Predicting anastomotic leak: Can we?

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Predicting anastomotic leak: Can we? Jennifer K. Lee M.D., Nitin Mishra M.D.

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www.elsevier.com/locate/yscrs S1043-1489(14)00016-5 http://dx.doi.org/10.1053/j.scrs.2014.04.003 YSCRS451

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Seminars in Colon and Rectal Surgery

Cite this article as: Jennifer K. Lee M.D., Nitin Mishra M.D., Predicting anastomotic leak: Can we?, Seminars in Colon and Rectal Surgery, http://dx.doi.org/ 10.1053/j.scrs.2014.04.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Predicting anastomotic leak: Can we? Jennifer K. Lee, M.D., Nitin Mishra, M.D.

From Department of Surgery, Rutgers Robert Wood Johnson Medical School and Atlantic Health System, New Jersey. Address for correspondence: Nitin Mishra, M.D., 3900 Park Avenue, Edison, NJ 08820 (email: [email protected]). (732) 494-6640, Fax: (732) 549-8204

Abstract Anastomotic leaks remain a feared complication in colorectal surgery. A myriad of variables have been evaluated but the variability among those studies provides little consensus on absolute risk factors and clinical application. Nevertheless, identifying these risk factors may assist the surgeon in mitigation of risk with preoperative optimization, intraoperative decision-making for diversion, and heightened postoperative vigilance for anastomotic leak. These risk factors can be organized into surgeon, patient and pathology-related categories. (word count: 72) Key words Colorectal anastomosis, anastomotic leak, risk factors

Introduction With prevalence ranging from 0.5-21%, anastomotic leaks remain one of the most serious complications in colorectal surgery (1, 2). Clinically significant leaks can occur in up to 14% of low anastomoses. Leaks lend themselves to increased morbidity and mortality, with the latter reported up to 27% in some studies (3, 4). Along with clinical consequences, anastomotic leaks lead to longer hospital stays, multiple interventions and overall increased health care costs when compared to patients without a leak. The underlying pathogenesis leading to anastomotic leaks is not entirely understood but is attributed to several factors affecting the integrity of the anastomosis. These factors are related to the surgeon, the patient and the pathology (5-7). Several retrospective and prospective studies have been performed to identify these factors. However, interpretation of the data is restricted by the wide breadth of diseases, patient populations, techniques, and an assortment of definitions for anastomotic leak among the literature (8). Anastomotic leak can present both within the immediate postoperative period and after discharge from the hospital, suggesting a multi-factorial pathogenesis leading to anastomotic dehiscence. Provided with predictors of anastomotic leak, the surgeon may be able to modify preoperative risk factors as well as adjust peri-operative decision-making

 

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and increase postoperative vigilance in those with risk factors. Even with optimization of the patient and improving technique, the rate of anastomotic leak has not significantly decreased over time. This reveals that there is more to the underlining pathology than is understood at this time. Surgeon-related factors The essential principles of a successful intestinal anastomosis include perfect technique joining two healthy ends of bowel without tension. Adequate blood supply and thus adequate oxygen delivery sustain the integrity. Various studies have explored the weight of these factors and practical ways in which they can be measured in order to determine whether an anastomosis will heal completely. These factors include blood supply, tension, hypoxia, resuscitation, blood loss and operative time. In addition to these factors, surgical technique, use of mechanical bowel preparation, experience of the surgeon and training/certification have also been considered as potential variables that may affect outcomes. Blood supply/Hypoxia Oxygen tension measurements of bowel both before resection and after anastomosis have been evaluated in both animal and human models (9-10). These studies have demonstrated a large drop in the oxygen tension after resection but

 

