Strategies in the Management of Fulminant Clostridium difficile Colitis

Classification

Definition

Non-severe

WBC <15 and Cr <1.5

Severe

WBC ≥15 and/or Cr ≥1.5

Fulminant

Hypotension, shock, ileus, megacolon

Data from: McDonald et al. [8]

Given the poor outcomes with current medical and surgical approaches to fulminant CDI, alternate treatment approaches have been explored. In this chapter, we will explore organ-preserving strategies in the management of fulminant CDI.

Currently, the standard of care for FCDC is timely TAC with end ileostomy. However, despite this early intervention, mortality rates remain high ranging from 35% to 57% [16, 18, 22, 23]; thus TAC for FCDC is usually reserved as a measure of last resort for many patients. This is in part due to the absence of absolute indications for surgery such as the rare events of colonic ischemia and perforation and the lack of clear guidelines on the optimal timing of surgical intervention for FCDC. Furthermore, patients who survive a TAC for FCDC often face a difficult and prolonged recovery, with significant morbidity [17]. Moreover, the majority of patients are left with a permanent ileostomy, as is demonstrated by the low gastrointestinal restoration rates following TAC for FCDC in the literature [17, 24].

However, in spite of the high mortality and morbidity associated with TAC, many studies have reported improved mortality for patients with FCDC who underwent early operative intervention [16, 19, 25]. Even though these studies were limited by retrospective designs, a recent systematic review confirmed that this procedure still provides a survival advantage compared to medical management alone [7].

Furthermore, a recent study by Stokes and coauthors reported a significantly decreased mortality in patients with CDI admitted under the care of gastrointestinal surgeons compared to patients admitted under general medical services [26]. Sailhamer and coauthors similarly reported a decreased mortality rate in patients admitted under the care of the surgical department compared to medical departments, with a shorter time from admission to operation and a trend toward a higher rate of operation [18]. These data show that timely surgical intervention improves survival as it prevents the development of multi-organ system failure.

Operative Interventions

Loop Ileostomy and Colonic Lavage

Indications and Contraindications

Loop ileostomy and colonic lavage for FCDC involve the creation of a loop ileostomy, an intraoperative colonic lavage with warmed polyethylene glycol (PEG) via the ileostomy, and postoperative antegrade instillation of vancomycin flushes into the diseased colon via the ileostomy (Fig. 35.1a, b) [27]. First described by Neal and coauthors in 2011, this single institution, single surgeon series compared 42 patients who underwent loop ileostomy and colonic lavage for FCDC with 42 historical patients who had undergone a TAC. Indications for operative management included a diagnosis of CDI either by endoscopy, toxin assay, or evidence of colitis on imaging with any sign of clinical worsening. These included signs of peritonitis, worsening abdominal distention, sepsis, new onset ventilator requirement, new or increasing vasopressor requirement, altered mental status, unexplained change in clinical status, non-improving leukocytosis, or bandemia, despite appropriate antibiotic therapy.

../images/465809_1_En_35_Chapter/465809_1_En_35_Fig1_HTML.png — Fig. 35.1

(a) Schematic illustration of loop ileostomy with lavage technique (a: Used with permission of Wolters Kluwer Health, Inc., from Neal et al. [27]). (b) Securing the Foley catheter. The Foley can be secured to the ileostomy appliance as shown here. Alternatively, it can be secured to the rod, or a tie around the catheter can be left long and held in place by the stoma bag

Absolute contraindications for loop ileostomy and colonic lavage include the rare situations of FCDC presenting with colonic perforation or ischemia. In addition, patients with toxic megacolon may not tolerate the lavage required for this procedure.

Principles and Quality Benchmarks of the Approach

The primary endpoint was resolution of clinical signs associated with CDI and normalization of peripheral leukocyte count. Both the historical TAC and experimental groups were comparably critically ill as evidenced by similarities in their APACHE-II scores, white blood cell counts, intensive care unit admission, preoperative intubation, need for vasopressors, and pharmacologic immunosuppression. The authors found that all patients achieved resolution of disease, with a significant reduction in the 30-day mortality in the loop ileostomy group compared to the historical control group who underwent a TAC (19% vs 50%, respectively; p = 0.006). In addition to the survival benefit, there was an increase in ileostomy reversal rates (reported at 79% at 6 months), which is considerably higher than the reported 20% rate of gastrointestinal restoration rates following TAC [24]. The authors were also able to perform the lavage laparoscopically in the majority of patients (83%). In their series, one patient required immediate conversion to TAC due to persistent abdominal compartment syndrome (ACS) that was not improved with the lavage, and one patient developed ACS 12 hours after the lavage and required conversion to TAC. In their series of 42 patients, only one patient had recurrent vasopressor requirement 12 days after surgery and required conversion to a TAC. Thus, in a minority of patients who undergo a lavage, a second surgery may be necessary. The authors’ hypotheses for the success of the lavage were that a diverting loop ileostomy poses minimal surgical stress for the critically ill patient and that since the fecal stream is diverted and the colonic lumen deprived of nutrition, mechanical lavage and local vancomycin delivery would result in successful removal of the bacteria and toxin.

