Mastery of IBD Surgery

© Springer Nature Switzerland AG 2019

Neil Hyman, Phillip Fleshner and Scott Strong (eds.)Mastery of IBD Surgeryhttps://doi.org/10.1007/978-3-030-16755-4_1

1. Nutritional Repletion in the Surgical Patient

Tarik Yuce¹ and Michael F. McGee¹  

(1)

Section of Colorectal Surgery, Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Michael F. McGee

Email: [email protected]

Introduction

Patients with Crohn’s disease (CD) and ulcerative colitis (UC) are prone to high rates of malnutrition [1]. There are several factors inherent to inflammatory bowel disease (IBD) that affect nutritional status including hypermetabolism associated with chronic inflammation, anorexia, and malabsorption [2] as well as intestinal obstruction and ileus. Assessing malnutrition in this patient population can be challenging as there is no gold-standard test available to evaluate a patient’s nutritional status [1]. However, managing the preoperative nutritional status of IBD patients is of critical importance due to the high risk of postoperative complications associated with nutritional deficits.

Patients with IBD requiring surgical intervention often present with multiple signs of malnutrition, including anemia, electrolyte abnormalities, low levels of surrogate nutritional markers (albumin, prealbumin, transferrin), and infection [3]. All of these have been shown to increase the risk of poor surgical outcomes [4]. Attempting to augment IBD patients’ nutritional status, via enteral or parenteral routes, prior to operative intervention may serve as a key step in improving postoperative outcomes. The role of preoperative parenteral nutrition (PN) versus early surgery in IBD patients requiring surgery is investigated below.

Search Strategy

A literature search of PubMed, MEDLINE and the Cochrane Database of Collected Research was completed to find English-language publications associated with Crohn’s disease, ulcerative colitis, nutritional status, parenteral nutrition, and postoperative outcomes from 1988 to 2018. Key search terms used were: inflammatory bowel disease, nutritional status, total parenteral nutrition, postoperative outcomes. Crohn’s disease, and ulcerative colitis. Studies that were non-English, or failed to compare PN to early surgery were excluded as well as those involving oral nutritional supplements, intravenous vitamin and mineral infusions, and postoperative nutritional therapy. Preference was given to randomized controlled trials, large randomized observational studies, cohort studies and meta-analyses. The references of each study were analyzed to search for additional articles that may be suitable for inclusion (Table 1.1).

Table 1.1

PICO table

Results

A thorough review of the literature showed a paucity of studies examining the role of preoperative PN in IBD patients. Aside from one meta-analysis, all identified studies examining the role of PN in IBD patients are retrospective, nonrandomized, case series and cohorts. The studies that addressed the role of preoperative PN in IBD patients are detailed below.

Jacobson [5] retrospectively studied the effect of preoperative PN on the rate of 30-day postoperative complications in patients with CD undergoing bowel resection. PN patients (n = 15) received a mean of 45 days (range 18–90) of preoperative PN. Controls (n = 105) were matched 7:1 by disease location, patient sex and age. The author found PN patients were associated with a significant reduction in early postoperative complications. PN patients also experienced an increase in weight and serum albumin concentrations during the preoperative period. Given these findings, the author concluded that a course of preoperative PN should be considered for patients with CD who require bowel resection. The largest limitation of the study arises from an assignment bias since the authors did not include steadfast indications for preoperative PN. Moreover, small sample size, variations in PN formulation and duration, and lack of information regarding the nutritional status of the control group further limit broader applicability of the study findings.

A retrospective review by Salinas et al. [6] found that UC patients receiving at least 7 days of preoperative PN had higher rates of postoperative complications when compared to those undergoing early surgery. However, when the authors excluded central line related complications, there was no difference in postoperative complications between the two groups. Logistic regression analysis showed that TPN use, even when accounting for perioperative risk factors, was associated with a non-significant trend toward increased rates of complications compared to non-TPN patients (postoperative complication OR = 1.42). Given this information, the authors concluded that there is no indication for routine use of preoperative PN in patients with UC compared to expeditious total abdominal colectomy. The authors acknowledged there may be an empiric role of PN for the most severely malnourished patients, but recognize their study does not support such a practice. Limitations of this study include lack of steadfast inclusion criteria for PN use, unknown PN composition, and variable PN duration.