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the effect this drop had on the viability of the anastomosis was less clear. One study measured doppler flow to measure microperfusion to a rectal stump (11). Flow reduction of 6.2% was evident in those without a leak compared to 16% in those with a leak (p<0.001) – a significant finding supporting the understanding that blood supply is crucial. There is, however, no practical application of these measurements. For now, surgeons intraoperatively evaluate viability by mucosa color and bleeding edges. Should there be a lack of bleeding or concern of poor blood supply to either the proximal or distal end of the intestine, an alternate site of fusion should be considered. Tension Tension on the anastomosis is generally considered to be unacceptable given the mechanical stress theoretically applied to the two ends of bowel. Nevertheless, measurements of tension are poorly studied. A 1986 study compared the tension tolerated by small bowel to small bowel anastomoses as compared to colonic anastomosis (12). This showed that the small bowel tolerated tension better than the colon. It appears that this was directly related to the laxity of the mesentery and thus the blood supply to the anastomosis itself. In general, any indication of tension should prompt further mobilization to lengthen the conduit. Resuscitation

 

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Restricted fluid strategies have shown to reduce postoperative complication rates in randomized controlled studies (13-15). The goal is to maintain baseline weight. In contrast, one study demonstrated an increase in overall complication rates with restricted fluid management, thereby making the role of restricted fluid resuscitation unclear when it comes to the specific effect on anastomotic leak rates. Blood loss/OR time Blood loss and length of operating time have both been shown to increase rates of overall complications. Leichtle et al. measured several variables among 4340 cases in a prospective study and found blood loss of greater than 100 mL (p=0.02, 95% CI 1.1-2.4) and 300 mL (p=0.003, 95% CI 1.32-3.76) as significant factors after multivariate regression (16).  Several studies have shown that substantial intraoperative blood loss and postoperative blood transfusions (most likely a marker of substantial intraoperative blood loss) are associated with increased risk for anastomotic leaks (1,4,17). As such, increased blood loss should be one of several factors to be considered when assessing the need for diversion in a patient at a high risk for anastomotic leaks. A prospective study of 391 elective colorectal resections identified a significantly higher leak rate when the operative procedure was ≥4 hours in duration compared with shorter procedures (5.1 vs. 0.5 %) (18).

 

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The current data is largely difficult to interpret given the various cut-off values for excessive blood loss and the range of reported number of transfusions. In addition, the degree of blood loss and length of operating time are often directly related to the difficulty of the operation. (17,19). Technique A) Hand sewn vs. Stapled Several studies, including a 2012 Cochrane review, show no significant difference in outcomes, including leak rate, between hand-sewn and stapled colon anastomoses. There was also no significant difference found between single and double layer closures (20-22). However, a meta-analysis of six trials with 955 participants with benign and malignant disease revealed that hand-sewn ileo-colic anastomoses were associated with a significantly higher rate of anastomotic leaks compared with stapled ileocolic anastomoses (6.0 vs. 1.4 %). (23, 24). B) Laparoscopic Vs. Open Laparoscopic resection has been shown to have no significant difference in outcomes compared to open resection in benign and cancer cases (25-27). C) Level of Inferior Mesenteric Artery (IMA) Ligation

 

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The level at which the IMA ligation occurs may play a role in anastomotic leak rates. A study by Trencheva et al demonstrated that high ligation of the inferior mesenteric artery had 3.8 times higher chance of leaking compared to low ligation. This outcome may be related to the fact that the proximal part of the anastomosis relies on marginal artery blood flow from middle colic vessels when high ligation is performed. Without compromising the needed number of lymph nodes, the study recommends careful consideration of the level of ligation in patients with risk factors for poor mesenteric blood flow (28). Nevertheless, a 2012 systematic review of the literature showed no significant difference in short-term outcomes, including anastomotic leak, between high and low ligation among a total of 8,666 patients (29). D) Leak test for anastomoses After construction of the anastomosis, many will test the connection with insufflation of air, normal saline or povidone-iodine. This is proposed to identify any disruption that may lend itself to anastomotic leak if missed. This provides a simple and reproducible method of predicting anastomotic leak. Most studies supporting air leak tests are small in size (30). A 2009 retrospective study performed by the Lahey Clinic investigated 998 left sided colorectal anastomoses without diversion, 90% of which were stapled. Air leaks were noted in 7.9% during the air leak test. Of these 7.7% clinical leaks were later diagnosed.

