ORIGINAL ARTICLE ANZJSurg.com

Role of inflammatory markers as predictors of laparotomy in patients presenting with acute abdomen Brendan H. Dias, Anthony P. Rozario and Santosh A. Olakkengil Department of Surgery, St. John’s Medical College, Bangalore, India

Key words acute abdomen, C-reactive protein, CRP, PCT, procalcitonin. Correspondence Dr Brendan H. Dias, Department of Surgery, St. John’s Medical College, Room C – 319, St. Johns Mens Hostel, Sarjapura Road, Koramangala, Bangalore – 34, India. Email: [email protected] B. H. Dias MS General Surgery; A. P. Rozario DNB General Surgery; S. A. Olakkengil DNB General Surgery. Accepted for publication 5 December 2014. doi: 10.1111/ans.12993

Abstract Background: There is a need for an ideal indicator of surgery in patients presenting with acute abdomen. Several markers have been analysed, but the search still continues as none have proven effective. This study aimed to analyse and compare the predictive value of plasma procalcitonin (PCT) strip test in patients presenting with acute abdomen and identify a useful cut-off value to differentiate patients that would benefit with surgery from those that require conservative management. Methods: A prospective study was conducted in the department of general surgery from June 2012 to June 2013. Plasma PCT was estimated by the semi-quantitative strip test. The levels of plasma PCT and other routinely used markers of inflammation were analysed and compared. Results: Of the total of 58 patients, 44 patients (76%) were men with a mean age of 45 years. Forty patients required emergency surgical intervention. A plasma PCT value of >0.5 ng/mL at admission was 80% sensitive and 100% specific for predicting need for antibiotics in patients with acute abdomen that were managed conservatively. The mean plasma PCT value in the patients undergoing surgery (5.0–10.0 ng/mL) was significantly more than in those managed conservatively (0.5–2.0 ng/mL). Using receiver operating characteristic (ROC) curves a cut-off for plasma PCT of >5.0 ng/mL was 75% sensitive and 100% specific for considering surgical intervention in patients presenting with acute abdomen. Conclusions: Plasma PCT (value >5 ng/mL) could be used as an adjunct to clinical examination to predict requirement of surgery in patients presenting with acute abdomen.

Introduction Clinical assessment remains the most important first step in evaluating patients with acute abdomen. However, clinical examination has been found to be only accurate in 47–76% of patients with acute abdominal pain.1 Even the most experienced surgeon will make correct diagnosis in only four out of five cases. This drops to 50% with junior doctors and doctors working in the community.2 Several inflammatory markers are being used routinely as an aid in the diagnosis of patients with acute abdomen such as C-reactive protein (CRP) and total leukocyte counts. Most studies on the value these inflammatory markers in patients with an acute abdomen have focused only on acute appendicitis.3 There are a few studies that have assessed the diagnostic role of these markers in the broad category of acute abdomen.4 Plasma procalcitonin (PCT) is a highly specific marker for the diagnosis of bacterial infection and sepsis. Several studies on plasma © 2015 Royal Australasian College of Surgeons

PCT have demonstrated its role in patients with ileus, in the diagnosis of sepsis, prognosis of acute severe pancreatitis and even as a prognostic marker following major surgery.5,6 Very little literature is available on the role of plasma PCT as a serological marker in the diagnosis and prognosis of acute abdomen as a broad category. Initiating a step in this direction, this study aimed to compare the various serological markers of acute inflammation in patients presenting with acute abdomen.

Materials and methods Source of data All patients presenting with acute abdomen to the emergency medicine department of St John’s Medical College Hospital, Bangalore from June 2012 to June 2013. Acute abdomen was defined as the sudden onset of abdominal pain of less than 24 h duration with no ANZ J Surg •• (2015) ••–••

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history of trauma. A total of 58 patients with acute onset abdominal pain were treated during the study period and included in our sample size.

Sample size A total of 58 patients were included in the study. Institutional Ethical Review Board clearance was obtained for the study.