Operative Technique

Exploratory laparotomy or diagnostic laparoscopy is carried out first to confirm the diagnosis and ensure that there is no colonic necrosis or perforation. A laparoscopic approach is preferable if the patient is a good candidate and if the surgeon is comfortable with the procedure; otherwise it can be undertaken using an open approach.

The second step involves the creation of a loop ileostomy. The loop ileostomy is ideally created 20 cm from the ileocecal valve so that an 18Fr Foley catheter, inserted into the distal limb of the ileostomy, can be positioned in the cecum. The Foley should be secured to the ileostomy at the end of the procedure using a 0-silk suture (Fig. 35.1b). Lavage of the colon is then performed with 8 liters of polyethylene glycol (PEG) solution warmed to 37 °C. The colonic lavage is performed with the use of the Foley catheter connected to a bag with the PEG solution using urological connection tubing, similar to the one used in cystoscopy. A rectal tube or management device should be inserted into the rectum and attached to a large drainage bag until the lavage is complete. The PEG solution is administered in increments, liter by liter, ensuring that effluent drainage is collected in the rectal tube. If the procedure is performed laparoscopically, pneumoperitoneum can be maintained at 7–10 mmHg during lavage. Laparoscopic bowel graspers may be used to aid in pushing the fluid along the colon. If performed by a laparotomy, the abdomen is kept open, and the surgeon can manually aid the movement of the fluid through the colon. If trouble is encountered getting fluid through the colon, the patient may be moved into the Trendelenburg/reverse Trendelenburg positions as well as left side up/down and right side up/down to move the fluid along the colon. Alternatively, though rarely required, the hepatic and/or splenic flexures may be mobilized. Due to fluid sequestration in the diseased and atonic colon, an ACS may occur during or after the operation. Although the authors do not recommend routinely monitoring for ACS, the surgeon should be aware of this possibility. The surgeon may choose to leave a drain in the paracolic gutters to drain excessive ascites and potentially reduce the risk of an ACS. Postoperatively, vancomycin flushes (500 mg in 500 mL of Lactated Ringers) are delivered to the diseased colon through the Foley catheter that was left in the efferent limb of the ileostomy. The first vancomycin flush is given after completion of the PEG flushes, and administration should be continued every 8 hours for 10 days or until the patient is clinically well .

Outcomes

Since earlier time to operation in patients with FCDC has been associated with faster recovery and better outcomes, the success of this procedure could be attributed to earlier time in surgical intervention. As such, this might encourage surgeons to intervene at the first signs of severe or complicated disease, using this minimally invasive procedure, rather than delaying to the point where a TAC is the last resort (Table 35.2) [28].

Table 35.2

Summary table comparing total abdominal colectomy vs. loop ileostomy and colonic lavage for fulminant Clostridium difficile colitis

Procedure	Pros	Cons
Loop ileostomy and colonic lavage	Minimally invasive option Apparent survival benefit Higher gastrointestinal restoration rates	Limited available data to support use, especially regarding recurrence rates May fail and some patients would require reoperation
Total abdominal colectomy	Definitive management, rare recurrence	High morbidity and mortality Low gastrointestinal restoration rates

Procedure

Pros

Cons

Loop ileostomy and colonic lavage

Minimally invasive option

Apparent survival benefit

Higher gastrointestinal restoration rates

Limited available data to support use, especially regarding recurrence rates

May fail and some patients would require reoperation

Total abdominal colectomy

Definitive management, rare recurrence

High morbidity and mortality

Low gastrointestinal restoration rates

Since the first description of this novel procedure, Ferrada and coauthors conducted the first multicenter study comparing TAC with loop ileostomy in the treatment of CDI [20]. This study retrospectively compared 77 patients who underwent TAC to 21 patients who underwent loop ileostomy and lavage for FCDC. The authors demonstrated that management of FCDC with loop ileostomy carried a significantly lower mortality rate than TAC (17.2% vs 39.7%). Further research is currently being undertaken in the form of a prospective national Canadian registry [29]. This registry will also collect information on strain of C. difficile to establish whether patients infected with some strains will be more likely to fail this minimally invasive operative management or suffer higher recurrence rates. Moreover, the registry will also allow for evaluation of the patient’s quality of life and documentation of long-term outcomes, including recurrence of CDI.

Turnbull-Blowhole Procedure

The Turnbull-Blowhole procedure was described as a less invasive option, compared to TAC, for critically ill patients with inflammatory bowel diseases. The procedure involves colonic decompression by a skin level colostomy and a loop ileostomy for toxic megacolon [30]. The goal of this operation is to divert the fecal stream and thereby deprive the colonic mucosa of nutrition without the stress of a radical operation.

