Friday, April 6, 2012

Antibiotics instead of surgery for appendicitis? I don’t think so.

Like the villain in a bad horror movie, the idea of treating appendicitis with antibiotics refuses to die.

A meta-analysis published yesterday on line in the British Medical Journal claims that treating uncomplicated appendicitis with antibiotics is better than surgical appendectomy. Four studies involving 900 patients were included in the paper. [Full text here.]

Treatment with antibiotics was said to have resulted in fewer complications [relative risk reduction of 31%] and similar hospital lengths of stay of just over 3 days for each group.

Medical news outlets such as MedPage Today “Antibiotics May Be Enough for Appendicitis,”  Eurekalert “Antibiotics a safe and viable alternative to surgery for uncomplicated appendicitis, say experts” and the BBC “Appendicitis: Antibiotics may be better than surgery” touted the study without much criticism. That will not be the case here.

The authors state, “Diagnosis of acute appendicitis at admission was confirmed by ultrasonography in one study and by computed tomography in two studies, although this was done only in some patients in the study by Hansson et al.” In the fourth study, the diagnosis was based on clinical factors only. Translation: An unknown number of patients in the group treated with antibiotics may not have actually had appendicitis.

There were issues concerning the methods of randomization in the four studies. The paper says, “Randomisation methods were reported as computer generated, external randomization [not explained, my comment], and by date of birth. The randomisation method was not clear in one study.” Date of birth is a notoriously poor way to randomize subjects in a study because the treating physicians can know which group the subject is assigned to before entering him in the experiment. This means that two of the four studies had questionable randomization schemes.

In one of the four studies, almost half of the patients [96/202] in the antibiotic group required appendectomy. And 20% of all patients treated with antibiotics required appendectomy within one year of entry into their respective studies.

The mean length of stay for both treatments was just over 3 days for both antibiotics and surgery. Maybe that is true in Europe where these four studies were done. Only one of those four studies included patients with complicated appendicitis. But here in the US, the median length of stay for almost 17,000 appendectomy patients with uncomplicated appendicitis is 1 day [Advani et al, Am J Surg]. In my personal series of 171 appendectomies during 2009-2011, the mean length of stay for all patients, including those with complicated appendicitis, was 2.4 days with a median of 1 day.

The complication rate comparison raises a “straw man.” The 25% rate of complications for the appendectomy group in the meta-analysis is more than twice that quoted in the series by Advani. Laparoscopic appendectomy results in fewer complications than open appendectomy. One of the studies used in the meta-analysis is from 1995, when very few laparoscopic appendectomies were being done.

The success rates for the two treatments are compared. According to the paper’s Table 2, 58.3% patients were successfully treated with antibiotics vs 92.6% successfully treated with surgery. Unsuccessful surgical treatment is defined as removal of a normal appendix.

The recurrence rate of appendicitis in those who underwent surgery was 0.

If I proposed treating you with drugs that had a 58.3% rate of success in curing your illness for one year with the possibility that you could still suffer another attack of the illness two or twenty years later, would you choose that treatment? Or would you opt for a treatment which would keep you in the hospital for less than 24 hours with no risk of recurrence of the problem?


Dana Dillon said...

Thanks for all you share. I've been following for a long time. As a retired surgical technologist,I enjoy reading about medical news.

Diana said...

As a surgeon, I don't think you understand the aversion that many people feel towards surgery. If I had the option of a pursuing a medical treatent that had a greater than 50% chance of helping me avoid surgery in the near term, I would definitely give it a try.

Skeptical Scalpel said...

Dana: Thanks for the kind words. I appreciate your following me on Twitter and posting some of my stuff in you "Daily."

Diana: Of course, it is your choice. Before you decide between appendectomy or antibiotics, you should talk to a few patients who have had the surgery.

Noman said...

I'm a 2nd year med student right now. Been following your blog for a while now. Learnt quite a bit.

My family had to face the situation a few months ago when my sister was diagnosed with appendicitis. My family has to pay for healthcare. The difference between the cost of antibiotics and a laproscopic surgery is astronomical. So ofcourse she went with antibiotics. However, should it recur we'd probably go with surgery

Skeptical Scalpel said...

Noman: I hadn't thought of that. Good point. I hope your sister is one of the lucky ones.

