Simple Acute Appendicitis versus Non-Perforated Gangrenous Appendicitis: Is There a Difference in the Rate of Post-Operative Infectious Complications?

Patients and Methods

This retrospective study reviews patients who have undergone either an open or laparoscopic appendectomy because of the presence of non-perforated simple acute or gangrenous appendicitis at the University of Miami/Jackson Memorial Medical Center. The on-call Acute Care Surgery (ACS) service manages patients with non-perforated simple acute and gangrenous appendicitis. According to the university protocol for acute simple or gangrenous appendicitis, patients are operated on typically within six hours of patient admission. Simple acute appendicitis was defined as an inflamed appendix without any signs of gangrene or perforation. Gangrenous appendicitis was defined as an inflamed appendix with signs of grossly necrotic tissue but no frank perforation or abscess.

The service registry was queried for all patients between 2010–2012 with a diagnosis of acute appendicitis (ICD-9 code 540). Individual charts were further examined to determine patient eligibility for this study. Inclusion criteria were patients with the presence of a non-perforated simple acute appendicitis or non-perforated gangrenous appendicitis as confirmed grossly by specimen appearance. Operative cases excluded were those with a perforated appendicitis, interval appendectomy, primary diagnosis other than acute appendicitis, or patients younger than 18 years.

For all patients included in the study, demographic information such as age and gender, surgical approach (open versus laparoscopic), and the rate of post-operative infectious complications, specifically superficial wound infections and/or abscess formation, were compared between groups. The Fisher exact test was used to assess categorical data and t-test was used to compare continuous data with statistical significance set to p≤0.05. This study was approved by the local university's Institutional Review Board.

Results

Over the two-year study period, a total of 566 patients were identified with appendectomies. Among these patients, 372 patients met study criteria. There were 336 patients that were diagnosed with non-perforated simple acute appendicitis and 36 patients that were diagnosed with non-perforated gangrenous appendicitis. The mean age of patients with a diagnosis of simple acute appendicitis was 33.5 (SD±15.6) whereas the mean age of patients with a diagnosis of non-perforated gangrenous appendicitis was 37.9 (SD±19.3) (p=0.53). Although 221 patients (66%) with simple appendicitis were male, only 13 patients (36%) with non-perforated gangrenous appendicitis were male (p=0.0005). Three patients (8%) with non-perforated gangrenous appendicitis underwent open appendectomy whereas 16 patients (5%) with a diagnosis of simple acute appendicitis underwent open appendectomy (p=0.39). The remaining patients within either group underwent laparoscopic appendectomy.

There was no difference in the rate of post-operative cellulitis between the simple appendicitis group (n=2; 0.6%) and the non-perforated gangrenous group (n=0; p=0.64) (Table 1). However, a significantly greater proportion of patients with a diagnosis of non-perforated gangrenous appendicitis developed a post-operative intra-abdominal abscess (5.6%) in comparison to patients with a diagnosis of non-perforated simple acute appendicitis (0.6%) (p<0.05) (Table 1).

Overall, within the non-perforated gangrenous appendicitis group, 31 patients (86%) received IV antibiotics postoperatively. Predominately, IV piperacillin/tazobactam was administered for a range of one to five days with the exception of two cases where IV cefoxitin was used for a range of one to four days. Furthermore, 15 patients (42%) within the overall group of non-perforated gangrenous appendicitis patients received PO antibiotics at discharge in addition to receiving IV antibiotics postoperatively. All of these patients were prescribed PO amoxicillin-clavulanic acid for seven days. All patients in the study received one dose of pre-operative IV antibiotics within 30 minutes of skin incision as per hospital protocol. In reference to the two patients who developed a postoperative intra-abdominal abscess, both received post-operative IV antibiotics although neither received PO antibiotics at discharge. For the first patient, the culture was positive for Escherichia coli, which was resistant to amoxicillin-clavulanic acid, ampicillin, and cefazolin. It was also tested and was negative for extended-spectrum beta-lactamase (ESBL) production. For the second patient, the culture was positive for three organisms: 1) Proteus mirabilis, which was resistant to ampicillin and cefazolin 2) Enterococcus avium, which was pan-susceptible, and 3) Escherichia coli, which was resistant to ampicillin, tetracycline, trimethoprim-sulfamethoxazole, and intermediate to amoxicillin-clavulanic acid. This isolate was not tested for ESBL.

Discussion

Current guidelines recommend treating gangrenous non-perforated appendicitis with the same antimicrobial regimen as non-perforated simple acute appendicitis. However, in practice many clinicians commonly consider gangrenous appendicitis to pose a greater risk of post-operative infections and often prescribe such patients an extended course of post-operative antibiotics. We were surprised to find that this occurred commonly in our own institution. The purpose of this study was to determine whether there is a difference in the rate of post-operative infectious complications between non-perforated simple acute appendicitis and gangrenous appendicitis without perforation.

