World Journal of Surgery

, Volume 33, Issue 7, pp 1374–1383 | Cite as

Systematic Review and Pooled Estimates for the Diagnostic Accuracy of Serological Markers for Intestinal Ischemia

  • Nicholas J. Evennett
  • Maxim S. Petrov
  • Anubhav Mittal
  • John A. Windsor



Intestinal ischemia is a potentially catastrophic abdominal emergency that presents a significant diagnostic challenge in the critical care setting. We performed a systematic review of the literature to define the diagnostic accuracy of serological markers of intestinal ischemia.


Observational studies on the performance of markers of intestinal ischemia were identified within the MEDLINE and EMBASE electronic databases. All studies from which it was possible to derive true positive, false positive, false negative, and true negative results were included. A random-effects model was used to calculate the pooled estimates of diagnostic accuracy.


A total of 20 articles examining 18 different serological markers were identified that met the inclusion criteria. The global measures of test performance (diagnostic odds ratio and area under the summary receiver operating characteristic curve) for markers investigated in three or more studies were d-lactate (10.75 and 0.86, respectively), glutathione S-transferase (GST; 8.82 and 0.87, respectively), intestinal fatty-acid binding protein (i-FABP; 7.62 and 0.78, respectively), and d-dimer (5.77 and 0.53, respectively).


The performance of the currently available serological markers is suboptimal for routine clinical use, but novel markers of intestinal ischemia such as d-lactate, GST, and i-FABP may offer improved diagnostic accuracy. The early diagnosis of intestinal ischemia remains a challenge, and further research is required to identify improved serological markers and to demonstrate their clinical utility in the individual patient.


Severe Acute Pancreatitis Acute Abdomen Serological Marker Index Test Intestinal Ischemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Dr. Petrov is Kenneth Warren Fellow of the International Hepato-Pancreato-Biliary Association (IHPBA). The authors are grateful to Dr. Michael Gillham (Auckland City Hospital, Auckland, New Zealand) for critically reviewing the manuscript.


