Serum markers for early detection of patients with mesenteric ischemia after cardiac surgery

Abstract

Objective: Mesenteric ischemia (MESI) is a rare but often fatal complication in patients after cardiac surgery. Non-specific clinical symptoms and lack of specific laboratory parameters complicate the diagnosis. We evaluated potential serum markers for MESI in cardiac surgery patients.

Methods: Between March and October 2012, serial serum samples of 567 elective cardiac surgery patients were collected 1, 24, and 48 h after the operation, and concentrations of potential markers for MESI [α-glutathione-S-transferase (αGST), intestinal fatty-acid-binding protein (iFABP), and D-lactate] were measured retrospectively. In patients requiring laparotomy, blood samples obtained 72, 48, 24, and 12 h before the laparotomy were additionally measured and compared to all other patients (control group).

Results: Laparotomy was performed in 18 patients at 11±7 days after cardiac surgery. MESI was found in 9/18 patients. Already 1 h after cardiac surgery, the serum concentrations of D-lactate (37±18 vs. 25±20 nmol/mL, p<0.01) and αGST (82±126 vs. 727±1382 μg/L, p<0.01) in patients undergoing laparotomy were increased compared to the control group. Between patients with and without MESI, differences were only found for iFABP 24 h after cardiac surgery (1.1±0.4 vs. 2.9±0.6 ng/mL, p=0.04) and up to 72 h before laparotomy (0.56±0.72 vs. 2.51±1.96 ng/mL, p=0.01).

Conclusions: D-lactate and αGST were early markers for gastrointestinal complications after cardiac surgery. Before laparotomy, lowered iFABP levels indicated MESI. Routinely used, these markers can help identify patients with gastrointestinal complications after cardiac surgery early, and might be useful for the evaluation of new therapeutic or preventive strategies.

Keywords: D-lactate; biomarker; cardiac surgery; iFABP; mesenteric ischemia; αGST.

©2018 Dohle D.-S., et al., published by De Gruyter, Berlin/Boston.

Figures

Figure 1:

Already 1 h after cardiac surgery and 24 and 48 h thereafter, the serum concentrations of D-lactate and αGST in patients undergoing laparotomy were increased compared to the control group. Timeline of αGST (A), D-lactate (B), and iFABP (C) mean serum concentrations and 95% confidence interval (CI) at 1, 24, and 48 h after cardiac surgery for the control group and the laparotomy group.

Figure 2:

Comparing laparotomy patients with and without MESI up to 3 days before laparotomy, no significant differences between these two groups were found for αGST and D-lactate, but the iFABP-2 levels were significant lower in the MESI group. Timeline of αGST (A), D-lactate (B), and iFABP (C) mean serum concentrations and 95% CI at 1, 24, and 48 h after cardiac surgery for the control, MESI, and non-MESI group at 1, 24, and 48 h after cardiac surgery and 72, 48, 24, and 12 h before laparotomy.

