Appendicitis has long been considered a surgical emergency that will lead to perforation, sepsis, and death if invasive intervention is not timely. Despite this foregone conclusion, a number of trials have challenged the necessity of cold steel in managing acute appendicitis.
Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial
Salminen P, Paajanen H
This randomized controlled trial compared traditional surgical management of acute appendicitis to conservative treatment with antibiotic therapy alone. It randomized 530 patients with CT-confirmed noncomplicated appendicitis to surgical management or a short course of IV antibiotics (three days of ertapenem), followed by a seven-day course of oral levofloxacin. A total of 272 (99.6%) of the 273 patients randomized to the surgical group underwent successful appendectomy. Seventy patients (27.3%) randomized to conservative therapy underwent appendectomy within one year of initial presentation.
Let's pause for a moment. The vast majority of patients (72.7%) were treated successfully with antibiotics alone for a disease that has been considered a surgical necessity for the past century. Despite these impressive numbers, the trial was deemed unsuccessful because the rate of treatment failure in the conservative group crossed the predetermined noninferiority margin of 24 percent. These statistical inadequacies are based less on the inferiority of antibiotic therapy and more on the authors' unfortunate choice of how they defined noninferior.
Noninferiority trials are intended to ask a specific question: Is a new treatment comparable with the traditional therapy? This type of trial is undertaken when the new treatment provides certain advantages that would make it preferable over the old one. (JAMA 2015;313:2371; Ann Intern Med 2006;145:62). One might prefer to use this new treatment, for example, if it is cheaper, safer, or less invasive rather than expose the patient to the cost, risk, or intrusive nature of the existing strategy. The novel treatment, because of these differences, must demonstrate a near-equivalent efficacy within a degree of certainty to reject the null hypothesis.
The authors in this case estimated a 25 percent treatment failure rate (defined as the need for surgical intervention within a year of initial presentation) in the patients randomized to conservative treatment and set their noninferiority margin at no more than 24 percent.
The authors found that 27 percent of patients randomized to antibiotic therapy required an appendectomy within one year of initial presentation. Similar results were demonstrated in three additional trials examining medical therapy for acute appendicitis. The one-year failure rates were cited as 24 percent, 23.6 percent, and 37 percent, respectively. (World J Surg 2006;30:1033; Br J Surg 2009;96:473; Lancet 2011;377:1573.) The Cochrane group examined the same question, and found similar rates of treatment failure in patients treated with antibiotics alone (26.6%). (Cochrane Database Syst Rev 2011 Nov 9;:CD008359.) Given that the previous evidence indicates the rate of antibiotic failure is consistently greater than 25 percent, the expectation by Salminen, et al. that they would find the noninferiority of antibiotic therapy with a noninferiority margin of 24 percent was optimistic, to say the least.
More importantly, were appendectomy rates at one year truly the most appropriate criteria with which to define inferiority? This trial was not negative because medical management proved to be inferior to surgical appendectomy; it was negative because the authors asked the wrong question. The trial was not completely equitable, either: 99.6 percent of the patients in the surgical arm of this trial underwent appendectomies while only 27 percent of the patients in the medical management arm were exposed to an invasive procedure. What concerns us as clinicians is not whether 20 percent or 27 percent of those initially treated with antibiotics will eventually require an appendectomy, but whether treatment with antibiotics alone leads to an unacceptably high rate of serious complications.
The authors should have asked, “How many patients randomized to medical management avoided surgery without experiencing acute complications related to delays in treatment (perforation, abscesses, sepsis)?” The answer in this study would have been entirely different had they asked this. Fifteen (5.8%) of 257 patients randomized to medical management required appendectomy during their initial hospital admission. Five (1.9%) patients in the antibiotic group experienced perforations requiring surgical intervention compared with two of 273 (0.7%) patients randomized to an immediate surgical intervention.
Certainly, there is a great deal to be determined before this noninvasive strategy can be considered mainstream practice. This was a small underpowered cohort in which the participating surgeons performed primarily open laparotomies. It is unclear how this strategy translates to the United States where the primary approach to appendectomies is laparoscopic intervention. And it is unknown whether patients require three days of broad-spectrum IV therapy followed by a seven-day course of oral therapy. What is strikingly obvious is that a shared decision-making strategy that considers the patient's values and wishes certainly seems like a reasonable approach in a disease state that was once considered a surgical necessity.
Share this article on Twitter and Facebook.
Access the links in EMN by reading this on our website or in our free iPad app, both available at www.EM-News.com.
Comments? Write to us at email@example.com.Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.