SAFETY AND EFFICACY OF ANTIBIOTICS COMPARED WITH

APPENDICECTOMY FOR TREATMENT OF UNCOMPLICATED ACUTE

APPENDICITIS:META-ANALYSIS OF RANDOMISED

CONTROLLED TRIALS

Krishna K Varadhan, Keith R Neal, Dileep N Lobo

BMJ April 2012

BACKGROUND Appendicitis is common infection that occur in abdomen. Appendicectomy has been the mainstay for the

treatment for acute appendicitis The advent of laparoscopic surgery and the low

threshold for operative intervention have led to a risk of high negative appendicectomy rates with unnecessary surgery related morbidity.

Antibiotic treatment was often considered as a bridge to surgery in patients with suspected appendicitis but no clear indications for appendicectomy such as signs of perforation or peritonitis. Less morbidity associated with antibiotic treatment than surgery in uncomplicated acute appendicitis

OBJECTIVE

To compare the safety and efficacy of antibiotics versus appendicectomy for treatment of uncomplicated acute appendicitis

METHOD

Inclusion Criteria RCTs comparing antibiotic treatment with

appendicectomy for uncomplicated acute appendicitis in adult patients

RCTs with well defined diagnostic and treatment protocols which reported at least two of the outcome measures (complications, treatmet efficacy, length of stay, readmissions) published between January 1996 – December 2011

Exclusion Criteria Non-randomised studies, retrospective

studies, case series studies Studies that reported outcomes in patients

with complicated appendicitis (local or contained perforation with an appendicular abscess or mass).

Methods

Assesing the methodological quality of the RCTs using method of randomisation, concealment of allocation, blinding, description of dropouts and withdrawals, intention to treat analysis, and duration of follow-up.

Evaluation for methodological quality of the RCTs and to rate the quality of evidence and strength of recommendations of the meta-analysis using GRADE (the grading of recommendations assessment, development, and evaluation ) system, as recommended by the Cochrane Collaboration.

The GRADE system assess the RCTs across five main domains for each outcome: limitations of the study design and execution; inconsistency, indirectness, and imprecision of results; and publication bias.

Accordingly, the recommendation for either antibiotic treatment or appendicectomy was graded as very low, low, moderate, or high.

Outcome measure

The primary outcome measure was complications.

The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions.

Outcome measure

Data Collection &Statistical Analysis The meta analysis was done using Review

Manager version 5.1 software Mantel-Haenszel method was used to combine

the summary statistic and assessed the statistical heterogeneity by using the I2 method alongside the χ2 P value.

Random effect model was used to provide a conservative estimate of the results.

We considered the results to be statistically significant at the P<0.05 level if the 95% confidence interval did not include the value .

Result Four randomised controlled trials with a total of

900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria.

Antibiotic treatment was associated with a 63% (277/438) success rate at one year.

There is a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004).

No significant differences were seen for treatment efficacy or length of stay.

Table 1. Summary of outcome

Table 2. GRADE analysis: antibiotics versus appendicetomy for uncomplicated acute appendicitis—quality assessment

Limitations of the Study

The major confounders that may have had an influence on the outcomes are:

diagnosis of appendicitistype and duration of antibiotic treatmentreporting of complications,and planned discharge after either antibiotic

treatment or appendicectomy.

CONCLUSION

Antibiotics can be used safely as primary treatment in patients presenting with acute uncomplicated appendicitis

CRITICAL APPRAISAL

The validity of the research Interpretation of the result Applicability of the result

I. EVALUATION OF THE VALIDITYOF THE REVIEW

1. Is the clinical question clearly focused with regard to: the population?

Yes people with acute uncomplicated appendicitis

the intervention?

Yes antibiotics versus appendicectomy the outcome measures?

Yes complications, length of stay, readmissions, treatment efficacy

2. Are the criteria for the selection of the studies to be included in the review in accordance with: the specifications of the foregoing question in

regard to populations, interventions, and results?

Yes the type of research design that will be chosen?

Yes RCT

3. Is the literature search method clearly specified?

Yes the authors used the search strategy

developed by the Cochrane Collaboration Group Is there a high probability that some

relevant studies may have been omitted?

No

4. Have the identified studies been evaluated for methodological quality?

Yes GRADE system: systematic assessments of all RCTs across five main domains for each outcome: limitations of the study design and execution; inconsistency, indirectness, and imprecision of results; and publication bias

5. Was the methodological quality evaluation carried out by more than one person independently, and the degree of agreement between them established?

Yes the 1st & 2nd author search and evaluate the sources of the meta analysis; any disagreements were resolved by discussion with the 3rd author

II. INTERPRETATION OF THE RESULTS OF THE REVIEW

1. Were the results consistent from one study to another?

Yes

2. What were the overall results of the review?

Antibiotic therapy relative risk reduction of 31% (risk ratio 0.69); no significant differences in treatment efficacy or length of stay.

3. How precise were the results?

95% CI 0.54 – 0.89, p=0.004

III. APPLICABILITY OF THE RESULTS OF THE REVIEW IN CLINICAL PRACTICE

1. Are my patients similar to the patients included in the original studies? Yes

2. Is the intervention feasible in my setting? Yes

3. Have all the clinically relevant results been taken into consideration? Yes

4. Do the benefits outweigh the potential harm?

Yes