References

1. 1. Rodriguez R, Robich MP, Plate JF, Trooskin SZ, Sellke FW. Gastrointestinal complications following cardiac surgery: a comprehensive review. J Card Surg 2010;25:188–97.
   2. Rodriguez R, Robich MP, Plate JF, Trooskin SZ, Sellke FW. Gastrointestinal complications following cardiac surgery: a comprehensive review. J Card Surg. 2010;25:188–97.
2. 1. Pang PYK, Sin YK, Lim CH, Su JW, Chua YL. Outcome and survival analysis of intestinal ischaemia following cardiac surgery. Interact Cardiovasc Thorac Surg 2012;15:215–8.
   2. Pang PYK, Sin YK, Lim CH, Su JW, Chua YL. Outcome and survival analysis of intestinal ischaemia following cardiac surgery. Interact Cardiovasc Thorac Surg. 2012;15:215–8.
3. 1. Venkateswaran RV, Charman SC, Goddard M, Large SR. Lethal mesenteric ischaemia after cardiopulmonary bypass: a common complication? Eur J Cardiothorac Surg 2002;22:534–8.
   2. Venkateswaran RV, Charman SC, Goddard M, Large SR. Lethal mesenteric ischaemia after cardiopulmonary bypass: a common complication? Eur J Cardiothorac Surg. 2002;22:534–8.
4. 1. Asimakopoulos G. Systemic inflammation and cardiac surgery: an update. Perfusion 2001;16:353–60.
   2. Asimakopoulos G. Systemic inflammation and cardiac surgery: an update. Perfusion. 2001;16:353–60.
5. 1. Ohri SK, Becket J, Brannan J, Keogh BE, Taylor KM. Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH. Ann Thorac Surg 1994;57:1193–9.
   2. Ohri SK, Becket J, Brannan J, Keogh BE, Taylor KM. Effects of cardiopulmonary bypass on gut blood flow, oxygen utilization, and intramucosal pH. Ann Thorac Surg. 1994;57:1193–9.
6. 1. Rossi M, Sganga G, Mazzone M, Valenza V, Guarneri S, Portale G, et al. Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation. Ann Thorac Surg 2004;77:612–8.
   2. Rossi M, Sganga G, Mazzone M, Valenza V, Guarneri S, Portale G. et al. Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation. Ann Thorac Surg. 2004;77:612–8.
7. 1. Vermeulen Windsant IC, de Wit NCJ, Sertorio JTC, van Bijnen AA, Ganushchak YM, Heijmans JH, et al. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage. Front Physiol 2014;5:340.
   2. Vermeulen Windsant IC, de Wit NCJ, Sertorio JTC, van Bijnen AA, Ganushchak YM, Heijmans JH. et al. Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage. Front Physiol. 2014;5:340.
8. 1. Abboud B, Daher R, Sleilaty G, Madi-Jebara S, Asmar El B, Achouch R, et al. Is prompt exploratory laparotomy the best attitude for mesenteric ischemia after cardiac surgery? Interact Cardiovasc Thorac Surg 2008;7:1079–83.
   2. Abboud B, Daher R, Sleilaty G, Madi-Jebara S, Asmar El B, Achouch R. et al. Is prompt exploratory laparotomy the best attitude for mesenteric ischemia after cardiac surgery? Interact Cardiovasc Thorac Surg. 2008;7:1079–83.
9. 1. Ghosh S, Roberts N, Firmin RK, Jameson J, Spyt TJ. Risk factors for intestinal ischaemia in cardiac surgical patients. Eur J Cardiothorac Surg 2002;21:411–6.
   2. Ghosh S, Roberts N, Firmin RK, Jameson J, Spyt TJ. Risk factors for intestinal ischaemia in cardiac surgical patients. Eur J Cardiothorac Surg. 2002;21:411–6.
10. 1. Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg 2009;33:1374–83.
    2. Evennett NJ, Petrov MS, Mittal A, Windsor JA. Systematic review and pooled estimates for the diagnostic accuracy of serological markers for intestinal ischemia. World J Surg. 2009;33:1374–83.
11. 1. Acosta S, Nilsson T. Current status on plasma biomarkers for acute mesenteric ischemia. J Thromb Thrombolysis 2012;33:355–61.
    2. Acosta S, Nilsson T. Current status on plasma biomarkers for acute mesenteric ischemia. J Thromb Thrombolysis. 2012;33:355–61.
12. 1. Demir IE, Ceyhan GO, Friess H. Beyond lactate: is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia? Dig Surg 2012;29:226–35.
    2. Demir IE, Ceyhan GO, Friess H. Beyond lactate: is there a role for serum lactate measurement in diagnosing acute mesenteric ischemia? Dig Surg. 2012;29:226–35.
13. 1. Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, et al. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci USA 1985;82:7202–6.
    2. Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M. et al. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci USA. 1985;82:7202–6.
14. 1. Agellon LB, Toth MJ, Thomson ABR. Intracellular lipid binding proteins of the small intestine. Mol Cell Biochem 2002;239:79–82.
    2. Agellon LB, Toth MJ, Thomson ABR. Intracellular lipid binding proteins of the small intestine. Mol Cell Biochem. 2002;239:79–82.
15. 1. Deitch EA, Morrison J, Berg R, Specian RD. Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. Crit Care Med 1990;18:529–36.
    2. Deitch EA, Morrison J, Berg R, Specian RD. Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. Crit Care Med. 1990;18:529–36.