Grivceva Stardelova et al. [7] retrospectively compared a heterogeneous group of CD and UC patients receiving preoperative PN (n = 29) to controls (n = 61) before undergoing unspecified surgery. PN patients trended toward an improvement in preoperative Crohn’s Disease Activity Index (CDAI) scores and BMI, although neither finding reached significance. Additionally, there was no difference in length of stay between the two groups. The authors argue that there may be a role for preoperative PN in patients with severe disease and malnutrition, while acknowledging the many limitations of their study.

Yao et al. [8] studied severely malnourished patients (BMI < 15 kg/m²) with CD who received PN (n = 16) versus those who received intravenous fluids (n = 16) prior to surgery. There was no significant difference in postoperative complications; however patients in the PN group experienced a significant increase in BMI and a higher rate of convalescence (returning to work) within 6 months. Limitations of this study include small sample size, lack of randomization, and limited and inconsistent description of methods, results, and statistical data.

Lashner et al. [9] retrospectively examined the effect of preoperative PN on patients with CD undergoing small bowel resection, ileocecectomy and segmental/total colectomy. Despite having more extensive disease, PN patients had a shorter segment of bowel resected in small bowel and ileocecectomy groups at the expense of a longer hospital stay. PN use was not associated with outcome differences in segmental or total colectomy patients. Study limitations include patient selection bias for PN and inability to determine the minimum effective duration of PN.

Li et al. [10] authored the largest study to date investigating preoperative PN in which 498 patients underwent 708 intestinal surgeries for Crohn’s disease. The authors retrospectively stratified patients based on preoperative immunosuppressant exposure and PN use, and then analyzed surgical outcomes. A 4 week period of preoperative PN afforded patients a longer preoperative immunosuppressant-free interval and was associated with reductions in urgent surgery and fecal diversion when compared to non-PN groups. Notably, preoperative PN was associated with decreases in both infectious and non-infectious postoperative complications.

Another analysis by the same author [11] examined a 123 patient subset of the above study limited to CD patients with enterocutaneous fistulas, revealed that 3 months of preoperative TPN increased patients’ serum albumin levels and decreased C reactive protein at the time of surgery when compared to controls. Moreover, rates of postoperative intra-abdominal septic complications was significantly reduced in PN patients when compared to controls (3.6% vs. 17.6%, OR = 5.7, p = 0.02). Both studies are limited by their retrospective nature, heterogeneity of resection types and locations, and assignment biases arising from lack of randomization.

A recent meta-analysis performed by Brennan et al. [12] examined the differential surgical outcome effects of preoperative PN in CD patients. In a pooled group of 5 studies comprised of 280 patients, there was a trend toward lower complications in PN patients when compared to non-PN patients; however differences were not significant (15% vs. 24.4%, OR = 0.65, p = 0.43).

Recommendations

Malnourished patients with small bowel or ileocolic Crohn’s disease requiring resection likely benefit from preoperative PN compared to early surgery (Evidence: low; Recommendation: weak). Malnourished ulcerative and Crohn’s colitis patients requiring simple colectomy likely benefit from prompt colectomy without anastomosis compared to preoperative PN (Evidence: low; Recommendation: weak).

The literature regarding PN versus early surgery for IBD patients lacks the robust data provided by randomized controlled trials and hinders the ability to make strong recommendations. The available studies over the past 30 years, while low in quality, show that delaying surgery for selected IBD patients in lieu of preoperative PN may reduce postoperative complications. Cost, patient preference, and long-term follow-up data are strikingly absent. Moreover, the utility of preoperative PN in the contemporary setting of modern-day IBD medicines, minimally invasive surgery, and enhanced recovery programs is untested.

Personal View

It is logical to believe that better nourished patients fare better than malnourished patients; however the retrospective studies only weakly support delaying IBD resections for preoperative PN; and this is conditional based upon etiology and location of the diseased segment. Several hindrances challenge interpretation of the literature. Foremost, variation arising from disease location can be substantial between UC and CD, which introduces significant heterogeneity in studies and obfuscates treatment effect. Since studies are small, authors are forced to pool together patients to please statisticians. But study cohorts can be quite diverse with regard to disease severity, chronicity, and location. Second, most retrospective studies lack steadfast inclusion criteria for preoperative PN treatment rendering treatment allocation discretionary. Lastly, most studies also lack patient nutritional stratification, so it is plausible to believe that patient selection and assignment biases may play just as large of a role in influencing outcomes as PN treatment does.

