More negative data about the nonoperative management of simple appendicitis

If you think I am the only one urging restraint in the adoption of nonoperative management of patients with uncomplicated appendicitis, you are wrong. A pediatric surgeon and a research fellow from Harvard and Massachusetts General Hospital have recently published their thoughts on the matter online in Annals of Surgery.

They call their opinion piece “Ulysses Syndrome” because they liken the fate of those undergoing nonoperative management to the “10-year ordeal filled with unexpected peril and ample misfortune” that befell Ulysses while attempting to go home.

Here are a few highlights.

Nonoperative treatment of appendicitis in children: Is it safe?

After writing my 21st post about appendicitis back in November, I swore I would not write about it again for the foreseeable future.

Well, the future is now because investigators from the United Kingdom and Canada just published a meta-analysis including 10 papers and 413 children about the efficacy and safety of nonoperative treatment for appendicitis in children.

They concluded that nonoperative management is effective in 96% of children with acute uncomplicated appendicitis during their initial hospitalizations with just 17 (4%) children requiring appendectomy before discharge. An additional 68 (16.4%) developed recurrent appendicitis later, and 19 of these patients were treated with the second course of antibiotics. The other 49 underwent appendectomy with histologic evidence of recurrent appendicitis.

Another 11 patients underwent appendectomy in the follow-up period for various reasons. In all, 77 (18.6%) patients initially treated with antibiotics eventually underwent appendectomy.

Although the initial hospital length of stay for appendectomy was shorter than that of patients treated with antibiotics, complication rates were similar.

These findings were met with headlines like "Antibiotics, not surgery, could treat appendicitis in children, study suggests" from The Guardian and "Is Surgery Always Needed for Kids' Appendicitis?" from US News.

What are the problems with this paper?

A medical oncologist weighs in on the treatment of appendicitis

It was an interesting fortnight for the debate about the treatment of appendicitis.

On November 1, David Agus, a medical oncologist and Director of the University Of Southern California's Center for Applied Molecular Medicine, had some thoughts about how appendicitis should be treated. He cited the Finnish randomized trial of antibiotics vs. surgery and said a 70% cure rate was good enough.

In a brief article on the Fortune magazine website, Agus wondered why appendectomy "continues to reign supreme." He said it was "because 24/7 we’re taught you have to take it out if there’s appendicitis” and that the healthcare community is "stubborn and pigheaded" [pigheaded means stubborn] and that we focus on treatment instead of prevention.

Antibiotics vs. surgery for appendicitis: Critique of a meta-analysis

A meta-analysis can be useful when looking at a topic that has been studied by several different groups of investigators. The pooling of data from different published papers can sometimes bolster a conclusion about the effectiveness of a treatment.

However, a meta-analysis is only as good as the studies it includes, and the biases of those performing the meta-analysis can color the results.

Last month, a meta-analysis concerning antibiotics vs. surgery for the treatment of uncomplicated acute appendicitis by investigators from Nottingham University Hospitals was published in the World Journal of Surgery.

The authors concluded that “antibiotic therapy represents a safe, efficacious and viable treatment option for the treatment of uncomplicated acute appendicitis.” I disagree.

Five randomized trials involving 1430 subjects were included in the meta-analysis. After one year of follow-up, the efficacy of treatment for those receiving antibiotics was 62.2% compared with those undergoing appendectomy whose treatment efficacy was 88%. Depending on the inclusion or exclusion of a particularly weak study there was said to be a 39-52% risk reduction for complications in the antibiotic group.

This meta-analysis has so many problems that it is hard to know where to start.

Appendicitis and shared decision-making

Staying with the current theme of appendicitis on my blog, here is a summary of recent developments. A JAMA Surgery Viewpoint suggested that because of the findings of a Finnish randomized trial, surgeons now should give patients with appendicitis a choice between an appendectomy or treatment with antibiotics.

The paper acknowledged my criticisms of the Finnish study which found that simple appendicitis could be treated successfully with antibiotics in almost 75% of patients.

I respect the authors of the JAMA Surgery article and am happy they referenced the blog post noting my concerns about that Finnish trial: the trial compared antibiotics to open appendectomy—an operation with more complications than the more commonly performed laparoscopic appendectomy; the antibiotic used in the Finnish trial is not a first line choice in the United States; patients were followed for only one year.