Exclusion criteria (1) (2) (3) (4)

History of trauma. Prolonged cardiogenic shock with impaired organ perfusion. Lung cancer or medullary carcinoma of thyroid. Cases diagnosed as acute pancreatitis.

enough serum for performing CRP and plasma PCT level determination then that sample was be discarded and a fresh sample was drawn. (6) Plasma PCT was estimated using a semi-quantitative strip test (B.R.A.H.M.S PCT-Q test). (7) Descriptive and inferential statistical analysis was carried out on the data collected using the Statistical Package for the Social Sciences (SPSS) 17 (SPSS, Inc., Chicago, IL, USA). (8) The values of plasma PCT and CRP were blinded and were not used in the management of patients. These markers were only done as a part of the study. Hence, the decision to manage the patients was based on clinical signs and other routine laboratory investigations such as the total counts.

Results Study design The study was designed as an observational study using a prospective study design.

Protocol of the procedure (1) Inclusion and exclusion criteria were applied to all patients presenting with acute abdomen to the emergency medicine department of our hospital. (2) Patients were educated about the study and only those patients consenting to participate in the study were included. (3) The levels of the inflammatory markers were blinded and the treating surgeon was not aware of the levels of these markers. (4) Database collection included documentation of medical history, age, sex, prehospital interval, vital signs, abdominal signs and drug history. (5) CRP and plasma PCT level determination was performed on the same serum sample drawn for other biochemical tests. The drawn blood was put in different vacutainers and labelled accordingly for the different tests. If there is not

Out of the total of 58 patients 44 patients (76%) were men and 14 were women with a mean age of 45 years (range, 22–82 years). The patients were divided into two groups: those managed conservatively (n = 18) and those requiring surgical intervention (n = 40). The patient characteristics are given in Table 1. There were two deaths. Both were due to multi-organ dysfunction secondary to severe abdominal sepsis.

Requirement of emergency surgical intervention Forty out of the 58 patients (69%) required emergency surgical intervention. Eight patients required multiple surgeries. Only plasma PCT values were found to correlate with requirement for surgery. It was also found that the mean plasma PCT value in the patients undergoing surgery (5.0–10.0 ng/mL) was significantly more than in those managed conservatively (0.5–2.0 ng/mL); P < 0.001 (Table 2). A cut-off for plasma PCT of >5.0 ng/mL was 75% sensitive and 100% specific for considering surgical intervention in patients presenting with acute abdomen (Fig. 1).

Table 1 Patient characteristics Patient characteristics

Number of patients (%)

Age (years) 18–40 >40 Sex Male Female Duration of symptoms pre-hospitalization (h) 24 Co-morbid conditions Type 2 diabetes mellitus Hypertension Hospitalization Total days 7 HDU requirement ICU requirement

Conservatively managed (%)

Requiring surgery (%)

30 (52%) 28 (48%)

12 (67%) 6 (33%)

18 (45%) 22 (55%)

44 (76%) 14 (24%)

15 (83%) 3 (17%)

29 (73%) 11 (27%)

36 (62%) 22 (38%)

13 (72%) 5 (28%)

23 (57%) 17 (43%)

8 (14%) 8 (14%)

3 (17%) 1 (6%)

5 (13%) 7 (18%)

34 (59%) 24 (41%) 42 (72%) 10 (17%)

16 (89%) 2 (11%) 8 (44%) 1 (6%)

18 (45%) 22 (55%) 34 (85%) 9 (23%)

HDU, High Dependency Unit; ICU, Intensive Care Unit.

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Predictors of laparotomy in acute abdomen

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Table 2 Mean CRP, plasma PCT and total leukocyte counts in surgical and non-surgical groups Laboratory parameter (mean value) Plasma PCT CRP Leukocyte count

Patients requiring surgery

Patients managed conservatively

P-value

5.0–10.0 10.96 11936

0.5–2.0 11.97 11226

9 mg/dL at admission was 80% sensitive and 100% specific for need for antibiotics while a total leukocyte count of >11 000 was 90% sensitive and 87% specific for predicting need for antibiotics. In patients requiring surgery, only plasma PCT showed a significant positive correlation with regard to predicting the need for antibiotics.

PCT as an independent predictor of surgery

Fig. 1. Receiver operating characteristic (ROC) curve for requirement of surgery. PCT, procalcitonin.

