Enterocutaneous and enteroatmospheric fistulas

INTRODUCTION — A fistula is an abnormal connection between two epithelialized hollow spaces or organs. Strictly speaking, an enterocutaneous fistula connects the small bowel to the skin. A more liberal interpretation of the term, however, also includes enteric fistulas originating from the colon, stomach, and esophagus. (See 'Classification' below.)

The clinical features, diagnosis, and management of enterocutaneous fistulas are reviewed here. Enteroatmospheric fistulas, which are a subset of enterocutaneous fistulas that occur in the setting of an open abdomen, are also discussed here.

Fistulas that occur in other areas of the body are discussed in other topics, including:

●Colovesical fistulas (see "Colovesical fistulas")

●Urogenital tract fistulas in women (see "Urogenital tract fistulas in females" and "Rectovaginal and anovaginal fistulas")

●Anorectal fistulas (see "Anorectal fistula: Clinical manifestations and diagnosis" and "Operative management of anorectal fistulas" and "Perianal Crohn disease")

●Pancreatic fistulas

●Duodenal fistulas (see "Postgastrectomy duodenal leak")

●Tracheoesophageal fistulas (see "Tracheo- and broncho-esophageal fistulas in adults")

●Bronchopleural fistulas (see "Bronchopleural fistula in adults")

CLASSIFICATION — Enterocutaneous fistulas can be classified according to source, output volume, and etiology.

By source — The most common method of defining a fistula is by its organ of origin (eg, gastro-, duodeno-, entero-, jejuno-, ileo-, colo-, recto-) followed by the point of its termination (eg, -cutaneous, -atmospheric). However, at initial presentation, the specific segment of bowel involved (ie, the enteric origin of the fistula) is often unknown, and a broader designation (eg, enterocutaneous rather than jejunocutaneous) is used until the anatomy of the fistula can be delineated. (See 'Diagnosis' below.)

Fistulas originating from different organ systems will have very different outputs. Electrolyte and nutritional losses can vary greatly between organs of origin. As an example, gastric output has a higher acidity. This information may prove essential in the management of enterocutaneous fistulas. (See 'Fluid therapy' below.)

By output volume — The physiologic consequences of enterocutaneous fistulas may depend on the quantity of fluid put out by the fistula, which may differ by the location (proximal versus distal) and the length or diameter of the fistula. An alternative classification defines fistulas by the quantity of their output:

●A low-output fistula drains less than 200 mL/day.

●A moderate-output fistula drains between 200 and 500 mL/day.

●A high-output fistula drains more than 500 mL/day.

In general, high-output fistulas are less likely to heal spontaneously, and patients with high-output fistulas are at a higher risk for metabolic disturbances, fluid loss, and malnutrition. For such patients, controlling external fistula output is as important as replacing fluid and electrolyte loss during the chronic phase of management. (See 'Fistula output reduction' below.)

By etiology — Enterocutaneous fistulas can also be classified according to their etiologies (eg, iatrogenic, spontaneous), which are further discussed below. (See 'Etiology and risk factors' below.)

EPIDEMIOLOGY — Although a few studies have reported postoperative prevalences of enterocutaneous fistulas in patients undergoing surgery for trauma (1.5 percent [1]), general surgery (3.6 percent [2]), and Crohn disease (15 to 35 percent [3,4]), the prevalence of enterocutaneous fistulas in the general population (including both iatrogenic and spontaneous cases) is not well known. The National Inpatient Sample (NIS) noted 317,000 admissions between 2004 and 2014 with a diagnosis of enteric fistula, costing the United States hospital systems more than 500 million dollars annually [5].

ETIOLOGY AND RISK FACTORS — Various etiologies can lead to fistula formation (table 1). Most enterocutaneous fistulas are iatrogenic/postoperative (75 to 85 percent); a minority (15 to 25 percent) develop spontaneously [6].

Iatrogenic fistulas — Iatrogenic causes of enterocutaneous fistula include trauma and surgery (ie, postoperative fistulas). Postoperative fistulas develop from either a bowel anastomotic leak (50 percent) or a missed enterotomy (45 percent), with a small percentage from erosion of foreign material (eg, mesh for hernia repair, vascular graft) into adjacent bowel [7]. Preoperative factors that increase the likelihood of the development of a postoperative fistula include Crohn disease, malnutrition, immunosuppression, traumatic injury, infection, smoking, and emergency procedures [8,9].

Enteroatmospheric fistulas — Enteroatmospheric or exposed fistulas occur in the midst of an open abdomen with no overlying soft tissue (picture 1). The open abdomen is usually the result of a damage control laparotomy, which leaves the abdomen open after trauma or emergency surgery to prevent intra-abdominal hypertension/abdominal compartment syndrome [10,11]. (See "Abdominal compartment syndrome in adults".)

A review of 517 patients from the American Association for Surgery in Trauma (AAST) registry with open abdomen found that 111 patients (21 percent) developed an enterocutaneous fistula, an enteroatmospheric fistula, or intra-abdominal sepsis. Independent risk factors included large bowel resection, large-volume resuscitation, and an increasing number of abdominal re-explorations [12]. The risks of open abdomen are further discussed separately. (See "Management of the open abdomen in adults", section on 'Complications of open abdomen'.)