  1. 1.
    Kairaluoma MI, Karkola P, Heikkinen D et al (1977) Mesenteric infarction. Am J Surg 133:188–193PubMedCrossRefGoogle Scholar
  2. 2.
    Martin B (2007) Prevention of gastrointestinal complications in the critically ill patient. AACN Adv Crit Care 18:158–166PubMedGoogle Scholar
  3. 3.
    Reilly PM, Wilkins KB, Fuh KC et al (2001) The mesenteric hemodynamic response to circulatory shock: an overview. Shock 15:329–343PubMedCrossRefGoogle Scholar
  4. 4.
    Ceppa EP, Fuh KC, Bulkley GB (2003) Mesenteric hemodynamic response to circulatory shock. Curr Opin Crit Care 9:127–132PubMedCrossRefGoogle Scholar
  5. 5.
    De Backer D, Creteur J, Silva E et al (2003) Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med 31:1659–1667PubMedCrossRefGoogle Scholar
  6. 6.
    Lundberg J, Lundberg D, Norgren L et al (1990) Intestinal hemodynamics during laparotomy: effects of thoracic epidural anesthesia and dopamine in humans. Anesth Analg 71:9–15PubMedCrossRefGoogle Scholar
  7. 7.
    van der Voort PH (2006) The incomplete puzzle of vasoactive medication in (abdominal) sepsis. Crit Care Med 34:1565–1566PubMedCrossRefGoogle Scholar
  8. 8.
    Woo K, Major K, Kohanzadeh S et al (2007) Laparotomy for visceral ischemia and gangrene. Am Surg 73:1006–1008PubMedGoogle Scholar
  9. 9.
    Kougias P, Lau D, El Sayed HF et al (2007) Determinants of mortality and treatment outcome following surgical interventions for acute mesenteric ischaemia. J Vasc Surg 46:467–474PubMedCrossRefGoogle Scholar
  10. 10.
    Angelelli G, Scardapane A, Memeo M et al (2004) Acute bowel ischaemia: CT findings. Eur J Radiol 50:37–47PubMedCrossRefGoogle Scholar
  11. 11.
    Kozuch PL, Brandt LJ (2005) Review article: diagnosis and management of mesenteric ischaemia with an emphasis on pharmacotherapy. Aliment Pharmacol Ther 21:201–215PubMedCrossRefGoogle Scholar
  12. 12.
    Furukawa A, Kanasaki S, Kono N et al (2009) CT diagnosis of acute mesenteric ischemia from various causes. AJR Am J Roentgenol 192:408–416PubMedCrossRefGoogle Scholar
  13. 13.
    Brandt LJ, Boley SJ (2000) AGA technical review on intestinal ischemia. American Gastrointestinal Association. Gastroenterology 118:954–968PubMedCrossRefGoogle Scholar
  14. 14.
    Glenister KM, Corke CF (2004) Infarcted intestine: a diagnostic void. Aust N Z J Surg 74:260–265CrossRefGoogle Scholar
  15. 15.
    Oldenburg WA, Lau LL, Rodenberg TJ et al (2004) Acute mesenteric ischaemia: a clinical review. Arch Intern Med 164:1054–1062PubMedCrossRefGoogle Scholar
  16. 16.
    Whiting P, Rutjes AW, Reitsma JB et al (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 10:25CrossRefGoogle Scholar
  17. 17.
    Zamora J, Abraira V, Muriel A et al (2006) Meta-DiSc: a software for meta-analysis of test accuracy data. BMC Med Res Methodol 12:31CrossRefGoogle Scholar
  18. 18.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  19. 19.
    Moses LE, Shapiro D, Littenberg B (1993) Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med 12:1293–1316PubMedGoogle Scholar
  20. 20.
    Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 21:1237–1256PubMedCrossRefGoogle Scholar
  21. 21.
    TS Higgins JP, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefGoogle Scholar
  22. 22.
    Acosta S, Nilsson TK, Bjorck M (2004) d-dimer testing in patients with suspected acute thromboembolic occlusion of the superior mesenteric artery. Br J Surg 91:991–994PubMedCrossRefGoogle Scholar
  23. 23.
    Block T, Nilsson TK, Bjorck M et al (2008) Diagnostic accuracy of plasma biomarkers for intestinal ischaemia. Scand J Clin Lab Invest 68:242–248PubMedCrossRefGoogle Scholar
  24. 24.
    Delaney CP, O’Neill S, Manning F et al (1999) Plasma concentrations of glutathione S-transferase isoenzyme are raised in patients with intestinal ischaemia. Br J Surg 86:1349–1353PubMedCrossRefGoogle Scholar
  25. 25.
    Feretis CB, Koborozos BA, Vyssoulis GP et al (1985) Serum phosphate levels in acute bowel ischemia. An aid to early diagnosis. Am Surg 51:242–244PubMedGoogle Scholar
  26. 26.
    Fried MW, Murthy UK, Hassig SR et al (1991) Creatine kinase isoenzymes in the diagnosis of intestinal infarction. Dig Dis Sci 36:1589–1593PubMedCrossRefGoogle Scholar
  27. 27.
    Icoz G, Makay O, Sozbilen M et al (2006) Is d-dimer a predictor of strangulated intestinal hernia? World J Surg 30:2165–2169PubMedCrossRefGoogle Scholar
