Int J Colorectal Dis (2014) 29:775–781 DOI 10.1007/s00384-014-1900-4

REVIEW

Systematic review: outpatient management of acute uncomplicated diverticulitis J. D. Jackson & T. Hammond

Accepted: 2 May 2014 / Published online: 25 May 2014 # Springer-Verlag Berlin Heidelberg 2014

Abstract Purpose of review Acute uncomplicated diverticulitis is traditionally managed by inpatient admission for bowel rest, intravenous fluids and intravenous antibiotics. In recent years, an increasing number of publications have sought to determine whether care might instead be conducted in the community, with earlier enteral feeding and oral antibiotics. This systematic review evaluates the safety and efficacy of such an ambulatory approach. Methods Medline, Embase and Cochrane Library databases were searched. All peer-reviewed studies that investigated the role of ambulatory treatment protocols for acute uncomplicated diverticulitis, either directly or indirectly, were eligible for inclusion. Results Nine studies were identified as being suitable for inclusion, including one randomised controlled trial, seven prospective cohort studies and one retrospective cohort study. All, except one, employed imaging as part of their diagnostic criteria. There was inconsistency between studies with regards to whether patients with significant co-morbidities were eligible for ambulatory care and whether bowel rest therapy was employed. Neither of these variables influenced outcome. Across all studies, 403 out of a total of 415 (97 %) participants

In relation to the above systematic review, each author made equal contribution to the study conception and design, acquisition of data, analysis and interpretation of data and writing of the manuscript. J. D. Jackson Barts and The London School of Medicine and Dentistry, London, UK J. D. Jackson (*) Manly Hospital, Darley Road, Manly, Sydney, NSW 1655, Australia e-mail: [email protected] T. Hammond Broomfield Hospital, Chelmsford, Essex, UK

were successfully treated for an episode of acute uncomplicated diverticulitis using an outpatient-type approach. Cost savings ranged from 35.0 to 83.0 %. Conclusion Current evidence suggests that a more progressive, ambulatory-based approach to the majority of cases of acute uncomplicated diverticulitis is justified. Based on this evidence, the authors present a possible outpatient-based treatment algorithm. An appropriately powered randomised controlled trial is now required to determine its safety and efficacy compared to traditional inpatient management. Keywords Diverticular . Diverticulitis . Management . Uncomplicated . Outpatient . Ambulatory

Introduction Diverticular disease is extremely common, affecting at least 50 % of the Western population by their ninth decade [1–4]. The most frequent complication of diverticular disease is acute diverticulitis. It affects up to one fifth of patients with the disease during the course of their lifetime [5–7]. Acute diverticulitis is typically classified as either complicated or uncomplicated. Uncomplicated disease refers to inflammation confined to the bowel wall and/or pericolonic fat, whilst the former is associated with abscesses, fistulae, intestinal obstruction and perforation [8]. Complicated disease may require surgical or radiologically guided intervention. The majority of patients, however, present with uncomplicated disease and can be managed conservatively [9–11]. Most research into acute diverticulitis has concentrated on identifying parameters for surgical intervention. This has resulted in a paucity of data addressing the optimal management of uncomplicated disease. The traditional approach of inpatient admission for bowel rest, intravenous fluids and intravenous antibiotics is not evidence-based [12, 13]. This

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management strategy imposes a considerable clinical and financial burden on health care providers. For instance, in 2011–2012, uncomplicated diverticular disease of the large intestine accounted for 87,202 patient admissions in England alone [14]. The mean length of hospital stay was 5.6 days. At a daily bed cost of £225 [15], this amounts to an annual cost of over £100 million in one country alone. Over the past 10 years, an increasing number of publications have sought to determine whether acute uncomplicated diverticulitis (AUD) can be managed in the community. The aim of this systematic review is to assess whether ambulatory treatment protocols are safe and effective.

