Laparoscopic Lavage for Perforated Diverticulitis With Purulent Peritonitis

Context Patients who have perforated diverticulitis with purulent peritonitis are frequently managed surgically with open colon resection, often together with formation of a stoma. Laparoscopic lavage has been proposed as an alternative surgical approach that might involve less morbidity, including a decreased need for additional operations. Contribution This randomized trial of patients who have perforated diverticulitis with purulent peritonitis found that laparoscopic lavage resulted in a decreased need for reoperations compared with open colon resection. Implication Laparoscopic lavage may be an option for the management of perforated diverticulitis with purulent peritonitis. Diverticulosis of the colon is a common condition in Western countries. The incidence increases with age to reach 34% to 56% of persons older than 70 years (1, 2). In the presence of diverticulosis, 15% to 25% also develop diverticulitis. This can be divided into uncomplicated and complicated disease in which complicated diverticulitis may require surgical intervention (35). Complicated diverticulitis is mostly classified according to the Hinchey grading system (grades I to IV) (6). In Hinchey grades III and IV, diverticular perforation into the abdominal cavity has resulted in purulent or fecal peritonitis, respectively. These conditions require emergency surgical intervention and are associated with high morbidity (25% to 75%) and mortality (2% to 30%) (710). Historically, the Hartmann procedure has been most commonly performed, which includes colon resection and colostomy; another option is resection of the affected part of the colon with primary anastomosis with or without diverting ileostomy (9, 11, 12). The strategy in both cases is to reverse the stoma in a second surgery, with subsequent risk for morbidity and mortality (13). Although stoma reversal is a scheduled surgical procedure, it must be considered as a consequence of the primary procedure and due to perforated diverticulitis. The other option is to avoid further surgery, which will leave the patient with a permanent stoma. Recent literature suggests that perforated diverticulitis with purulent peritonitis could be treated with a less invasive approach and reduce the risk for subsequent procedures. On the basis of prospective data, it was suggested in 2008 (14) that Hinchey grade III perforated diverticulitis could be managed by laparoscopic lavage alone, with reduced risk for morbidity and mortality. The potential benefits of laparoscopic lavage are suggested by case series or retrospective studies and 1 prospective study (15), but they are not substantiated in recently published results from 2 randomized trials (16, 17). In addition, there is 1 ongoing randomized trial (18). We previously published the protocol and short-term results of the present trial (19, 20). The hypothesis in this trial was that laparoscopic lavage as emergency treatment of perforated diverticulitis with purulent peritonitis could be a definitive treatment and would lead to fewer patients in need of further surgeries. The primary objective of this trial was to compare laparoscopic lavage and the Hartmann procedure with regard to the percentage of patients with 1 or more reoperations within 12 months. Secondary objectives included analysis of mortality, adverse events, length of hospital stay, and health-related quality of life. Methods Study Design This prospective, open-label, randomized, controlled trial compared laparoscopic lavage and the Hartmann procedure. Nine departments of surgery in Sweden and Denmark included patients from February 2010 until February 2014. The trial was approved by the Board of Ethical Approval in Gothenburg, Sweden (registration number 378-09) and the Danish ethical committee (protocol H-4-2009-088). A detailed description of the protocol has previously been published (19) and is available at www.ssorg. net. Patients We included patients who had suspected acute perforated diverticulitis and imaging showing intra-abdominal free air or fluid and were candidates for surgery (as judged by the surgeon). Those unfit for surgery or participating in conflicting trials were not included. Patients gave written informed consent. Those with other diagnoses, such as colorectal cancer found in the resected specimen or diagnosed at a later colon examination (which was part of the trial protocol), or those who withdrew their consent after being randomly assigned were not included in the per-protocol analysis of the primary outcome. A screening log was held, with monthly review of all patients discharged with a diagnosis of diverticulitis. Those who could be included but were not were recorded retrospectively. Randomization The on-call surgeon enrolled the participants in accordance to the inclusion criteria. The protocol did not require the surgeon to specialize in colorectal surgery. Diagnostic laparoscopy was performed. If Hinchey grade