Total leukocyte count, CRP and PCT levels versus hospital stay In patients managed conservatively, none of the studied inflammatory markers could predict requirement of High Dependency Unit (HDU) care or Intensive Care Unit (ICU) care and prolonged hospitalization (Table 3). In patients requiring surgery, only CRP levels at admission were found to correlate with the total hospital stay and requirement of HDU or ICU care (Table 4). Neither plasma PCT levels nor the CRP levels were found to correlate with the development of postoperative complications.

Total leukocyte count, CRP and PCT levels versus antibiotic requirement In patients managed conservatively, plasma PCT, CRP levels and total leukocyte counts were all found to be good indicators for requirement of antibiotics and the levels of these markers correlated well with the duration of antibiotic use. Using ROC curve analysis (Fig. 2), a plasma PCT value of >0.5 ng/mL at admission was 80% sensitive and 100% specific for predicting the need for antibiotics in patients with acute abdomen © 2015 Royal Australasian College of Surgeons

A total of 10 out of the 40 operated patients had perforation peritonitis with frank abdominal signs and radiographs showing gas under the diaphragm, two cases had frank clinical signs of acute appendicitis and in two cases the clinical signs and radiographs strongly suggested a diagnosis of acute intestinal obstruction. These patients would not warrant any further serological tests in our clinical setting and would require emergency surgery. Hence, we evaluated the predictive value of plasma PCT in patients where the pretest probability of surgery is not high by exclusion of these 14 cases from the total of 58 cases. These cases were excluded in order to assess the role of plasma PCT as an independent predictor of surgery. We have already seen that plasma PCT values correlates with surgical requirement in Figure 1. However, in order to assess the role of plasma PCT as an independent marker, we need to exclude those cases that would ordinarily not warrant the use of plasma PCT in the clinical setting. Hence, these 14 cases were excluded only because the pretest probability of surgery in these patients was high. Using ROC curve analysis, only plasma PCT values correlated with surgery and a cut-off value of plasma PCT of >5 ng/mL was found to be 73% sensitive and 80% specific for considering emergency surgical intervention in these patients (Fig. 3).

Discussion We analyzed a total of 58 patients who presented with acute abdomen. We excluded patients with a diagnosis of acute pancreatitis as a cause for the acute abdomen. The reason for this exclusion was because the management of acute pancreatitis is mainly conservative, and studies have mainly focused on predicting the severity of the disease, the development of necrosis and organ failure. Hence, the challenge faced in these patients is mainly in assessing their prognosis and course during hospitalization. However in other causes for acute abdomen challenges are faced in diagnosis, requirement of emergency surgical intervention, requirement of imaging studies and in differentiating a surgical abdomen from other causes of acute abdomen. Hence our study focused on the role of inflammatory markers as predictors of surgical intervention in patients presenting with acute abdomen.

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Table 3 Correlation coefficients for hospitalization (conservative management) Correlation coefficient (n = 18) Pearson’s coefficient PCT CRP WBC Spearman’s rho PCT CRP WBC

Hospital stay (P)

HDU stay (P)

ICU stay (P)

0.342 (0.164) 0.105 (0.679) 0.059 (0.817)

0.304 (0.220) 0.003 (0.989) 0.194 (0.441)

