Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis

  • Review
  • Intervention

Authors


Abstract

Background

The management of people at high risk of perioperative death due to their general condition (high-risk surgical patients) with acute calculous cholecystitis is controversial, with no clear guidelines. In particular, the role of percutaneous cholecystostomy in these patients has not been defined.

Objectives

To compare the benefits (temporary or permanent relief of symptoms) and harms (recurrence of symptoms, procedure-related morbidity) of percutaneous cholecystostomy in the management of high-risk individuals with symptomatic gallstones.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) inThe Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded to December 2012 to identify the randomised clinical trials. We also handsearched the references lists of identified trials.

Selection criteria

We included only randomised clinical trials (irrespective of language, blinding, or publication status) addressing this issue.

Data collection and analysis

Two review authors collected data independently. For each outcome, we calculated the P values using Fisher's exact test or mean difference (MD) with 95% confidence intervals (CI).

Main results

We included two trials with 156 participants for this review. The comparisons included in these two trials were percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy (1 trial; 70 participants) and percutaneous cholecystostomy versus conservative treatment (1 trial; 86 participants). Both trials had high risk of bias.

Percutaneous cholecystostomy with early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy: There was no significant difference in mortality between the two intervention groups (0/37 versus 1/33; Fisher's exact test: P value = 0.47). There was no significant difference in overall morbidity between the two intervention groups (1/31 versus 2/30; Fisher's exact test: P value = 0.61). This trial did not report on quality of life. There was no significant difference in the proportion of participants requiring conversion to open cholecystectomy between the two intervention groups (2/31 percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus 4/30 delayed laparoscopic cholecystectomy; Fisher's exact test: P value = 0.43). The mean total hospital stay was significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group (1 trial; 61 participants; MD -9.90 days; 95% CI -12.31 to -7.49). The mean total costs were significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group (1 trial; 61 participants; MD -1123.00 USD; 95% CI -1336.60 to -909.40).

Percutaneous cholecystostomy versus conservative treatment: Nine of the 44 participants underwent delayed cholecystectomy in the percutaneous cholecystostomy group. Seven of the 42 participants underwent delayed cholecystectomy in the conservative treatment group. There was no significant difference in mortality between the two intervention groups (6/44 versus 7/42; Fisher's exact test: P value = 0.77). There was no significant difference in overall morbidity between the two intervention groups (6/44 versus 3/42; Fisher's exact test: P value = 0.49). The number of participants who underwent laparoscopic cholecystectomy was not reported in this trial. Therefore, we were unable to calculate the proportion of participants who underwent conversion to open cholecystectomy. The other outcomes, total hospital stay, quality of life, and total costs, were not reported in this trial.

Authors' conclusions

Based on the current available evidence from randomised clinical trials, we are unable to determine the role of percutaneous cholecystostomy in the clinical management of high-risk surgical patients with acute cholecystitis. There is a need for adequately powered randomised clinical trials of low risk of bias on this issue.

Résumé scientifique

Cholécystostomie percutanée chez des patients atteints d'une cholécystite aiguë lithiasique présentant des risques chirurgicaux élevés

Contexte

La prise en charge des personnes présentant des risques élevés de décès périopératoire en raison de leur état de santé général (patients présentant des risques chirurgicaux élevés) et souffrant d'une cholécystite aiguë lithiasique est en débat et ne fait l'objet d'aucune recommandation claire. Plus particulièrement, le rôle de la cholécystostomie percutanée chez ces patients n'a pas été défini.

Objectifs

Comparer les effets bénéfiques (soulagement temporaire ou permanent des symptômes) et néfastes (réapparition des symptômes, morbidité liée à la procédure) d'une cholécystostomie percutanée dans la prise en charge de personnes particulièrement à risque souffrant de calculs biliaires symptomatiques.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL) de The Cochrane Library, ainsi que dans MEDLINE, EMBASE et Science Citation Index Expanded jusqu'en décembre 2012, afin d'identifier des essais cliniques randomisés. Nous avons également effectué des recherches manuelles dans les listes bibliographiques des essais identifiés.