Nonetheless, where there is smoke, there is fire. Despite relatively low quality data and only a glimmer of evidence-based guidance in IBD, several non-IBD studies have shown a beneficial role of preoperative PN that may be extrapolated to IBD surgery. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group trial found a 7–15 day course of pre-operative PN reduced postoperative complications from 43% to 5% for severely malnourished patients undergoing laparotomy and non-cardiac thoracotomy [13]. In contrast, for mildly malnourished patients, the overall complication rate was similar regardless of PN use, and infection-specific complications was actually higher in PN patients (14.1% vs. 6.4%). However, the study comes from an era where the detrimental effects of hyperglycemia was not well understood and overfeeding was commonplace. A dated, but thorough, review of over 1300 pooled malnourished surgical patients showed preoperative PN reduced the risk of postoperative complications by an estimated 10% [14].

The authors espouse a judicious policy of an approximately 7 day course of preoperative PN for severely malnourished small bowel CD patients intolerant of enteral supplementation, commensurate with recent European societal guidelines [15]. Patients with severe nutritional risk have been defined as those with at least one of the following criteria: (a) weight loss > 10–15% within 6 months (b) BMI < 18.5 kg/m² (c) serum albumin < 3.0 g/dL absent hepatic or renal dysfunction or (d) Subjective Global Assessment (SGA) Grade C or Nutrition Risk Screening Score > 5 [15]. Regardless of nutritional state, ulcerative colitis patients typically will undergo timely colectomy, ileostomy, and rectal stump closure without preoperative PN since minimally invasive techniques are typically successful and anastomoses are avoided. The authors do not typically perform restorative proctocolectomy in the malnourished state and instead advocate for a 3-stage procedure. Patients with isolated Crohn’s colitis amenable to laparoscopic colectomy are typically not offered preoperative PN, and instead undergo prompt minimally invasive surgery and liberal use of fecal diversion. Patients with complicated colonic Crohn’s disease (e.g. fistula, abscess, phlegmon) that requires extensive surgery or runs the risk of collateral organ damage may be considered for preoperative PN on a conditional basis that accounts for surgical urgency, immunosuppressant use, and other patient comorbidities.

References

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Mijac DD, Janković GL, Jorga J, Krstić MN. Nutritional status in patients with active inflammatory bowel disease: prevalence of malnutrition and methods for routine nutritional assessment. Eur J Intern Med. 2010;21:315–9.Crossref

2.

Wędrychowicz A, Zając A, Tomasik P. Advances in nutritional therapy in inflammatory bowel diseases: review. World J Gastroenterol. 2016;22:1045–66.Crossref

3.

Massironi S, Rossi RE, Cavalcoli FA, Della Valle S, Fraquelli M, Conte D. Nutritional deficiencies in inflammatory bowel disease: therapeutic approaches. Clin Nutr. 2013;32:904–10.Crossref

4.

Ho JW, Wu AH, Lee MW, et al. Malnutrition risk predicts surgical outcomes in patients undergoing gastrointestinal operations: results of a prospective study. Clin Nutr. 2015;34:679–84.Crossref

5.

Jacobson S. Early postoperative complications in patients with Crohn’s disease given and not given preoperative total parenteral nutrition. Scand J Gastroenterol. 2012;47:170–7.Crossref

6.

Salinas H, Dursun A, Konstantinidis I, Nguyen D, Shellito P, Hodin R, Bordeianou L. Does preoperative total parenteral nutrition in patients with ulcerative colitis produce better outcomes? Int J Color Dis. 2012;27:1479–83.Crossref

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Grivceva Stardelova K, Misevska P, Zdravkovska M, Trajkov D, Serafimoski V. Total parenteral nutrition in treatment of patients with inflammatory bowel disease. Prilozi. 2008;29:21–43.PubMed

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Yao GX, Wang XR, Jiang ZM, Zhang SY, Ni AP. Role of perioperative parenteral nutrition in severely malnourished patients with Crohn’s disease. World J Gastroenterol. 2005;11:5732–4.Crossref

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Lashner BA, Evans AA, Hanauer SB. Preoperative total parenteral nutrition for bowel resection in Crohn’s disease. Dig Dis Sci. 1989;34:741–6.Crossref

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Li Y, Zuo L, Zhu W, Gong J, Zhang W, Gu L, Guo Z, Cao L, Li N, Li J. Role of exclusive enteral nutrition in the preoperative optimization of patients with Crohn’s disease following immunosuppressive therapy. Medicine. 2015;94:1–9.