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requiring readmission and/or conversion to traditional diverticulitis inpatient care within the time period specified by the individual study. Data collection Each reviewer independently recorded data on a specifically formatted Excel spreadsheet. The data sought from each study included the following: type of study; selection criteria of trial participants; imaging modality, if any, used to confirm diagnosis and grade severity; nature of intervention, including type, form and duration of antibiotic therapy, and use of any bowel rest or dietary advice; measures and rates of success; and methods and duration of follow-up.

Methods Data analysis This review was written according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines [16]. Search strategy Two reviewers independently searched the Medline, Embase and Cochrane Library databases. Search strategies were as follows: Medline and Embase—search terms ‘diverticulitis’ (all fields) AND ‘outpatient’ (all fields), ‘diverticulitis’ (all fields) AND ‘out-patient’ (all fields), and ‘diverticulitis’ (all fields) AND ‘home’ (all fields); Cochrane Library—search terms ‘diverticulitis’ (title, abstract or keyword) AND ‘outpatient’ (title, abstract or keyword), ‘diverticulitis’ (title, abstract or keyword) AND ‘out-patient’ (title, abstract or keyword), and ‘diverticulitis’ (title, abstract or keyword) AND ‘home’ (title, abstract or keyword). No date range was imposed on any search. The last search was performed on 9 April 2013. Based on their titles, the abstracts of potentially relevant studies were consulted to identify studies suitable for inclusion in the review. The full texts of all potentially eligible articles were then retrieved. The references sections of all included studies were also consulted to ensure that no potentially eligible studies were omitted. No language restrictions were imposed. No unpublished data or abstracts were included.

The data from all of the studies was combined to generate an overall measure of primary outcome success. The risk of bias in individual studies was evaluated by scoring the various potential sources of bias as low, high or unclear [17]. Disagreement was resolved by discussion between the two authors.

Results Using the above search criteria, nine articles were identified as being suitable for inclusion. The applied search strategy is illustrated in Fig. 1, and a summary of all included studies is shown in Table 1. The authors graded the significance of the evidence presented in each study according to the Oxford Centre for EvidenceBased Medicine classification [26]. There was a high risk of selection, performance and detection bias in all studies (see Fig. 2). The articles employed a range of methodologies: one RCT [18], seven prospective cohort studies [8, 19–24] and one retrospective cohort study [25]. Both the RCT [18] and the retrospective cohort study [25] measured the efficiency of treatment protocols that, although trialled in the inpatient setting, could easily be translated to the outpatient setting. The authors determined that although these protocols are yet to be proven in an ambulatory setting, they are of sufficient interest to be included in this review.

Selection criteria Diagnosis and severity staging Using the above search strategy, all peer-reviewed studies that investigated the role of outpatient treatment protocols for AUD, either directly or indirectly, were considered eligible for inclusion. The primary outcome measure was the success rate of outpatient, or oral inpatient, treatment. Success was defined as not

All studies, except one [18], employed imaging as part of their selection criteria. One study primarily utilised ultrasound (US) [23], reserving computer tomography (CT) for those patients in whom US image resolution was poor (i.e. due to obesity or intestinal gas). The

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Fig. 1 Search strategy

remaining studies used CT as their primary imaging tool [8, 19–22, 24, 25]. For all those studies that employed either CT or US, the presence of colonic diverticulum with bowel wall thickening and/or pericolic fat stranding was a prerequisite for diagnosing AUD [8, 19–25]. Patients were excluded from participation if imaging demonstrated free perforation, colonic obstruction or an abscess/phlegmon ≥3 cm. In three of the studies, an abscess less than either 2 [23] or 3 cm [19, 21], was regarded as sufficiently small to still consider patients for outpatient care. In these studies, patient readmission rates did not differ from the rates demonstrated in studies that excluded patients with any evidence of abscess, regardless of size [8, 20, 22, 24, 25]. One study did not employ any imaging modality to confirm the diagnosis of diverticulitis [18]. This was done in order to replicate the decision-making and treatment process necessitated in some community hospitals and in general practice surgeries.