Critères de sélection

Nous avons uniquement inclus des essais cliniques randomisés (indépendamment de la langue, de la mise en aveugle ou du statut de la publication) abordant ce sujet.

Recueil et analyse des données

Deux auteurs de la revue ont indépendamment collecté des données. Pour chaque critère de jugement, nous avons calculé les valeurs de P en utilisant le test exact de Fisher ou la différence moyenne (DM) avec des intervalles de confiance (IC) à 95 %.

Résultats principaux

Nous avons inclus deux essais totalisant 156 participants dans cette revue. Les comparaisons incluses dans ces deux essais étaient une cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce versus une cholécystectomie laparoscopique tardive (1 essai ; 70 participants) et une cholécystostomie percutanée versus un traitement conservateur (1 essai ; 86 participants). Les deux essais présentaient des risques élevés de biais.

Une cholécystostomie percutanée avec une cholécystectomie laparoscopique précoce versus une cholécystectomie laparoscopique tardive : Il n'y avait aucune différence significative au niveau de la mortalité entre les deux groupes expérimentaux (0/37 versus 1/33 ; test exact de Fisher : valeur de P = 0,47). Il n'y avait aucune différence significative au niveau de la morbidité globale entre les deux groupes expérimentaux (1/31 versus 2/30 ; test exact de Fisher : valeur de P = 0,61). Cet essai n'a pas documenté la qualité de vie. Il n'y avait aucune différence significative au niveau de la proportion de participants nécessitant une conversion en une cholécystectomie ouverte entre les deux groupes expérimentaux (2/31 cas de cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce versus 4/30 cas de cholécystectomie laparoscopique tardive ; test exact de Fisher : valeur de P = 0,43). La durée d'hospitalisation totale moyenne était significativement inférieure dans le groupe de la cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce par rapport au groupe de la cholécystectomie laparoscopique tardive (1 essai ; 61 participants ; DM - 9,90 jours ; IC à 95 % - 12,31 à - 7,49). Les coûts totaux moyens étaient significativement inférieurs dans le groupe de la cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce par rapport au groupe de la cholécystectomie laparoscopique tardive (1 essai ; 61 participants ; DM - 1 123 USD ; IC à 95 % - 1 336,60 à - 909,40).

Une cholécystostomie percutanée versus un traitement conservateur : Neuf des 44 participants du groupe de la cholécystotomie percutanée ont fait l'objet d'une cholécystectomie tardive. Sept des 42 participants du groupe de traitement conservateur ont fait l'objet d'une cholécystectomie tardive. Il n'y avait aucune différence significative au niveau de la mortalité entre les deux groupes expérimentaux (6/44 versus 7/42 ; test exact de Fisher : valeur de P = 0,77). Il n'y avait aucune différence significative au niveau de la morbidité globale entre les deux groupes expérimentaux (6/44 versus 3/42 ; test exact de Fisher : valeur de P = 0,49). Le nombre de participants ayant fait l'objet d'une cholécystectomie laparoscopique n'était pas rapporté dans cet essai. Par conséquent, nous n'avons pas pu calculer la proportion des participants ayant fait l'objet d'une conversion en une cholécystectomie ouverte. Les autres critères de jugement : la durée d'hospitalisation totale, la qualité de vie et les coûts totaux, n'étaient pas rapportés dans cet essai.

Conclusions des auteurs

D'après les preuves dont nous disposons actuellement grâce aux essais cliniques randomisés, nous ne sommes pas en mesure de déterminer le rôle de la cholécystostomie percutanée dans la prise en charge clinique de patients atteints d'une cholécystite aiguë présentant des risques chirurgicaux élevés. D'autres essais cliniques randomisés, d'une puissance statistique adéquate et avec de faibles risques de biais, devront être réalisés à ce sujet.