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Li G, Ren J, Wang G, Hu D, Gu G, Liu S, Ren H, Wu X, Li J. Preoperative exclusive enteral nutrition reduces the postoperative septic complications of fistulizing Crohn’s disease. Eur J Clin Nutr. 2014;68:441–6.Crossref

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Brennana GT, Haa I, Hogana C, Nguyena E, Jamala MM, Bechtoldb ML, Nguyena DL. Does preoperative enteral or parenteral nutrition reduce postoperative complications in Crohn’s disease patients: a meta-analysis. Eur J Gastroenterol Hepatol. 2018;30:997–1002.Crossref

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Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med. 1991;325:525–32.Crossref

14.

Klein S, Kinney J, Jeejeebhoy K, Alpers D, Hellerstein M, Murray M, Twomey P. Nutrition support in clinical practice: review of published data and recommendations for future research directions. Clin Nutr. 1997;16:193–218.Crossref

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Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, Laviano A, Ljungqvist O, Lobo DN, Martindale R, Waitzberg DL, Bischoff SC, Singer P. ESPEN guideline: clinical nutrition in surgery. Clin Nutr. 2017;36:623–50.Crossref

© Springer Nature Switzerland AG 2019

Neil Hyman, Phillip Fleshner and Scott Strong (eds.)Mastery of IBD Surgeryhttps://doi.org/10.1007/978-3-030-16755-4_2

2. Preoperative Bowel Prep

Benjamin D. Shogan¹  

(1)

University of Chicago, Chicago, IL, USA

Benjamin D. Shogan

Email: [email protected]

Introduction

Preoperative preparation of the colon prior to surgical resection was first introduced in 1966 [1]. The strategy employs the use of a mechanical bowel prep with or without oral antibiotics to reduce the bacterial biomass in the intestine as an empirical method to decrease infectious complications.

The literature on the utility of preoperative bowel prep is dominated by patients undergoing surgery for malignancy or benign disease, rather than patients undergoing surgery for inflammatory bowel disease (IBD). Patients requiring surgery for IBD represent a specific subset of patients with a relatively high risk of postoperative complications [2]. Additionally, preoperative anatomic considerations such as intestinal stenosis or enterocutaneous fistulas, and previous infections with or without opportunistic microorganisms often associated with IBD patients will give the IBD surgeon pause when prescribing a preoperative prep. In this chapter, we will review the available data on the utility of mechanical bowel prep and preoperative oral antibiotics in surgical patients, paying particular attention to the unique considerations for patients undergoing surgery for IBD.

Search Strategy

We performed a comprehensive literature search of Medline, PubMed, and Google Scholar to identify all of the English-language publications related to preoperative bowel prep and postoperative complications between 1970 and 2018. Key search terms included: (‘mechanical bowel prep’ or ‘MBP’ or ‘preoperative bowel prep’) and (‘oral antibiotics’ or ‘preoperative antibiotics’ or ‘preoperative PO antibiotics’) and (‘colorectal’ or ‘colorectal surgery’) and (‘inflammatory bowel disease’ or ‘IBD’ or ‘ulcerative colitis’ or ‘Crohn’s’). References of each relevant publication were reviewed. Because of the paucity of studies investigating the effect of bowel prep specifically on IBD patients, each article was reviewed to determine if subset analysis was conducted for the IBD cohort. Retrospective, prospective, observational, and randomized studies were included (Table 2.1).

Table 2.1

PICO table

Results

Mechanical bowel prep (MBP) and oral antibiotics are the two primary modalities in which the practicing surgeon can prepare the bowel for surgery. Investigators have studied the effects of MBP and oral antibiotics independently as well as in a combined approach to reduce infectious complications, particularly surgical site infections (SSI) and anastomotic leak.