Celeste Drury said...

I had my appendix removed last year after suffering from all the typical symptoms of it and quite severely. When they had finished running all the tests and put me under for the surgery later that night, I was then told I was very lucky I got in when I had, because it was close to becoming a complicated case and rupturing.

Had I gone in and been told I had the option of taking antibiotics for it on the assumption that it was a normal case, I would not have taken it, as scared of being cut open as I was - I'd have still chosen surgery all the way. There is no way in heck that I would ever want to have risked going through what I felt before I had it removed again, ever. At least in having it removed I know that that can never happen again.

Though I did at the time of my ultrasound want to kill my examiner when he kept pressing the area of my appendix, even though I repeatedly told him it hurt like all the names under the sun to the point that I was almost in tears - I get that he has to be sure of where it's hurting etc, but I thought it was just bordering on cruel at that point.

E: To add. Yes, the recovery can be quite painful and a bit slow - I wasn't able to do any heavy lifting really or exert myself for about a month and had pain for several after, but as I say, I've never got to worry about missing more time off work by being hospitalised again because of it.

Anonymous said...

Short postop for appy. Really. I'd rather not be septic, but that's just me.

IDK, thinking all this has to do with The Big Pullback of Healthcare. Insurance companies are coming up with more to deny. Keep your eyes peeled, there's much, much more to come.

For those obsessed about the evils of Obamacare - you've left the backdoor unlocked...


Anonymous said...

Take mine out. There is still no good evidence for me to not do the appendectomy. The pain that patients have with acute appendicitis is relieved nearly immediately and the post operative pain from laparoscopic appendectomy is little... especially compared with the preoperative pain.

Kellie (General Surgeon)

Skeptical Scalpel said...

Good point. That's the other fact omitted from the argument. The pain of appendicitis is totally alleviated by appendectomy. Nearly every patient I have ever done an appendectomy on says the pain of the three small incisions is much preferable to the pre-op pain.

Anonymous said...

I can attest to an antibiotic failure experience.
Had acute appendicitis. Surgeon opted not to operate because there was "too much inflammation", kept me on abx and repeat scans for weeks. (My husband is a doc and clearly expressed wish for sugical approach.) During all this time, I remained acutely ill. By the time
I could get an app't with another surgeon, I had
a chronic abscess and fistula. Took a year to feel well again.

Skeptical Scalpel said...

Anonymous, thanks for that comment. Of course, surgery can result in complications too, but what happened to you could have been avoided with a 35-40 minute operation. said...

You offer some interesting critiques of the randomization of the relative studies, but I find your comparison of mean and median lengths of stay to be... deceptive. Compare means to means (in this case just over 3 days in the study and 2.4 days in your experience) and appear to be potentially fairly equivocal. Comparing a mean to a median is (in my opinion at least) useless, especially when you don't have the other median to look at.

All that aside, I am very firmly in the 'save the appendix if you can' camp. You can take an appendix out later, but you can never replace it. Despite the common belief that the appendix is a vestigial organ, the idea that the appendix is actually a biologically relevant and useful organ is growing. I've written about this on my blog (I don't meant to plug my blog here, but if you're interested it is very easy to find the 3 part series I did- or I'll come back and link it here if you prefer), but the general concept is that the appendix evolved to be a safe house (complete with biofilms) for health promoting commensal bacteria. In the not-too-distant past (and today, in undeveloped countries), these bacteria could repopulate the gut after severe diarrheal-causing infections caused an evacuation of the gut. How is this useful in the modern world? It's a relatively small study, but there was a very interesting paper that came out at the end of last year that showed that having your appendix was protective against a recurrence of C. diff- again, the health-promoting commensal bacteria are able to repopulate and out-compete that pathogenic ones.

I'm currently on my surgical clerkship (I'm a "3rd year" MD/PhD student), and I'm in awe of what surgeons can do... I do wish, however, that appendectomy was not the first-line treatment for appendicitis. It's a useful little organ- you never know when you may need it!

goingtomedschool said...

As a medical scribe in the Emergency Room I have often heard our physicians reassure the patients that appendectomy may not be necessary because of this/these new studies regarding antibiotics and appendicitis.