 

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Comparably, 3.8% of those with negative air leak tests had clinical leaks, as well as 8.1% of untested anastomoses (p<0.03). When comparing repairs after a positive air leak test, suture repair alone had higher clinical leak rate compared to recreated anastomoses and diversion (12% vs 0% vs 0%). The data from this study favors air leak testing of all left-sided anastomoses, whether stapled or handsewn (31). E) Use of drains A randomized trial found no increase in anastomotic leaks with drains in patients undergoing elective colonic resection, while a large observational study found a significant increase in anastomotic leaks with drains in patients undergoing a low anterior resection for rectal cancer (32, 33). The use of prophylactic drains in intraperitoneal colonic surgery is not supported by current data. Prophylactic drainage of the pelvis after complex pelvic surgery may decrease the development of pelvic collections however it is not clear whether drains influence the rates of anastomotic leak. (34) Experience and Certification Another variable closely related to technique among studies examining anastomotic leak rates is the experience and certification of the surgeons performing the surgery. A retrospective study of 514 surgeons performing 15,427

 

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colectomies between 1994 and 1997 showed improved outcomes with more experience and volume of cases. While anastomotic leak was not specifically investigated, the study concluded surgeons without American Board of Surgery certification had significantly higher complication rates (35). Although colorectal surgery subspecialty certification did not significantly affect outcomes in this study, a 1998 study suggested otherwise. In the setting of rectal cancer and complications like recurrence (36). Newman et al. reported on 683 patients involving 52 surgeons, 5 of which were colorectal surgeons who performed 109 (16%) of the operations. Multivariate analysis showed that the risk of local failure was increased and disease-specific survival was decreased in patients of both noncolorectal trained surgeons and those of surgeons performing < 21 resections. The authors concluded that in the setting of rectal cancer, outcomes are with both colorectal surgical subspecialty training and a higher frequency of rectal cancer surgery. Therefore, the surgical treatment of rectal cancer patients should be performed exclusively by colorectal surgeons with more experience (36,37). Mechanical bowel preparation (MBP) Several meta-analyses, prospective trials and Cochrane reviews found no significant difference in overall AL rate for patients with an MBP compared to

 

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those not having a MBP. This conclusion applied to both low anterior resection and intraperitoneal anastomosis (38). Use of Protective stoma for low anterior resections Proximal fecal diversion by a protective stoma reduces the overall risk of a reoperation following a low anterior anastomosis; however, it is unclear whether it prevents leaks. A meta-analysis of 4 randomized trials including 358 patients undergoing a low anterior resection for rectal cancer found patients with a protective stoma had significantly fewer anastomotic leaks compared with patients who had no protective stoma (9.6% vs. 22.8%). In addition, patients with a protective stoma had significantly fewer reoperations for leaks (OR 0.27, 95% CI 0.17-0.59) (39). Patient-related factors Various patient-related factors have been studied. Except for a select few, most risk factors have shown varied results in available studies. American Society of Anesthesia (ASA) classification and nutritional status have been consistently found to be a risk factor for anastomotic leak. Various other reports have suggested age, obesity and smoking to be associated with higher rates of anastomotic leak; however, these studies varied in their cut-off for age and

 

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quantity of smoking and alcohol intake. This heterogeneity makes application of this knowledge less clear and generalizablet to all populations.. ASA/CCI ASA and Charlson Comorbidity Index (CCI) are two scales measured preoperatively to provide a generalized assessment of the patient. The ASA score, as measured by the anesthesiologist, provides an assessment of perioperative adverse events where as the CCI score predicts the ten-year mortality depending on comorbidities. For CCI, factors such as congestive heart failure, chronic pulmonary disease and diabetes are one point each where as diabetes with end organ damage and kidney disease are 2 points each. The ASA score has been shown to have an effect on anastomotic leak rate. Specifically, an ASA score of 3 or greater is associated with higher anastomotic leak rate(3-4, 40-43). Buchs et al also identified an ASA score of 3 or greater to be an increased risk factor in a study of 811 anastomoses performed (p=0.004). Overall leak rate was 3.8%. They identified a 2.5 time increase in anastomotic leak risk with every unit increase in ASA score. Limitations of the ASA score include variability among anesthesiologists in subjectively assigning the class. The role of CCI is also variable among studies. Trencheva et al identified the CCI score of 3 or higher to be a risk factor to anastomotic leak (28). In