Mechanical Bowel Prep Alone

MBP using a purgative, given via enema or orally, is used to rid the colon of its fecal burden preoperatively. Despite its ubiquitous use for generations, the utility of using MPB alone in preventing complications is largely unfounded. Since 1990, at least fifteen randomized controlled trials (RCT), encompassing all colorectal operations for all indications, have shown that preoperative MBP does not significantly reduce the incidence of superficial or deep SSI, or anastomotic leak in patients undergoing elective colorectal surgery [3–16]. The Cochrane Collaboration has published four updates on this topic, most recently in 2011 encompassing 18 trials, concluding that prophylactic MBP given orally or via enema is of no value to patients [17–20].

Most recently in 2018, a meta-analysis analyzed 23 RCT’s and 13 observational trials, including a total of 21,568 patients undergoing colorectal surgery for all indications [21]. Similar to the previous reviews, they reported that MBP was not associated with any significant differences in SSI, anastomotic leak rate, intra-abdominal infections, or hospital length of stay.

There is also evidence that the use of MBP may cause harm. In addition to patient discomfort while taking the purgative, the diarrhea from MBP can cause dehydration, electrolyte dysfunction, and is associated with postoperative intestinal dysmotility [8, 22, 23]. These concerns are particularly important in IBD patients, who are often at baseline malnourished from their chronic disease. Further, incomplete MBP may actually cause increased stool spillage at surgery, resulting in increased deep pelvic infections [24].

While these results are overwhelmingly compelling, the majority of the included patients in these studies underwent surgery for malignancy or diverticular disease. Of the 36 studies in 2018 meta-analysis, only 12 studies included IBD patients and of these, IBD patients generally made up only 5% of the study group. In fact, to the best of our knowledge, there has been no RCT trials and only a few observational studies specifically investigating the impact of MBP alone in IBD patients.

Review of the few investigations that include only IBD patients provide contradictory conclusions. Barker et al. in 1971 found that patients undergoing a segmental or total colon resection for either Crohn’s colitis or ulcerative colitis with complete emptying of their colon after a MBP were significantly less likely to get an SSI, compared to patients found to have residual intraluminal stool [25]. More recently, Lesalnieks et al. retrospectively reviewed 549 patients who underwent elective colorectal resections in patients with Crohn’s disease [26]. They found that intraabdominal septic complications (anastomotic leak, intraabdominal abscess, peritonitis) was reduced from 26% to 12% in patients whom received a MBP. When stratified by disease phenotype, MBP did not have an effect on patients with stricturing disease, but did have a beneficial effect in reducing infectious complications in patients with penetrating disease (12% vs. 26%; p = 0.003) and colonic resection for colonic Crohn’s disease (14% vs. 32%; p = 0.043). The authors commented that the number of patients in the stricturing cohort may have been too low to detect a significant difference. Alternatively, it maybe that given the potential obstructive symptoms in patients with stricturing disease, they were unable to complete the MBP thus limiting its effect.

While these results are intriguing, and may represent insight into how MBP differentially effects patients with IBD, the retrospective nature of this study severely limits the confidence of the results. The MBP group consisted mostly of patients operated between 1992 and 2004, whereas nearly all surgeries in the no MBP were performed after 2005. As IBD surgery has evolved over the last three decades, this creates significant demographic differences between the two cohorts; the patients in the MBP group had significantly more open surgeries, were more likely to be on high-dose steroids, and less likely to be using a TNF-alpha inhibitor.

Preoperative oral Antibiotics with or without MBP

While the benefit with MBP alone is not supported by the literature, the addition of preoperative oral antibiotics is more compelling. In 1973, Nichols et al. reported that the addition of oral neomycin and erythromycin to a MBP completely prevented SSI in patients undergoing colon surgery, compared to a 30% incidence of SSI in the MBP alone cohort [27]. Shortly after his landmark paper, a handful of studies published in the 1970s confirmed that oral antibiotics protected against SSI, making its use routine [28–31].

