Date: May 24th, 2017

Reference: Georgiou et al. Efficacy and Safety of Nonoperative Treatment for Acute Appendicitis: A Meta-analysis. Pediatrics 2017.

Guest Skeptic: Dr. Ross Fisher is a Paediatric Surgeon in Sheffield, England. When he is not waxing lyrical about presentation skills (P Cubed) over at ffolliet.com, giving the Greatest Presentation in the World at SMACC or expounding his views on paediatric trauma management he can be found at Sheffield Children’s Hospital principally dealing with surgical oncology, vascular access and all sorts of neonatal surgical problems.

Case: It is 7pm on a quiet evening in the emergency department and Bobby comes in. He’s 12 years old and complains of a belly ache, pointing to his right iliac fossa pain. It has been going on for about 36 hours now, initially peri-umbilical and associated with nausea, poor appetite and malaise.  It has increased in severity and is now localized in his right iliac fossa. He is particularly worried as he is ice hockey captain. Their hockey team is playing in the regional finals in two weeks’ time. His blood work shows an elevated WBC count and the ultrasound is consistent with acute uncomplicated appendicitis (AUA).

Background: Appendicitis is the most common paediatric surgical emergency. It has a lifetime risk of over 7% but the peak incidence is in the second decade of life. Acute, uncomplicated appendicitis if promptly diagnosed can be effectively treated by surgery, the recovery from which, is relatively short.

There is a small but increasing number of publications in the adult literature proposing management of the problem using simply intravenous antibiotics. This is called Non Operative Treatment of Appendicitis (N.O.T.A). This would avoid the risks of general anaesthesia, any surgical scar and allow quicker return to full activity.

We have covered N.O.T.A. on the SGEM#115 – Complicated. Appendicitis management used to be so easy. The diagnosis was made, the surgeon was called and the appendix was removed.

For over a century the mainstay treatment of acute appendicitis has been an appendectomy. There have been refinements to the surgical procedure since Fitz first described it in 1886. My approach in this case would be to remove the appendix thru a small, 3cm incision particularly in a boy: less number of scars, quicker procedure, similar pain relief and recovery. In girls I would probably use a laparoscope.

REBEL EM covered the issue of N.O.T.A. in adults when it reviewed a pilot study by Dr. David Talan (Ann Emerg Med 2016). Paediatric surgery is completely separate from adult surgery and the implications of practice in adults is not the same in children. There is not a lot of cross over for physicians who have both an adult and paediatric practice in the understanding that children are different.

Clinical Question: Is non-operative treatment (N.O.T.) for acute uncomplicated appendicitis safe and effective in children?

Reference: Georgiou et al. Efficacy and Safety of Nonoperative Treatment for Acute Appendicitis: A Meta-analysis. Pediatrics 2017.

  • Population: Paediatric patient under 18 years of age diagnosed with acute, uncomplicated appendicitis (AUA).
    • Exclusions Complicated appendicitis (perforation, rupture, abscess, or appendix mass), studies of mixed adults and children or studies of acute appendicitis in only in children with malignancy.
  • Intervention: Course of intravenous antibiotics to treat AUA
  • Comparison: Primary appendicectomy
  • Outcome:
    • Primary outcome Discharge from hospital without appendicectomy during the initial hospital episode.
    • Secondary outcomes Adverse effects of N.O.T., complications, long term efficacy (no appendicectomy at final reported follow-up), recurrent appendicectomy (confirmed by histology or treated with second course of N.O.T.), and hospital length of stay.

Authors’ Conclusions: Current data suggest that NOT is safe. It appears effective as initial treatment in 97% of children with AUA, and the rate of recurrent appendicitis is 14%. Longer-term clinical outcomes and cost-effectiveness of NOT compared with appendicectomy require further evaluation, preferably in large randomized trials, to reliably inform decision-making.”

checklistQuality Checklist for Therapeutic Systematic Reviews:

  1. The clinical question is sensible and answerable. Yes
  2. The search for studies was detailed and exhaustive. Yes
  3. The primary studies were of high methodological quality. No
  4. The assessment of studies were reproducible. Yes
  5. The outcomes were clinically relevant. Yes
  6. There was low statistical heterogeneity for the primary outcomes. Yes
  7. The treatment effect was large enough and precise enough to be clinically significant. No. The authors conclude themselves “the study highlights the lack of robust evidence comparing the two modalities.”

Key Results: The study identified 413 patients who were selected or randomized to non-operative treatment of acute uncomplicated appendicitis.

N.O.T. was successful in 396/413 of cases

  • Primary outcome: 17/413 patients failed N.O.T. and required surgery during the primary admission. This gave a result of 97% (95% CI; 95%-99%) of patients treated with N.O.T. were successful.
  • Secondary Outcomes:
    • Adverse effects of N.O.T. – None were reported
    • Long term efficacy of N.O.T. (no appendicectomy at final reported follow-up) – 336/413 or 82% (95% CI; 77% to 87%)
    • Recurrent episode of appendicitis (confirmed by histology or treated with second course of N.O.T.) – 68/396 or 14% (95% CI; 7% to 21%)
    • Hospital length of stay – Mean difference of 0.5 days less with appendicectomy (95% CI; 0.2 t o 0.8)

Screen Shot 2015-04-25 at 3.11.12 PM

This study attempts to answer an important question that challenges the current standard of care. There are no perfect studies and one of the big problems with systematic reviews is they are only as good as the included studies.

