Influence of non-surgical risk factors on anastomotic leakage after major gastrointestinal surgery: Audit from a tertiary care teaching institute.

CONTEXT: The occurence of anastomotic leakage after gastointestinal resection and anastomosis is associated with significant mortality and morbidity. AIMS: There is dearth of evidence in the literature on the influence of various non-surgical factors in causing anastomotic leakage although many studies have identified their possible role.
MATERIALS AND METHODS: A retrospective audit of all the anastomotic leakages occurring between September 2009 and April 2012 in our institute was performed to identify the potential non-surgical factors that can influence anastomotic leakage. A total of 137 out of 1246 patients who developed anastmotic leak were analyzed. All the potential non-surgical causes of anastomotic leakage available in the literature were analyzed by univariate analysis and stepwise multiple logistic regression analysis was done after adjusting for the type of surgery. An intergroup comparison among the patients based on the type of surgery was also performed.
RESULTS: THE FOLLOWING FACTORS WERE FOUND TO BE INDEPENDENTLY ASSOCIATED WITH INCREASED RISK OF ANASTOMOTIC LEAK: (1) albumin <3.5 g/dl, (2) anemia <8 g/dl, (3) hypotension (4) use of inotropes, and (5) blood transfusion. The majority of anastomotic leaks occurred after pancreatic surgeries followed by esophagectomies and occurred least after colonic resections. The risk for anastomotic leak was four times more in patients who required inotropic support in the perioperative period and three times more in patients who developed hypotension.
CONCLUSIONS: Our study is the first retrospective audit to identify the influence of non-surgical factors for anastomotic leakage and the need for further observational studies in this direction.

INTRODUCTION

Anastomotic leakage is an uncommon but dreaded complication after major gastrointestinal surgeries like esophagectomies, pancreaticoduodenectomies, hepaticojejunostomies, low anterior resection of rectum, etc., Any anastomotic leak affects the morbidity and mortality associated with surgery to a variable degree. A low rectal anastomosis may have a leakage rate as low as 5% while anastomosis after esophagectomies and pancretoduodenectomies may have leakage rates as high as 20%.[1] The mortality rates after leakage from cervical anastomosis is higher than leakage after thoracic anastomosis in esophagectomies.[2] Besides the skill and technique involved during surgery various non-surgical factors are believed to influence the occurrence of anastomotic failure and leakage. They include male sex, ASA score, emergency surgery, obesity, smoking and alcohol abuse, perioperative fluid management, blood transfusion among the many.

The aim of this retrospective audit was to identify the influence of non-surgical risk factors on the occurrence of anastomotic leakage after major gastrointestinal surgeries.

MATERIALS AND METHODS

All the patients who developed anastomotic leakage following major abdominal surgery before discharge from September 2009 to April 2012 in GB Pant Hospital, New Delhi, were identified. The anesthesia charts of these patients were retrieved and an audit was performed to identify the non-surgical risk factors associated with anastomotic leakage.

The preoperative data registered included the age, gender, ASA score, body mass index (BMI), smoking history, diabetes, hemoglobin level, albumin level, and lung function.

The perioperative data included the duration of surgical procedure, perioperative blood loss, blood transfusion, colloid administration, mean arterial pressure, need for inotropic support, administration of epidural analgesia, and duration of postoperative mechanical ventilation. The experience of the surgeon and anesthetist were not recorded as all the surgeons and anesthetists had similar experience.

The intraoperative complications like hypotension, requirement of inotropes, blood and blood products transfusion, and requirement of postoperative mechanical ventilation were recorded.

Hypotension was defined as the fall in mean arterial pressure 20% below the baseline.

“Major leaks” were defined as those which required surgical intervention and “minor leaks” which were managed conservatively.

All the patients were divided into groups based on the type of surgery. The groups were statistically compared by using Chi-square test for categorical variables and Fischer's exact t test for continuous variables; P < 0.05 was considered significant. All the variables were entered in stepwise logistic regression analysis and adjusted ORs with 95% CI were calculated. The statistical analysis was performed using a statistical software package (SPSS for Windows, version 11.0, SPSS Inc., Chicago, IL, USA).

RESULTS

A total of 140 out of 1246 patients developed anastomotic leakage after major abdominal surgeries before discharge. In three patients, some data were missing. A total of 137 patients were included for analysis.

The majority of anastomotic leaks occurred after pancreatic surgeries (40.9%) followed by esophagectomies (24.0%), choledochal cyst resections (17.5%), Roux-Y-hepaticojejunostomies for benign biliary stricture (15.3%), and colonic resections (2.1%). The mortality was highest with esophageal leaks (18.1%) followed by pancreatic leaks (12.5%) and was least with hepaticojejunostomies for choledochal cyst (8.3%). The characteristics of the anastomotic leakages are shown in Table 1.

Table 1

The characteristics of anastomotic leaks after major abdominal surgery

There was not much of variation in the preoperative variables [Table 2] except that the mean hemoglobin in the patients with carcinoma of colon was significantly lower than other patients. The albumin level was significantly lower in patients with carcinoma of esophagus and carcinoma of pancreas.