In the decades that followed, there seemed to be a steady trend to omit the oral antibiotics and focus exclusively on IV antibiotic prophylaxis. However, there has been a renewed interest in the addition of oral antibiotics (most commonly neomycin, erythromycin, and/or metronidazole) to the preoperative bowel prep regimen. A meta-analysis compiled 16 RCT’s and a total of 2669 patients comparing the addition of oral antibiotics to MBP [32]. Patients undergoing surgery with a diagnosis of IBD were in the minority, encompassing only 129 patients (4.8%) of the total cohort. Regardless, the authors reported that oral antibiotics significantly decreased the risk of SSI (RR: 0.57; 95% CI: 0.43–0.76), but showed no effect on the risk of anastomotic leak (RR: 0.63; 95% CI:0.28–1.41).

More recent RCT’s have offered conflicting results. In an noninferiority study, Yamaguchi et al. found that intravenous perioperative prophylaxis alone is not inferior to combined prophylaxis with preoperative oral kanamycin and metronidazole in patients undergoing laparoscopic colon surgery for colorectal cancer [33]. In a more recent RCT, Anjum et al. found that oral metronidazole and levofloxacin conferred a significantly decreased risk of SSI and anastomotic leak in 190 patients undergoing colon surgery [34]. Although a subset analysis was not conducted, patients with the diagnosis of IBD represented 20% of the cohort.

Database studies have also favored the use of oral antibiotics. Using the American College of Surgeons National Surgical Quality Improvement (NSQIP) database, 8442 patients undergoing elective colorectal resection were queried [35]. MBP with oral antibiotics was associated with reduced anastomotic leak (OR = 0.57, 95% CI: 0.35–0.94), SSI (OR = 0.40, 95% CI: 0.31–0.53), and postoperative ileus (OR = 0.71, 95% CI: 0.56–0.90). While there were no significant differences in demographics, the authors did not report how many patients were undergoing surgery for IBD. Using NSQIP data from the similar time period, a different group investigated the effect of the addition of oral antibiotics to MBP stratified by procedure [36]. They found that MBP plus oral antibiotics showed a benefit in the reduction of SSI infections that was most significant in patients undergoing ileocolic resections compared to other procedures, potentially a proxy for patients undergoing surgery for IBD.

Shwaartz et al. focused a NSQIP database study of 3679 patients undergoing colorectal surgery only for IBD [37]. After controlling for demographics, clinical, and procedural variables, MBP plus oral antibiotics was protective against ileus, anastomotic leak, SSI, deep space infection, and septic shock. MBP alone or oral antibiotics alone did confer a benefit for any postoperative complication. Unfortunately, they did not do a subset analysis on the effect of each regimen stratified by the type of surgical procedure.

The fact that the addition of oral antibiotics to MBP reduces complications, while MBP alone has no efficacy, begs the question of whether oral antibiotics are the critical component of combined preoperative bowel preps. While it has long been thought that orally administered antibiotics would only be effective if the bowel is first cleansed of its stool burden, there is little known regarding the potential benefits of oral antibiotics alone. To shed light on this topic, in 2017 Garfinkle et al. utilized the NSQIP database to analyze the effects of oral antibiotics alone in 40,446 patients undergoing elective colorectal surgery [38]. IBD patients were in the minority, comprising only 10.2% of the entire cohort. Oral antibiotics alone offered a protective benefit for SSI (OR = 0.63; 95% CI: 0.45–0.87), anastomotic leak (OR = 0.60; 95% CI: 0.34–0.97), and ileus (OR = 0.79; 95% CI: 0.59–0.98). Oral antibiotics with MBP offered no superiority compared to oral antibiotics alone. These results are similar to a retrospective review of 9940 Veterans Affair patients, showing that the use of oral antibiotics alone was associated with a 67% decrease in SSI (OR = 0.33, 95% CI: 0.21–0.50) whereas oral antibiotics plus MBP was associated with a 57% decrease in SSI’s (OR = 0.43, 95% CI: 0.34–0.55) [39]. This line of inquiry is in its infancy and these studies have set the stage for multiple active RCT’s containing an oral antibiotic only cohort to help determine the role of oral antibiotics without MBP in a preoperative prep regimen [40, 41].