In their publication in 1971, Turnbull and colleagues described a diverting loop ileostomy and a transverse colostomy (Fig. 35.1a, b). The authors recommended a sigmoid colostomy be created if the sigmoid remained significantly dilated. Although this procedure has been used by surgeons for cases of FCDC, evidence to support its use is lacking. The authors believe this procedure could be an alternative in severely ill patients in whom intestinal lavage may lead to colonic perforation .

Non-operative Interventions

Nasojejunal Lavage

Drawing from the success of the colonic lavage proposed by Neal and colleagues, some surgeons described the use of nasojejunal PEG irrigation as an alternative to surgical intervention. The authors consider this procedure an option for the management of early severe disease, albeit without entirely replacing loop ileostomy and colonic lavage or TAC. To date, the specific indication(s) for this intervention are not clear, and the outcomes of this method have not yet been determined. However, it is a possible alternative for patients who are not surgical candidates or who refuse surgery. A randomized trial of nasojejunal intestinal lavage for the treatment of C. difficile is underway and will provide evidence on this procedure as a potential early alternative to surgical intervention [31].

Fecal Microbiota Therapy (FMT)

Another non-operative approach for FCDC, fecal microbiota transplant (FMT), aims to recolonize the colon with normal intestinal flora. FMT was first introduced in the English language [technically first introduced in fourth century China] with a four person case series in 1958 [32]. Subsequently there have been numerous reports and randomized trials that show FMT is a successful and safe treatment for recurrent CDI [33–36].

Indications and Contraindications

Current guidelines from both gastrointestinal and infectious disease societies recommend using FMT after three recurrences of CDI [8, 37]. While there are no guidelines on the use of FMT in FCDC, several groups have recently reported successful treatment of severe and fulminant CDI with FMT with 1 month survival of 70–100% [38–42]. The exact timing of FMT in this disease process remains unknown, but Hocquart and colleagues showed that a single FMT performed 48 hours after severe CDI diagnosis was associated with significant mortality benefit at 3 months compared to standard-of-care (17% vs 69%, p < 0.0001) [42]. Based on the available data, FMT for FCDC should be considered in patients not responding to standard of care antibiotics for 48 hours. A multidisciplinary approach is paramount with these patients to coordinate plan of care. Patients with bowel perforation or evidence of colonic ischemia should not undergo FMT. Relative contraindications to performing FMT include patients with severe immunocompromised status, though recent case reports have shown FMT to be successful in these patients [43–45]. It is recommended not to pursue FMT in patients who are on concomitant non-CDI antibiotics for other conditions.

Principles and Quality Benchmarks of the Approach

Our current understanding of the disease pathogenesis is that a disruption in the host intestinal flora and metabolic pathways allows Clostridium difficile to proliferate and produce a diarrhea-causing toxin [46–48]. FMT is the process of transferring healthy stool containing colonic microbes and metabolic products from a healthy individual into a patient with disease. FMT has been shown to restore microbial diversity and richness as well as bile acid metabolism in patients with CDI, leading to clinical cure [49, 50].

Preoperative Planning, Patient Work-Up, and Optimization

A multidisciplinary approach should be used in these patients with input from infectious disease, surgery and gastroenterology services. Prior to FMT, potential donors undergo screening including laboratory testing as outlined by FMT Working Group [51]. In the cases of fulminant CDI, there is not enough time to screen donors. In these cases, stool should be easily available and accessible to be administered within 48 hours of patient presentation. The majority of practitioners now use frozen stool either from a local donor or from a stool bank, such as OpenBiome (Somerville, MA, USA). Standard-of-care antibiotics can be held for 6–12 hours before the procedure, though there is no consensus on this practice. Colonic bowel preparation with 4 L of PEG solution is recommended if there is no ileus or bowel obstruction, though there is no consensus on this practice.

Operative Setup and Technique

While FMT can be administered via upper or lower gastrointestinal (GI) tract, it is recommended to perform via lower GI tract with either flexible sigmoidoscopy or colonoscopy in these patients. FMT can be performed at bedside, operating room, or endoscopy suite.

Upper GI route includes delivery via nasogastric tube, nasoduodenal tube, push enteroscopy, percutaneous gastrostomy tube, and percutaneous jejunotomy tube. Lower GI delivery includes colonoscopy, flexible sigmoidoscopy, or enema. In patients with ileus, it is advisable to administer FMT via lower GI delivery. FMT via upper GI route should be administered at the most distal site and with a maximum of 100 cc of product. FMT via lower GI route should be administered at the most proximal extent of exam [terminal ileum or colon] with approximately 250 cc of product. While any of the above delivery mechanisms can be utilized with similar rates of efficacy [75–90%], for patients with fulminant CDI, it is recommended to perform via flexible sigmoidoscopy or colonoscopy in order to assess for pseudomembranous colitis. If pseudomembranes are visualized, vancomycin should be restarted within 24 hours (Fig. 35.2). Serial FMTs, using the above approach, are performed every 3–5 days until pseudomembranes are resolved (Fig. 35.3).