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Non Operative Treatment of Acute Appendicitis. A possible new paradigm shift?

Michael Macias

By Michael Macias

By Michael Macias

Appendicitis is one of the most common entities that requires urgent surgical evaluation in the emergency department. We see appendicitis on the CT scan read and our fingers immediately dial the number of our local surgeon. This is one of the entrained behaviors of the well practiced emergency physician. Diagnosing appendicitis is our bread and butter, as is passing it along to the surgeon. Yet a significant amount of data has slowly been trickling into the surgical literature that in many of the cases of appendicitis,  rushing the gurney to the OR may not actually be what is best for the patient. This is where non operative treatment of acute appendicitis (NOTA) is born. A randomized clinical trial, comparing antibiotics versus appendectomy in primary treatment option for acute appendicitis in unselected patients, showed that treatment efficacy was 90.8 % for antibiotic therapy and 89.2% for surgery. Minor complications were equal and major complications were found to be 3-fold higher in the surgical group. Further supportive, a meta analysis comparing conservative treatment with appendectomy for complicated appendicitis (abscess or phlegmon) showed that conservative treatment was associated with significant fewer overall complications, wound infections, abdominal/pelvic abscesses, ileus/bowel obstruction and re-operation. Recently, The NOTA Study was published in the Annals of Surgery, which delved further into this topic, to assess the safety and efficacy of NOTA and to monitor long term follow up for non operative patients.

On to the study...


The NOTA Study (Non Operative Treatment for Acute Appendicitis): Prospective Study on the Efficacy and Safety of Antibiotics (Amoxicillin and Clavulanic Acid) for Treating Patients With Right Lower Quadrant Abdominal Pain and Long-Term Follow-up of Conservatively Treated Suspected Appendicitis. Annals of Surgery 2014 July 260 (1): 109-17.

  • Study Design: Single cohort, prospective observational study 

  • Population: Patients who presented to the emergency room with between January 1, 2010 and December 31, 2010 and underwent an initial trial of non operative management (NOM) with amoxicillin/clavulanate, 3 g/daily,  and seen at a follow-up visit 5 days after an initial assessment in the emergency department.

Inclusion & Exclusion Criteria 

Alvarado versus AIR Score

Consort diagram and flowchart of study

  • Intervention protocol: Patients not needing immediate surgery were treated with 5- to 7- days of amoxicillin and clavulanic acid therapy, 1g orally, three times daily. Patients were then assessed in clinic 5 days later and if they were not improving or worsened they underwent appendectomy. If improved, patients were then followed up via telephone interviews conducted at 7 and 15 days, 6 months and 1 and 2 years. 


Tempogram of study

  • Outcome Measures: 
    • Short-term efficacy of antibiotic treatment: Failure of NOM with 7 days of amoxicillin and clavulanic acid therapy which was defined by lack of clinical improvement and/or worsening abdominal pain and/or localized/diffuse peritonitis. 
    • Long-term efficacy of antibiotic treatment: This was defined as (1) incidence of recurrence of clinical episodes of appendicitis up to follow up at 2 years; (2) definite improvement with NOM without need for surgery up to follow up at 2 years. 
    • Safety of antibiotics treatment: Defined as major side effects from antibiotics or treatment related complications such as allergy or delayed treatment complications such as abscess formation.
    • Secondary Outcome measures: (1) Minor complications such as bloating, diarrhea, flatulence, headache and heart burn (at 7 days, 15 days) (2) Abdominal pain after discharge assessed by numeric rating scale (at 5,7 and 15 days) (3) Length of hospital stay (4) Outpatient clinic follow (number of follow up appointments) (5) Sick leave days (6) Cost analysis 
  • Results

    • Short term NOM failure rate was 11.9% (19/159 patients) and all patients were operated on within 7 days. 

      • Antibiotic treatment was shown to be safe with no major side effects registered

      • Long term NOM failure rates

        • 15 days: No recurrence

        • 6 months: 17 additional recurrence episodes (10.7%); 10 (59%) of these were successfully treated with further antibiotic cycle

        • 1 year: 3 further recurrence episodes, meaning that at 1 year follow up the total failure rate was 12.6% (20/159 patients)

        • 2 year: 2 further recurrence episodes, meaning that at 2 year follow up the total failure rate was 13.8% (22/159 patients); 14/22 were treated non operatively 


Characteristics of included patients and results

Results from 2 year follow up 

  • Interpretation: Antibiotic treatment of acute appendicitis appears to be safe and effective and majority of recurrence can be treated with second course of antibiotic therapy. 
  • Comments: Though a prospective cohort study, the study was compliant with accepted best practice guidelines of the STROBE statement and seems appropriate for assessing efficacy of NOTA. One impressive point of the paper was the fact that there was no loss to follow up, leaving missing data minimal. The paper however leaves you with questions regarding which patients the study actually is applicable to given that there is not significant discussion of the patient population in terms of age, comorbidity and previous abdominal surgeries. These factors play strongly into clinical decision making with regards to abdominal pain and imaging evaluation and are not apparent here. Furthermore, there is also a concern related to diagnosis. There were multiple modalities used for diagnosis, including 10% of patients being diagnoses with appendicitis by clinical suspicion alone. This would tend towards increasing the apparent efficacy of antibiotics therapy for appendicitis given the non blinded approach. Overall, this is a study that supports the beginning of a paradigm shift to considering conservative management of appendicitis as an alternative to immediate surgery. The long history of appendicitis being a surgical diagnosis will make dispersion and acceptance of further evidence for NOTA difficult and overall paradigm shift will require more definitive studies with clear comparison with the standard of care. 

Original Article

Original Article


  1. The NOTA Study (Non Operative Treatment for Acute Appendicitis). Saverio S, Sibilio A, Giorgini E, et al. Annals of Surgery 2014 July 260 (1): 109-17.
  2. A meta-analysis comparing conservative treatment versus acute appendectomy for complicated appendicitis (abscess or phlegmon). Simillis C, Symenoides P, Shorthouse A, et al. Surgery. 2010;147:818–829.
  3. Randomized clinical trial of antibiotic therapy versus appendectomy. Hansson J, Korner U, Khorram-Manesh A, et al. Br J Surg. 2009;96:473–481.