The efficacy of oral antibiotic alone to prevent complications is highly relevant to the practicing IBD surgeon. It seems likely that patients would benefit from oral antibiotics alone even when undergoing procedures in which the colon is already resected or diverted (i.e. diverting loop ileostomy takedown, ileal pouch anal anastomosis; IPAA). Further, if oral antibiotics are effective alone, surgeons could selectively forego MBP in patients that are at high risk of intolerance of MBP such as those with stricturing or penetrating disease. While almost nothing is known about the efficacy of oral antibiotics in these groups, Oshima et al. randomized 195 patients undergoing open IPAA to receive preoperative kanamycin and metronidazole verses no antibiotics [42]. They reported that the addition of oral antibiotics significantly decreased the SSI rate compared to those patients not receiving antibiotics (6.1% vs. 22.4%; p = 0.0024). Further, on multivariate analysis lack of oral antibiotics was independently associated with the development of SSI (OR 0.178; 95% CI 0.057–0.552). Anastomotic leak was not assessed between the groups. Further studies are needed, but extrapolation of these results to other procedures such as diverting loop ileostomy takedown are intriguing.

Finally, the benefit of oral nonabsorbable antibiotics has to be weighed against the potential for bacterial resistance and opportunistic infections. In most studies, the addition of oral antibiotics to a MBP has not been shown to increase the incidence of C. diff infections, and contrary to expectations has been associated with a decreased risk [43]. In the previously mentioned study by Oshima of ulcerative colitis patients, oral antibiotics alone did not influence C. diff rates concluding that it can be safely given (Table 2.2).

Table 2.2

Studies investigating preoperative bowel prep specific to IBD patients

Recommendations Based on Data

While the retrospective study by Lesalnieks et al. showing a benefit of MBP alone in IBD patients is of interest, the abundance of evidence from high quality RCT’s, albeit with limited inclusion of IBD patients, strongly refutes the benefit for the use of MBP alone. Thus based on the available data, we do not recommend the routine use of MBP alone as a preoperative strategy. Strength of recommendation: strong, level of evidence: high

There is high quality evidence for both non-IBD and IBD patients that the utilization of preoperative oral antibiotics in combination with a MBP on the day before surgery is beneficial in reducing postoperative complications. Because the majority of investigations combine different classes of antibiotics, a specific regimen cannot be strongly recommended. Thus based on the available data, we recommend the routine use of preoperative MBP and nonabsorbable oral antibiotics for patients undergoing bowel resection for IBD.

Strength of recommendation: strong, level of evidence: high.

There is limited moderate and high quality evidence that preoperative oral antibiotics alone is beneficial in reducing postoperative complications. Thus based on the available data, we recommend oral antibiotics alone in IBD patients that might not tolerate a MBP or if there colon is resected or diverted. Strength of recommendation: weak, level of evidence: low.

Personal View

The lack of efficacy of MBP in preventing infectious complications is supported by biological data. Low-tech culture dependent methods have shown that MBP alone does not influence the bacterial counts within stool, nor reduce the mucosal colonization of the common GI organisms E. coli or Bacteroides [15, 44]. On the other hand, 48 h of oral neomycin and metronidazole significantly decreases E. coli and Bacteroides recovered from feces [44]. Particularly for anastomotic leak, animal models have lent support to oral antibiotics. Even in the presence of ischemia, oral antibiotics completely protected against anastomotic leak in dogs, whereas MBP alone had no effect on intestinal healing in an experimental rat model [45, 46].

While it has generally be taught that decreasing infection complications following bowel prep is simply a consequence of the reduction of the bacterial fecal load, this simplistic view has been outweighed by the recent explosion in advances in microbial sciences demonstrating the enormous diversity, redundancy, and functional importance that resides within the intestinal microbiome. Advanced non-culture based techniques (i.e. 16 s rRNA sequencing) have let us gleam the first insights into the influence of preoperative interventions on intestinal communities. Recent studies demonstrate that bowel prep is associated with a reduction in certain potentially pathogenic phyla (i.e. Firmicutes) while at the same time causing a reduction in potentially beneficial organisms (i.e. Lactobacillaceae) [47–49]. Because we do not fully understand the bacterial mediated mechanism of SSI, anastomotic leak, or ileus, we are currently unable to predict how this balance actually impacts potential offending organisms.

