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ORIGINAL ARTICLE
Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 34-39

Evaluation of risk factors associated with hyperbilirubinemia after surgery of perforation peritonitis


Department of General Surgery, JLN Medical College, Ajmer, Rajasthan, India

Date of Web Publication29-May-2018

Correspondence Address:
Dr. Amit Singh
Department of General Surgery, JLN Medical College, Ajmer, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ssj.ssj_54_17

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  Abstract 

Aim: Gastrointestinal (GI) perforation repair is a commonly performed surgery worldwide. Postoperative septic conditions are frequently accompanied by cholestasis and postoperative jaundice. Our study was conducted to evaluate the risk factors and outcome of postoperative hyperbilirubinemia in patients with perforation peritonitis.
Materials and Methods: A prospective observational study of 100 patients was conducted between January 2013 and December 2014; they underwent surgery for generalized peritonitis caused by GI perforations in the Department of Surgery of JLN Medical College and Associated Group of Hospitals, Ajmer, Rajasthan, India. Postoperative hyperbilirubinemia is defined as serum total bilirubin level of ≥5 mg/dl within 1 month after surgery. In all the patients with postoperative hyperbilirubinemia, risk factors and outcome were assessed. Data analyses done with Fisher's exact test, Mann–Whitney test, Chi-square test, Student's t test, and repeated-measures analysis of variance were used for statistical comparisons.
Results: In our study of 100 patients, M:F ratio was 2.12. Sixteen percent of the total patients belonged to hyperbilirubinemia group and 84% belonged to no hyperbilirubinemia group. In the hyperbilirubinemia group, anemia was seen in 37.5%, poor nutrition in 44%, and shock in 62.5%, and these patients also had increased total leukocyte count counts, bilirubin level, aspartate aminotransferase level, and decreased platelet count, whereas in the no hyperbilirubinemia patients anemia was seen in 11%, poor nutrition in 15%, and shock in 15% cases and all of them had normal blood investigations. Postoperatively, in the hyperbilirubinemia group, cardiac and respiratory support was needed in 62% and 72% cases, respectively, renal insufficiency in 56% cases, prolonged paralytic ileus in 72%, and mortality in 62% cases. Infection-related complications developed in 20 patients (12 patients of hyperbilirubinemia group and 8 patients of no hyperbilirubinemia group).
Conclusion: In our study, we concluded that in cases of perforation peritonitis, hyperbilirubinemia was associated with advanced age, poor nutritional status, and prolonged time until surgical intervention, and these patients with postoperative hyperbilirubinemia showed higher morbidity and mortality after surgery.

Keywords: Emergency laparotomy, perforation peritonitis, postoperative hyperbilirubinemia, septicemia shock


How to cite this article:
Porwal R, Singh A, Jain A, Kumawat G. Evaluation of risk factors associated with hyperbilirubinemia after surgery of perforation peritonitis. Saudi Surg J 2018;6:34-9

How to cite this URL:
Porwal R, Singh A, Jain A, Kumawat G. Evaluation of risk factors associated with hyperbilirubinemia after surgery of perforation peritonitis. Saudi Surg J [serial online] 2018 [cited 2018 Oct 15];6:34-9. Available from: http://www.saudisurgj.org/text.asp?2018/6/2/34/233491


  Introduction Top


Perforation peritonitis is a common surgical emergency encountered across the world that requires optimum surgical care. In spite of advanced care, latest new-generation antibiotics, management of peritonitis is continued to be quite difficult and associated with considerable morbidity and mortality. Intraabdominal infection and septic conditions after surgery are frequently accompanied by cholestasis and postoperative jaundice which are thought to be mediated in parts by inflammatory cytokines and may predispose to multiple organ failure. However, the risk factors and outcome of patients in whom hyperbilirubinemia develops after surgery for generalized peritonitis are not well understood. Our study was conducted to evaluate the risk factors and prognostic importance of postoperative hyperbilirubinemia in patients with gastrointestinal (GI) perforation and generalized peritonitis.


  Materials and Methods Top


A prospective observational study of 100 patients was conducted between January 2013 and December 2014; they underwent surgery for generalized peritonitis caused by GI perforations in the Department of Surgery of JLN Medical College and Associated Group of Hospitals, Ajmer, Rajasthan, India.

