Abstract
Introduction
Appendicitis is an acute inflammation of the appendix that can lead to an abscess, ileus, peritonitis, or death. Appendicitis is the most common abdominal surgical emergency, with a lifetime risk of approximately 7% to 9% in the USA. Mortality from acute appendicitis is less than 0.3%, but rises to 1.7% after perforation.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute appendicitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, laparoscopic surgery, ligation, open surgery, stump inversion, and surgery.
Key Points
The incidence of acute appendicitis is falling, although the reasons are unclear.
Appendicitis is the most common abdominal surgical emergency, with a lifetime risk of approximately 7% to 9% in the USA.
Potential causes of appendicitis include faecoliths, lymphoid hyperplasia, fibrous bands, foreign bodies, and caecal carcinoma, all of which can lead to obstruction of the appendix lumen.
Mortality from acute appendicitis is <0.3%, but rises to 1.7% after perforation.
Spontaneous resolution of acute appendicitis has been reported in at least 10% of episodes.
Very limited evidence suggests that conservative treatment of acute appendicitis with antibiotics may reduce pain and morphine consumption, but that one third of people are likely to be readmitted with acute appendicitis requiring surgery within 1 year.
Standard treatment for acute appendicitis is appendicectomy.
Clinical trials to compare surgery with no treatment would be considered unethical, and have not been done.
There is good evidence that laparoscopic surgery in adults reduces wound infections, postoperative pain, duration of hospital stay, and time off work compared with open surgery, but increases the risk of intra-abdominal abscesses.
Limited evidence suggests that laparoscopic surgery in children may reduce wound infections and duration of hospital stay compared with open surgery, but it has not been shown to reduce other complications.
There is some evidence to suggest that stapling reduces operative time compared with endoloops, but no reliable evidence to suggest that it reduces other complications.
We don't know how natural orifice surgery compares with laparoscopic surgery, as we found no RCTs.
There is limited evidence to suggest that stump inversion has an increased rate of wound infection compared with simple ligation, and no difference in rate of intra-abdominal abscess formation.
The most common complication of appendicectomy is wound infection, with intra-abdominal abscess formation less common.
Treatment with surgery plus antibiotics reduces wound infections and intra-abdominal abscesses compared with surgery alone in adults with simple or complicated appendicitis.
However, in children, the benefit of antibiotics may be limited to those with complicated appendicitis.
About this condition
Definition
Acute appendicitis is acute inflammation of the vermiform appendix.
Incidence/ Prevalence
The incidence of acute appendicitis is falling, although the reason for this is unclear. The reported lifetime risk of appendicitis in the USA is 8.7% in men and 6.7% in women, and about 35,000 cases are reported annually in England. Appendicitis is the most common abdominal surgical emergency requiring operation.
Aetiology/ Risk factors
The cause of appendicitis is uncertain, although various theories exist. The predominant theories centre on luminal obstruction of the blind-ending vermiform appendix as the primary pathology. Obstruction prevents escape of secretions, and without resolution leads to a rise in intraluminal pressure within the appendix. This can lead to subsequent mucosal ischaemia, and the stasis provides an ideal environment for bacterial overgrowth. The most common cause of obstruction has been traditionally attributed to lymphoid hyperplasia, which may present with acute catarrhal appendicitis, with a gradual onset of symptoms. Lymphoid hyperplasia may be caused by infections (bacterial, viral, fungal, parasitic) or by inflammation, such as in inflammatory bowel disease. A more abrupt course of symptoms has been described in acute obstructive appendicitis from faecoliths. Other, rarer, causes of obstruction may include parasites (more common in developing countries), fibrous bands, foreign bodies, or carcinoid and caecal carcinoma. Some studies have shown inflammation and mucosal ulceration occurring before appendiceal dilatation, pointing to inflammation, infection, or both being the primary causes of obstruction.
Prognosis
The prognosis of untreated appendicitis is unknown, since RCTs comparing treatment versus no treatment would be unethical. The standard treatment for appendicitis is appendicectomy, although spontaneous resolution has been reported in at least 10% of patients. The recurrence of appendicitis after conservative management, and recurrent abdominal symptoms in certain people, suggest that chronic appendicitis and recurrent acute or subacute appendicitis may also exist. The mortality from acute appendicitis is <0.3%, rising to 1.7% after perforation. The most common complication of appendicectomy is wound infection, occurring in 5% to 33% of cases. Intra-abdominal abscess formation occurs less frequently, in 2% of appendicectomies. A perforated appendix in childhood does not seem to have subsequent negative consequences for female fertility.