 

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contrast, Tan et al reviewed 505 colorectal resections and found that while the ASA score of 3 or greater was an independent risk factor for anastomotic leak (ASA III: p=0.049, ASA IV: p=0.012), a higher CCI scores did not increase the risk of anastomotic leak (p>0.05) (44). In this study, individual components of each index were evaluated showing significance in those with congestive heart failure (p<0.001) and metastatic disease (p=0.019). The study did not identify a significant risk factor with comorbidities such as IBD or intraoperative factors such as blood loss. Nutrition/Albumin Nutrition is one of the few risk factors that has been consistently identified as a risk factor for anastomotic leak. In particular, a weight loss of >10% from preoperative weight and an albumin of less than 3.0 to 3.5 have been associated with higher rates of anastomotic leak (17,41,43,45). Patients with greater than 10% weight loss or albumin less than 3.5 may benefit from preoperative nutritional optimization. Enteral approach is preferred to parenteral but either one may be used. The usual recommended duration of preoperative nutritional supplementation is 7 days (17, 45). Gender

 

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Various studies have shown male gender to be a risk factor for anastomotic leak, including several studies noting higher risk in males in the setting of low rectal cancers (28,46,47). In contrast, this increased risk of anastomotic leak in males was not seen in intraperitoneal anastomotic leak (42). This may imply that the increased incidence of anastomotic leak in low rectal cancer cases may be due to the challenges faced with the narrower male bony pelvis. BMI Numerous studies have shown increased rates of anastomotic leak with increasing BMI for left colon and rectal resections(48,49). BMI appears to play less of a role in right colectomies (48,49). Buchs et al identified a BMI of >25 to be an increased risk factor (p=0.04) (3). Smoking/Alcohol Smoking and alcohol have been considered a possible risk factor for anastomotic leak. Studies evaluating alcohol use as a risk factor are difficult to interpret as limitations of patient reports and cut-off amounts of alcohol use are varied (50,51). In summary, the rate of anastomotic leak is likely related to a number of patient-related factors; however the individual impact these factors have is

 

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extremely difficult to distinguish. Even so, the presence of these factors should be considered preoperatively and intra-operatively when taking into consideration the need for fecal diversion as well as heighten the surgeon’s awareness for perioperative complications.

Pathology-related factors Emergent cases The priority of an emergent case is typically patient salvage and for this reason an anastomosis is often avoided. Nevertheless, in the absence of shock or sepsis, an anastomosis may still be considered. Several studies support this approach, although the majority the study results are skewed as there is a propensity to avoid anastomosis on left-sided resections and less hesitancy with right-sided resections. In a study focusing on left-sided intraperitoneal anastomoses performed after on-table lavage, an emergency operation (P = 0.03; odds ratio, 4.6; 95 percent confidence interval, 1.9-9.8) was found to be an independent risk factor associated with anastomotic leak. This finding was also supported in subsequent study (42,49). Steroids/IBD/Chemotherapy

 