intake [8, 22, 24]; signs of severe sepsis [24]; comorbidities including diabetes mellitus, heart failure, renal failure, end-stage cancer and chronic obstructive pulmonary disease [8, 22, 23]; patients with a compromised immune status [20, 21, 24]; inability to understand dietary restrictions or to self-care [22]; lack of adequate family or social support [8, 19, 21, 24]; and preference not to pursue home treatment [20]. Only three studies specifically excluded patients with chronic co-morbidities from outpatient-type care [8, 22, 23]. One study employed a Hospital at Home policy [20]. This involved daily nurse visits to patients’ homes and physician visits two to three times per week. Using this approach, 24 patients with AUD and concurrent cardiac disease, chronic renal failure or diabetes were successfully managed in the community. There were no treatment failures.

Treatment protocol and follow-up Suitability for outpatient management Across all studies, the non-radiological exclusion criteria employed included the folowing: age over 80 [23] or 90 years [24]; vomiting or inability to tolerate oral

The commonest antibiotic regimens employed were either metronidazole [8, 18, 19, 21, 22, 24, 25] and a cephalosporin (i.e. ciprofloxacin [8, 18, 19, 21, 22, 24, 25] or cefpodoxime [23]), or co-amoxiclav [8, 22, 25]. In their Hospital at Home policy, Rodriguez-Cerrillo

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Table 1 Summary of included studies Author Reference

Year of Study design publication (level of evidence)

Management protocol

Alonso et al. [8]

2010

7 days PO abx, step-wise progression to regular diet

Ridgway et al. [18]

2009

Park et al. [19]

2011

Rodríguez-Cerrillo 2010 et al. [20] Martín Gil et al. [21] 2009

Peláez et al. [22]

2006

Mizuki et al. [23]

2005

Moya at al. [24]

2012

Al-Sahaf et al. [25]

2008

Prospective cohort (3)

Results

70 patients 68 patients treated without complication 2 patients required admission Randomised controlled PO group—PO abx, nil dietary restrictions PO group—41 patients, nil treatment failures trial (2) IV group—IV abx, IV fluids only on the IV group—38 patients, nil treatment failures first 24 h Prospective cohort (3) PO group—4 days PO abx, nil dietary PO group—40 patients, nil treatment failures restrictions IV group—63 patients, nil treatment failures IV group—7–10 days IVabx, initial bowel rest Prospective cohort (3) Initial home IV abx, conversion PO abx 24 patients, nil treatment failures when clinical condition improved Prospective cohort (3) 7–10 days PO abx 74 patients, 70 patients treated without Liquid diet only on the first 3 days complication 4 patients required admission Prospective cohort (3) 7 days PO abx 40 patients, 38 patients treated without Clear liquid diet only on the first 2 days complication 2 patients required readmission Prospective cohort (3) 10 days PO abx 70 patients Sports drink first 3 days 68 patients treated without complication 2 patients required hospitalization Prospective cohort (3) PO group—PO abx, immediate liquid diet PO group—30 patients treated without IV group—IV abx for at least 5 days, IV complication, 2 patients required fluids only on the first 48 h admission IV group—44 patients, nil treatment failures Retrospective cohort (3) IV abx first 24 h, then conversion PO abx 26 patients, nil treatment failures to complete 10-day course Step-wise progression to regular diet

PO per os, abx antibiotics, IV intravenous

Reporting

bias

Attrition bias

Detection

bias

Performance

bias

Alonso et al. 8 Ridgway et al. 19 Park et al. 20 Rodríguez-Cerrillo et al. 21 Martín Gil et al. 22 Peláez et al. 23 Mizuki et al. 24 Moya et al. 25 Al-Sahaf et al. 26

Selection

Author Reference

bias

Fig. 2 Author evaluation of the various sources of potential bias for all included studies. Red high risk, green low risk. Risk evaluated on a study by study basis with reference to Cochrane Collaboration Guidance [17]