Spontaneous fistulas — The mnemonic "FRIEND" describes common etiologies for spontaneous enterocutaneous fistulas, which include foreign body, radiation, inflammation (eg, Crohn disease) or infection (eg, tuberculosis, actinomycosis), epithelialization, neoplasia, and distal obstruction [10]. These etiologies also describe conditions in which fistulas are less likely to heal spontaneously. Diverticular disease and appendicitis are also reported as uncommon etiologies of fistulas.

Crohn disease is the most common etiology for spontaneous fistulas; the prevalence varies by patient populations [10,13]. Between 27 and 35 percent of patients undergoing surgery for Crohn disease had a fistula [3,4], while 15.4 percent of patients with complicated Crohn disease, but who had not had surgery, had a fistula [14]. Crohn-related fistulas are typically treated initially with immunosuppressive drugs (thiopurines), biologic agents (TNF inhibitors), and antibiotics (metronidazole) to reduce inflammation and diarrhea. Medical treatment of Crohn-related fistulas is discussed in another topic. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Features of transmural inflammation'.)

CLINICAL FEATURES — The most common presentation of an enterocutaneous fistula is in a postoperative patient who fails to recover normally from abdominal surgery. The patient often presents first with abdominal symptoms, including increased pain, nausea and vomiting, obstipation, and fullness or induration of the abdominal wall. These may be accompanied by fever and leukocytosis. A wound infection is then typically recognized 7 to 10 days postoperatively, and following incisional drainage, enteric contents appear in the surgical wound [7]. An enteric fistula can be distinguished from a wound infection by the presence of bile in the wound. As opposed to infection or seroma, bilious output will stain gauze and dressings an orange/brown or green color. Frank stool can also be noted in the wound of a colonic fistula.

Enterocutaneous fistulas are characterized by leakage of enteric or bowel contents through the abdominal wall. The leakage is also referred to as effluent. Depending upon the location and origin of the fistula, it can be through a prior abdominal wound, incision, or an area of "virgin" abdomen. Leakage of effluent can cause irritation of the skin, loss of fluids and electrolytes, malnutrition, and infection. In addition, as a fistula is forming, the patient may become acutely ill secondary to leakage of effluent into the abdominal cavity.

DIAGNOSIS — The diagnosis of an enterocutaneous fistula is clinical. It should be suspected in a postoperative patient who fails to recovery normally from abdominal surgery and has bilious wound drainage. The diagnosis of enterocutaneous fistula can be confirmed by the appearance of enteric contents draining from the abdominal wall. If in doubt, bilirubin levels can be sent from the wound drainage to determine if contents are enteric.

By definition, an enteroatmospheric fistula can only be diagnosed in a patient with an open abdomen. Similar to enterocutaneous fistulas, the diagnosis can be confirmed by the presence of enteric contents draining from an opening in a segment of bowel within the open abdominal wound.

However, the organ of origin of an enterocutaneous or enteroatmospheric fistula is often not defined until imaging studies can be performed. (See 'Diagnostic evaluation' below.)

Diagnostic evaluation — For stable patients with an enterocutaneous or enteroatmospheric fistula, we perform abdominal computed tomography (CT) with and without oral and intravenous contrast at least 7 to 10 days after fluid and electrolyte resuscitation, infection control, and appropriate wound care [15]. CT can not only help delineate the anatomy of the fistula but also demonstrate associated intra-abdominal abscesses, fluid collections, or areas of distal intestinal obstruction. These are all risk factors for fistula formation and persistence. (See 'Etiology and risk factors' above.)

If abdominal CT does not elucidate fistula anatomy, a gastrointestinal contrast study is performed. Either a small bowel follow-through or contrast enema is selected depending upon the suspected level of the fistula (upper versus lower gastrointestinal tract). It should be noted that only the portion of the bowel in continuity will be evaluated by traditional contrast studies. As an example, a mass or stricture (inflammatory or malignant) distal to the fistula may not be well demonstrated, because most of the contrast is drained via the fistula.

Alternatively, for enterocutaneous fistulas that have a well-defined cutaneous opening, a fistulogram can be performed by injecting a water-soluble contrast agent into the opening to define the fistula tract. Although a fistulogram can document intestinal continuity and evaluate for distal obstruction [7,16,17], it rarely identifies the specific origin of the tract [10].

Small fistulas or low-output fistulas may not be apparent on imaging. Another simple method to determine whether or not an enterocutaneous or enteroatmospheric fistula is indeed present is by the administration of dye (eg, indigo carmine, methylene blue, charcoal), which can be ingested or added to enteric feeding or instilled as a solution into the gastrointestinal tract during endoscopy. The presence of dye in the effluent confirms the diagnosis of an enteric fistula.

Differential diagnosis — Drainage from an abdominal incision following gastrointestinal surgery may represent a surgical site infection rather than an enterocutaneous fistula. The character of the drainage, and whether drainage persists once the wound has been opened, usually makes the distinction as the presence of feces or bile is definitive evidence of an enterocutaneous or enteroatmospheric fistula. (See "Wound infection following repair of abdominal wall hernia".)

TREATMENT OVERVIEW — The treatment of enterocutaneous and enteroatmospheric fistulas requires a systematic approach and is carried out in phases (table 2 and algorithm 1).

Initial acute management focuses on control and treatment of sepsis, which requires surgery in some patients but can be accomplished nonoperatively in others (eg, with antibiotics and catheter drainage). (See 'Acute management' below.)

