Wednesday, June 17, 2015

Antibiotics for appendicitis? No thanks

The long-awaited Finnish randomized controlled trial of antibiotics vs. surgery for appendicitis was just published in JAMA. Depending on your perspective, 73% of patients were successfully treated with antibiotics or 27% of patients failed antibiotics and needed surgery.

The good news is that it was a large multicenter study involving 273 patients randomized to surgery and 257 to antibiotics. Patients included in the study had uncomplicated appendicitis as diagnosed by CT scan.

The bad news is that the paper has many limitations.

Of the patients who underwent appendectomy as the primary treatment, only 15 (5.5%) had laparoscopic surgery. The authors state that open appendectomy was selected as the protocol operative technique because laparoscopic instruments may not be available worldwide and apparently many surgeons in Finland are not experienced in performing laparoscopic appendectomies.

In most Western countries, laparoscopic appendectomy is the procedure of choice. In the United States, at least 80% of all appendectomies (not just those done in patients with early or simple appendicitis) are done laparoscopically. Laparoscopic appendectomy has a much lower complication rate than open. This renders the comparison of complications of surgery (20.5%) and antibiotics (2.8%) in the Finnish randomized trial meaningless. The Finnish authors did not consider failure of antibiotic treatment a complication. Had they done so, the complication rate would have been higher for the antibiotic group.

The hospital length of stay for the surgery patients in the JAMA study was a median of three days. A paper from Texas published last year found that of 345 patients who had laparoscopic appendectomies for uncomplicated appendicitis, 88% were managed as outpatients. They spent a total of about eight hours in the hospital from admission to discharge and had a complication rate, including readmission, of 2.8%.

The antibiotic chosen for the in-hospital treatment in the JAMA study nonoperative group was ertapenem—a once-a-day drug that costs $80 per dose. How available is ertapenem in low- and middle-income countries?

The follow-up in the current paper was only one year. Is it realistic to expect that no more patients will have recurrences of appendicitis in the following years?

The inconvenience and costs of the extra hospitalization for the 27% of patients who failed antibiotic therapy were not addressed.

The stated goal of the trial was to prove the noninferiority of antibiotic therapy for appendicitis. By the authors' own admission, the result failed to meet their prespecified criterion for noninferiority. In plain English, this means the trial showed antibiotic therapy is inferior to surgery for the treatment of uncomplicated acute appendicitis.

Early last year, I blogged about the potential problems with this study and said, "A randomized trial of antibiotics vs. surgery for uncomplicated appendicitis is underway in Finland. Judging from the wording of the abstract describing the trial, the authors are markedly biased toward the use of antibiotics. Despite this, let's hope it sheds some much needed light on this subject." Too bad that did not happen.

Other than Dr. Edward Livingston, a surgeon who wrote a favorable editorial accompanying the paper in JAMA, I do not know of any surgeons who would opt for antibiotics to treat appendicitis for themselves or their family members.

A more realistic randomized trial is planned by surgeons in Washington State. Until that study is published, I’ll stick with surgery for uncomplicated appendicitis.

Addendum: The spelling of ertapenem was corrected on 6/18/15.


Doctor James said...

You must be a surgeon. You wrote that the article is "biased towards antibiotics" (despite that the author states repeatedly that they failed to find that ABx were non-inferior to surgery). You yourself come off as incredibly biased towards surgery. Why don't we all just try to put our personal bias aside and take the evidence at face value? I understand that surgeons must be as terrified as you sound that people may consider ABx vs surgery, but next time I'd appreciate a less biased assessment of the evidence.

Skeptical Scalpel said...

Doctor James, I am a retired surgeon. If antibiotics become the standard of care for the treatment of appendicitis, it will have no impact at all on me. I am not terrified.

I would be most interested in your take on the paper from Finland. Are you OK with a 27% one-year failure rate? In what other illness would we accept that one of four patients will fail a treatment when a perfectly good alternative already exists? That alternative, by the way, is not open appendectomy--the comparator used in the study.

Skeptical Scalpel said...

Doctor James, here's what a presumably unbiased internist from Yale thinks about the Finnish study

He uses the word "crazy."

Doctor James said...

Interesting stuff. Well, the standard of care won't be changing anytime soon that's for sure. Will be cool to see what that upcoming study shows. keep up the interesting posts!

Anonymous said...

Maybe the best thing is to let the patient decide? Show them the data and let them make the decision. If they are willing to deal with the consequences, so be it.

I had a surgeon afraid to operate. I ended up with an emergency hospitalization because I was told 'you are going to die'. Several months later, I got the surgery.

Sometimes you all are right. Sometimes patients are. Luck of the draw sometimes. :)

Aren't you glad you retired? :)

Skeptical Scalpel said...

Doctor James, it takes about 20 years for the standard of cars to change. You'll need to be patient.

Skeptical Scalpel said...

Anon, I hate that suggestion. Most patients cannot understand the nuances of making such a decision. Doctors should present the alternatives and recommend a course of action. To not do so is abdicating one's responsibility.

Anonymous said...

I'm a bit confused by everyone saying that laparoscopic appendectomy is clearly better than open appendectomy.

I only perform laparoscopic appendectomies, but the cochrane review of this shows that there are more wound infections with open, more intra-abdo abscesses in the laparoscopic group, but that the overall complication rate is about the same.
If I had to choose, I would choose an abscess over a wound infection
Also the length of stay and return to work is only marginally better in the laparoscopic group. While not studied, I imagine that bowel obstructions is less in the laparoscopic group

Laparoscopy is certainly better if the diagnosis is not certain, and in obese patients, but everyone saying that laparoscopy is clearly better, including the internist from Yale, should look at the Cochrane study

artiger said...

Anonymous, most of my laparoscopic appendectomies are done on an outpatient basis, as opposed to a one or two day stay with open cases. Also, with our population getting larger and larger, laparoscopic appendectomy becomes the easier operation.

Skeptical Scalpel said...

Anon, if this is the Cochrane review you are referring to [], the authors came out in favor of the laparoscopic approach. There are a few more recent papers which show an even greater advantage for laparoscopic vs. open in terms of infections.

Artiger, laparoscopic is easier on both obese and non-obese patients.

Anonymous said...

with govt healthcare this will be the norm soon and then all the insurances will no longer pay for surg either .
what the surgeons think does not matter one bit.
It is not about the patient , it is about the money.
with the govt , that is all it is about. money.

Skeptical Scalpel said...

I hope you're wrong, but what do I know? You may be right.

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