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Date: November 16th, 2022

Reference: Lipsett SC, Monuteaux MC, Shanahan KH, et al. Nonoperative Management of Uncomplicated Appendicitis. Pediatrics 2022

Dr. Angelica DesPain

Guest Skeptic: Dr. Angelica DesPain is an Assistant Professor of Pediatrics and a pediatric emergency medicine physician at the Baylor College of Medicine Children’s Hospital of San Antonio in San Antonio, TX.

Case: A 10-year-old boy comes into the emergency department (ED) with right lower quadrant (RLQ) pain for the past two days. He also has had nausea, vomiting, loss of appetite but no fevers. You order an ultrasound and find that he has acute appendicitis without evidence of perforation or appendicolith. His white blood cell count is 11,000 and his C reactive protein (CRP) is mildly elevated. After you tell the family the news, the parents express concern about their child having surgery. They ask you and the surgeon, “Does he absolutely need surgery, or can we treat this medication alone?”

Background: The SGEM has covered diagnosing appendicitis using speed bumps (SGEM#23), a clinical decision instrument (SGEM#155) and point of care ultrasound (SGEM#274).

The current standard of care for nonperforated acute appendicitis is immediate laparoscopic appendectomy. However, over the last decade nonoperative treatment of appendicitis (NOTA) with antibiotics alone has become an alternative treatment option for non-perforated acute appendicitis. These authors call this alternative nonoperative management of uncomplicated acute appendicitis (NOM).

The SGEM has looked at the evidence for NOTA/NOM in adults a few times including SGEM#115, SGEM#256 and SGEM#345. We have also looked at it specifically in children with pediatric general surgeon and rock star Dr. Ross Fisher with an episode called: The First Cut is the Deepest (SGEM#180).

In adults, randomized control trials suggest that nonoperative management with antibiotics alone may be a reasonable treatment approach for individuals without appendicolith [1-3]. Although, up to 39% of patients may experience failure by the five-year mark [4]. In children, there have been two randomized and several nonrandomized prospective trials. Most recently, the two prospective pediatric studies published their 5-year data and observed a similar five-year failure rate of nonoperative management of 30-40% [5-6].

The shift from immediate operative management to now up to 3 in 10 cases being treated with IV antibiotics leaves a lot of questions as to whether nonoperative management is an appropriate option for nonperforated pediatric acute appendicitis.

 Clinical Question: How do the risks and complications compare between nonoperative management vs immediate operative intervention for acute nonperforated appendicitis?

 There are actually four questions these authors are trying to address with this paper.

  1. What are the trends in NOM of nonperforated acute appendicitis?
  2. What are the early and late treatment failure rates with NOM?
  3. How does subsequent healthcare utilization compare between children undergoing immediate operative management and those undergoing NOM?
  4. How do the rates of perforated appendicitis and postsurgical complications compare between children undergoing immediate operative management and those who experience failure of NOM?

Reference: Lipsett SC, Monuteaux MC, Shanahan KH, et al. Nonoperative Management of Uncomplicated Appendicitis. Pediatrics 2022

  • Population: <19 years of age seen across 47 EDs in the Pediatric Health Information System (PHIS) database from January 2011 through March 2020 who were ascribed a primary diagnosis of appendicitis based on ICD-9 and 10 codes. To increase the specificity of the case definition, the study only included patients who either underwent appendectomy or received a parenteral antibiotic during the index visit.
    • Excluded: complex chronic condition and those with a previous visit with a diagnosis of appendicitis or a procedure code for an appendectomy (these would exclude prior cases of nonoperative management) 
  • Intervention: Nonoperative management (NOM) of nonperforated acute appendicitis 
  • Comparison: Appendectomy for nonperforated acute appendicitis 
  • Outcomes: Because they had four questions they were trying to answer, we are not actually sure what their primary versus secondary outcomes were. They were all just…outcomes.
    1. Trends in NOM
    2. Treatment failure rate for NOM, divided into early (≤14 days) vs late (>14 days); 1, 2, 5-year failure rates
    3. Subsequent healthcare utilization for NOM vs immediate management
    4. Rates of perforated appendicitis and postsurgical complications between children undergoing immediate operative management versus those who opted for NOM
  • Type of Study: Retrospective cohort study using data obtained from the Pediatric Health Information System (PHIS),

Authors’ Conclusions: Nonoperative management of nonperforated pediatric appendicitis is increasing. Although the majority of children who undergo NOM remain recurrence-free years later, they carry a substantial risk of perforation at the time of recurrence and may experience a higher rate of postoperative complications than children undergoing an immediate appendectomy.

Quality Checklist for Observational Study:

  1. Did the study address a clearly focused issue? Yes
  2. Did the authors use an appropriate method to answer their question? Yes
  3. Was the cohort recruited in an acceptable way? Yes
  4. Was the exposure accurately measured to minimize bias? Unsure 
  5. Was the outcome accurately measured to minimize bias? Unsure
  6. Have the authors identified all-important confounding factors? Unsure 
  7. Was the follow up of subjects complete enough? Unsure
  8. How precise are the results? Unsure
  9. Do you believe the results? Yes
  10. Can the results be applied to the local population? Unsure
  11. Do the results of this study fit with other available evidence? Yes
  12. Funding of the Study: None

Results: They included 73,544 patients who had non-perforated appendicitis in the study group. 63,150 (85.9%) underwent appendectomy at the index visit and 10,394 (14.1%) underwent nonoperative management (NOM). Median age was 11.4 years and 61.2% were male.

Key Result: NOM for acute nonperforated appendicitis has grown in popularity. It is associated with a risk of perforation at the time of failure, higher rates of subsequent healthcare utilization, and slightly higher rates of postsurgical complications.