Once sepsis is controlled, the treatment enters a chronic phase, which focuses on wound management, fluid/electrolyte replacement, and nutritional optimization. It may be appropriate to transfer patients to a specialized center for this phase of the care and beyond [18], where improved outcomes, including a lower mortality rate, have been realized [10,19,20]. This phase of fistula management optimizes the condition for spontaneous healing while simultaneously preparing the patient for possible definitive management. Most contemporary studies report that approximately one-third of enterocutaneous fistulas will close spontaneously within five to six weeks with conservative measures [13,21-27]. (See 'Chronic management' below.)

For fistulas that fail to close spontaneously, the final stage of management is definitive fistula repair, which may be endoscopic or surgical. As long as fistula output is gradually decreasing and the wound (or tract) shows signs of healing, surgery should be delayed. Surgical fistula repair should not be attempted for at least three to six months from the inciting event to allow time for spontaneous healing and patient conditioning. Specialized centers often delay definitive operations for 6 to 12 months [6]. Prerequisites to definitive fistula repair include eradication of infection, optimization of nutrition, and clinical evidence of softening scars and abdominal wall on physical exam. (See 'Nonoperative fistula closure' below and 'Operative fistula closure' below.)

ACUTE MANAGEMENT — Initial treatment of enterocutaneous and enteroatmospheric fistulas focuses on the identification and management of sepsis, especially in the case of acute postoperative fistulas. In this acute phase, the etiology of the fistula is often not important.

Fistula-associated abdominal sepsis (eg, intra-abdominal abscess, gastrointestinal perforation, or subcutaneous infection) needs to be recognized and promptly treated with antibiotics, percutaneous catheter drainage, and/or operative drainage or source control. Prompt treatment of abdominal sepsis will reduce the risk of mortality as well as progressive organ dysfunction [28,29]. Infection and sepsis account for over 70 percent of mortality associated with these fistulas [13].

Treatment of sepsis — Patients who have diffuse peritonitis or evidence of free gastrointestinal perforation on imaging studies require urgent surgical exploration. It is rare that an enterocutaneous fistula can be resected or closed primarily in the acute phase, particularly if it is a postoperative complication. Thus, operative sepsis control should focus on infection drainage and exteriorization of any leaking small or large intestine. A common mistake is to repair or primarily redo the anastomosis in the infected field in order to avoid a stoma. No new anastomoses should be created in a critically ill patient or in the presence of significant intra-abdominal contamination. Diversion of the fecal stream by ostomy is often required and is the preferred approach. In the setting of acute sepsis, diversion is highly recommended to prevent further complications. Resection of healthy bowel that may be involved in an inflammatory process should also be avoided.

Hemodynamically stable patients without diffuse peritonitis should undergo abdominopelvic computed tomography (CT) to identify any intra-abdominal source of sepsis, such as intra-abdominal abscess or fluid collection. Patients with a contained fluid collection or abscess may undergo image-guided percutaneous drainage (ultrasound or CT) [30]. Drainage is usually performed through the anterior abdominal wall. However, abscesses deep in the pelvis or obscured by other organs may be accessed with a variety of other approaches, including transgastric, transrectal, transvaginal, and transgluteal [18]. The drainage catheter is usually left in place until output is less than 10 mL in 24 hours or until definitive fistula surgery. Catheter fistulogram during this period permits assessment of resolution of the abscess cavity and determination of direct communication of drainage catheter with the bowel. Operative drainage is needed if sepsis does not resolve with catheter drainage.

Antibiotic management in septic patients should follow the Surviving Sepsis Guidelines [31]. Once source control is obtained by operative or catheter drainage, empirical antibiotics should be discontinued after another five to seven days. (See "Antimicrobial approach to intra-abdominal infections in adults", section on 'Duration of therapy'.)

Antibiotic management in nonseptic patients with an enterocutaneous fistula is controversial. Because no studies have demonstrated improved outcomes with antibiotic therapy in these patients and there are increasing concerns for multidrug-resistant bacteria, we do not suggest routine antibiotic coverage for patients who are not septic and have no acute signs of infection.

Restoration of hemodynamic stability — Treatment of sepsis in the acute phase also requires restoration of hemodynamic stability. Resuscitation with fluids, repletion of electrolytes, and restoration of normotension may be required on a case-by-case basis; some may require vasopressors in an intensive care unit (ICU) setting. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

CHRONIC MANAGEMENT — Chronic management of fistulas entails evaluation and treatment of fluid, electrolyte, and nutritional losses and specialized wound care to manage the intestinal effluent (table 2 and algorithm 1). In those with high-output fistulas, drug therapies may be instituted to reduce fistula output.

Fluid therapy — Aggressive correction of hypovolemia and electrolyte loss should occur early in treatment. Hyponatremia, hypokalemia, and hypomagnesium are the most common electrolyte abnormalities. Ongoing fluid losses from moderate-output upper gastrointestinal fistulas should be replaced with saline and potassium supplementation with serial measurements of serum electrolytes. The composition of replacement fluid should mimic that of fluid lost as much as possible (table 3) [32]. Replacing fluid losses cc per cc may be necessary to help prevent dehydration and hypovolemia.

High-output fistulas may require direct electrolyte analysis of the fistula effluent to make an appropriate choice of replacement fluid. The St. Mark's Intestinal Failure Unit has created a worksheet to help calculate daily losses for patients with high-output fistulas [33]. (See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Clinical manifestations and treatment of hypokalemia in adults".)

