Acute Surgery v. Antibiotics for Acute Non-perforated Appendicitis

Incomplete

Svensson JF, et al. "Nonoperative treatment with antibiotics versus surgery for acute nonperforated appendicitis in children: a pilot randomized controlled trial". Annals of Surgery. 2015. 26(1):67-71.
PubMed • Full text

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Clinical Question

In children with uncomplicated (non-perforated) appendicitis, can antibiotics be used in place of surgical interventions without significant complications?

Bottom Line

In children with uncomplicated appendicitis, non-operative treatment (an antibiotic regimen) can be utilized in place of surgical interventions without significant complications of the short term but is not recommended a standard of practice until further investigation by a larger RCT.

Major Points

Non-operative treatment with antibiotics of uncomplicated appendicitis in children is a feasible and safe therapy for treatment. The pilot study outlines room for improvement and states that recommendations based of this study alone are not recommended. Patients enrolled in the study expressed high interest in avoiding surgery. The pilot RCT of Non-operative Treatment with Antibiotics Versus Surgery for Acute Non-perforated Appendicitis in Children demonstrated there was effective treatment in 92% patients given antibiotic therapy in place of surgery. Although success rate is high, other parameters should be analyzed further such as hospitalization duration and long-term consideration of the appendix.

The pilot RCT included 50 individuals where 24 were given per-protocol non-operative therapy and 26 patients had an appendectomy. With a follow up of a year, there was no significant difference in treatment success as it relates to safety for the two handles of the study (antibiotics vs. surgery).

Guidelines

The Society for Surgery of the Alimentary Tract (2013)

• The preferred treatment in cases of acute appendicitis is surgical removal.
• Antibiotic therapy intravenously should be utilized in conjunction with fluid and electrolytes prior to surgery. Continuation of the antibiotics is indicated in the event of perforation or irrigation of the peritoneal cavity.
• Non-operative management has been associated with treatment but “is not a widely accepted treatment and in some patients has led to recurrent appendicitis”2.

World Society of Emergency Surgery (2013)

• The treatment of choice for acute appendicitis is, and remains, an appendectomy.
• Antibiotic therapy is indicated in patients with uncomplicated acute appendicitis but lacks effectiveness because of significant recurrence rates in the long term. It does significantly have more positive short-term patient outcomes in comparison to surgery.
• Antibiotic therapy is indicated in patients that are contraindicated for surgery.

Design

• Randomized controlled trial
• n=50
• Non-operative treatment with antibiotics (n=24)
• Surgery for acute appendicitis in children (n=26)
• Setting: Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
• Enrollment: February 2012- October 2012
• Mean Follow-up: 1 year
• Analysis: Per protocol analysis
• Primary Outcome: Children in each group achieving resolution of symptoms without significant complications

Population

Inclusion Criteria

Clinically diagnosed with acute appendicitis, having gotten an appendectomy prior to the trial. Those eligible to have gotten appendicolith were included.

Exclusion Criteria

Patients that were excluded from this study were those that were suspected to have a perforated appendicitis on the basis of generalized peritonitis, those that had an appendiceal mass that was diagnosed by clinical examination and/or imaging, or those that had previous, non-operative treatment of acute appendicitis.

Baseline Characteristics

• Between the ages of 5 and 15
• Male: 26
• Female: 24
• 43 of the 50 total patients had duration of symptoms <48 hours.

Note: No further patient baseline characteristics outlined in trial

Interventions

• Patients were randomized into appendectomy or nonoperative with antibiotics alone.
  • Allocated to surgery (not specified if open or laparoscopic)
  • Received preoperative prophylaxis with metronidazole 20mg/kg.
    • Some given further antibiotic treatment depending on appendicitis severity
    • Trimethoprim/sulfamethoxazole/metronidazole was given intravenously for 24 hours to those with gangrenous appendicitis, and trimethoprim/sulfamethoxazole/metronidazole was given intravenously for at least 3 days for those patients with perforated appendicitis.
• Allocated to antibiotic treatment alone
  • Minimum of 48 hours of: IV meropenem 10mg/kg for three doses every 24 hours and IV metronidazole 20 mg/kg for one dose every 24 hours
  • Once oral formulations could be tolerated:
    • For 8 additional days: Oral ciprofloxacin 20mg/kg for two doses every 24 hours and metronidazole 20mg/kg for one dose every 24 hours
• Criteria for discharging patients, surgical or antibiotics alone (established a priori)
  • Afebrile 24 hours, with or without oral antibiotics, adequate pain relief on oral analgesia, tolerating a light diet, and mobile

Outcomes

Comparisons are surgical group vs. non-operative treatment group

Primary Outcomes

Symptoms resolved with no significant complications

• 26/26 (100%) vs. 22/24 (92%); P = 0.23

Secondary Outcomes

Median elapsed time from initial randomization to final discharge

• 34.5 hours (16.2-95.0 hours) vs. 51.5 hours (29.9-86.1 hours); P=0.0004

Complications (during 1 year follow up)

• Surgical group: No minor or major complications
• Non-operative treatment group: No minor complications, 1 major complication

Appendectomy after start of treatment

• Non-operative treatment group: 9/24 (38%)
  • 2/24 had early appendectomy (during time of primary antibiotic treatment)
  • 1/24 had appendectomy after 9 months due to recurrent acute appendicitis
  • 6/24 had an appendectomy who were negative for appendicitis on histopathological examination
    • 5/6 had appendectomy due to recurrent abdominal pain
    • 1/6 had appendectomy due to parental wish

Subgroup Analysis

Comparisons are non-operative treatment vs. surgery group Cost of initial inpatient stay

• 30,732 (18,980–63,863) SEK vs. 45,805 (33,042–94,638) SEK; (P < 0.0001)

Total cost of treatment

• 34,587 (19,120–146,552) SEK vs. 45,805 (33,042–94,638) SEK; (P = 0.11)

Criticisms

• Not adequately powered to detect differences in treatment efficacy
• Did not offer routine interval appendectomy
• Length of hospitalization was not similar for each treatment group

Funding

The study was funded through the costs paid by the patients. There was a fee per day of in-hospital care, an operating room fee and antibiotic costs.