Surgery versus Conservative Antibiotic Treatment in Acute Appendicitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background/Aims: Although standard treatment typically consists of an early appendectomy, there has recently been an increase in the use of antibiotic therapy as primary treatment for acute appendicitis (AA). The aim of this analysis is to systematically evaluate the evidence available in relevant literature in order to compare the relative effectiveness of antibiotic therapy as a viable alternative to appendectomies in the treatment of AA. Methods: Literature was searched for randomized clinical trials (RCTs) comparing the efficacy of surgery versus antibiotic therapy. Differences in pooled odds ratios (OR) for outcomes within 95% confidence intervals (CI) were calculated. Results: Four RCTs were identified including 741 patients. Efficacy was significantly higher for surgery (OR = 6.01, 95% CI = 4.27–8.46). No differences were found in the numbers of perforated appendices (OR = 0.73, 95% CI = 0.29–1.84) and patients treated with antibiotics (OR = 0.04, 95% CI = 0.00–3.27). Complication rates were significantly higher for surgery (OR = 1.92, 95% CI = 1.30–2.85). Conclusion: Although a nonsurgical approach in AA can reReceived: February 17, 2010 Accepted after revision: January 24, 2011 Published online: May 3, 2011 Dr. Luca Ansaloni, MD Unit of General Surgery, Ospedali Riuniti Largo Barozzi 1 IT–24128 Bergamo (Italy) Tel. +39 03 526 9712/9368, E-Mail lansaloni @ ospedaliriuniti.bergamo.it © 2011 S. Karger AG, Basel 0253–4886/11/0283–0210$38.00/0 Accessible online at: www.karger.com/dsu D ow nl oa de d by : 54 .7 0. 40 .1 1 1/ 9/ 20 18 3 :2 2: 35 A M Systematic Review of Surgery vs. Antibiotics in Treating AA Dig Surg 2011;28:210–221 211 described 425 of 500 patients with suspected AA who were treated conservatively with either antibiotics or traditional Chinese medicine; upon follow-up examination, only 7% presented with symptoms of recurrence [5] . In both of these studies, patients were assessed by individual history and clinical examination. The treatment method differed without standardization and there was no consecutive follow-up. Moreover, conservative antibiotic treatment has also been described in the cases of 9 US submariners [6] and in 247 patients aboard Soviet ships at sea [7] . The latter is a review of conservative treatment outcomes in 252 patients with AA on vessels of the Kalingrad fishing industry from 1975 to 1987, where Gurin et al. [7] reported a recovery rate of 84.1% with only the use of antibiotics. The authors found no difference in outcomes based on presenting symptoms or age, but found that conservative treatment was most effective when administered within 12 h of symptom onset, ideally within the first 6 h. More recently, Kaminski et al. [8] reported a 5% recurrence rate within a median follow-up time of 4 years in 864 patients with AA treated solely with antibiotics. Furthermore, other researchers have reported a high success rate for the nonoperative medical treatment of AA as compared to the high complication rates of appendectomies performed in suboptimal conditions during situations of remote medical care [9–11] . Furthermore, the use of preoperative antibiotic treatment in AA can be implemented as a means of delaying an appendectomy, particularly during twilight hours, in which case the incidence of perforation, complications, and hospitalization in children operated within 6 h was equivalent to the rates of those who underwent surgery between 6 and 18 h after admission [12] . Even the conservative management of appendiceal mass has been advocated [13–15] , although some recommend interval appendectomy [13] in the case of a cecal neoplasm or recurrent AA supervenes. Generally speaking, many of these experiences did not receive much attention and, consequently, early appendectomy remained the standard treatment for AA in order to avoid perforations, even though population-based evaluations have indicated significant long-term risks following surgical intervention for AA [16] . It has been shown that small bowel obstruction requiring surgery occurs in 1.3% of individuals by 30 years and that the 30-day mortality is 0.24% with an increased standard mortality ratio [17, 18] . A negative appendectomy is particularly encumbered with problems. Using the standardized mortality ratio to describe the excess mortality in the operated patients compared with the general population in Sweden, Blomqvist et al. [18] found a 3.5-fold excess mortality after an appendectomy for nonperforated appendicitis and 6.5fold excess mortality after perforated appendicitis. Surprisingly, the standardized mortality ratio after negative appendectomy with a discharge diagnosis of nonspecific abdominal pain as the only diagnosis that could motivate an exploration was increased 9.1-fold. This result is in accordance with the report by Flum and Koepsell [19] who found a 3-fold increase in mortality after negative appendectomy compared with appendectomy for appendicitis. Due to this excess mortality associated with appendectomy for nonperforated appendicitis and with negative appendectomy with a discharge diagnosis of nonspecific abdominal pain, suggesting that appendectomy is not a harmless operation, antibiotic treatment for AA has received increased attention in recent years [20, 21] . Several studies have indicated that even perforated AA in children can be effectively treated with antibiotics [22] . In addition, retrospective studies analyzing adults with conservatively treated perforated AA suggest that late recurrences were often very mild and treatable [23, 24] . More recently, four randomized controlled trials (RCTs) compared the respective efficacies of surgery and conservative antibiotic treatment in AA [25–28] . The aim of this systematic review (SR) and meta-analysis (MA) was to evaluate the available evidence, comparing the effectiveness and safety of appendectomy versus conservative antibiotic regimens in the treatment of AA.