Endocan: Can It Predict Post-Operative Pneumonia?

Patients undergoing cardiac surgery, such as coronary artery bypass graft or valve replacement surgery, may be prone to suffer from respiratory complications after surgery. These complications can range from hospital-acquired pneumonia to ventilator-associated pneumonia, to the most severe, and feared form of respiratory infection, namely acute respiratory distress syndrome (ARDS). These infections represent a major public health challenge in intensive care units (ICUs), occurring in up to 15% of critically ill patients.

Patients who contract ARDS after cardiac surgery have a mortality rate of up to 80%. The difficulty lies in the timely diagnosis of respiratory complications after surgery since the signs of infection are non-specific and may be hard to distinguish from conventional clinical and biological signs of the organism’s response to surgery. Cardiac surgery, and particularly cardiopulmonary bypass used to oxygenate blood through an extracorporeal circuit during the procedure, stimulates an acute, non-specific inflammatory reaction in the organism causing dysfunction of the pulmonary endothelium. In this context, we recently investigated the utility of a novel marker named endocan in signaling the onset of infection in patients who recently underwent cardiac surgery.

Endocan is a novel soluble dermatan sulfate proteoglycan. It is encoded by the esm1 gene, which is mainly expressed in the endothelial cells in human lung and kidney tissues. Endocan is released from the pulmonary endothelium in response to local or systemic injury and has been shown to fluctuate in several disease states, such as sepsis and ventilator-associated pneumonia. Low endocan levels at admission (<5.5 ng/mL) in patients with septic shock or multiple trauma have been shown to reflect an insufficient response of the lung to injury, resulting in suboptimal protection against infection, translated in clinical terms as higher rates of ARDS. Conversely, in the context of cardiac surgery, an endocan release has been shown to signal response to injury and may herald the onset of infection.

We investigated the utility of endocan levels to predict post-operative pneumonia in patients undergoing coronary artery bypass graft surgery and found that patients in whom endocan levels were elevated (above a threshold of 12.1 ng/mL) at 6 hours after surgery, were more likely to go on to develop pneumonia. We also showed, in a specific study of the kinetics of endocan levels after surgery, that there is a sharp rise in endocan release immediately after surgery, in response to injury, with a progressive decline thereafter to return to (almost) normal levels. This rise at 6 hours is meaningful for prognosis as it corresponds to a statistically significant increase in the risk of infection in these patients.

Identifying potential complications on the basis of endocan elevations made it possible to make the diagnosis 3 days earlier than by the traditional method of waiting for characteristics symptoms to appear. This advance on the diagnosis could allow earlier initiation of antibiotic therapy, thus warding off more serious infection and improving outcomes. However, the current state of knowledge precludes starting antibiotic therapy on the basis of endocan levels alone. Further research is warranted to confirm its prognostic value in this indication, with a view to guiding therapy in the future.

References:

1. De Freitas Caires N, Gaudet A, Portier L, Tsicopoulos A, Mathieu D, Lassalle P: Endocan, sepsis, pneumonia, and acute respiratory distress syndrome. Crit Care 2018, 22:280.
2. Stephens RS, Shah AS, Whitman GJ: Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg 2013, 95:1122-1129.
3. Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD: Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983, 86:845-857.
4. Laffey JG, Boylan JF, Cheng DC: The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology 2002, 97:215-252.
5. Scherpereel A, Depontieu F, Grigoriu B, Cavestri B, Tsicopoulos A, Gentina T, Jourdain M, Pugin J, Tonnel AB, Lassalle P: Endocan, a new endothelial marker in human sepsis. Crit Care Med 2006, 34:532-537.
6. Kupeli I, Salcan S, Kuzucu M, Kuyrukluyildiz U: Can endocan be a new biomarker in ventilator-associated pneumonia? Kaohsiung J Med Sci 2018, 34:689-694.
7. Gaudet A, Parmentier E, Dubucquoi S, Poissy J, Duburcq T, Lassalle P, De Freitas Caires N, Mathieu D: Low endocan levels are predictive of Acute Respiratory Distress Syndrome in severe sepsis and septic shock. J Crit Care 2018, 47:121-126.
8. Ioakeimidou A, Pagalou E, Kontogiorgi M, Antoniadou E, Kaziani K, Psaroulis K, Giamarellos-Bourboulis EJ, Prekates A, Antonakos N, Lassale P et al: Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction. Eur J Clin Microbiol Infect Dis 2017.
9. Mikkelsen ME, Shah CV, Scherpereel A, Lanken PN, Lassalle P, Bellamy SL, Localio AR, Albelda SM, Meyer NJ, Christie JD: Lower serum endocan levels are associated with the development of acute lung injury after major trauma. J Crit Care 2012, 27:522 e511-527.
10. Palud A, Parmentier-Decrucq E, Pastre J, De Freitas Caires N, Lassalle P, Mathieu D: Evaluation of endothelial biomarkers as predictors of organ failures in septic shock patients. Cytokine 2015, 73:213-218.
11. Perrotti A, Chenevier-Gobeaux C, Ecarnot F, Bardonnet K, Barrucand B, Flicoteaux G, Lassalle P, Chocron S: Is Endocan a Diagnostic Marker for Pneumonia After Cardiac Surgery? The ENDOLUNG Study. Ann Thorac Surg 2017, In Press.
12. Perrotti A, Chenevier-Gobeaux C, Ecarnot F, Barrucand B, Lassalle P, Dorigo E, Chocron S: Relevance of Endothelial Cell-Specific Molecule 1 (Endocan) Plasma Levels for Predicting Pulmonary Infection after Cardiac Surgery in Chronic Kidney Disease Patients: The Endolung Pilot Study. Cardiorenal Med 2017, 8:1-8.