The results of this retrospective review suggest that patients with gangrenous appendicitis may have different rates of infectious complications. The rate of intra-abdominal abscess formation was found to be significantly higher in patients with non-perforated gangrenous appendicitis as compared with those patients with simple acute appendicitis. However, the rate of cellulitis between the two groups was not significantly different. Overall, patients with gangrenous appendicitis received an extended course of post-operative antibiotics, suggesting that clinicians consider this group to be more prone to infectious complications postoperatively. Within our patient population, 86% of patients with non-perforated gangrenous appendicitis received intravenous antibiotics, predominantly piperacillin-tazobactam or cefoxitin, postoperatively prior to discharge. Furthermore, 42% of patients with non-perforated gangrenous appendicitis received oral antibiotics, specifically amoxicillin-clavulanic acid for a course of seven days total, upon discharge. The two patients with non-perforated gangrenous appendicitis who developed an intra-abdominal abscess received intravenous antibiotics postoperatively but did not receive oral antibiotics upon discharge. Both of these patients received the same treatment for their intra-abdominal abscess: Percutaneous drainage and intravenous antibiotics. One patient received amoxicillin-clavulanic acid for seven days after drainage, the other patient received ciprofloxacin and metronidazole for seven days after drainage. There was no difference in the rate of post-operative complications between laparoscopic versus open procedures. The results of this study suggest that patients with non-perforated gangrenous appendicitis are more likely to develop an intra-abdominal abscess postoperatively, despite the fact that the gangrenous group overall received more antibiotics. It is possible that the administration of a longer postoperative duration of antibiotic therapy is not effective in the prevention of certain post-operative infectious complications, such as intra-abdominal abscesses. The two patients in our study with non-perforated gangrenous appendicitis who developed an intra-abdominal abscess only received intravenous antibiotics postoperatively but did not receive oral antibiotics upon discharge, so it is also possible that the actual duration in these particular cases was not long enough. Furthermore, the longer duration of antibiotic coverage that most clinicians are intuitively using in cases of gangrenous appendicitis may actually be preventing worse infections from occurring or preventing certain types of infection (such as cellulitis) from occurring. It is not possible to determine the answer to these questions from our current study and further research is warranted, but our study does suggest that the classic separation between perforated and non-perforated appendicitis is naive and that other factors should be considered.

The administration of antibiotics for patients with appendicitis is standard of care [10, 11]. A Cochrane review in 2005 of 45 randomized controlled trials concluded that peri-operative antibiotics were superior to placebo or no treatment for the prevention of post-operative infectious complications, specifically surgical site infections and intra-abdominal abscess formation, in patients undergoing appendectomies [13]. The studies included both children and adults in the patient population, cases of both simple acute appendicitis as well as complicated appendicitis with perforation and any antibiotic regimen implemented. Although current guidelines recommend that antibiotics must be given for intra-abdominal infections, the antibiotic type, dose, and duration of treatment continue to be debated. However, several studies show that there is no difference in the rate of post-operative infectious complications when patients with appendicitis receive differing doses of antibiotics. For instance, a randomized controlled trial of 377 patients with acute appendicitis by Hussain et al. demonstrated that there was no difference in the rate of surgical site infections among patients undergoing open appendectomies who received a pre-operative dose of antibiotics versus those who received a pre-operative plus post-operative dose of antibiotics [14]. However, these studies do not isolate patients with gangrenous appendicitis, which may carry a greater risk of post-operative infectious complications.

Nonetheless, the inappropriate overuse of antibiotics leads to complications as well, emphasizing the importance of a balance between the risks and benefits of antibiotics use [4–8]. Some studies report high rates of antibiotic-related complications without overall clinical benefit. In a retrospective review of 728 patients over five years with non-perforated appendicitis, Coakley et al. demonstrated that the use of post-operative antibiotics did not reduce infectious complications and in fact was associated with poorer outcomes, specifically with higher rates of Clostridium difficile associated infections and urinary tract infections as well as longer length of stay [15]. Mui et al. conducted a randomized study of 269 patients who underwent open appendectomies for non-perforated acute appendicitis. The patients were randomized to receive one, three, or five peri-operative doses of antibiotics [16]. There were no differences in the rate of infectious complications or in the hospital length of stay amongst the three groups. However, there were more complications related to the antibiotics in the group receiving five doses of antibiotics compared with the other two groups. Neither study distinguished between subsets of patients with gangrenous versus non-gangrenous appendicitis.

There are several limitations to this retrospective review of post-operative complications in patients with non-gangrenous appendicitis versus non-perforated simple appendicitis. First, it is a review of a single-center experience. Second, antibiotic choice was not protocolized. Third, the determination of whether or not the appendix was gangrenous was dependent on the resident, fellow, or attending physician who provided a gross description of the specimen within the patient's operative note. Therefore, there could conceivably be variability in the interpretation of “acutely inflamed” versus “gangrenous” or “necrotic” appendicitis.

Conclusion

In conclusion, this study suggests that non-perforated gangrenous appendicitis is associated with a higher rate of post-operative abscess formation. Further investigation through a prospective quality assurance program is therefore warranted.