III perforated diverticulitis was found, patients were randomly assigned to either laparoscopic lavage (intervention) or the Hartmann procedure (control). Randomization was stratified by hospital in blocks of 10 with a 1:1 allocation ratio. The sequence was computer-generated by an independent statistician. Allocation was concealed to the staff by sequentially numbered, opaque, sealed envelopes. The circulating nurse in the operating room opened the envelope after the surgeon decided to randomly assign the patient to a group. Procedures In the intervention group, laparoscopic lavage was performed with saline at body temperature, 3 L or more, until clear fluid was returned. In the control group, colon resection and colostomy with open technique was performed (the Hartmann procedure). Both groups received a passive drain in the pelvis, which was left in place for at least 24 hours. The postoperative care was conducted according to local guidelines. All specimens removed during surgery in the Hartmann group had pathologic analysis. If a diagnosis other than diverticulitis was found, the patient was not included in the secondary analysis. Data were collected prospectively by health care professionals using clinical record forms at baseline, during the operation, for the postoperative period until discharge from the hospital, and at each follow-up (6 to 12 weeks, 6 months, and 12 months). Assessment at follow-ups included clinical examination, listing of adverse events, and readmissions or reoperations. Colon examination (colonoscopy or computed tomography colonography) was to be performed within 12 months to exclude other possible diagnoses. All patients were asked to complete the EuroQol 5-dimensional questionnaire (EuroQol-5D) containing generic (nonspecific) instruments at discharge and both the EuroQol-5D and Short Form-36 Health Survey (SF-36) (2123) at 6 and 12 months. The validated Swedish and Danish translations of the instruments were used (2426). EuroQol-5D allows for comparisons between patients with different diseases and representative normative populations and includes 5 dimensions of health (mobility, self-care, usual activities, pain or comfort, and anxiety or depression). The answering categories were no problems, low levels of problems, and severe problems. It also assesses global health from worst imaginable health state (score of 0) to best imaginable health state (score of 100) using a visual analogue scale. The questionnaire reflects the respondent's situation at the day of completion. The SF-36 is a generic instrument consisting of 8 sections and can be used to evaluate a patient's health status with a 14-day recall period. It was summarized into physical and mental component summary scores (27). Outcomes The primary outcome was the percentage of patients with 1 or more reoperations within 12 months. We defined the term 12-month follow-up used in the protocol as 12 months plus 30 days for practical reasons because all follow-up visits were not performed at exactly 12 months. Secondary outcomes were number of reoperations, hospital readmissions, total length of hospital stay during 12-month follow-up, postoperative adverse events, incisional hernia, bowel obstruction, mortality, persisting stoma at 12 months, and quality of life. Data on adverse events were collected prospectively in the clinical record forms, and before analysis, they were classified retrospectively according to ClavienDindo (28). This classification is based on the type of treatment required for the adverse event. Before classification, a decision was made to combine Hinchey grade I and II cases to reduce the risk for misclassification. Percutaneous drainage without general anesthesia was not registered as a reoperation but as an adverse event. Statistical Analysis In a retrospective study, 40% of patients who had the Hartmann procedure because of perforated diverticulitis had another operation at least once within 12 months after the index procedure (7). To detect a 75% reduction in the relative risk for the primary end point, 32 evaluable patients per group were required, assuming an annual incidence of 40% in the control group with 80% power using a 2-sided chi-square test at the 5% significance level. A statistical analysis plan was created before the analysis. The main analysis population consisted of all randomly assigned patients. In addition, an analysis of a per-protocol population was performed. The primary and secondary outcomes were analyzed with a generalized linear model using robust variance estimation and a log-link function with group as the factor, site as the covariate, and log (time in study) as the offset (29). For the primary outcome, we used a Poisson distribution because the model failed to converge for a binomial distribution (30). For the secondary outcomes, we used a negative binomial distribution. Length of hospital stay (total number of days during 12-month follow-up) had a right-skewed distribution and was analyzed by a linear mode