Duodenal or pancreatic fistulas may require bicarbonate replacement to prevent metabolic acidosis. (See "Approach to the adult with metabolic acidosis", section on 'Overview of therapy'.)

Nutritional support — Nutritional optimization is critical to successful resolution of the fistula. Data demonstrate that nutritionally optimized patients with serum albumin of ≥4 mg/dL have lower mortality from surgical interventions [34]. In addition, the spontaneous healing rate of the fistula improves from 7 to 81 percent when nutrition is optimized [35]. The nutritional needs of a patient with an enterocutaneous or enteroatmospheric fistula are met with enteral feeding, parenteral feeding, or a combination of the two. The decision is primarily dependent upon fistula output (algorithm 1).

Nutritional goals — Depending on the amount of output, the baseline energy requirement for a patient with an enterocutaneous or enteroatmospheric fistula may be 1 to 2.5 times that of a healthy adult [36]. The requirement may be even higher for patients with ongoing infection, large open abdominal wounds, and high-output fistulas.

The estimated nutrition needs for a patient with a low-output fistula range from 20 to 30 kcal/kg per day of total caloric intake and 1 to 1.5 g/kg per day of protein intake. Those with a high-output fistula require 25 to 35 kcal/kg per day of total caloric intake and 1.5 to 2.5 g/kg per day of protein intake (due to up to 75 g of protein loss in the effluent) [6]. Required doses of vitamins and trace elements, such as vitamin C, zinc, copper, and selenium, which promote healing, may be increased substantially [6]. The addition of fish oil or omega-3 fatty acids has also been shown to improve immune function [37] after severe injury [38], abdominal operation [39], and in patients in the intensive care unit [40]. There are no trials directly investigating the effect of omega-3 fatty acid nutritional supplements specifically in the treatment of enterocutaneous fistula.

It may be necessary to carefully calculate the composition and quantity of daily output to determine repletion requirements. Ongoing assessment of the patient's nutritional, electrolyte, and fluid status may be necessary for patients with high-output fistulas [41]. Serum albumin, prealbumin, transferrin, C-reactive protein, weight, and anthropometrics should be followed over time [6].

Low-output fistulas (<200 mL/day) — Enteral feeding is always preferred to parenteral nutrition because this route preserves the intestinal mucosal barrier and has positive effects on immunologic and hormonal gut functions. However, although the patient may eat well, absorption of nutrition may be compromised by the fistula to the degree determined by its output and location. With proximal fistulization (jejunal), the patient may not have adequate absorptive capacity in the functioning intestines to maintain nutrition. Additionally, the output from the fistula may increase in quantity with enteral feeding and become excessive, requiring fluid supplementation. For patients trying enteral feeding, the goal enteric output is <1.5 L/day. The following is our protocol for managing nutrition in patients with low-output fistulas (algorithm 1):

●After the patient has been stabilized and sepsis treated, we generally try a short period of bowel rest (days) to see if the fistula output would reduce and/or if the fistula would spontaneously close. During this brief period of bowel rest, the patient may or may not need total parenteral nutrition (TPN) depending on his/her baseline nutritional status.

●If the fistula output does not decrease with bowel rest and the fistula does not close, the patient is then started on an oral diet while we continue to monitor and manage output. 

●If the fistula output increases substantially with oral diet, we will generally stop oral diet and start TPN to see if that decreases output. TPN has been known to reduce fistula output [6].

Moderate- or high-output fistulas (>200 mL/day) — Patients with moderate- to high-output enteric fistulas may be intolerant to oral nutrition secondary to inability to control sepsis, poor absorption, greater fluid and nutrient loss from fistula output, or difficulty with infection or excoriation of the skin.

Output from the fistula may decrease with an elemental diet [42]. One specialized intestinal failure unit reported lowering fistula output by limiting the intake of low-sodium fluids (free fluids) to 500 mL/day and encouraging the patient to drink an electrolyte solution containing high concentrations of sodium and glucose (up to 1000 mL per day) [43]. Drug therapies may also be successful, including anticathartics (eg, loperamide, diphenoxylate, codeine), histamine-2 receptor antagonists and proton pump inhibitors [21], cholestyramine, and somatostatin analogues. (See 'Fistula output reduction' below.)

In general, patients with output greater than 1.5 L/day, less than 75 cm of intestinal length prior to the fistula, or intestinal discontinuity may require parenteral nutritional supplementation. In these cases, parenteral nutrition may be required exclusively or as an adjunct to oral nutrition. Parenteral nutritional support should be initiated slowly after correction of fluid, electrolyte, and vitamin deficits has been completed [36,44,45]. (See "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription".)

Wound care — The main goal in wound care is to protect the skin near the external fistula opening from the corrosive effects of the enteric or pancreatic contents and promote wound healing. Wound care for most low-output fistulas requires nothing more than a gauze cover. Moderate-output fistulas can be controlled with an ostomy appliance. The real challenge is management of high-output fistulas and enteroatmospheric fistulas.

Bag drainage — Skin protection creams and effluent collection bags must be tailored to the unique characteristics of each fistula, but the principles are similar to those used in the care of a colostomy or ileostomy [22]. The assistance of a skilled enterostomal therapist is helpful. (See "Ileostomy or colostomy care and complications".)