Patients with localized peritonitis and in whom peritonitis was caused by acute appendicitis were excluded from the study. In the postoperative period, all the patients were divided into hyperbilirubinemia group and no hyperbilirubinemia group. Postoperative hyperbilirubinemia is defined as serum total bilirubin level of >5 mg/dl within 1 month of surgery.

Risk factors and outcome were analyzed. The analyzed factors were age, gender, perforation sites, accompanying illness (brain, heart, lung, liver, renal disease, and malignancy), anemia, nutritional status, presence of preoperative shock, time of onset until operation, antibiotic use during surgery, operation time, blood loss, preoperative leukocyte count, platelet count, preoperative serum levels of aspartate aminotransferase, and total bilirubin.

The preoperative values of all the parameters obtained within 24 h before surgery used for analysis.

  • The anemia has been defined as a hemoglobin level of <10 mg/dl
  • The poor nutrition has been defined as body mass index of <17
  • Preoperative shock has been defined as systolic blood pressure of <90 mm of hg.


The level of significance is set at P < 0.05.

Fisher's exact test, Mann–Whitney test, Chi-square test, Student's t test, and repeated-measures analysis of variance were used for statistical comparisons.


  Results Top


In our study of 100 patients, M:F ratio was 2.12:1. Sixteen percent of the total patients belonged to the hyperbilirubinemia group and 84% belonged to the no hyperbilirubinemia group. The mean age in our study was 51 ± 10 years for the hyperbilirubinemia group and 46 ± 6 years for the no hyperbilirubinemia group. In the hyperbilirubinemia group, maximum cases (50%) were observed with colorectal perforation as compared to gastroduodenal perforations (44%) in the no hyperbilirubinemia group. In the hyperbilirubinemia group, anemia was seen in 37.5%, poor nutrition in 44%, shock in 62.5%, and pulmonary disease in 21%, and these patients also had increased total leukocyte count counts, bilirubin level, aspartate aminotransferase level, and decreased platelet count, whereas in the no hyperbilirubinemia group anemia was seen in 11%, poor nutrition in 15%, shock in 15% cases, and pulmonary disease in 2.3% cases and all of these patients had normal blood investigations [Table 1].
Table 1: Results of the present study

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In the hyperbilirubinemia group, average time from diagnosis to surgery was 29 ± 13 h and average operative time was 240 ± 90 min with an average intraoperative blood loss of 600 ± 120 ml, whereas in the no hyperbilirubinemia group, average time from diagnosis to surgery was 18 ± 5 h and operative time was 180 ± 40 min with average blood loss of 550 ± 90 ml [Table 1].

Postoperatively, in the hyperbilirubinemia group, cardiac and respiratory support was needed in 62% and 72% cases, respectively, renal insufficiency in 56% cases, prolonged paralytic ileus in 72%, and mortality in 62% cases, whereas in the no hyperbilirubinemia group, cardiac and respiratory support was needed in 6% and 9.5% cases, respectively, renal insufficiency in 7% cases, prolonged paralytic ileus in 7%, and mortality in 4% cases [Table 1]. Infection-related complications developed in 20 patients (12 patients of hyperbilirubinemia group and 8 patients of no hyperbilirubinemia group); these included eight patients in a septic state due to continued abdominal peritonitis, wound infections in five, adult respiratory distress syndrome or pneumonia in three, residual intraabdominal abscesses in four, and suture dehiscence in four patients. Complications that were not infection related occurred at a similar incidence in both groups and developed in five patients; these included intractable arrhythmia in one patient and postoperative confusion, myocardial infarction, pneumothorax, and deep-venous thrombosis in one each. The changes in postoperative serum bilirubin levels in the hyperbilirubinemia group were examined according to the prognosis. Transient increase in serum bilirubin was seen in those patients from the hyperbilirubinemia group who survived; they showed the highest level of total serum bilirubin (5.0 ± 4.8 mg/dl) on postoperative day (POD) 3–5, following which there was a gradual decrease. However, the patients with postoperative hyperbilirubinemia who died showed a gradual and continued increase in serum bilirubin levels even after POD 5, the highest levels (20.0 ± 9.2 mg/dl) usually being evident soon before death. The highest serum bilirubin level of the survivors was on POD 4.2 ± 3.8, whereas that of the patients who died was seen on POD 22.3 ± 7.0 [Figure 1].
Figure 1: Bilirubin level on postoperative period

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  Discussion Top


GI perforation with generalized peritonitis is still associated with considerable morbidity and mortality. Perforation of the lower GI tract, advanced age, delay in diagnosis, organ insufficiency, and accompanying diseases such as cancer and diabetes may result in poor prognosis. Cholestasis and postoperative jaundice may predispose to multiple organ failure. The present study evaluated the risk factors and prognostic importance of postoperative hyperbilirubinemia using data obtained from patients with GI perforation and generalized peritonitis.