NA NA NA

0.311 (0.209) −0.005 (5 ng/mL was 73% sensitive and 80% specific suggesting that plasma PCT could be used for considering emergency surgery. In a prospective study by Salem et al.4 on the role of CRP in acute abdomen, it was confirmed that CRP alone was not useful in differentiating a self-limiting condition like non-specific abdominal pain from other important surgical causes of acute abdomen. CRP was also not able to differentiate between surgical conditions requiring surgery/intervention from those who were treated non-operatively. Our study confirms this, and the CRP and leukocyte counts in our study did not correlate with surgery. However, a retrospective study7 on CRP as an independent surgical indication marker for appendicitis demonstrated that CRP leads to precise prediction of the severity of acute appendicitis for treatment. They concluded that the CRP level; and neither the white blood cell (WBC) count nor the neutrophil percentage, can lead to an appropriate decision on whether surgery or non-surgical treatment needs to be offered to patients with a strong clinical suspicion of acute appendicitis. Similar studies using plasma PCT are lacking in literature. A study by Ivancˇevic´ et al.8 suggested that PCT measurements may be useful for early, preoperative diagnosis of abdominal sepsis. They found that patients with sepsis had significantly higher plasma PCT values than those with severe inflammatory response syndrome. Another study by Rau et al.9 showed that plasma PCT significantly contributes to earlier and better stratification of patients at risk of developing septic complications and provides excellent prognostic assessment in severe abdominal inflammation. An interesting observation made by the authors was with regard to four patients in the study who had no abdominal signs of sepsis and were hence conserved. These patients also presented with acute abdomen and had elevated plasma PCT levels in the range of 5–10 ng/mL at admission. However as these results were blinded to the treating team they were provisionally admitted for observation based on negative clinical examination and normal leukocyte counts. The patients deteriorated and were operated later. Operative findings of mesenteric ischaemia were observed in these patients. These patients had prolonged hospital stay and two of these patients died because of sepsis contributing to the only mortality observed in the study. If plasma PCT values were used in these patients, significant mortality and morbidity could be avoided. A prospective study by Markogiannakis et al.10 on the predictive value of PCT for bowel ischaemia and necrosis in bowel obstruction concluded that PCT on presentation is a very useful for the diagnosis or exclusion of intestinal ischaemia and necrosis in acute bowel obstruction and could serve as an additional diagnostic tool to improve clinical decision making.

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Conclusions The acute abdomen is a challenge to the surgeon handling outpatient emergencies in any institution. Clinical examination has proven to be inaccurate in many cases resulting in diagnostic delays and significant morbidity and mortality. In our study, we found that plasma PCT (cut-off of >5 ng/mL) was able to predict requirement of emergency surgical intervention, and could be an important adjunct to clinical examination in identifying those cases with acute abdomen that require emergency surgery. This test can be rapidly performed in the emergency setting and does not require additional resources or investment.

Limitations Our study has limitations. It is a pilot study and the sample size is relatively small. Hence, although our study shows that plasma PCT could be an independent marker for emergency surgical requirement, further larger studies on the role of plasma PCT in the setting of acute abdomen are required before it is recommended as an independent predictor of surgery.

References 1. Ng CS, Watson CJE, Palmer CR et al. Evaluation of early abdominopelvic computed tomography in patients with acute abdominal pain of unknown cause: prospective randomised study. BMJ 2002; 325: 1387–9. 2. Briton J. Acute abdomen. In: Morris PJ, Wood WC (eds). Oxford Textbook of Surgery. Oxford: OUP, 2000. 3. Albu E, Miller BM, Choi Y, Lakhanpal S, Merthy RN, Gerst PH. Diagnostic value of C-reactive protein in acute appendicitis. Dis. Colon Rectum 1994; 37: 49–51. 4. Salem TA, Molloy RG, O’Dwyer PJ. Prospective study on the role of C-reactive protein in patients with acute abdomen. Ann. R. Coll. Surg. Engl. 2007; 89: 233–7. 5. Rau BM, Kemppainen EA, Gumbs AA et al. Early assessment of pancreatic infections and overall prognosis in severe acute pancreatitis by procalcitonin (PCT). A prospective international multicenter study. Ann. Surg. 2007; 245: 745–54. 6. Maruna P, Gurlich R, Frasco R et al. Procalcitonin in the diagnosis of postoperative complications. Sb. Lek. 2002; 103: 283–95. 7. Paterson-Brown S, Vipond MN. Modern aids to clinical decisionmaking in the acute abdomen. Br. J. Surg. 1990; 77: 13–8. 8. Ivancˇevic´ N, Radenkovic´ D, Bumbaširevic´ V et al. Procalcitonin in preoperative diagnosis of abdominal sepsis. Langenbecks Arch. Surg. 2008; 393: 397–403. 9. Rau B, Krüger CM, Schilling MK. Procalcitonin: improved biochemical severity stratification and postoperative monitoring in severe abdominal inflammation and sepsis. Langenbecks Arch. Surg. 2004; 389: 134–44. 10. Markogiannakis H, Memos N, Messaris E et al. Predictive value of procalcitonin for bowel ischemia and necrosis in bowel obstruction. Surgery 2011; 149: 394–403.

Role of inflammatory markers as predictors of laparotomy in patients presenting with acute abdomen.

There is a need for an ideal indicator of surgery in patients presenting with acute abdomen. Several markers have been analysed, but the search still ...
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