealed a significant reduction in median duration of prescribed antibiotics in the first 28 days for the PCT-guided intervention group (5 days [IQR 3 - 8 days] vs 7 days [IQR 4 - 10 days], p < 0.001) in 1546 critically ill patients. SAPS revealed a survival benefit of PCT-guidance at 28 days (19.6% vs 25%, p 0.0012) and 1 year after randomization this survival benefit persisted (34.8% vs 40.9%, p 0.006).