Therefore, empirical use of decades old bowel prep studies betrays the complexity of the microbial communities and their vast functional diversity in the gut. Each patient can maintain their own unique (yet overlapping) compliment of bacterial species, whose metabolism can influence immune, endocrine, and metabolic functions. This personalized microbial milieu means that the effects of a preoperative prep are likely patient dependent, associated with their preoperative microbiome, and therefore not generalizable across populations [48]. It may stand to reason that in selected patients, MBP and/or antibiotic administration may inadvertently enrich pathogenic organisms that cause postoperative complications, whereas in others it eradicates them. This is especially true in the IBD population who at baseline contain an altered microbiome. Malnourishment, high-dose steroids, and chronic antibiotics, all common in IBD patients, can each have an independent effect on the microbiome; how these variables influence the efficacy of a bowel prep is unstudied. Trials that not only analyze clinical outcomes after bowel prep, but that seek to understand the compositional and functional changes of the microbiome are critical as a path forward in developing the next generation bowel prep.

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© Springer Nature Switzerland AG 2019

Neil Hyman, Phillip Fleshner and Scott Strong (eds.)Mastery of IBD Surgeryhttps://doi.org/10.1007/978-3-030-16755-4_3

3. Extended Venous Thromboembolism Prophylaxis After Surgery for Inflammatory Bowel Diseases

Chun Hin Angus Lee¹ and Stefan D. Holubar¹  

(1)

Department of Colon and Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA

Stefan D. Holubar

Email: [email protected]

Introduction

Surgical patients with inflammatory bowel disease (IBD) bring unique risk factors for venous thromboembolism (VTE), including Virchow’s triad of inflammation-associated hypercoagulability, stasis (ex. bed-rest from fatigue between frequent trips to the bathroom, prolonged operations), and the obvious trauma of surgery [1–3]. In this population, we are all aware that VTE includes not only lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE), but for IBD patients we must also keep in mind upper-extremity DVT related to central access for enteral nutrition, post-operative portomesenteric vein thrombosis (PMVT), and rarely cerebral venous sinus thrombosis [4, 5]. All of these can present silently or symptomatically, both before and after surgery.

According to Big Data studies, the average risk of post-operative VTE after surgery for IBD is approximately 4%, likely higher for ulcerative colitis (UC, 4–6%), and lower for Crohn’s disease (CD, 2–3%) [6–9]. At a national level, this translates to >40,000 surgical IBD patients in the United States who develop VTE per year, with an estimated annual added cost of over $17 million dollars per year [10]. In addition to the financial burden posed to healthcare system in relation to readmission and treatment, patients also can suffer from the short- and long-term sequelae of VTE and its treatment, including acute mortality (from PE), therapeutic anticoagulation (AC) related bleeding complications including intracranial hemorrhage, and lower extremity post-thrombotic syndrome. Thus, many IBD surgeons find the above rates unacceptable, and several strategies may be used to decrease the rate of post-operative VTE. The first two are early detection and risk-stratification, both of which we will briefly discuss. The third strategy, which is the focus of this chapter, is extended post-operative, specifically post-discharge, chemoprophylaxis. We will review the literature supporting the efficacy of extended prophylaxis, bleeding associated with various medications, and the costs and cost-effectiveness of various strategies.

Search Strategy

Relevant PICO (Population, Intervention, Comparator, Outcome) questions were generated (Table 3.1). A comprehensive literature search of Cochrane Database of Collected Research, EMBASE, MEDLINE, and PubMed was performed to identify all of the English-language publications between January 2000 and March 2018 using the following search terms: (‘inflammatory bowel disease’ or ‘IBD’ or ‘ulcerative colitis’ or ‘Crohn’s’) and (‘colorectal’ or ‘colorectal surgery’ or ‘surgery’ or ‘surgical’ or ‘operation’ or ‘operative’ or ‘perioperative’ or ‘pre-operative’ or ‘post-operative’) and (‘venous thromboembolism’) and (‘prophylaxis’ or ‘chemoprophylaxis’). Retrospective, prospective, observational, randomized controlled trials (RCTs), systematic reviews, and meta-analyses were included. In addition, we searched the reference section of each relevant article to identify additional articles pertaining to this topic which included the most recent revision of the American College of Chest (ACCP) Physicians VTE Prophylaxis Guideline [1] which is an excellent resource. Given the lack of RCTs of VTE prophylaxis for IBD patients undergoing colorectal surgery on this topic, a second search substituting the IBD diagnostic terms for ‘cancer’ and substituting