Plain language summary

External drainage of gallbladder for high-risk surgical patients with acute calculous cholecystitis

Removal of the gallbladder (cholecystectomy) is generally recommended for people with symptoms related to gallstones. People at high risk of surgical complications - that is, elderly people and people with co-existing illness - can become very unwell as a result of inflammation of the gallbladder. During anaesthesia and surgery, the body's ability to tolerate stress is lowered, particularly in elderly people and people with co-existing illness. Thus, surgery can be detrimental to these people who are already unwell. The optimal clinical management of these people is not known. External drainage of gallbladder contents with a tube using guidance from scans (percutaneous cholecystostomy) has been proposed as the one of the ways that these patients can be treated. By draining the contents of gallbladder, any infected material can be removed from the body and this might improve the health. Some consider percutaneous cholecystostomy as the only treatment required and perform cholecystectomy only in those who develop further complications while others recommend routine cholecystectomy following percutaneous cholecystostomy. We sought to review all the information available in the literature on this topic and obtained information from randomised clinical trials (studies designed to lower the risk of arriving at wrong conclusions due to researcher's favouritism or differences in the type of people undergoing the different treatments) to determine the optimal method of managing these people. Two review authors collected data independently as a way of quality control.

We identified two trials with 156 participants for this review. The comparisons included in these two trials were 1) percutaneous cholecystostomy plus laparoscopic cholecystectomy (key hole removal of gallbladder) immediately after the general condition improves (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy) versus planned delayed laparoscopic cholecystectomy performed routinely (1 trial; 70 participants) and 2) percutaneous cholecystostomy versus conservative treatment (supportive treatment and antibiotic treatment) (1 trial; 86 participants). Both trials were at high risk of systematic error (prone to arrive at wrong conclusions because of the way the trials were designed and data were analysed). There was no significant difference in the proportion of participants who died or developed complications between any of the comparison groups. Quality of life was not reported in any of the trials. There was no significant difference in the proportion of participants requiring conversion to open cholecystectomy in the only comparison that reported this outcome (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy). The mean total hospital stay and mean costs were significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group. Because of the few trials included in this review and due to their low sample size, there is risk of random errors (play of chance). Based on the current available evidence, we are unable to determine the role of percutaneous cholecystostomy in the clinical management of high-risk surgical patients with acute cholecystitis. There is a need for well-designed clinical trials with low risk of systematic error and random errors on this issue.

Résumé simplifié

Drainage externe de la vésicule biliaire chez des patients atteints d'une cholécystite aiguë lithiasique présentant des risques chirurgicaux élevés

L'ablation de la vésicule biliaire (cholécystectomie) est généralement recommandée chez les personnes présentant des symptômes liés à des calculs biliaires. L'état de santé des personnes présentant des risques élevés de complications chirurgicales, à savoir les personnes âgées et les personnes souffrant d'une maladie concomitante, peut se dégrader suite à une inflammation de la vésicule biliaire. Pendant l'anesthésie et la chirurgie, la capacité de l'organisme à tolérer le stress est amoindrie, surtout chez les personnes âgées et celles souffrant d'une maladie concomitante. Par conséquent, la chirurgie peut être néfaste pour ces personnes dont l'état de santé est déjà préoccupant. Nous ignorons quelle prise en charge clinique serait optimale pour ces personnes. Le drainage externe du contenu de la vésicule biliaire effectué via l'insertion d'un drain guidé (cholécystostomie percutanée) a été proposé comme méthode de traitement de ces patients. En drainant le contenu de la vésicule biliaire, toute matière infectée peut être retirée de l'organisme afin d'améliorer l'état de santé du patient. Certains considèrent la cholécystostomie percutanée comme étant le seul traitement requis et pratiquent une cholecystectomie uniquement chez les patients développant d'autres complications, alors que d'autres recommandent une cholecystectomie systématique suite à une cholécystostomie percutanée. Notre objectif était de passer en revue toutes les informations disponibles à ce sujet dans la littérature. Nous avons trouvé des informations dans des essais cliniques randomisés (études conçues pour éviter tout risque de conclusions erronées en raison du favoritisme du chercheur ou des différences entre les types de patients faisant l'objet de différents traitements) afin de déterminer la méthode optimale de prise en charge de ces personnes. Deux auteurs de la revue ont indépendamment collecté des données comme méthode de contrôle de la qualité méthodologique.