●For enterocutaneous fistulas, a pouch should be placed around the fistula. The adjacent skin should be protected with semipermeable barrier dressing or other skin protectants. Wound protectors and wound managers may be used to minimize skin irritation and collect effluent as with surgical ostomy. (See "Ileostomy or colostomy care and complications", section on 'Pouch systems and routine ostomy care'.)

Effluent from the fistula is often acidic and copious and can result in significant denudation and excoriation of the surrounding skin. Cellulitis or fungal infection is not uncommon with poorly controlled fistula output. Sophisticated pouching systems available at specialty centers that care for these patients can protect the skin, divert the effluent, and are key to allowing patients to function prior to surgery. Good pouching can convert an inflamed, painful wound into a functional stoma.

●Control of intestinal contents from an enteroatmospheric fistula will minimize damage to the healing bed of granulation tissue until definitive closure of the fistula can be undertaken 6 to 12 months later. Management options include the creation of a "floating stoma" by sewing exposed bowel mucosa circumferentially to a plastic sheet that is used as an interface to attach the stoma appliance and be placed on the surface of the exposed bowel [46]. A similar technique has also been described using an abdominal closure device, progressively approximating and inverting the edges of the skin to convert an open wound to a pouchable stoma [47].

Negative pressure wound therapy — Although there are no high-quality studies comparing negative pressure wound therapy (figure 1) with traditional drainage bags, the use of negative pressure wound therapy in fistula management has become widespread because surgeons are familiar with the technology from its successful application to other problematic wounds [48]. (See "Negative pressure wound therapy", section on 'Mechanism of action'.)

While many case series reported that negative pressure wound therapy accelerated fistula closure [49-51], none reported improved rates of fistula closure. In a few case reports, negative pressure wound therapy led to new fistula formation [52]. Nevertheless, most would agree that negative pressure wound therapy may be effective for high-output fistulas and hard-to-pouch fistulas and may improve the patient's quality of life by protecting surrounding skin and gathering effluent [6].

Negative pressure wound therapy can also simplify management of enteroatmospheric fistulas. Continuous suction of the fistula output minimizes contact time between intestinal fluid and exposed peritoneum by effectively controlling intestinal spillage. A useful technique for superficial enteroatmospheric fistulas is to intubate the fistulas and bring the tubes out perpendicularly through the sponge of the negative pressure dressing (picture 2) [53]. With this technique, the majority of intestinal effluent is collected in the tubes. The sponge serves as a stable rig that anchors the tubes, prevents dislodgement, and collects any residual fluid that might leak around the tubes. Care must be used when applying a negative pressure wound dressing in the setting of exposed but uninvolved bowel because the dressing can cause formation of additional fistulas, especially if fresh suture or staple lines in the bowel are exposed [52,54]. Additional protection can be provided by placing another layer of plastic or a biologic dressing between the bowel and the negative pressure sponge [55]. (See "Negative pressure wound therapy", section on 'Enterocutaneous fistula'.)

Fistula output reduction — In patients with a high-output fistula, fistula output reduction is critical to simplifying fluid management, optimizing wound care, and enabling enteral nutrition. Anticathartics, somatostatin and analogues, antisecretories, and cholestyramine have been used to reduce the output from intestinal fistulas, especially when the output exceeds 1.5 L/day (table 4) [32].

Anticathartics — Anticathartics such as loperamide hydrochloride (Imodium) and diphenoxylate-atropine (Lomotil) may be used for diarrhea and high-output fistulas. Loperamide is available in 2 mg tablets over the counter, while diphenoxylate requires a prescription for 2.5 mg tablets. Patients should titrate the dosage to output, with a typical maximal dose of 16 mg of loperamide and 20 mg of diphenoxylate daily. Both are also available in liquid form, which may be more useful for patients with poor absorption. Both medications are best used approximately 20 minutes prior to the consumption of foods. 

In a British intestinal failure unit, higher doses of loperamide (up to 40 mg/day) and codeine (up to 240 mg/day) have been used to control otherwise refractory high-output fistulas [13,43].

Opiates, such as tincture of opium and codeine, have also been used for their anticathartic property to treat high-output fistulas [32,56].

Somatostatin and analogues — Intestinal fistula output can be reduced with somatostatin and its analogues (eg, octreotide). Somatostatin reduces fistula output, but its clinical use is limited by a very short half-life. Octreotide, with a half-life of two hours, reduces pancreatic secretions and may facilitate absorption of water and electrolytes. Somatostatin and its analogues are generally renally cleared, so attention must be paid to renal function in these patients.

A systematic review identified eight trials and found that somatostatin analogues decrease the duration of enterocutaneous fistulas (weighted mean difference [WMD] -6.37 days, 95% CI -8.33 to -4.42) and duration of hospital stay (WMD -4.53 days, 95% CI -8.29 to -0.77) but did not increase the rate of spontaneous closure [57]. A separate review found similar results but noted that somatostatin had a more significant effect compared with somatostatin analogues [58]. Octreotide does not significantly reduce the need for operation in patients with Crohn disease fistulas [59,60]. Octreotide may adversely affect immune function as a result of growth hormone inhibition [61,62], but there are no clinical data to confirm this possibility. It is also important to keep in mind that if the patient has one of the barriers to spontaneous closure (table 5), such as distal obstruction, octreotide will be futile and will delay the surgical procedure ultimately needed to obtain definitive closure.