So my question is will these studies affect the emergent need of appendectomies? I know that if a surgery is not considered emergent, the patient will be discharged and the surgery is scheduled for some time in the future. From your post it seems like this could be a bad outcome.

How do you feel about this?

Skeptical Scalpel said...

Principleintopractice: Thanks for the thoughtful comments. Your blog is interesting. I enjoyed reading your posts on the appendix.

The appendix may have some function but to my knowledge, there is no convincing evidence that removing the appendix has any effect on disease states or longevity in humans. Appendectomy is a very common operation. Don't you think that some detrimental effect of the surgery would have come to light by now?

And what proof is there that an appendix that has been inflamed and is successfully treated with antibiotics will function properly? Would its flora be the same after treatment? Does it look the same after an episode of inflammation?

Goingtomedschool: Thanks for commenting. I'm afraid that uncritical acceptance of the findings reported in the BMJ paper may lead to more stories like that of "Anonymous" above. said...

I'm glad you enjoyed my posts- thanks for giving them a look!

You raise some interesting questions: some I've been pondering, and some I hadn't yet thought about. I'll agree that there are no grossly-evident detrimental effects of removing the appendix, but I think there are some subtleties that are worth considering. First there is the recent paper that shows that having an appendix is protective against a recurrence of C. diff. Also, the apparent correlation between the appendix and some cases of inflammatory bowel disease, such as Crohn's, seems to imply that the appendix may be an important mediator of the immune system in the gut. Much like removing someone's tonsils or adenoids does not cause any acute or overt deficit, removing a part of the immune system probably does have some effect. Because of the complex nature of the immune system, teasing out the consequences of the removal of these organs is difficult, but interesting (or it is to me)...

I've spent some time thinking about the effects of a bought of appendicitis on the long-term functionality of the appendix. Firstly, I would ask 'how many removed appendices are truly dysfunctional?' in the first place. While there are definitely pathologic appendices removed, many perfectly healthy appendices are removed on a daily basis, some 'just for the heck of it' because we're already in there. As to a truly inflamed, but saved w/ antibiotics, appendix... I think this bares a bit of thought. I expect the etiology and the stage at which the infection is caught is important. Yes- a course of heavy duty antibiotics may wipe out most, if not all, of the commensal bacteria stashed away in the biofilms of the appendix, but this niche could be recolonized by reintroduced commensals, and if any bacteria is going to survive a considerable antibiotics-assault, it is probably those sequestered within the biofilm.

I am not opposed to appendectomy in a truly emergent situation, but I am distressed by the apparent 'if in doubt, take it out' attitude that we seem to have acquired.

Also, my 2c in response to @Goingtomedschool... Just because something is not an emergent surgical condition, does not mean it is not an emergent medical condition requiring hospitalization and close monitoring. I tend to think that appendicitis is something that warrants close medical attention and surgery if necessary, not guaranteed surgery.


Skeptical Scalpel said...

The paper about C diff and appendectomy merely shows an association. There's no evidence of cause and effect. Also, it was a retrospective data mining. The finding may have been by chance. If you look at enough variables, some will be significant by chance.

Very few normal appendices are being removed these days. For right lower quadrant pain, most surgeons have rates of normal appendices on path of < 10%. Incidental appendectomies during other procedures are rarely done now. There is no "if in doubt, take it out."

WDG said...

I know my dad had a very emergent appendectomy in his 20's (plowed all day very sick and drove himself to hospital in next town that eve, dragged himself into hospital where nun threw him onto the stretcher after he said "you gotta help me" and his appendix ruptured in the elevator on the way up to OR. They must have ripped him open 'cause his abd. scar was a mess. We always teased him as kids about having 2 "belly buttons". Well fast forward to Dad in his 70's and he's on dialysis (IDDM) and he insists he won't go without his little bottle of Immodium because he had diarrhea/loose stools while trapped in the chair. He was a proud man and was embarrassed. Some time later he was diagnosed with CDiff.
So just wondered about the association with his appendectomy and not fighting off the Cdiff at this later point in his life?

Skeptical Scalpel said...

WDG, thanks for commenting. A brief literature search reveals that C diff is more common in people who still have their appendices. Appendectomy may be protective. The theory is that the intact appendix may serve as a reservoir for re-inoculation of the C diff. It's an association, not a proven causation. Here's the link

Term papers said...