Nous avons identifié deux essais totalisant 156 participants pour cette revue. Les comparaisons incluses dans ces deux essais étaient 1) une cholécystostomie percutanée plus une cholécystectomie laparoscopique (ablation par un petit trou (« key hole ») de la vésicule biliaire) dès les premiers signes d'amélioration de l'état de santé général (cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce) versus une cholécystectomie laparoscopique tardive planifiée pratiquée de façon systématique (1 essai ; 70 participants) et 2) une cholécystostomie percutanée versus un traitement conservateur (traitement de soutien et traitement antibiotique) (1 essai ; 86 participants). Ces deux essais présentaient des risques élevés d'erreur systématique (risques de tirer des conclusions erronées en raison de la méthode utilisée pour concevoir les essais et pour analyser les données). Il n'y avait aucune différence significative au niveau de la proportion de participants ayant décédé ou développé des complications entre les groupes témoins. Aucun essai ne rendait compte de la qualité de vie. Il n'y avait aucune différence significative au niveau de la proportion de participants nécessitant une conversion en une cholécystectomie ouverte dans l'unique comparaison qui rendait compte de ce critère de jugement ( cholécystostomie percutanée suivie d'une cholécystectomie laparoscopique précoce versus une cholécystectomie laparoscopique tardive). La durée d'hospitalisation totale moyenne et les coûts moyens étaient significativement inférieurs dans le groupe de la cholécystostomie percutanée suivie d'une chlecystectomie laparoscopique précoce par rapport au groupe de la cholécystectomie laparoscopique tardive. En raison du faible nombre d'essais inclus dans cette revue et de la taille réduite de l'échantillon, il existe des risques d'erreurs aléatoires (effet du hasard). D'après les preuves dont nous disposons actuellement, nous ne sommes pas en mesure de déterminer le rôle de la cholécystostomie percutanée dans la prise en charge clinique de patients atteints d'une cholécystite aiguë présentant des risques chirurgicaux élevés. Des essais cliniques correctement conçus, avec de faibles risques d'erreurs systématiques et aléatoires, devront être réalisés sur ce sujet.

Notes de traduction

Traduit par: French Cochrane Centre 24th September, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Summary of findings(Explanation)

Summary of findings for the main comparison. Intervention versus control for high-risk surgical patients with acute calculous cholecystitis
  1. 1 High risk of bias in the trial(s) included.
    2 The confidence intervals of risk ratio overlapped 0.75 and 1.25.
    3 Publication bias could not be assessed because of the low number of trials.

Intervention versus control for high-risk surgical patients with acute calculous cholecystitis
Patient or population: high-risk surgical patients with acute calculous cholecystitis.
Settings: secondary or tertiary setting.
Intervention: intervention versus control.
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Number of participants
(studies)
Quality of the evidence
(GRADE)
Assumed riskCorresponding risk
Control Intervention
Percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy
Mortality 30 per 1000 9 per 1000
(0 to 215)
RR 0.3
(0.01 to 7.08)
70
(1 study)
⊕⊝⊝⊝
very low 1,2,3
Serious adverse events 61 per 1000 27 per 1000
(2 to 285)
RR 0.45
(0.04 to 4.7)
70
(1 study)
⊕⊝⊝⊝
very low 1,2,3
Percutaneous cholecystostomy versus conservative treatment
Mortality 167 per 1000 137 per 1000
(50 to 373)
RR 0.82
(0.3 to 2.24)
86
(1 study)
⊕⊝⊝⊝
very low 1,2,3
Serious adverse events 71 per 1000 136 per 1000
(36 to 511)
RR 1.91
(0.51 to 7.15)
86
(1 study)
⊕⊝⊝⊝
very low 1,2,3
*The basis for the assumed risk is the control group risk in the study. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