Unfortunately, there are not many high-quality studies on the topic of non-operative treatment of appendicitis.

Dr. Nigel Hall

Dr. Nigel Hall

Through the power of the social media we reached out to one of the authors to help us understand the paper better. Dr. Nigel Hall is an Associate Professor of Paediatric Surgery University of Southampton and a Consultant Paediatric and Neonatal Surgeon at the Southampton Children’s Hospital.

Listen to the podcast on iTunes to hear Dr. Hall’s responses to our nerdy questions.

  1. Included studies:
    • Observational Studies: Nine of the studies were non-randomized (six prospective and three retrospective) which introduces bias. It also means these studies can only concluded association not causation.
    • Non-Comparator Studies: Four of the included studies did not have a comparison group so we do not know how non-operative treatment would compare to traditional treatment in that study population.
    • Randomized Control Trial: Only one of the included studies was an RCT. This was a small pilot study of 50 patients in Sweden that had its own limitations. The biggest issue besides study size was lack of blinding. Patients, caregivers and the surgeons were all aware of treatment allocation, which introduces bias.
  2. Diagnosis of Acute Uncomplicated Appendicitis: This is another problem with this study because the exact diagnosis of AUA itself is problematic.  The paper utilises either ultrasound or CT to make the diagnosis. The literature suggests a diagnostic accuracy for ultrasound of between 80 and 90% for AUA and similar for CT. The spread includes male and female patients, with differing pathologies. There is no proof, nor can there be, of diagnosis but similarly no comment on the diagnostic accuracy of these investigations. In addition, It is important to emphasise that AUA is appendicitis without gross surrounding inflammation, bowel wall thickening, free fluid or pus and, as such, is a more challenging diagnosis than complicated appendicitis.
  3. Treatment with Antibiotics or Appendicectomy: All ten studies had different antibiotic treatment protocols. This included different intravenous and oral antibiotics regimes making it hard to know what would be the best strategy to use.
    • Many surgeons would identify appendicectomy as a further investigation such that the procedure allows more accurate visualisation of the intra-abdominal milieu, alternative pathologies including ovarian, Meckel diverticulum and unsuspected alternates as well as exclusion of such in recurrent abdominal pain. Comparison of non-operative treatment and appendicectomy is not identical.
  4. Safety: It is well recognized that adverse events are under reported in the medical literature. Even if the included studies had rigorous reporting mechanisms for adverse events there were just over 400 patients treated with non-operative treatment. This is too small to claim safety of rare events but rather that no adverse events were observed.
  5. You Said There would be No Math: We were a little confused by the statistics presented in the paper. Some of the numbers did not make sense. As an example, 17 out of 413 patients required surgery in first admission calculates to 95.9% (396/413) success rate as the primary endpoint, not 97% as stated. We noticed the same slight differences for some of the secondary outcomes as well.

One more comment from paediatric surgeon Dr. Ross Fisher.

Dr. Ross Fisher

Dr. Ross Fisher

This interesting question about understanding the natural history of appendicitis. Lots of people are throwing scoring techniques, blood tests, ultrasound and even as we discussed the use of intense abdominal radiation in CT scanning to try and increase our accuracy in diagnosis and we are still at the same place we have been before.

What even is “acute uncomplicated appendicitis”? Is it a starting point for further and progressive inflammation, is it simply mild self limiting inflammatory response, or is it an acute bacterial infection. The evidence of progression of appendicitis is not available. If it is an acute bacterial infection, why does it get better simply by removing it? If it is a self limiting inflammation, why give antibiotics or even intervene when clearly their may be children who do not present to hospital and better without intervention? There is more that we need to know even to understand appendicitis before we can fully understand the management of it.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: The authors conclude that the current data suggests that non-operative treatment is “safe.” It would be more accurate to conclude that the current data suggests that non-operative treatment is not associated with any  adverse events.

SGEM Bottom Line: Non-operative treatment of acute uncomplicated appendicitis is not ready for prime time.

Case Resolution: As the surgeon, I would come and discuss the diagnosis of acute uncomplicated appendicitis with the patient and family. I would recommend appendicectomy and encourage them if all goes well Bobby should recover quickly and he should be back on the ice in time for the finals.

Clinically Application: Non-operative treatment of acute uncomplicated appendicitis is interesting. More and better-quality evidence is needed before applying non-operative treatment in the paediatric population.

What Do I Tell My Patient? I would tell Bobby and his parents that he has appendicitis. The appendix has not ruptured and he needs to be seen by the surgeon and they will probably recommend taking out his appendix today. If all goes well he should be able to play in the hockey finals.

Keener Kontest: Last weeks’ winner was Matt Corey a Physician Assistant from Phoenix, Arizona. He actually got the first part of it correct. The full answer is “Chasing the Dragon” is inhaling pyrolized (heated) heroin or opioids through a straw. The user inhales the smoke chasing the vapour trail with a straw to get all of the drug. It has resulted in toxic encephalopathy with symmetric spongiform degeneration seen on MRI and carries a poor prognosis. I will be sending Matt a cool skeptical prize.

Listen to the SGEM on iTunes to hear this weeks’ question. If you know the answer to the question then send an email to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

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Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.