Good Article About Antibiotics instead of surgery for appendicitis? I don’t think so.

Skeptical Scalpel said...

Term, thank you for the comment and for reading my blog.

Anonymous said...

Regularly read the General Surgery News and saw your last opinion in the July issue. As a fellow surgeon I always thought it would be fun to be able to "rant" once in awhile about the incredible amount of ridiculousness we are exposed to on a daily basis. Kudos to you for actually taking the time to do it. Reading the comments above I would only add that periodically we do see someone who has ruptured appendicitis that is several days old with either an established abscess or a large phlegmon in whom antibiotics (with or without drainage) is the preferred method of treatment with an interval appendectomy done laparoscopically in the near future. (I typically wait about 6 weeks). This courtesy of our Pediatric Surgery colleagues. This approach has proven invaluable in certain patients who would otherwise likely end up with an open procedure or even a cecectomy/hemicolectomy and who would not tolerate that very well because of co-morbidities/obesity/age/etc. The comment from one of the anonymous posters above about the surgeon waiting should be taken cautiously since every patient is different and perhaps waiting was the best answer for them.

Skeptical Scalpel said...

Thanks for the kind words. It's nice to have the freedom to say what I want. I have no problem treating established perfed appendicitis with antibiotics. I agree that operating on them can be difficult. I'm not sure the all need so-called interval appendectomies though. One review suggested that only about 7% of such patients with develop appendicitis again.

Anonymous said...

I, too, am enjoying your blog and your frank discussion on different topics.

My appendectomy happened when I was 14. That was over 30 years ago, when laparoscopic was not an option. My surgeon told my parents that had we waited a few more hours to go forward, my appendix would surely have burst, as he'd not seen one that inflamed before. He asked me if he could keep it, he wanted to put it in a jar on his desk. Mom was ok with that, and I was done with it, so I agreed.

The pain I felt post-op was pretty close to the pain I felt pre-op and during the exam when the medical staff was pressing to find the originating site of the pain.

If I could go back and have a do-over, I would still opt for the permanent solution of surgery over the potential temporary relief of antibiotics.

Would love to hear what you have to say on the subject of tonsillectomies in adults.

Argle Bargle said...

OK, so give a listen to me. Two days ago I developed pain in just the right spot to be my appendix. Is it appendicitis? I sure hope not, but a couple of signs are there: 1) the location of the pain, 2) intermittent fever. The fever pops up at 99.7 for some hours, then back to 98.6. There's a good chance I have an appendicitis. If money were no object, I'd say snip it and be done with it.

But life isn't as easy as a medical diagnosis.. and a medical diagnosis can be tough.

My wife embezzled our savings to prop up a failing business she had with a guy who turned out she was having an affair with and ran off with. So now I'm broke, no insurance, just getting by and trying to make a home for 3 of my 4 children. I have NO health insurance.

The pain in my side currently is middling. I was hospitalized for some particle in my lung giving me pneumonia and the infection went to my diaphragm which spasmed and began to keep me from breathing and body wanted to strangle me. I call that a 10. The pain where my appendix is located is maybe a 4 by comparison.

So, now, here I am having to make a decision: do I hunt down a surgical solution I can not afford, lose my home and maybe be one of those "failed surgeries" where it turns out to be a gall-bladder problem or urinary tract infection? Or do I visit my GP and request a regimen of antibiotics in hopes of alleviating the problem?

I'm probably being Captain Obvious here, but doctors treat patients, not diseases. And there is much more to a patient than a disease.

Skeptical Scalpel said...

Sorry to hear about all of your troubles.

Disclaimer: What I am about to say is not medical advice, which can only be given if I had an opportunity to examine you.

99.7 is not a fever. Most authorities do not consider a temp to be a fever unless it is 100.4 or higher.

You did not mention any GI symptoms such as anorexia, nausea, vomiting or diarrhea. It is quite rare to have appendicitis without at least one of those.

Antibiotics do not seem to be indicated in your case, and they have unpleasant and occasionally dangerous side effects.

Please let me know how this turns out.

Argle Bargle said...

