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Three Part Question

In [elderly patients presenting to Emergency Departments with abdominal pain and suspected acute mesenteric ischemia] what is the accuracy of [plasma biomarkers] in supporting the diagnosis and help in [decision making]?

Clinical Scenario

A 79 years old man presents to the Emergency Department with acute onset of central abdominal pain and one attack of bloody diarrhoea. The pain is severe and not relieved by simple analgesia. Abdominal examination shows central abdominal tenderness but no guarding. On general examination the pulse was 110/minute irregular but other examination was unremarkable, serum amylase was also normal. The patient gave a history of hyperlipaedemia, hypertension, smoking and peripheral vascular disease. You started titrated doses of morphine to relive the pain.
You suspect acute mesenteric ischaemia and wonder if any blood test can help in supporting or excluding the diagnosis.

Search Strategy

Medline,CINAHL search using EBSCO and EMBASE search using OVID interface (1950- September 2013)
Search (((((((elderly[ti] or geriatric[ti]))) OR ((("Aged"[Mesh] or "Aged, 80 and over"[Mesh] or "Frail Elderly"[Mesh]))))) AND ((((acute mesenteric ischaemia or acute mesenteric ischemia or AMI or bowel ischaemia or bowel ischemia or bowel infarction))) OR ((mesenteric and acute)))) AND (("Hematologic Tests"[Mesh] or "blood test" or "plasma biomarker" or (plasma and biomarker))))) NOT myocardial infarction.
we also searched google schoolar for relevant articles and dissertations.

Search Outcome

64 papers were found of which 6 were relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Kulacoglu H et al 2005 Turkey	Experimental animal study of 30 male Albino rats	Lab study of albino rats divided into 3 groups. Group 1 acted as non-operative control. Group 2 had open manipulation of SMA. Group 3 had ligation of SMA. D Dimers Lactate measured in the 3 groups.	Both Group II (p=0.016) and Group III (p=0.001) had significantly higher D-Dimers levels in the first postoperative hour compared with the level in Group I. At 6 hours D Dimers were high and continued to rise in Group 3 only but the difference between group 2 and 3 was not significant. Serum L Lactate was higher only in group 3 at 1(p<0.003) and 6 hours (p<0.001) post ligation.	The use of blood D-dimer and L Lactate levels are of value in ruling out mesenteric ischaemia but cannot be used in isolation duo to low specificity. The levels increased in group 2 that had surgery with no ligation.	Animal study, the applicability of the results in humans is too early to determine.
T. Block et al 2008 Sweden	71 patients over the age of 50 years old with non-traumatic abdominal pain	Prospective study. Blood sample was taken within 24 hours from the onset of pain	D‐lactate, alpha glutathione S‐transferase, intestinal fatty acid binding protein, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) were analysed. D‐Dimers were analysed using four different commercially available test kits.	D‐dimer was associated with intestinal ischaemia (p = 0.001) independently of which assay was used. No patient presenting with a normal D‐dimer had intestinal ischaemia. D‐dimer >0.9 mg/L had a specificity, sensitivity and accuracy of 82 %, 60 % and 79 %, respectively. Total LD, isoenzymes of LD 1–4 and liver isoenzyme of ALP (ALP liver) were significantly higher in patients with intestinal ischaemia, and accuracies for LD 2 (cut‐off 2.3 µkat/L) and ALP liver (cut‐off 0.7 µkat/L) were 69 % and 66 %, respectively	Small sample size. Use of the age of 50 years old as a cut point. No clear inclusion and exclusion criteria. Timing of the blood samples is not fixed.
Acosta S et al 2012 Sweden	Review article of 20 animal and 11 human studies	Review article of human and animal studies	D-Dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations	The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen suspected of having acute mesenteric ischaemia.	Review of mixed animal and human studies. Non systematic review.
Evennett NJ et al 2009 UK	Review of 20 articles examining 18 different serological markers. Studies were included if it provided both the sensitivity and the specificity of a serologic marker for the diagnosis of intestinal ischemia (index test), or when it provided the data on individual study subjects, allowing authors to derive the sensitivity and the specificity. The reference test was diagnosis at surgery or autopsy.	Review of animal and human studies	Sensitivity of WBC80%,Ph 38%,DD 89%. Specificity of WBC 50%, PH 84%, DD 40%. Positive Likelihood ratio for WBC 1.57, PH 2.49, DD1.48. Negative Likelihood ratio for WBC 41%, PH 71%, DD 30%.	The performance of the currently available serological markers such as Lactate,GST, (Intestinal Fatty Acid Binding Protein)iFABP may help in early diagnosis but this is too early and remain of suboptimal evidence for routine clinical use, further research is required.	Non systematic review. The applicability of the findings of the review need further well designed human study
Thuijls G et al 2011 Netherland	50 consecutive patients with suspected AMI	Prospective observational study	22 patients with proved AMI,compared to 24 patients with non-proven AMI.	Plasma and especially urinary I-FABP and L-FABP levels and urinary I-BABP levels can improve early diagnosis of intestinal ischemia. Furthermore, plasma I-BABP levels can help in localizing ileal ischemia.	Small sample size
Acosta S et al 2001 Sweden	Fourteen patients suspected of having acute bowel ischaemia were analysed for an increase in plasma D-dimer level.	Observational study	Six patients had embolic or thrombotic occlusion of the SMA and all had significantly higher D-dimer levels than those without thromboembolic occlusion (P < 0.05). Four patients with strangulation of the small bowel due to adhesions and one with a ruptured aortic aneurysm also had raised D-dimer values.	In patients with suspected thromboembolic occlusive disease of the SMA, a raised level of D-dimer indicated the presence of acute bowel ischaemia, whatever the cause. A more extensive prospective study is needed to evaluate a potential survival benefit using the test as a marker of the need for urgent laparotomy.	Small sample size, observational study

Comment(s)

Many markers have been investigated. Early evidence from animal and human studies suggest that D Dimers to be the most practical to use with high sensitivity but low specificity. D-Dimers may be used as part of decision making tool to help in risk stratification of patients with suspected intestinal ischaemia. Other plasma biomarkers such as Intestinal Fatty Acid Binding Protein (iFABP), D‐lactate, alpha glutathione S‐transferase, creatine kinase B, isoenzymes of lactate dehydrogenase (LD) and alkaline liver phosphatase (ALP) had been tried but found to have insufficient accuracy for this group of patients.

References

1. Kulacoglu H, Kocaerkek Z, Moran M, Kulah B, Atay C, Kulacoglu S, Ozmen M, Coskun F Diagnostic value of blood D-dimer level in acute mesenteric ischaemia in the rat: an experimental study Asian J Surg 2005 Apr;28(2):131-5
2. Block T, Nilsson TK, Björck M, Acosta S Diagnostic accuracy of plasma biomarkers for intestinal ischaemia Scand J Clin Lab Invest 2008;68(3):242-248
3. Acosta S, Nilsson T Current status on plasma biomarkers for acute mesenteric ischemia J Thromb Thrombolysis 2012 May;33(4):355-61
4. 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: 1374-1383
5. Thuijls G, van Wijck K, Grootjans J, Derikx JP, van Bijnen AA, Heineman E, Dejong CH, Buurman WA, Poeze M Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins Ann Surg 2011 Feb;253(2):303-8
6. Acosta S, Nilsson TK, Björck M Preliminary study of D-dimer as a possible marker of acute bowel ischaemia Br J Surg 2001 Mar;88(3):385-8