In our study of 100 patients, M: F ratio was 2.12:1. This is comparable to trials by Sujit et al.[1] and Bali et al.[2]. In contrast to our study, a high male preponderance is seen in trials by Memon et al.[3] [Table 2].
Table 2: Comparison of results of the present study with various previous studies

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In our study, 16% of the total patients belonged to the hyperbilirubinemia group and 84% belonged to the no hyperbilirubinemia group; our results are comparable to the study by Nishida et al.,[4],[5] where out of the 229 patients, 17% of patients developed postoperative hyperbilirubinemia and the other 83% of patients showed normal or mildly increased postoperative serum bilirubin levels (no hyperbilirubinemia group).

The mean age in our study was 51 ± 10 years for the hyperbilirubinemia group and 46 ± 6 years for the no hyperbilirubinemia group; our results are comparable to Nishida et al.[4],[5] according to whose observation the mean age was 51 ± 10 years in the hyperbilirubinemia group and 46 ± 4 years in the no hyperbilirubinemia group. The older age incidence in hyperbilirubinemia group may due to increase susceptibility of older age patients to sepsis, and thus, they are more predisposed to sepsis-induced cholestasis; however, there was no sexual difference found between both the hyperbilirubinemia group and the no hyperbilirubinemia group, with M:F ratio being similar in both the groups.

In the hyperbilirubinemia group, maximum cases (50%) were observed with colorectal perforation as compared to gastroduodenal perforations (44%) in the no hyperbilirubinemia group. This observation was similar to Nishida et al.[4],[5]

Colorectal perforation is associated with fecal peritonitis; hence there are more chances of postoperative infections and are thus susceptible to develop hyperbilirubinemia in the postoperative period.

In this series of study, there was a higher incidence of anemia (37.5%) in the hyperbilirubinemia group, whereas only 11% of patients of the no hyperbilirubinemia group had preoperative anemia; our results are similar to Nishida et al.[4],[5] who noticed anemia in 12 patients (31%) of hyperbilirubinemia group and only 20 patients (11%) of the no hyperbilirubinemia group [Table 2]. The high incidence of anemia in hyperbilirubinemia may due to excessive production of bilirubin group due to hemolysis and unrestrained blood transfusions.

In our study, the nutritional status of hyperbilirubinemia was poor as compared to the other group, with 44% patients in the hyperbilirubinemia group having poor nutrition and only 15% patients of the no hyperbilirubinemia group having poor nutrition; these results are similar to Nishida et al.[4],[5] who noticed poor nutrition in 18 patients (46%) of the hyperbilirubinemia group and in 29 (15%) patients of the no hyperbilirubinemia group.

As was studied by Webster et al.[6], poor nutrition is associated with poor immune response to infection, leading to increased susceptibility to postoperative sepsis and to cholestasis.

In our study, 62.5% of patients in the hyperbilirubinemia group had preoperative shock, whereas only 15% of patients of the no hyperbilirubinemia group had preoperative shock, showing that hyperbilirubinemia has a strong relation with preoperative shock; our results are similar to Nishida et al.[4],[5] who also noticed a stronger correlation between preoperative shock and postoperative hyperbilirubinemia.

Chu et al. suggest that hypotension in the perioperative period would reduce hepatic perfusion and hypoxemia, further decreasing the hepatic oxygen supply. Hypoxia of intestinal cells leads to activation of hepatic macrophages (Kupffer cells) with consecutive release of mediators. All these factors contribute to increased bilirubin level in the postoperative period; Aikaterini et al.[7] observed a strong correlation between preoperative shock and postoperative hyperbilirubinemia after cardiac surgery.