Specialized centers typically try somatostatin analogues for three days in an effort to decrease output in a fistula that produces >1 L/day. If the output decreases within those three days, the treatment is continued for a longer period of time [13,43].

Antisecretories — Proton pump inhibitors and histamine-2 receptor antagonists decrease the volume and acidity of gastric output and have been a part of standard drug treatment for high-output fistulas [13]. However, none of the acid reduction therapies have been shown to increase the rate of spontaneous fistula closure.

Cholestyramine — For the uncommon bilioenteric fistula (eg, biliary-colonic), cholestyramine can be tried. It is available in powder form and dosed at 9 mg twice daily prior to meals. Each of these medications can be used for the treatment of diarrhea, with anecdotal evidence of decreased fistula output. In addition, patients with a fistula proximal to the terminal ileum may find reduced output after the addition of cholestyramine.

NONOPERATIVE FISTULA CLOSURE — The following nonsurgical treatments have been attempted to close or better control fistulas that do not close spontaneously. These methods are generally appropriate after the patient has been stabilized from the acute phase of an enterocutaneous or enteroatmospheric fistula.

Endoscopic therapies — Endoscopic therapy may be used to temporarily control the initial leak and limit infection, or as a definitive technique to close the fistula. The ability to intervene endoscopically is limited by endoscopic accessibility, which is determined by the location of the fistula. Fistulas in the esophagus, stomach, or colon are most amenable to endoscopic closure. Endoscopic manipulation may transiently increase intraluminal pressure, which may increase the risk of sepsis acutely. Thus, endoscopic therapy should only be pursued in stable, nonseptic patients by experienced providers.

●Covered enteric stents have been used to treat early postoperative leaks of the colon and esophagus. Success rates vary by location, and a major concern of stenting is postplacement migration. When temporary stents were used to treat esophageal leaks, fistulas, and perforations, primary closure was achieved in 74 percent of patients, but stent migration rate occurred in 28 percent [63]. A study of 22 patients with colonic fistulas treated with stents noted a closure rate of 86 percent, but 69 percent of patients had diversion during the healing phase [64].

●Endoscopic clipping of the intraluminal end of the fistula has also been successful. Over- or through-the-scope clips can be deployed endoscopically to close the internal opening of the fistula, preventing further soilage and promoting sealing of the fistula. Data are limited, but the largest series of 108 patients demonstrated a fistula closure rate of 42.9 percent at a median follow-up of about five months [65]. This technology is primarily used for acute fistulas and postoperative perforations and is not well suited for chronic fistulas. Potential complications include increasing the size of the fistula and causing further damage to surrounding tissues.

●Fistula plugs can also be used to close the internal opening of the fistula. Plugs are generally made from porcine submucosa. Placement is also limited by endoscopic access, but case reports demonstrate success rates of up to 80 percent [66-68].

Fibrin sealant — Small series also demonstrated successful fistula closure with multiple applications of fibrin glue. Placement of fibrin glue reduced median time to closure and increased rate of closure when compared with control groups [69]. Several applications may be necessary to achieve closure, and success is limited by the ability to treat the entire tract prior to drying of the glue. Ideal fistulas for fibrin glue treatment are long, narrow, low output, and devoid of distal obstruction and Crohn disease.

OPERATIVE FISTULA CLOSURE — Approximately one-third of enterocutaneous fistulas will close spontaneously within five to six weeks with conservative measures [22-25]. In one retrospective review of 79 patients with enterocutaneous fistulas, spontaneous closure occurred in 23 (29 percent) after a median of 39 days (range 7 to 163) [70].

Predictors of spontaneous closure are given in the table (table 5) [34,71]. Generally, fistulas with low output, long track, or proximal location are most likely to heal with conservative measures. Barriers to closure include distal obstruction, a short epithelialized fistula tract, infection, and malignancy [21,71]. Given that an enteroatmospheric fistula is an exposed hole in the bowel lumen without overlying skin or soft tissue, there should be no realistic expectation of its spontaneous closure.

Timing of surgery — Patients with enterocutaneous fistulas that do not close with five to six weeks of nonoperative management are unlikely to heal spontaneously and will likely need surgery to definitively manage the fistula. In a review of patients with enterocutaneous fistulas, 90 percent of spontaneous closures occurred in the first month after resolution of sepsis and 10 percent during the second month [21]. No patients achieved spontaneous closure after two months [70].

Although the timing of definitive surgery to close the fistula is a matter of judgment, surgery should be delayed as long as fistula output is gradually decreasing and the wound (or tract) shows signs of healing [51]. Surgery should generally be postponed for at least three to six months to allow for resolution of inflammation, which may reduce the risk of bowel injury. Specialized centers often delay the definitive surgery for 6 to 12 months (algorithm 1).

The presence of a fistula is usually associated with a severe inflammatory response that leads to dense adhesions, known as "obliterative peritonitis," which make early surgery hazardous [34,72]. Dense adhesions begin to form in the open abdominal wound after approximately one week of exposure and remain treacherous for at least six to eight weeks. In one study, the mortality rate associated with surgery between days 11 and 42 after presentation of the fistula (21 percent) was significantly higher than the mortality rate of either operating before day 11 (13 percent) or after day 42 (11 percent) [34]. Recurrence rates of postoperative fistula also appear to be higher with earlier surgery [73].

Preoperative preparation — Before any definitive operative closure of an enterocutaneous fistula, the patient should be nutritionally replete, free of infection, and have supple, soft tissues adjacent to the fistula [10,74].

