Abstract
Introduction
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about 1.5 times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (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 17 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: early cholecystectomy, laparoscopic cholecystectomy, minilaparoscopic cholecystectomy, observation alone, open cholecystectomy, and percutaneous cholecystostomy.
Key Points
Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae.
About 95% of people with acute cholecystitis have gallstones.
It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.
Early cholecystectomy within 7 days of onset of symptoms is the treatment of choice for acute cholecystitis.
Early surgery reduces the duration of hospital admission compared with delayed surgery, but does not reduce mortality or complications.
Up to one quarter of people scheduled for delayed surgery may require urgent operations because of recurrent or worsening symptoms.
Laparoscopic cholecystectomy may reduce the duration of hospital admission and improve intra-operative and postoperative outcomes compared with open cholecystectomy, but it may increase the risk of bile duct injury.
Up to one quarter of people having laparoscopic cholecystectomy may need conversion to open surgery because of risks of complications or uncontrolled bleeding.
Minilaparoscopic surgery may be associated with slightly longer operative times than laparoscopic surgery, although it may reduce pain scores and the need for postoperative analgesia.
Routine abdominal drainage in both uncomplicated laparoscopic and open cholecystectomy is associated with an increase in wound infections compared with no drainage.
About this condition
Definition
Acute cholecystitis results from obstruction of the cystic duct, usually by a gallstone, followed by distension and subsequent chemical or bacterial inflammation of the gallbladder. People with acute cholecystitis usually have unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever. About 95% of people with acute cholecystitis have gallstones (calculous cholecystitis) and 5% lack gallstones (acalculous cholecystitis). Severe acute cholecystitis may lead to necrosis of the gallbladder wall, known as gangrenous cholecystitis. This review does not include people with acute cholangitis, which is a severe complication of gallstone disease and generally a result of bacterial infection.
Incidence/ Prevalence
The incidence of acute cholecystitis among people with gallstones is unknown. Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. The number of cholecystectomies carried out for acute cholecystitis increased from the mid 1980s to the early 1990s, especially in older people. Acute calculous cholecystitis is three times more common in women than in men up to the age of 50 years, and is about 1.5 times more common in women than in men thereafter.
Aetiology/ Risk factors
Acute calculous cholecystitis seems to be caused by obstruction of the cystic duct by a gallstone, or local mucosal erosion and inflammation caused by a stone, but cystic duct ligation alone does not produce acute cholecystitis in animal studies. The role of bacteria in the pathogenesis of acute cholecystitis is not clear; positive cultures of bile or gallbladder wall are found in 50% to 75% of cases. The cause of acute acalculous cholecystitis is uncertain and may be multifactorial, including increased susceptibility to bacterial colonisation of static gallbladder bile.
Prognosis
Complications of acute cholecystitis include perforation of the gallbladder, pericholecystic abscess, and fistula caused by gallbladder wall ischaemia and infection. In the US, the overall mortality from untreated complications is about 20%.
Aims of intervention
To reduce mortality and morbidity associated with acute cholecystitis, with minimal adverse effects of treatment.
Outcomes
Mortality; morbidity (including gallstone-related complications, persistent pain, intolerance to food, gastrointestinal upset, recurrent attacks of cholecystitis); intra-operative outcomes (includes duration of surgery and need for nasogastric tube); postoperative outcomes (duration of hospital stay, complications, antibiotic use, and analgesia use); quality of life. Postoperative fall in haemoglobin and conversion of a planned laparoscopic cholecystectomy to an open cholecystectomy are surrogate outcomes and are reported in further information on studies.
Methods
Clinical Evidence search and appraisal April 2011. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2011, Embase 1980 to April 2011, and The Cochrane Database of Systematic Reviews, Issue 1, 2011 (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, with any level of blinding (including "open" studies), and containing any number of individuals of whom at least 80% were followed up. There was no minimum length of follow-up required to include studies. 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 relative risks (RRs) and odds ratios (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 Acute cholecystitis.
| Important outcomes | Intra-operative outcomes, Morbidity, Mortality, Postoperative outcomes, Quality of life | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for acute cholecystitis? | |||||||||
| at least 16 (at least 1255) | Mortality | Early versus delayed cholecystectomy | 4 | −1 | 0 | −1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for differences in surgeon expertise |
| 17 (at least 1289) | Morbidity | Early versus delayed cholecystectomy | 4 | −1 | 0 | −2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for differences in surgeon expertise and for unclear outcome assessment |
| at least 16 (at least 1255) | Postoperative outcomes | Early versus delayed cholecystectomy | 4 | −1 | 0 | −1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for differences in surgeon expertise |
| 1 (70) | Morbidity | Percutaneous cholecystostomy followed by early cholecystectomy versus medical treatment followed by delayed cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and no intention-to-treat analysis |
| 1 (70) | Postoperative outcomes | Percutaneous cholecystostomy followed by early cholecystectomy versus medical treatment followed by delayed cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and no intention-to-treat analysis |
| 1 (70) | Morbidity | Laparoscopic cholecystectomy versus open cholecystectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 4 (606) | Intra-operative outcomes | Laparoscopic cholecystectomy versus open cholecystectomy | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results for duration of surgery. Directness points deducted for population differences and differences in techniques |
| 4 (601) | Postoperative outcomes | Laparoscopic cholecystectomy versus open cholecystectomy | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for population differences and differences in techniques |
| 13 (777) | Intra-operative outcomes | Laparoscopic cholecystectomy versus minilaparoscopic cholecystectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for inclusion of poor-quality RCTs |
| at least 3 (at least 215) | Postoperative outcomes | Laparoscopic cholecystectomy versus minilaparoscopic cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data in some outcomes and inclusion of poor-quality RCTs |
| 3 (529) | Postoperative outcomes | Routine abdominal drainage versus no drainage in uncomplicated laparoscopic cholecystectomy | 4 | –3 | 0 | 0 | +2 | Moderate | Quality points deducted for inclusion of poor-quality studies, low event rate, and sparse data in 1 outcome. Effect-size points added for OR >5 or <0.2 |
| 1 (64) | Morbidity | Laparoscopic cholecystectomy versus no treatment/observation | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| at least 17 (at least 3090) | Postoperative outcomes | Routine abdominal drainage versus no drainage in uncomplicated open cholecystectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for methodological weaknesses of included trials |
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
- Laparoscopic cholecystectomy
Laparoscopic cholecystectomy involves removal of the gallbladder using a projection camera and 5–10-mm trocar ports. Conversion from laparoscopic to open cholecystectomy is needed if the laparoscopic procedure cannot be completed without risking injury to surrounding structures or when bleeding cannot be stopped. Open cholecystectomy is required in people who have a fistula from the gallbladder into the bile duct or intestine, and in some people who have perforation and abscess in the right upper quadrant.
- 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.
- Minilaparoscopic cholecystectomy
This procedure involves removal of the gallbladder using a projection camera and 2–3-mm trocar ports.
- 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.
- Open cholecystectomy
Open cholecystectomy involves removal of the gallbladder by laparotomy. Open cholecystectomy is required in people who have a fistula from the gallbladder into the bile duct or intestine, and in some people who have perforation and abscess in the right upper quadrant.
- 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.
Contributor Information
Dr Valerie Halpin, Legacy Good Samaritan Hospital, Portland, OR, USA.
Aditya Gupta, Legacy Health System, Portland, USA.
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