Table 2

The preoperative variables in patients developing anastomotic leak

Among the perioperative variables [Table 3], the mean blood pressure was significantly lower and requirements for blood transfusion were significantly higher in patients with carcinoma of esophagus. The perioperative administration of colloid was significantly higher in patients with carcinoma of pancreas.

Table 3

Perioperative variables in patient developing anastomotic leak

The occurrence of perioperative hypotension and requirement of blood transfusion was more in the group of patients with carcinoma of esophagus [Table 4]. The need for inotropes was significantly more in the patients with carcinoma of pancreas [Table 4].

Table 4

Incidence of intraoperative complications in patients developing anastomotic leak

A stepwise multiple logistic regression analysis was done after adjusting the variables for the type of surgery. The following factors were found to be independently associated with increased risk of anastomotic leak: (1) albumin < 3.5 g/dl) (2) anemia < 8 g/dl, (3) hypotension (4) use of inotropes, and (5) blood transfusion [Table 5]. The risk for anastomotic leak was four times more in patients who required inotropic support in the perioperative period and three times more likely in patients who developed hypotension [Table 5].

Table 5

Independent risk factors for anastomotic leak after major abdominal surgery

DISCUSSION

The present study identifies the potential non-surgical risk factors associated with anastomotic leakage after major abdominal surgery. Although many studies are available in the literature[345] on the role of surgical factors causing anastomotic leakage, very few studies have identified the role of non-surgical factors which are independently associated with increased risk of anastomotic leakage. The most important pathophysiological basis for anastomotic leakage is believed to be ischemia of the gut conduit. This causes a fall in the oxygen tension of the gut submucosa which in the absence of a good collateral circulation gives rise to gut dehiscence and finally produces anastomotic leak.[67]

Our study has reviewed most of the potential non-surgical factors that have been cited in the literature as potential risk factors for anastomotic leakage. It is believed that hypoalbuminemia affects anastomotic healing by impairing collagen synthesis due to lack of essential amino acids. It also reduces the host immunocompetence and makes them more vulnerable for anastomotic leakage. In our study the serum albumin in patients with leak was significantly low (P < 0.001) and patients with serum albumin <3.5 g/dl had significant greater leak. Therefore, correction of albumin levels through feeding jejunostomy may be useful in patients with hypoalbuminemia.

Both low protein and low hemoglobin affects the perfusion and oxygenation of the anastomotic margins and predisposes to anastomotic leakage. Some studies have confirmed this by doing ROC analysis in patients with large bowel cancer resections.[89] However, more translational studies are required to understand the combined effects of hypoalbuminemia and anemia on gut microcirculation for better understanding the mechanism of anastomotic leakage.

Our study has also found that hypotension and the use of inotropes are independent risk factors for anastomotic leakage. This is because intraoperative hemodynamic aberrations, particularly hypotension predisposes to microvascular ischemia at the anastomotic site. One study has also found an increased anastomotic leakage with diastolic hypertension (defined as diastolic blood pressure > 90 mmHg) and the cause was attributed to microvascular ischemia.[10] Another study by Deeba, et al.[11] has found that rapid intraluminal sampling microdialysis of glucose and lactates are important factors for detection of bowel ischemia. This suggests that the hypotension may be associated with increase in lactate level in the gut mucosa increasing the susceptibility for leakage. Zakrison, et al.[12] had investigated the effect of vasopressor use in the ICU in 223 patients with 259 gastointestinal anastomosis and found that vasopressor use was associated with increased anastomotic leakage (P = 0.02, OR = 3.25). They also found that multiple vasopressors and prolonged exposure produced even higher leaking rates.

The effect of blood transfusion in activating systemic coagulation by increasing the levels of prothrombin 1 and 2 along with thrombin-antithrombin complexes has been studied. The net effect is an increased formation of microthromboses in the perianastomotic area leading to increased leakage. Our patients who had altered hemostatic balance due to hypercoagulable state after blood transfusion had more anastomotic leakage as evidenced by the odds ratio.

The increased gastrointestinal motility following epidural analgesia has been reported by some authors to be detrimental to the healing of bowel anastomosis[13] while some authors have considered it to be beneficial.[14] We did not find any risk of increased anastomotic leakage after epidural analgesia in this study.

Our study had a few limitations. One, being a retrospective audit it had all the inherent drawbacks of its design. It did not compare the variables between patients who had anastomotic leak and who did not. Two, our study did not take into consideration the anastomotic leakage which occurred after discharge from the hospital. This is because we did not find any evidence in the literature on the duration up to which the cause of anastomotic leakage can be attributed to the non-surgical factors occurring in the perioperative period. Third, although we adjusted the risk factors to the type of surgery before multiple logistic regressions and also made intergroup comparisons of the variables, we did not have the data on the duration of the adverse events like duration of inotrope use, duration of hypotension before its correction, duration of mechanical ventilation, etc., This information cannot be accurately retrieved from our present anesthesia charts because of its design and we feel the need for a change in its format.

CONCLUSIONS

To conclude, ours is the first retrospective study from India to review the non-surgical factors responsible for anastomotic leakage after major abdominal surgeries. This is despite the well-accepted belief on the influence and dependency on the non-surgical factors on outcome after anastomotic leak. We also believe that our study will pave the way for more prospective and observational studies on the effects of non-surgical risk factors for anastomotic leakage after specific surgeries.