I'm leaving in moments to visit my GP. I woke to a fever of 101 early this morning. I have not had vomiting, but I have been nauseous. I have a rather rock-solid stomach and I find it hard to vomit even when coping with the occasional round of food poisoning. I am printing the Lancet article as well as yours to take to my doctor. I really hope it's some lame gall-bladder thing.

Anonymous said...

I Was recently went to the ER for lower right quadrant pains. It had been going on for about four days before I went in. They gave me four ultrasounds which where inconclusive and a CT which showed and enormous amount of inflammation around my appendix. They are not entirely sure weather my appendix was involved but they said it sure looked like a mess on the CT. My WBC was 14.2 when I was admitted and during my 4 day stay with antibiotic treatment, went down to 5.2. The antibiotics i was treated with broad range IV antibiotics during my stay, and was given 7 days of augmentin after my release 5 day ago. I sat in the waiting room for 18 hours but after I finally got in and on antibiotics I felt a lot better within hours. the second day I felt like nothing was wrong. I had a follow up ct with contrast and a lieter of ISOVIEW. Which showed a night and day difference from the original CT. I am hoping the infection does not rebound after the antibiotics, but we will see. My symptoms where atypical of what you would normally see also. I did have pain in my lower right quadrant but i had no rebound pain after pressing nor did i feel nasious dizzy or anything else for that mater. I also still had an appetite during the pain but it did get worse after eating a meal.

Skeptical Scalpel said...

Time will tell. I'm not sure why no one recommended surgery. You didn't mention what the size of your appendix was. That would be nice to know. If you were feeling better, why have another CT? Now you've had 2 CT scans plus a 4-day stay in the hospital. I suppose if the pain recurs, you will have another CT scan or two.

Please give me some follow-up on this. Good luck.

Anonymous said...

I am currently being treated with antibiotics for an appendicitis with a 1cm abscess. I had had the appendicitis for almost 8 days when I finallu went to the doctor. I was atypical as far as symptoms go. I had no fever, 1 night of really bad stomach cramping, then pain in 1 area of my lower right quadrant, more pain and bloating when I ate, decreased appetite, but no vomiting. I was sent for a CT scan and then to emergency. The surgeons wanted to do IV antibiotics which made me extremely sick. I was hospitalized for 5 days. I am home on my 3rd type of antibiotics due to not tolerating the others well. I still feel blah, hurting in right side and now there is another tender spot at my right waist. If I could do it all over again, I would have had them take it. I will go for a follow up and will request an appendectomy. I don't know if I have to wait for the 6 week mark or not. This is very frustrating and I feel like I could have been on the road to recovery and I'm still hurting.

Axel Ellrodt said...

About ATBx vs Blade in the Finnish stydy :

1- Wouldn't the appropriate comparison be :
- antibiotics, and if failed, surgery (within a to be defined time frame )
- vs surgery first
With as endpoints : meaningful (to be defined) complications, at 1 year (5 would be more interesting, but we want to see some results in our lifetime ! )

2- Ertapenem IV 3 days isn't a reasonable option. We're trying to limit the use of fluoquinolones, ≥ 3d generation cephalosporins, let alone the penems !

3 Appies with appendicoliths were excluded, lets us not forget .

Otherwise I regret most what I read on the ATBx vs balde for appies is tainted with anecdotal case reports for/against , bad faith for against, both sides. I'm not specifically alluding to this blog.

I have no appendix.

My personal conflictual interest might be antibiotics first.

I tend to consider we need better studies to change to some to-be-defined ATBx RX in well defined cases to make an informed choice. Surgery still the gold standard for me.

The topic reminds me of a few quotes:

Faced with the choice between changing one's mind and proving that there is no need to do so, almost everyone gets busy on the proof.
--John Kenneth Galbraith 

Dr. Otis Brawley, chief medical officer of the American Cancer Society, suggested that is what doctors like Dr. Kapoor are doing. “We in medicine need to look into our soul and we need to learn the truth,” he said. “If your income is dependent on you not understanding something, it is very easy not to understand something.”

It is difficult to get a man to understand something when his job depends on not understanding it. Upton Sinclair (1878 – 1968)

Leg-pullingly yours

Skeptical Scalpel said...

Axel, thanks for commenting. I think we need a two-year follow-up at least. Agree ertepenem is not a good choice. I enjoyed the quotes.

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