  28. 28.
    Kanda T, Fujii H, Tani T et al (1996) Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology 110:339–343PubMedCrossRefGoogle Scholar
  29. 29.
    Lange H (1989) Differential diagnostic significance of lactate in acute abdominal diseases. Chirurg 60:356–360PubMedGoogle Scholar
  30. 30.
    Lange H, Toivola A (1997) Warning signals in acute abdominal disorders. Lactate is the best marker of mesenteric ischemia. Lakartidningen 94:1893–1896PubMedGoogle Scholar
  31. 31.
    Leo PJ, Simonian HG (1996) The role of serum phosphate level and acute ischemic bowel disease. Am J Emerg Med 14:377–379PubMedCrossRefGoogle Scholar
  32. 32.
    Murray MJ, Gonze MD, Nowak LR et al (1994) Serum d(–)-lactate levels as an aid to diagnosing acute intestinal ischemia. Am J Surg 167:575–578PubMedCrossRefGoogle Scholar
  33. 33.
    Sutherland F, Cunningham H, Pontikes L et al (2003) Elevated serum interleukin 6 levels in patients with acute intestinal ischemia. Hepatogastroenterology 50:419–421PubMedGoogle Scholar
  34. 34.
    Acosta S, Bjorck M (2003) Acute thrombo-embolic occlusion of the superior mesenteric artery: a prospective study in a well defined population. Eur J Vasc Endovasc Surg 26:179–183PubMedCrossRefGoogle Scholar
  35. 35.
    Gearhart SL, Delaney CP, Senagore AJ et al (2003) Prospective assessment of the predictive value of alpha-glutathione S-transferase for intestinal ischemia. Am Surg 69:324–329 discussion 329PubMedGoogle Scholar
  36. 36.
    Lieberman JM, Sacchettini J, Marks C et al (1997) Human intestinal fatty acid binding protein: report of an assay with studies in normal volunteers and intestinal ischemia. Surgery 121:335–342PubMedCrossRefGoogle Scholar
  37. 37.
    Assadian A, Assadian O, Senekowitsch C et al (2006) Plasma d-lactate as a potential early marker for colon ischaemia after open aortic reconstruction. Eur J Vasc Endovasc Surg 31:470–474PubMedCrossRefGoogle Scholar
  38. 38.
    Graeber GM, Clagett GP, Wolf RE et al (1990) Alterations in serum creatine kinase and lactate dehydrogenase. Association with abdominal aortic surgery, myocardial infarction and bowel necrosis. Chest 97:521–527PubMedCrossRefGoogle Scholar
  39. 39.
    Poeze M, Froon AH, Greve JW et al (1998) d-lactate as an early marker of intestinal ischaemia after ruptured abdominal aortic aneurysm repair. Br J Surg 85:1221–1224PubMedCrossRefGoogle Scholar
  40. 40.
    Cronk DR, Houseworth TP, Cuadrado DG et al (2006) Intestinal fatty acid binding protein (i-FABP) for the detection of strangulated mechanical small bowel obstruction. Curr Surg 63:322–325PubMedCrossRefGoogle Scholar
  41. 41.
    Polk JD, Rael LT, Craun ML et al (2008) Clinical utility of the cobalt-albumin binding assay in the diagnosis of intestinal ischemia. J Trauma 64:42–45PubMedCrossRefGoogle Scholar
  42. 42.
    Deville WL, Buntinx F, Bouter LM et al (2002) Conducting systematic reviews of diagnostic studies: didactic guidelines. BMC Med Res Methodol 2:9PubMedCrossRefGoogle Scholar
  43. 43.
    Deitch EA, Morrison J, Berg R et al (1990) Effect of hemorrhagic shock on bacterial translocation, intestinal morphology, and intestinal permeability in conventional and antibiotic-decontaminated rats. Crit Care Med 18:529–536PubMedCrossRefGoogle Scholar
  44. 44.
    Lee ES, Bass A, Arko FR et al (2006) Intraoperative colon mucosal oxygen saturation during aortic surgery. J Surg Res 136:19–24PubMedCrossRefGoogle Scholar
  45. 45.
    Besselink MG, van Santvoort HC, Buskens E et al (2008) Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–659PubMedCrossRefGoogle Scholar
  46. 46.
    Mofidi R, Deans C, Duff MD et al (2006) Prediction of survival from carcinoma of oesophagus and oesophago-gastric junction following surgical resection using an artificial neural network. Eur J Surg Oncol 32:533–539PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2009

Authors and Affiliations

  • Nicholas J. Evennett
    • 1
  • Maxim S. Petrov
    • 2
    • 3
  • Anubhav Mittal
    • 3
  • John A. Windsor
    • 3
  1. 1.Department of SurgeryInstitute of Child HealthLondonUK
  2. 2.Department of SurgeryNizhny Novgorod State Medical AcademyNizhny NovgorodRussia
  3. 3.Department of Surgery, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

Personalised recommendations