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Steroid use is common in the inflammatory bowel disease (IBD) patient and various studies exist confirming the negative effects of steroids on general healing by decreasing activation and infiltration of inflammatory cells (4,40,41). Many patients with IBD will require operations. Unfortunately, there is a lack of data regarding the timing and safety of stopping steroids. The effect of steroids on anastomotic leak as a specific complication is not as well defined. Slieker et al found long-term (p=0.02, 95% CI 1.24-14.76) and perioperative corticosteroids (p=0.001, 95% CI 3.32-100.15) to be independent risk factors for anastomotic leak in a prospective study of 259 left-sided anastomoses (52). The use of immunomodulators and anti-TNF alpha therapy appears to be safe in the treatment of IBD and stopping their use is acceptable preoperatively. In the setting of infliximab use in UC, Mor et al found that infliximab increased the occurrence of J-pouch leaks and pelvic sepsis although other studies have questioned that association. It is worth noting that the majority of patients who leaked while on Remicade were also noted to be taking concomitant steroids suggesting that the patients who leaked were more likely t represent a more severely ill group than those who were more likely to leak due to Remicade(53). In regards to Crohn’s disease, several factors have been identified including histologically involved margins, intraabdominal abscess, presence of fistulas, and malnutrition (17,54). Involvement of the microscopic margin has

 

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been shown to be statistically significant for anastomotic leak risk (17,55,56). This finding provides an added concern in the setting of a patient population in which bowel length preservation is essential. Chemotherapeutic agents may also contribute to the risk for anastomotic leak. In particular, bevacizumab (Avastin ®, Roche, Basel, Switzerland) has been shown to increased the risk of anastomotic leak if used before and after surgery. Anastomotic leaks have been reported at various times in the post-operative period ranging from the immediate post-operative day up to 40 months postoperatively. These findings support delaying surgery at least 6 weeks after the last dose and resuming treatment almost a month after surgery (57). Radiation The effect of radiation on the bowel and its oxygen supply is also a confounding factor that surgeons should be wary of when determining bowel viability. The point of transaction should not only depend on adequate blood supply but also on extent of radiation changes. The current data is open to debate with several retrospective studies reporting positive, negative and inconclusive association between neoadjuvant radiation and risk of anastomotic leak. (6, 58-63) Location of pathology

 

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Distance from the anal verge is widely understood to be an independent risk factor for anastomotic leak. High anastomotic leak rates have been consistently reported with resections below the peritoneal reflection (1,3,28,42). Comparing ileocolic and colocolonic anastomotic leak, relative risk for anastomotic leak is higher with colorectal anastomoses (RR 11.06; (95% CI, 3.3236.85) (50). Other factors such as technical difficulty, blood supply and increased tension may be causal in the elevated risk of low anastomoses for anastomotic leak but there is a lack of evidence to support exactly why (64). Metastatic disease/concomitant liver resection With improved medical treatment of metastatic colorectal cancer, patients who were once considered unresectable at the time of diagnosis may prove otherwise after several months of systemic chemotherapy. In fact, 5-year survival rates have been shown to improve with resection of synchronous liver metastases, although the strategy for approaching these resections is still controversial (65). Concomitant resection of stage IV disease may increase the incidence and effect of anastomotic leak (66,67). Nakajima et al studied 86 patients who underwent simultaneous resection of the primary colon tumor and hepatic tumor. Postoperative morbidity was 64% and anastomotic leak 21%. Six of the anastomotic leak group patients required reoperation. Patients in the group who did not have a synchronous liver resection had an anastomotic leak rate of 7.1%.

 

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Operating time greater than 8 hours was a significant factor for anastomotic leak on multivariate analysis (p<0.01; 95% CI, 2.09-20.9). Other variables such as extent of resection and total time of the Pringle maneuver were not predictive factors for anastomotic leak in this study. They concluded that stage resections should be considered in cases when the surgical stress may be expected (67). Conclusion Anastomotic leaks remain a devastating complication despite evolution of anastomotic techniques and preoperative modification of identified risk factors for postoperative complications. Despite a wide range of literature describing various possible contributing factors, there remain a variety of conclusions. Some variables, such as those related to pathology, cannot be modified. Other factors continue to be investigated including microbiological variables that may contribute to the pathogenesis of anastomotic leak. What is clear from these studies is the complexity of factors that contribute to the success of an anastomosis. While most studies focus on a few risk factors, there remains a complex interaction among the patient, surgeon and pathology-related factors. The key remains in identifying these factors in order for surgeons to modify their approach to the individual patient in order to mitigate outcomes and to anticipate postoperative complications in those deemed to have a high risk for anastomotic leak.

 

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