Open Access

Limitation of (1→3)-β-D-glucan monitoring in major elective surgery involving cardiopulmonary bypass

  • Gordon P Otto1, 2,
  • Katrin Ludewig1, 2,
  • Ilse D Jacobsen1, 3,
  • Barbara Schaarschmidt1, 2,
  • Bernhard Hube1, 3, 4 and
  • Michael Bauer1, 2Email author
Critical Care201317:437

https://doi.org/10.1186/cc12718

Published: 12 June 2013

Measuring (1→3)-β-D-glucan has recently been advocated for detection of invasive candidiasis. Our data indicate that the rate of false positive results is potentially high in some patient collectives of risk; for example, after cardiac artery bypass grafting (CABG).

The recently published guidelines from the Surviving Sepsis Campaign recommend the use of (1→3)-β-D- glucan as a surrogate for invasive candidiasis [1]. Fungal infections are increasing, are underestimated by conventional culture, and are associated with high mortality [2, 3]. Testing for fungal wall constituents can detect candidiasis early, but its additional value in critically ill patients remains unclear [4]. We investigated (1→3)-β-D-glucan levels in patients with sepsis and compare the values with those of postoperative patients after CABG, reflecting a well-defined ICU cohort.

After institutional approval by Local Ethics Committee Jena, 21 patients (aged ≥18 years) with sepsis, severe sepsis or septic shock according to American College of Chest Physicians/Society of Critical Care Medicine criteria, 23 patients after onpump CABG as well as 21 healthy controls were enrolled. All patients or legal surrogates gave informed consent. Patients' characteristics are presented in Table 1. Blood sampling was performed in patients on the day of diagnosis (sepsis) or on the first postoperative day (CABG). The measurement of (1→3)-β-D-glucan was performed by WAKO Inc. (Osaka, Japan).
Table 1

Characteristics of the patients

 

Sepsis

CABG

P value

Age (years)

72 (56 to 78)

60 (54 to 68)

<0.05

APACHE II score

19 (17 to 25)

7 (6 to 11)

<0.001

SOFA score

9 (7 to 12)

4 (2 to 5)

<0.001

C-reactive protein (mg/l)

162 (127 to 200)

59 (43 to 96)

<0.001

ICU LOS (days)

23 (12 to 39)

1 (1 to 1)

<0.001

Hospital LOS (days)

42 (23 to 62)

11 (10 to 13)

<0.001

Data presented as median (interquartile range). APACHE, Acute Physiology and Chronic Health Evaluation; CABG, cardiac artery bypass grafting; LOS, length of stay; SOFA, Sequential Organ Failure Assessment.

We found increased (1→3)-β-D-glucan levels in patients with sepsis compared with healthy controls (Figure 1), but patients after CABG exhibited the highest median (1→3)-β-D-glucan values; none developed signs of invasive candidiasis and the median ICU length of stay was 1 day. Eleven of 18 (61%) patients with sepsis reached (1→3)-β-D-glucan levels above the upper limit of normal (11 pg/ml). An incidence rate of 61% for invasive candidiasis appears very high [2], suggesting that cutoff values in the ICU setting where translocation might occur warrant reappraisal. Similarly, eight out of 18 (44%) patients after CABG presented elevated levels.
Figure 1

(1→3)-β-d-glucan levels in critically ill patients. Concentration of (1→3)-β-D-glucan levels in healthy controls, patients with sepsis and patients after cardiac artery bypass grafting. Dotted line represents upper limit of normal (11 pg/ml). CABG, cardiac artery bypass grafting.

Since the highest levels of (1→3)-β-D-glucan were found in CABG patients after onpump surgery, we assume - similarly to patients undergoing haemodialysis [5] - that (1→3)-β-D-glucan might have derived from membranes during onpump surgery rather than from infection or translocation. Since elevated (1→3)-β-D-glucan levels in these patients do not reflect invasive candidiasis (data not shown), elevated (1→3)-β-D-glucan levels need careful interpretation in patients treated with artificial membranes. Longitudinal measurements of (1→3)-β-D glucans in critically ill patients might be more useful as a surrogate for invasive candidiasis. A contribution of fungal pathogen-associated molecular patterns from the circuit triggering at least in part the systemic inflammatory response to cardiopulmonary bypass has yet to be tested.

Abbreviations

CABG: 

cardiac artery bypass grafting.

Declarations

Acknowledgements

This publication was supported by the Federal Ministry of Education and Research (BMBF, FKZ 01EO1002) to the Center of Sepsis Control and Care (CSCC, project number D1.21), and the Ministry of Thuringia (ProExcellence, PE 108-2), the Thuringian Foundation for Technology, Innovation and Research (STIFT) and the German Sepsis Society, and unrestricted grants provided by WAKO Inc. (Osaka, Japan). The authors would like to thank Edith Walter and Anke Braune for their excellent technical support.

Authors’ Affiliations

(1)
Center for Sepsis Control and Care, Jena University Hospital
(2)
Department of Anesthesiology and Intensive Care, Jena University Hospital
(3)
Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute
(4)
Friedrich Schiller University

References

  1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med 2013, 39: 165-228. 10.1007/s00134-012-2769-8View ArticlePubMedGoogle Scholar
  2. Guery BP, Arendrup MC, Auzinger G, Azoulay E, Borges Sa M, Johnson EM, Muller E, Putensen C, Rotstein C, Sganga G, Venditti M, Zaragoza Crespo R, Kullberg BJ: Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I. Epidemiology and diagnosis. Intensive Care Med 2009, 35: 55-62. 10.1007/s00134-008-1338-7View ArticlePubMedGoogle Scholar
  3. Bloos F, Hinder F, Becker K, Sachse S, Mekontso Dessap A, Straube E, Cattoir V, Brun-Buisson C, Reinhart K, Peters G, Bauer M: A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis. Intensive Care Med 2010, 36: 241-247. 10.1007/s00134-009-1705-zView ArticlePubMedGoogle Scholar
  4. Alam FF, Mustafa AS, Khan ZU: Comparative evaluation of (1, 3)-β-d-glucan, mannan and anti-mannan antibodies, and Candida species-specific snPCR in patients with candidemia. BMC Infect Dis 2007, 7: 103. 10.1186/1471-2334-7-103PubMed CentralView ArticlePubMedGoogle Scholar
  5. Kanda H, Kubo K, Hamasaki K, Kanda Y, Nakao A, Kitamura T, Fujita T, Yamamoto K, Mimura T: Influence of various hemodialysis membranes on the plasma (1→3)-β-d-glucan level. Kidney Int 2001, 60: 319-323. 10.1046/j.1523-1755.2001.00802.xView ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2013

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