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Fig. 3 Treatment algorithm for outpatient care of acute uncomplicated diverticulitis

Clinical diagnosis acute diverticulitis

Stat dose broad spectrum intra-venous antibiotics according to hospital policy for intra-abdominal sepsis

Contrast tomography or ultrasound abdomen pelvis (depending on local expertise)

Colonic diverticular disease confirmed - no evidence complicated disease*

Colonic diverticular disease confirmed - evidence complicated disease** or Likely alternative diagnosis

No Is patient suitable for outpatient management?***

Admit and treat as per local hospital policy

Yes

Discharge home with advice to return to A&E promptly if clinical condition deteriorates Patient given contact number for nurse specialist advice Clinician discretion as to whether or not to prescribe oral broad spectrum antibiotics No dietary restrictions GP or district nurse to review patient at 7 days Colonoscopy at 4-6 weeks with subsequent outpatient clinic review

* Features of acute uncomplicated diverticulitis include inflammation confined to the bowel wall and/or pericolonic fat; ** complicated disease is associated with abscesses, fistulae, intestinal obstruction and/or perforation; *** patients not suitable for outpatient management include patients who: are vomiting/unable to tolerate oral intake; have significant co-morbidities including insulin dependent diabetes mellitus; are on immunosuppressive medication; are unable to self-care; have a lack of adequate family or social support; find home-treatment unacceptable.

et al. [20] initially treated patients with intravenous ertapenem or piperacillin/tazobactam, subsequently converting patients to oral fluoroquinolone and metronidazole. Once the diagnosis of AUD was established, some protocols allowed for patients to be discharged immediately on oral antibiotics, restricting patients to a liquid diet for up to 10 days [8, 22–24]. Other protocols kept patients under observation for 24 h, during which time they were fasted and given intravenous fluids and antibiotics [21, 25]. This was done to ensure no clinical deterioration occurred prior to discharge. Provided they remained well, patients were then discharged on oral antibiotics, with instructions to remain on a liquid or low residue diet for up to 72 h. One group arranged for nurses to administer intravenous antibiotics at home until the patients’ clinical condition improved [20]. In

their RCT, Ridgway et al. [18] randomized patients to receive either intravenous antibiotics and bowel rest or oral antibiotics and no dietary restrictions. The primary outcome measure was success of treatment based on resolution of symptoms; no advantage was demonstrated with the former approach. Antibiotics were generally prescribed for 7–10 days. One study [19] compared an outpatient regimen of 4 days of oral antibiotics and no dietary restrictions with an inpatient regimen of 7–10 days of intravenous antibiotics and bowel rest. No patient in the outpatient treatment arm required readmission, and 95 % (38 of 40) of the patients’ symptoms resolved within 4 days. In the majority of studies, patients were initially followed up in an outpatient clinic, 4–10 days after discharge [8, 19–23]. In only one study was this support provided by the patient’s general practitioner (GP)

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[25]. In seven of the nine studies, a follow-up colonoscopy, CT colonoscopy or barium enema was performed at least 1 month after the acute episode to exclude alternative diagnoses such as colonic carcinoma [8, 18, 19, 21, 22, 24, 25]. Success rates and economics By pooling the results of the included studies, 403 out of a total of 415 (97 %) participants were successfully treated for an episode of acute uncomplicated diverticulitis using treatment protocols that were either primarily based in the community or could be very easily transferred to the community. A median number of two patients per study, within a range of 0–4, were readmitted or converted to traditional inpatient care. The reasons included persistent abdominal tenderness, vomiting, fever, and family refusal to continue outpatient treatment. Four studies [19, 21, 23, 24] addressed the cost benefit of outpatient management and, unsurprisingly, all showed an advantage over inpatient care. Cost savings ranged from 35.0 to 83.0 %.