Aims of intervention
To reduce pain; prevent postoperative infection; shorten hospital stay; and hasten return to normal activity.
Outcomes
Mortality (from appendicitis), operation duration, return to normal activities, duration of hospital stay, quality of life, wound infection rates, intra-abdominal infection rates, pain, postoperative mortality (from surgery), other adverse effects (including postoperative fever, postoperative ileus, etc).
Methods
Clinical Evidence search and appraisal February 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to February 2010, Embase 1980 to February 2010, and The Cochrane Database of Systematic Reviews 2010, Issue 1 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded (where possible), and containing any number of individuals, of whom >80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Appendicitis.
| Important outcomes | Hospital stay, Intra-abdominal infection, Mortality (from appendicitis), Operation duration, Pain, Postoperative mortality (from surgery), Quality of life, Return to normal activities, Wound infection | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for acute appendicitis? | |||||||||
| at least 35 (8812) | Wound infection | Surgery plus antibiotics versus surgery plus placebo or surgery alone in adults | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for randomisation flaws |
| 10 (4468) | Intra-abdominal infection | Surgery plus antibiotics versus surgery plus placebo or surgery alone in adults | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for randomisation flaws. Consistency point deducted for different results for subgroup analyses |
| 7 (1198) | Wound infection | Surgery plus antibiotics versus surgery plus placebo or surgery alone in children | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for randomisation flaws. Consistency point deducted for different results for subgroup analyses |
| 6 (1003) | Intra-abdominal infection | Surgery plus antibiotics versus surgery plus placebo or surgery alone in children | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for randomisation flaws and uncertainty about statistical significance of result |
| 2 (120) | Pain | Antibiotics versus surgery | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for uncertainty about diagnosis |
| 1 (252) | Return to normal activities | Antibiotics versus surgery | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for analysis flaw. Directness points deducted for narrow inclusion criteria |
| at least 29 (at least 3102) | Hospital stay | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in RCTs included in analysis. Directness point deducted for heterogeneity in analysis |
| 25 (3047) | Operation duration | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in RCTs included in analysis. Directness point deducted for heterogeneity in analysis |
| at least 12 (at least 1178) | Return to normal activities | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in RCTs included in analysis. Directness point deducted for heterogeneity in analysis |
| at least 41 (at least 4954) | Wound infection | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for methodological flaws in RCTs included in analysis |
| 40 (4953) | Intra-abdominal infection | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for methodological flaws in RCTs included in analysis |
| at least 16 (at least 2010) | Pain | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in RCTs included in analysis. Directness point deducted for heterogeneity in analysis |
| 1 (100) | Quality of life | Laparoscopic surgery versus open surgery (in adults) | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 3 (176) | Hospital stay | Laparoscopic surgery versus open surgery (in children) | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting |
| 9 (1236) | Wound infection | Laparoscopic surgery versus open surgery (in children) | 4 | 0 | –1 | 0 | 0 | Moderate | Consistency point deducted for conflicting results |
| 11 (1636) | Intra-abdominal infection | Laparoscopic surgery versus open surgery (in children) | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for uncertainty about statistical significance of result |
| 2 (869) | Hospital stay | Stump inversion versus simple ligation | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (869) | Wound infection | Stump inversion versus simple ligation | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in included RCTs. Directness point deducted for clinical heterogeneity |
| 2 (869) | Intra-abdominal infection | Stump inversion versus simple ligation | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 3 (number of people in analyses not reported) | Hospital stay | Stapling versus endoloops in laparoscopic appendicectomy | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and methodological flaws in included RCTs. Directness point deducted for statistical and clinical heterogeneity |
| at least 4 (number of people in analyses not reported) | Operation duration | Stapling versus endoloops in laparoscopic appendicectomy | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and methodological flaws in included RCTs. Directness point deducted for statistical and clinical heterogeneity |
| 1 (417) | Wound infection | Stapling versus endoloops in laparoscopic appendicectomy | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for methodological flaws in included RCTs. Directness point deducted for clinical heterogeneity |
| 5 (number of people in analyses not reported) | Intra-abdominal infection | Stapling versus endoloops in laparoscopic appendicectomy | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for incomplete reporting of results and methodological flaws in included RCTs. Directness point deducted for statistical and clinical heterogeneity |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Complicated appendicitis
Perforated or gangrenous appendicitis, or the presence of a periappendicular abscess.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Negative appendicectomy
Term used for an operation performed for suspected appendicitis, in which the appendix is found to be normal on histological evaluation.
- Simple appendicitis
Clinically normal or inflamed appendix, in the absence of gangrene, perforation, or abscess around the appendix.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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