  • Outcomes:
    • Trends: NOM increased from 2.7% (2011) to 32.9% (2020). Odds ratio 1.1 per study quarter [1.01-1.51]
    • Failure Rate: 2084 (20.1%) failed NOM. Median time to failure was 2 days [IQR 1-5 days].
      • 4% early and 1.7% late.
      • 7% perforated vs 37.5% at index visit (p<0.001).
      • Failure rate at 1, 2, 5 years

  • Subsequent Healthcare Utilization: NOM higher rate of:
    • ED visits: 8% vs 5%
    • Hospitalization: 4.2% vs 1.4%
    • Abdominal imaging that included ultrasound and CT
  • Postsurgical Complications and Perforated Appendicitis: Higher risk of post-surgical complications within 12 months: 1.9% vs. 1.2%

1. Accuracy of Coding: This was a retrospective study using a large database, PHIS. While it houses a tremendous amount of data, there are limitations to its use. It relies on accuracy in coding and data that is inputted by all the hospitals that contribute. The non-prospective and non-randomized nature of this study leaves a lot to clinician preference and coding. Additionally, it may not capture some nuanced situations.

For example, if the family opted for NOM but the child perforated on initial visit, it is possible that patients were coded as perforated appendicitis and not included in this study.

Another example is if the family opted for NOM which failed on initial visit and was taken to the OR, that patient may have been coded as immediate surgical management.

2. Selection Bias: With the transition from ICD-9 to IC-10 coding during the study period, the authors chose to exclude hospitals that demonstrated an absolute change of 50% in the rate of either perforated appendicitis or NOM. This was made under the assumption these shifts were likely due to coding issues and excluded 20.7% (31,341 out of 150,983) of patients who had met inclusion criteria.  Was this assumption correct? How did they choose this cutoff of 50%? Why not 30%, 40%? Was this too conservative or too lenient? How would the hospitals whose patients were excluded by this decision have impacted the data?

3. Subsequent Encounters: This study evaluated whether there were any subsequent encounters for patients who opted for NOM. But what if that patient did not return to the initial hospital where they received treatment? There is a portion of pediatric acute appendicitis that is managed in the community and not at academic centers. There is a chance these patients may have been missed and skew the results to make it appear like NOM actually did better.

They included subsequent related ED visits for complaints of abdominal pain, vomiting, diarrhea, and dehydration in their analysis. I am not certain how they made the determination that these visits were “related” to appendicitis.

4. Clinical Data: The PHIS database does not contain any clinical information and clinical judgment is one of the pillars of evidence-based medicine. What were the reasons that some cases of appendicitis underwent NOM vs laparoscopic appendectomy?

What were the other clinical, laboratory, or radiographic findings that influenced management decisions? For those patients that were included in the treatment failure population, how many of those had elective interval appendectomies versus true recurrences? What were the histopathologic findings after the appendix was removed? We do not have that information.

5. Standard of Care: Laparoscopic appendectomy is the current standard of care for nonperforated appendicitis, but nonetheless we are seeing a growing trend towards nonoperative management. Keep in mind that the “standard of care” does not necessarily mean that it is the best care based on the evidence. It is important for us to keep questioning. Maybe there is a subset of children with acute nonperforated appendicitis who can safely avoid surgical intervention with minimal risk. Until then, we should acknowledge the limitations of what we know and engage in shared decision making with the family.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We acknowledge the authors’ conclusion that there is an increasing trend toward nonoperative management of acute nonperforated appendicitis. The associated risks and complications should be interpreted within the limitations of this study.

SGEM Bottom Line: Despite the growing practice of nonoperative management for nonperforated appendicitis, it may be associated with increased risks of perforation and other complications.

Case Resolution: You re-evaluate the patient and he has a soft abdomen. He is non-toxic appearing and his pain in minimal. The parent has discussed nonoperative management and surgical management with the surgeon and has elected for nonoperative management. You admit the patient on IV antibiotics to the surgical service for monitoring.

Clinical Application: The trend is increasing for NOM of uncomplicated acute appendicitis. For those undergoing NOM, treatment failure will occur in approximately 20% of patients and is most likely to occur within the first 5 days. Among those with NOM failure, almost half will present with perforated appendicitis and may experience more surgical complications and increased health care utilization. It is possible that our patients might not even know that they had an acute appendicitis if they re-present in the ED with abdominal pain after being treated nonoperatively. They will not have an abdominal surgical scar. We should be aware that nonoperative management is prevalent and these patients may be at higher risk for complications from a perforated appendicitis.

What Do I Tell the Patient (Parents)? Treating uncomplicated acute appendicitis with antibiotics is a reasonable choice. You should be aware that there is a chance that treating with antibiotics alone will not work, and your child could still need surgery in the future. In those cases, there tends to be more complications such as the appendix being perforated. Alternatively, your child could do totally fine.

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

References:

  1. Flum DR, Davidson GH, Monsell SE, et al; CODA Collaborative. A randomized trial comparing antibiotics with appendectomy for appendicitis. N Engl J Med. 2020;383(20):1907–1919
  2. Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: the APPAC randomized clinical trial. JAMA. 2015;313(23): 2340–2348
  3. Vons C, Barry C, Maitre S, et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open- label, non-inferiority, randomised con- trolled trial. Lancet. 2011;377(9777): 1573–1579
  4. Salminen P, Tuominen R, Paajanen H, et al. Five-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC randomized clinical trial. JAMA. 2018;320(12):1259–1265
  5. Patkova B, Svenningsson A, Almstrom M, Eaton S, Wester T, Svensson JF. Non- operative treatment versus appendectomy for acute nonperforated appendicitis in children: five-year follow up of a randomized controlled pilot trial. Ann Surg. 2020;271(6):1030–1035.