Nutritionally, data suggest that raising serum albumin level to >3.5 mg/dL reduces perioperative mortality rate to 0 percent [34]. Definitive surgical management of a fistula should also be delayed until the initial scar or incision is mobile and can be pinched between the examining thumb and index fingers, which signifies the existence of a plane between the skin/skin graft and underlying bowel [75].

Prior to surgery, abdominal computed tomography (CT) imaging should be repeated to rule out any residual intra-abdominal fluid collection or a distal obstruction and assess for evidence of Crohn disease, radiation enteritis, malignancy, or any other pathologies that could increase the likelihood of recurrence (table 5). Fluoroscopic exams, such as small bowel follow-through series and fistulograms, image contrast passage through the fistula in real time, which may help define the fistula anatomy. In addition, contrast injected retrograde through the fistula, drain, or rectum may help identify distal disease (eg, obstruction, stricture, or tumor) that will need to be addressed at the time of surgery. Endoscopic evaluation of the distal colon should also be considered prior to surgery. (See 'Diagnostic evaluation' above.)

Patients should also be mentally prepared for the surgery. They should be forewarned that the recurrence rate after surgery for enterocutaneous fistula can be as high as 20 to 36 percent [73] and that a diverting stoma may be required. Prior to surgery, the surgeon should mark potential stoma sites, particularly in patients with Crohn disease or diverticular disease, and consider placing ureteral stents if colon mobilization is anticipated. (See "Overview of surgical ostomy for fecal diversion", section on 'Preparation and counseling' and "Placement and management of indwelling ureteral stents", section on 'Prophylactic'.)

Surgical techniques — The aim of the surgery is to eliminate the fistula, which usually requires resection of the segment of bowel that is the origin of the fistula, reestablishment of gastrointestinal continuity, and tension-free closure of the abdomen with well-vascularized soft tissue [10]. Fecal diversion and bowel rest during the postoperative healing period can be used to minimize recurrence.

Since studies evaluating surgical techniques for managing enterocutaneous fistulas are generally heterogeneous and of low quality [76], the surgical approach described below is derived from expert opinions and our clinical experience.

Incision and adhesiolysis — For patients with an intact abdominal wall, the incision should be placed remote from prior incisions where bowel loops may be adherent to the abdominal wall. The incision should also preserve vascular supply to the soft tissue of the abdominal wall, which is critical to any successful complex abdominal wall reconstruction (eg, component separation).

Once the incision is made, lysis of adhesions is performed to free the abdominal wall circumferentially from adherent bowel. Expert surgeons recommend working laterally first to take down adhesions and deliver the bowel from the side of the abdomen least involved [7,77]. The adhesions are often dense, and the dissection should be slow and careful. The surgeon must be prepared to spend hours performing meticulous adhesiolysis and mobilizing the entire length of the gastrointestinal tract from the ligament of Treitz to the rectum, if necessary, to identify the fistula and approach it safely [10]. It is usually not advisable to schedule other major elective operations on the same day, because these demanding procedures often take all day.

During the surgery, the surgeon should identify normal areas of small bowel that are free from injury and primary disease where the fistula and any other pathology are found. In addition, there may be segments of bowel where serosal injuries or small iatrogenic full-thickness injury occurred during adhesiolysis. Each of these areas should be evaluated before decisions can be made about resection or repair based on the available bowel reserve. Issues with malabsorption and short bowel syndrome may occur with less than 100 cm of viable small bowel remaining, depending on whether the ileocecal valve is present and the remaining length of the colon. (See "Management of short bowel syndrome in adults".)

Fistula resection — Once the fistula and primary pathology (ie, source of infection/obstruction) have been clearly defined, the segment of bowel that contains the origin of the fistula is resected and gastrointestinal continuity reestablished. (See "Bowel resection techniques".)

We suggest a segmental resection of the bowel containing the fistula, rather than a wedge resection of the fistula. In a large series of patients with fistulas, patients who underwent segmental resection of the primary disease had a significantly lower rate of fistula recurrence than patients who had wedge resection (18 versus 33 percent) [73]. For patients with Crohn disease, complete resection of the enterocutaneous fistula, as well as the adjacent diseased bowel, is necessary to prevent recurrence [73].

Abdominal wall closure or reconstruction — Once an enterocutaneous fistula is resected and gastrointestinal continuity restored, the abdomen should be closed using standard techniques, provided this will not result in undue tension. (See "Principles of abdominal wall closure".)

The goal of the definitive surgery in the management of enteroatmospheric fistulas, besides closing the fistula, is to reconstruct the abdominal wall with durable, well-vascularized tissue. A two-team approach has the advantage of providing a well-rested plastic surgeon focused on reconstruction after a long and tedious visceral dissection by the general surgery team [10]. Closure of large or complex abdominal wall defects associated with enteroatmospheric fistulas may require advancement flap techniques. One option for abdominal closure is the component separation technique, provided the rectus abdominis muscle remains intact [78]. Defects up to 10 cm in the upper abdomen, 20 cm in the midabdomen, and 8 cm in the lower abdomen can be closed using this technique. Other options may include random, pedicle, or free flaps with microvascular reconstruction. (See "Overview of abdominal wall hernias in adults" and "Overview of component separation".)