Discussion This systematic review has shown that the majority of patients with AUD can be safely and effectively managed in the community. The economic benefits of such an approach were also demonstrated. There are, however, limitations to this review. There was a high risk of bias across all studies. All studies, except one RCT, were only of level III evidence, being either retrospective or prospective cohort studies. There was significant heterogeneity across studies in relation to selection criteria (radiological and non-radiological) and management protocols. In keeping with the recommendations of the Association of Coloproctology of Great Britain and Ireland (ACPGBI) [27], most of the studies employed imaging, either CT or US, as part of their selection process. Imaging is recommended because both uncomplicated and complicated diverticulitis present with a variable combination of vague, non-specific symptoms and signs, including pain, vomiting, bowel disturbance, per-rectal bleeding, nausea and/or fever. Biochemical variables are equally non-specific. For instance, a recent retrospective cohort study of 426 patients found that white blood cell count and body temperature were of no value in discriminating between patients with complicated and uncomplicated diverticulitis, and that whilst a markedly elevated C-reactive protein (CRP) was

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suggestive of complicated disease, a low CRP could not exclude complicated disease [28]. Imaging is therefore essential to confirm the clinically suspected diagnosis, stage disease severity and exclude alternative pathologies such as appendicitis. The American Society of Colon and Rectal Surgeons (ASCRS) [3] and the World Gastroenterology Organisation (WGO) [29] offer expert opinion on the clinical parameters that should be considered when considering patients for ambulatory care. The ASCRS state that patients should not have significant fever, excessive vomiting or marked peritonitis, and should have the opportunity for follow-up [3], whilst the WGO advise that only those patients with mild abdominal pain or tenderness and no systemic symptoms should be considered possible candidates [29]. Most studies included in this review did not specifically exclude patients with significant co-morbidities, but the likely effect of pre-selection bias has already been highlighted. In their retrospective analysis of 693 patients treated for AUD in the community, Etzioni et al. [30] found that patients with a high co-morbidity index (Charlson score ≥2) were not at increased risk of readmission compared to patients without significant comorbidities. Again however, given that only the healthiest patients were likely to have been considered for outpatient treatment, one cannot extrapolate this result to the general population. All included studies used antibiotics as part of their treatment protocols. However, a recent multicentre RCT conducted across 11 Scandinavian centres compared outcome in patients with CT-verified AUD treated with or without antibiotics [31]. Use of antibiotics failed to demonstrate any statistically significant benefits. This result is in keeping with the findings of an earlier, much smaller retrospective study [32]. It is hoped that the results of another RCT currently underway in the Netherlands, again designed to evaluate the role of antibiotics in AUD, will provide further clarification on this subject [33]. It would also seem that dietary restrictions are not only of little benefit to the patient but may prolong the time to recovery [34]. Across all studies, so few patients required any change to their package of care that the benefit of early clinic review is questionable, and perhaps indicates that GP or nurse-led telephone follow-up may be more practical [35]. Providing patients with a contact telephone number should their symptoms worsen is an intuitively important measure but one that was reported in only a single study [20]. In the longer term, the majority of studies performed follow-up colonoscopy, CT colonoscopy or barium enema. This is considered mandatory by both the ASCRS [3] and the ACPGBI [27] to exclude an underlying colonic carcinoma.

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In conclusion, current evidence suggests that a more progressive, ambulatory-based approach to the majority of cases of AUD is justified. An outpatient-based treatment algorithm is presented in Fig. 3; an appropriately powered randomised controlled trial is now required to determine its safety and efficacy compared with traditional inpatient management.

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18.

19.

20. Conflict of interest This systematic review has been written according to the standards laid down in the 1964 Declaration of Helsinki and its later amendments. The authors declare that they have no conflict of interest. 21.

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Systematic review: outpatient management of acute uncomplicated diverticulitis.

Acute uncomplicated diverticulitis is traditionally managed by inpatient admission for bowel rest, intravenous fluids and intravenous antibiotics. In ...
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