In our study, the use of antibiotics before and during surgery did not differ significantly between the two groups, with antibiotics during surgery used in 56% of patients in the hyperbilirubinemia group and 44% of patients in the no hyperbilirubinemia group; Nishida et al.[4],[5] also observed that the use of antibiotics before and during surgery did not differ significantly between the two groups. In 1997, Kirton et al.[8] found no significant difference in the outcome of patients of hollow viscus perforation receiving antibiotic therapy for 24 h postoperatively and those receiving antibiotic therapy for 5 days postsurgery.

In our study, the time when perforation occurred until surgery was longer 29 ± 13 in the hyperbilirubinemia group as compared to 18 ± 5 the no hyperbilirubinemia group; our results are comparable to Nishida et al.[4],[5] who also noticed that the time when perforation occurred until surgery was longer 28.9 ± 18.0 in the hyperbilirubinemia group as compared to 16.6 ± 23.5 in the no hyperbilirubinemia group. The more the time interval between time of onset and time of surgery, the more the chances of patients being in a state of advanced peritonitis, thus leading to increased postoperative sepsis and increased cholestasis.

In our study, the operative time was longer (240 ± 90) in the hyperbilirubinemia group as compared to that (180 ± 40) in the no hyperbilirubinemia group; our results are in contrast to Nishida et al.[4],[5] who do not observed a significant difference between two groups.

We observed that there is no significant difference in blood loss between the two groups as was shown by a previous study by Nishida et al.[4],[5]

In our study, patients in the hyperbilirubinemia group also had decreased preoperative platelet counts, increased preoperative white blood cell counts, total bilirubin, and aspartate aminotransferase levels; our results are similar to Nishida et al.,[4],[5] showing that the patient was in a state of advanced generalized peritonitis, which started a cascade of reactions releasing various cytokines leading to hepatic insult and increased bilirubin levels, with the exception of pulmonary diseases; the presence of preoperative associated disorders such as hepatic or renal disease appeared to be unrelated to postoperative hyperbilirubinemia similar to that shown by Nishida et al.[4],[5]

Preexisting pulmonary disorder predisposes patients to hypoxemia in the perioperative period which further decreases hepatic oxygen supply. Hypoxia of intestinal cells leads to activation of hepatic macrophages (Kupffer cells) with consecutive release of mediators. All these factors can contribute to increased bilirubin level in the postoperative period.

The patients in the hyperbilirubinemia group more frequently needed cardiac (62%) and respiratory (72%) support than those in the no hyperbilirubinemia group. These patients also suffered postoperative renal insufficiency (56%), prolonged GI paralysis (72%), or hematological dysfunction, including disseminated intravascular coagulation, more often than those in the no hyperbilirubinemia group. The overall mortality of the hyperbilirubinemia group was higher than that of the no hyperbilirubinemia group at 62% versus 4%.

A transient increase in serum bilirubin was seen in those patients from the hyperbilirubinemia group who survived. They showed the highest level of total serum bilirubin (5.0 ± 4.8 mg/dl) on POD 3–5, following which there was a gradual decrease. However, the patients with postoperative hyperbilirubinemia who died showed a gradual and continued increase in serum bilirubin levels even after POD 5, the highest levels (20.0 ± 9.2 mg/dl) usually being evident soon before death. The highest serum bilirubin level of the survivors was on POD 4.2 ± 3.8, whereas that of the patients who died was seen on POD 22.3 ± 7.0.

Postoperative hyperbilirubinemia in major surgery may be related to surgical insult, infection, bleeding and transfusion, and predisposed liver dysfunction. In the absence of infection, the perioperative use of steroids has been reported to suppress the postoperative increase in serum levels of inflammatory cytokines and bilirubin in patients undergoing major surgery, suggesting the role of surgical insult and inflammatory cytokines. Others have suggested that extensive surgical stress increases and changes bilirubin metabolism. Conversely, the present findings indicated that older age, a poor nutritional state, delay until surgery, an increase in the preoperative serum level of total bilirubin, and postoperative infection were related to postoperative hyperbilirubinemia in the setting of generalized peritonitis caused by GI perforation. The preoperative increase in serum bilirubin may have been due to advanced peritonitis, first because the incidence of predisposing liver diseases was similar in the two groups and also because the preoperative serum bilirubin level was related to the time from perforation until surgery. A poor nutritional condition has been reported as a predictor of postoperative morbidity following elective surgery. Thus, a delay from the time of perforation until surgery, a poor nutritional state, and older age may result in a relative increase in infectious and surgical insults, resulting in high morbidity and mortality. Although the exact mechanism is not known, an increase in the preoperative values of aspartate aminotransferase may be related to insufficient systemic circulation because patients with elevated values had frequently suffered from preoperative shock. In accordance with the results of previous reports, the findings of this study indicated that postoperative infection was closely related to postoperative hyperbilirubinemia and mortality.