The JAMA surgery paper answered three questions I posed in a previous post. One, the Viewpoint authors consider antibiotic therapy for appendicitis mainstream. Two, surgeons must assume that patients might opt for antibiotics despite at least a 25-30% chance of suffering a recurrence of appendicitis. Three, an informed consent discussion now should include a mention of antibiotics as an option.

I disagree with the Viewpoint authors’ assertion that antibiotics are as safe and effective as surgery for treating appendicitis. Based on one flawed study, antibiotic therapy cannot yet compare to the many years of excellent results of laparoscopic appendectomy.

Here are some other problems.

In 22% of kids with appendicitis, antibiotics do not prevent perforation

Those clambering aboard the "antibiotics for appendicitis" bandwagon should read this interesting paper about appendicitis in children.

A group of emergency physicians from Maimonides Medical Center in Brooklyn, New York found that "Increasing in-hospital time delay from ED presentation to OR appendectomy is associated with increased risk for developing appendicitis perforation in children who present with CT-documented uncomplicated appendicitis."

Children with simple appendicitis who were taken to the operating room longer than 9 hours from the time of ED presentation were much more likely to develop a perforation than those who had surgery in less than 9 hours.

During the four years of the study, 404 consecutive children ≤ 18 years of age had a CT scan diagnosis of acute appendicitis; 156 (38.6%) had evidence of perforation at the time of presentation and were not included in the final analysis.

Questions about antibiotics vs. surgery for acute appendicitis

A study from Finland suggesting that antibiotics may be a viable alternative to surgery for acute appendicitis has created a stir. As you might have expected, I had some concerns about the paper which you can read in my blog post here.

On Twitter, many surgeons have commented on both the paper and my post. Several interesting questions come to mind.

Based on this and other similar studies, is the treatment of acute appendicitis with antibiotics now a mainstream alternative to surgery?

Should surgeons now mention the Finnish study results during their informed consent discussions with patients?

Antibiotics instead of surgery for appendicitis? I'm still not convinced

Two recent papers have added more fuel to the debate about whether appendicitis can be managed without surgery.

The first paper is a prospective observational study from Italy involving 159 patients over the age of 14 who were thought to have uncomplicated appendicitis. Nonoperative management with oral antibiotics was planned for all of the patients.

Nonoperative management failed within 7 days in 19 (11.9%) patients, all of whom underwent immediate surgery. Appendicitis was found in 17 patients, and 2 had tubo-ovarian abscesses

The abstract says "After 2 years, the overall recurrence rate was 13.8% (22/159)." This is blatantly misleading. The overall recurrence rate was 19 recurrences within 7 days plus 22 more recurrences between 7 days and 2 years for a total of 41 (25.8%) recurrences with 27/159 (17%) of the patients requiring surgery.

If you look at this paper more carefully, you will find the following from Table 3:

Reviewing three studies that question dogma

I like studies that question accepted practices. I also like to question studies that question accepted practices. [See this post about discrediting discredited practices.]

Here are three new studies with surprising and thought-provoking results.

A few years ago, the idea of rapid response teams surfaced. These teams were supposed to be called when patients on regular floors became unstable. It was thought that such teams would be able to intervene more rapidly than simply paging the patient's physician.

Every hospital established rapid response teams, and early studies tended to confirm that they were efficacious. So all is well.

But a paper from the journal Critical Care Medicine shows that rapid response teams increase costs and intensive care unit admissions without showing any improvement in risk-adjusted patient outcomes.

Naysayers will complain that it wasn't a randomized prospective double-blind study. But it was a large before-and-after cohort study from a respected institution, the Mayo Clinic.

The authors concluded that hospitals should at least evaluate their own experiences with rapid response teams.

Another study, this time in JAMA, questions the validity of using rates of venous thromboembolic events as markers of hospital quality.

It seems the more diligently one looks for VTEs, the more one finds them. Hospitals that did more imaging studies looking for VTEs had significantly higher rates of VTE. They also had significantly higher rates of adherence to prophylaxis guidelines.

So if a patient was looking for a hospital with high quality care in the area of venous thromboembolic events, the rate of VTE might be very misleading.

A third study, also from JAMA, looked at the use of universal precautions for all ICU patients in an effort to decrease the incidence of colonization or infection by antibiotic-resistant organisms.

This was a randomized trial in 20 American ICUs, 10 of which involved health care workers donning gowns and gloves for all patient contact and 10 where gown and glove use was required only for patients with established MRSA or VRE colonization or infection. Over 26,000 patients were included.

Although the acquisition of MRSA or VRE declined from baseline in both groups, the difference was not statistically significant. [Digression. This may have been due to the famous "Hawthorne Effect," which is that behavior improves when subjects are aware that they are being watched.]