MORTALITY — Historically, mortality rates after developing an enterocutaneous fistula were as high as 65 percent in some series. Sepsis is responsible for 70 percent of case fatalities [13]. However, specialized care centers have been able to reduce morbidity and mortality greatly. With modern management strategies, most modern series report a mortality rate of 10 to 20 percent (table 6) [7,10,13,19,59,70,79].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Enteric fistula (The Basics)")

SUMMARY AND RECOMMENDATIONS

●A fistula is an abnormal connection between two epithelialized hollow spaces or organs. Enterocutaneous fistulas communicate between the lumen of the gastrointestinal tract and the skin. Enteroatmospheric fistulas communicate between the lumen of the gastrointestinal tract and the wound of an open abdomen. (See 'Introduction' above.)

●The majority of enterocutaneous fistulas occur in the postoperative setting, usually as a result of a bowel anastomotic leak or missed enterotomy. Approximately 20 to 30 percent of enterocutaneous fistulas arise spontaneously, most commonly due to Crohn disease. Other etiologies of spontaneous enteric fistula formation and persistence include foreign body, radiation, inflammation or infection (eg, tuberculosis, actinomycosis), epithelialization, neoplasia, and distal obstruction (table 1). (See 'Etiology and risk factors' above.)

●The most common clinical presentation of an enterocutaneous fistula is in a postoperative patient who fails to recover normally from abdominal surgery. The patient often presents first with abdominal symptoms and signs of bowel obstruction. A wound infection is then typically recognized 7 to 10 days postoperatively, and following incisional drainage, enteric contents appear in the surgical wound. (See 'Clinical features' above.)

●By definition, an enteroatmospheric fistula can only be diagnosed in a patient with an open abdomen. The diagnosis can be confirmed by the presence of enteric contents draining from an opening in a segment of bowel in the open abdominal wound. (See 'Diagnosis' above.)

●The organ of origin of an enterocutaneous or enteroatmospheric fistula is often not defined until imaging studies can be performed. We prefer abdominal computed tomography (CT) as the initial study for patients suspected to have an enterocutaneous or enteroatmospheric fistula, but only after the patient has been stabilized and sepsis treated. Other methods of identifying and characterizing enteric fistulas include gastrointestinal contrast studies, a fistulogram, and enteric administration of dye (eg, indigo carmine, methylene blue, charcoal). (See 'Diagnostic evaluation' above.)

●Acute management of enterocutaneous and enteroatmospheric fistulas focuses on fluid therapy to correct volume and electrolyte deficits and treatment of infection/sepsis (algorithm 1). In this acute phase, the etiology of the fistula is often not important. Fistula-associated abdominal sepsis (eg, intra-abdominal abscess, gastrointestinal perforation, or subcutaneous infection) needs to be recognized and promptly treated with antibiotics, percutaneous catheter drainage, and/or operative drainage or source control. However, we suggest against routine antibiotic coverage for patients with a nonseptic enterocutaneous or enteroatmospheric fistula (Grade 2C). (See 'Acute management' above.)

●Chronic management of enterocutaneous and enteroatmospheric fistulas entails evaluation and treatment of fluid, electrolyte, and nutritional losses, and specialized wound care to manage the intestinal effluent (table 2 and algorithm 1).

•Patients with low- and high-output fistulas have different caloric and nutritional goals. (See 'Nutritional goals' above.)

•For patients with a low-output fistula (<200 mL/day), a trial of bowel rest for several days after initial fluid and electrolyte resuscitation (table 3) and sepsis control may lead to spontaneous closure of the fistula. (See 'Low-output fistulas (<200 mL/day)' above.)

•For patients with a low-output fistula that does not close with bowel rest, oral diet should be started. If the fistula output increases with oral diet, and for patients with a moderate- or high-output fistula (>200 mL/day), medical therapies to reduce fistula output may be instituted with the goal of limiting output to <1.5 L/day. Choices of such medications include anticathartics, somatostatins and analogues, antisecretories, and cholestyramine (table 4). (See 'Fistula output reduction' above.)

•For patients with fistula output >1.5 L/day, less than 75 cm of intestinal length prior to the fistula, or intestinal discontinuity, total parenteral nutrition is required, either exclusively or to supplemental enteral nutrition. (See 'Moderate- or high-output fistulas (>200 mL/day)' above.)

●Approximately one-third of fistulas heal spontaneously with conservative measures within five to six weeks. For patients with a persistent enterocutaneous or enteroatmospheric fistula, definitive surgical fistula closure is required but should be delayed for at least three to six months from the inciting event. High-volume centers often delay definitive operations for 6 to 12 months (algorithm 1). Before consideration of definitive operative repair of fistulas, patients should be nutritionally replete, free of infection, and have supple soft tissues adjacent to the fistula. (See 'Operative fistula closure' above.)

●The goals of definitive surgery are to resect the fistula, reestablish gastrointestinal continuity, and provide a tension-free closure of the abdomen with well-vascularized soft tissue. We suggest a segmental resection of the bowel containing the fistula, rather than a wedge resection of the fistula (Grade 2C). Segmental bowel resection is associated with a lower recurrence rate. (See 'Surgical techniques' above and 'Fistula resection' above.)

●Modern care of enterocutaneous/enteroatmospheric fistulas, often provided at specialized centers, has reduced the mortality rate from 65 percent to 10 to 20 percent. (See 'Mortality' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge William Schecter, MD, who contributed to an earlier version of this topic review.