The mortality rate associated with gastroduodenal perforation has been reported to be between 0% and 18%, most studies reporting around 5%–6%. The poorest prognosis (12%–22%) was associated with colorectal perforation. These values are not significantly different from those found in the present study (13%).

For gastroduodenal and colorectal perforation, age, delay in surgical intervention, preoperative shock, and concomitant major illness such as diabetes or renal failure are suggested to be poor prognostic factors. A poor nutritional state is associated with high morbidity and mortality even in patients undergoing elective surgery. Surgery for patients with intraabdominal sepsis and hyperbilirubinemia is accompanied by high mortality rates.

In this study, the presence of preoperative shock, a decreased platelet count, nongastroduodenal location, postoperative infectious complications, and postoperative hyperbilirubinemia were shown to be independent risk factors predisposing to postoperative mortality. A decreased platelet count and shock may indicate the presence of systemic and overwhelming infection before surgery. Postoperatively, both infectious complications and hyperbilirubinemia were poor prognostic factors in patients operated on for GI perforation.


  Conclusion Top


In our study, we concluded that in cases of perforation peritonitis, hyperbilirubinemia was associated with advanced age, poor nutritional status, a decrease in the base excess, prolonged time until surgical intervention, and higher rate of postoperative infections, and these patients with postoperative hyperbilirubinemia showed higher morbidity and mortality after surgery, which reinforces the importance of controlling postoperative infections.

Key points:

  1. Hyperbilirubinemia was associated with advanced age, poor nutritional status, a decrease in the base excess, prolonged time until surgical intervention, and postoperative infectious complications in the setting of generalized peritonitis caused by GI perforation
  2. Patients with postoperative hyperbilirubinemia showed higher morbidity and mortality after surgery
  3. These results strongly suggest that postoperative hyperbilirubinemia in patients with GI perforation is related to infection and a poor prognosis, which reinforces the importance of controlling postoperative infections.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Chakma SM, Singh RL, Parmekar MV, Singh KHG, Kapa B, Sharatchandra KH, et al. Spectrum of perforation peritonitis. J Clin Diag Res 2013;7:2518-20.  Back to cited text no. 1
    
2.
Bali RS, Verma S, Agarwal PN, Singh R, Talwar N. Clinical study Perforation peritonitis and the developing world. ISRN Surg 2014;Article ID 105492. http://dx.doi.org/10.1155/2014/105492.  Back to cited text no. 2
    
3.
Memon AA, Siddiqui FG, Abro AH, Agha AH, Lubna S, Memon AS, et al. An audit of secondary peritonitis at a tertiary care university hospital of Sindh, Pakistan. World J Emerg Surg 2012;7:6.  Back to cited text no. 3
    
4.
Nishida T, Fujita N, Megawa T, Nakahara M, Nakao K. Postoperative hyperbilirubinemia after surgery for gastrointestinal perforation. Surg Today 2002;32:679-84.  Back to cited text no. 4
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5.
Nishida T, Nakahara M, Nakao K, Matsuda H. Biliary bacterial infection decreased the secretion of bile acids and bilirubin into bile. Am J Surg 1999;177:38-41.  Back to cited text no. 5
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6.
Webster NR, Galley HF. Nutrition in the critically ill patient. J R Coll Surg Edinb2000;45:373-9.  Back to cited text no. 6
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7.
Mastoraki A, Karatzis E, Mastoraki S, Kriaras I, Sfirakis P, Geroulanos S, et al. Postoperative jaundice after cardiac surgery. Hepatobiliary Pancreat Dis Int 2007;6:383-7.  Back to cited text no. 7
    
8.
Kirton OC, O'Neill PA, Kestner M, Tortella BJ. Perioperative antibiotic use in high-risk penetrating hollow viscus injury: A prospective randomized, double-blind, placebo-control trial of 24 hours versus 5 days. J Trauma 2000;49:822-32.  Back to cited text no. 8
    


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