16. 1. Nilsson J, Hansson E, Andersson B. Intestinal ischemia after cardiac surgery: analysis of a large registry. J Cardiothorac Surg 2013;8:156.
    2. Nilsson J, Hansson E, Andersson B. Intestinal ischemia after cardiac surgery: analysis of a large registry. J Cardiothorac Surg. 2013;8:156.
17. 1. Yamada T, Ochiai R, Takeda J, Kikuchi H, Ishibashi M, Watanabe K. Off-pump coronary artery bypass attenuates transient hepatocellular damage after myocardial revascularization. J Cardiothorac Vasc Anesth 2005;19:603–7.
    2. Yamada T, Ochiai R, Takeda J, Kikuchi H, Ishibashi M, Watanabe K. Off-pump coronary artery bypass attenuates transient hepatocellular damage after myocardial revascularization. J Cardiothorac Vasc Anesth. 2005;19:603–7.
18. 1. van Boven W-JP, Gerritsen WB, Driessen AH, van Dongen EP, Klautz RJ, Aarts LP. Minimised closed circuit coronary artery bypass grafting in the elderly is associated with lower levels of organ-specific biomarkers: a prospective randomised study. Eur J Anaesthesiol 2013;30:685–94.
    2. van Boven W-JP, Gerritsen WB, Driessen AH, van Dongen EP, Klautz RJ, Aarts LP. Minimised closed circuit coronary artery bypass grafting in the elderly is associated with lower levels of organ-specific biomarkers: a prospective randomised study. Eur J Anaesthesiol. 2013;30:685–94.
19. 1. Sun Y-J, Song D-D, Diao Y-G, Zhou J, Zhang T-Z. Penehyclidine hydrochloride preserves the intestinal barrier function in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 2013;146:179–85.
    2. Sun Y-J, Song D-D, Diao Y-G, Zhou J, Zhang T-Z. Penehyclidine hydrochloride preserves the intestinal barrier function in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2013;146:179–85.
20. 1. Assadian A, Assadian O, Senekowitsch C, Rotter R, Bahrami S, Fürst W, et al. Plasma D-lactate as a potential early marker for colon ischaemia after open aortic reconstruction. Eur J Vasc Endovasc Surg 2006;31:470–4.
    2. Assadian A, Assadian O, Senekowitsch C, Rotter R, Bahrami S, Fürst W. et al. Plasma D-lactate as a potential early marker for colon ischaemia after open aortic reconstruction. Eur J Vasc Endovasc Surg. 2006;31:470–4.
21. 1. Vermeulen Windsant IC, Hellenthal FA, Derikx JPM, Prins MH, Buurman WA, Jacobs MJ, et al. Circulating intestinal fatty acid-binding protein as an early marker of intestinal necrosis after aortic surgery: a prospective observational cohort study. Ann Surg 2012;255:796–803.
    2. Vermeulen Windsant IC, Hellenthal FA, Derikx JPM, Prins MH, Buurman WA, Jacobs MJ. et al. Circulating intestinal fatty acid-binding protein as an early marker of intestinal necrosis after aortic surgery: a prospective observational cohort study. Ann Surg. 2012;255:796–803.
22. 1. Schellekens DHSM, Grootjans J, Dello SAWG, van Bijnen AA, van Dam RM, Dejong CHC, et al. Plasma intestinal fatty acid-binding protein levels correlate with morphologic epithelial intestinal damage in a human translational ischemia-reperfusion model. J Clin Gastroenterol 2014;48:253–60.
    2. Schellekens DHSM, Grootjans J, Dello SAWG, van Bijnen AA, van Dam RM, Dejong CHC. et al. Plasma intestinal fatty acid-binding protein levels correlate with morphologic epithelial intestinal damage in a human translational ischemia-reperfusion model. J Clin Gastroenterol. 2014;48:253–60.
23. 1. Groesdonk HV, Klingele M, Schlempp S, Bomberg H, Schmied W, Minko P, et al. Risk factors for nonocclusive mesenteric ischemia after elective cardiac surgery. J Thorac Cardiovasc Surg 2013;145:1603–10.
    2. Groesdonk HV, Klingele M, Schlempp S, Bomberg H, Schmied W, Minko P. et al. Risk factors for nonocclusive mesenteric ischemia after elective cardiac surgery. J Thorac Cardiovasc Surg. 2013;145:1603–10.
24. 1. Petrat F, Drowatzky J, Boengler K, Finckh B, Schmitz KJ, Schulz R, et al. Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine. Eur Surg Res 2011;46:180–7.
    2. Petrat F, Drowatzky J, Boengler K, Finckh B, Schmitz KJ, Schulz R. et al. Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine. Eur Surg Res. 2011;46:180–7.
25. 1. Effenberger-Neidnicht K, Jägers J, Verhaegh R, de Groot H. Glycine selectively reduces intestinal injury during endotoxemia. J Surg Res 2014;192:592–8.
    2. Effenberger-Neidnicht K, Jägers J, Verhaegh R, de Groot H. Glycine selectively reduces intestinal injury during endotoxemia. J Surg Res. 2014;192:592–8.
26. 1. Petrat F, Rönn T, de Groot H. Protection by pyruvate infusion in a rat model of severe intestinal ischemia-reperfusion injury. J Surg Res 2011;167:e93–101.
    2. Petrat F, Rönn T, de Groot H. Protection by pyruvate infusion in a rat model of severe intestinal ischemia-reperfusion injury. J Surg Res. 2011;167:e93–101.