When only MRSA was looked at, a barely significant difference in acquisition was noted for the ICUs in which all personnel took precautions for all patients.

Other interesting findings were that personnel in the gown and gloves for all patients ICUs entered patient rooms significantly less frequently. The rate of occurrence of the adverse events was not different in the two groups.

To review.

Rapid response teams may not be as useful as once thought. They may lead to increased costs and ICU admissions.

Hospitals with higher rates of VTE may actually be better quality hospitals than those with lower rates.

Observing gown and glove precautions for all patients ICUs does not appear to affect the rate of acquisition of antibiotic-resistant organisms.

Choosing antibiotics for appendectomy and cholecystectomy: Are "big guns" needed?

An emergency medicine physician asked me to comment on the use of antibiotics in patients having surgery for acute appendicitis and acute cholecystitis. He said in hospitals where he has worked in three different areas—New York, Miami and San Francisco—surgeons are using Imipenem for cholecystitis and Zoysn for appendicitis.

He wondered why those drugs were chosen and offered a few theories. They are as follows:

1) Surgeons are trying to avoid resistant bugs, so they’re using bigger guns

2) There is more pressure to reduce post-op complication numbers, so they’re using bigger guns

3) It’s easier to give one antibiotic to cover multiple bacterial types, instead of, say, cipro/flagyl or cefoxitin/flagyl

4) Patients do better with these big gun antibiotics

5) Residents are being taught incorrectly, and are just developing bad habits

Yes, it is mandated that everyone needs a dose of prophylactic antibiotics within an hour of surgery for appendicitis and cholecystitis. Of course, there are nuances.
 
Appendicitis is a disease involving an inflamed, eventually infected appendix so the use of antibiotics is possibly therapeutic and not simply prophylactic.
 
For acute cholecystitis, a similar argument can be made. The problem here is that it is often difficult to tell acute cholecystitis (with possibly infected bile) from biliary colic (pain caused by a gallstone impacted in the neck of the GB) without infection. Sometimes the GB ultrasound says acute cholecystitis, the surgeon says acute cholecystitis and the path report says chronic cholecystitis. There are many other permutations of those three observations. (e.g., US-biliary colic, surgeon-biliary colic, path-acute cholecystitis, etc.)
 
Note: I do not routinely culture peritoneal fluid in appendicitis or bile in cholecystitis because by the time the culture report comes back, most patients have been home for two or three days. There is evidence to support not culturing either fluid.
 
Honestly, I’m not so sure that people with early acute appendicitis really need antibiotics. Unless the appendix is perforated, I use only one preop dose. There are also similar differences in the imaging reports, surgeon description and path reports for this disease too.

I doubt that patients with biliary colic benefit from antibiotics either. The problem is that one may not discover that acute cholecystitis is present until one is in the abdomen. The same issue occurs with appendicitis where an unsuspected perforation may be found at surgery.

At least for now, at least one pre-op dose of an appropriate antibiotic seems reasonable.
 
Where I practiced for the last few years, we did not use Imipenem for GBs and only occasionally is Zosyn used for appys. Most of us used Unasyn for both except in the penicillin-allergic patient. For that patient, we used Levaquin and Flagyl. The problem with the latter two drugs is that they each are supposed to be infused over an hour. This is not always possible because the surgery may be started within an hour in certain circumstances, such as when an operating room happens to be vacant and the patient is ready to go. It’s a rare event, but it does happen.
 
There is no evidence that patients with either disease, who usually present from home, have resistant bacteria, and postoperative complications, especially infections, are not common with either disease. There is no evidence that patients do better with “big gun” antibiotics. In fact, most of the evidence that prophylactic antibiotics are even needed in these two operations comes from the pre-laparoscopic era. Wound infections are extremely uncommon with laparoscopic appendectomies and cholecystectomies. This is probably due to the fact that the wounds are small and in most cases, the specimen is removed in a plastic bag so the infected organ does not touch the subcutaneous tissue.
 
If residents are being taught to use “big gun” antibiotics for these two diseases, I agree it’s incorrect. There is little hope of changing this.

It is similar to the unfounded practice of giving everyone who is NPO a proton pump inhibitor, which I wrote about here. There is no scientific rationale for it. Yet everyone does it, and no amount of discussion will convince people to stop.

[Note: A version of this post appeared on General Surgery News a few weeks ago. The version above is better because I thought about it more.]