About 10% to 15% of the adult western population have gallstones (NIH 1992; Halldestam 2004). The annual incidence of gallstones is about 1 in 200 people (NIH 1992). Only 1% to 4% of people with gallstones become symptomatic (biliary colic, acute cholecystitis, obstructive jaundice, gallstone pancreatitis) in one year (NIH 1992; Halldestam 2004). Surgeons currently prefer laparoscopic cholecystectomy over open cholecystectomy for cholecystectomy (Fullarton 1994; Livingston 2004) and advised it only for symptomatic gallstones (NIH 1992).

High-risk surgical patients - people with co-existing illnesses - may have pathological changes in cardiovascular, cerebrovascular, pulmonary, and renal functions, resulting in increased morbidity and mortality. Such morbidity may encompass cardiac morbidity such as myocardial infarction, congestive cardiac failure, and stroke; and pulmonary morbidity such as pneumonia and atelectasis (Parker 2004). Elderly people are at risk of complications of cholecystectomy, which include injury to vessels or bowel (Fletcher 1999) during port insertion for laparoscopic cholecystectomy, bile duct injury (Buanes 1996; Richardson 1996; Krahenbuhl 2001; Gurusamy 2006), and bile leak requiring endoscopic retrograde cholangio pancreatography (Johansson 2003; Kimura 2005). In addition to the above risks, high-risk surgical patients are also exposed to the risks of pneumoperitoneum in laparoscopic cholecystectomy. These include haemodynamic changes and alteration in pulmonary compliance (Gurusamy 2008). Emergency cholecystectomy in elderly people is associated with a mortality of between 8.6% (open cholecystectomy) and 22% (laparoscopic cholecystectomy) (Uecker 2001). One of the possible reasons is because of worsening of general condition because of sepsis (systemic infection) due to acute cholecystitis. Irrespective of whether cholecystectomy is performed, the patients receive antibiotic treatment and supportive treatment which involves fluid treatment and regular monitoring of patients.

Description of the intervention

Because of the increased risks of emergency surgery in elderly people (Ozturk 2007), and the increased risk of gallbladder perforation due to acute cholecystitis in elderly people and in those with cardiovascular diseases (Stefanidis 2006), interim percutaneous cholecystostomy (Macri 2006) or percutaneous aspiration (Curro 2006) have been used as clinical managements in order to delay cholecystectomy. In addition, percutaneous cholecystostomy has been proposed as replacement for cholecystectomy in high risk surgical patients (Kortram 2012). Percutaneous cholecystostomy can be performed under local anaesthesia and is usually performed under image guidance such as ultrasound or CT scan (computerised tomography scan).

How the intervention might work

Percutaneous cholecystostomy works by decompressing the infected bile or pus in the gallbladder, thereby removing the infected collection without removing the source of infection (ie, gallbladder). By removing the infected bile or pus in the gallbladder, inflammation of the gallbladder can be reduced, thereby avoiding septicaemia and resulting in an improvement in the high-risk patient's general condition. This may be used as the definitive treatment in addition to antibiotic and fluid management in very ill patients whose general condition is not expected to improve enough to allow cholecystectomy or may allow cholecystectomy at a later date in high risk surgical patients whose general condition might improve after removal of the septic focus. However, not removing the gallbladder may increase the risk by not removing the source of infection.

Why it is important to do this review

There have been no previous meta-analyses or systematic reviews of the options available for the management of acute cholecystitis in high-risk surgical patients.

Objectives

To compare the benefits (temporary or permanent relief of symptoms) and harms (recurrence of symptoms, procedure-related morbidity) of percutaneous cholecystostomy in the management of elderly or high-risk individuals with symptomatic gallstones.

Methods

Criteria for considering studies for this review

Types of studies

We considered all randomised clinical trials which compare one intervention versus another in elderly or high-risk surgical patients with acute cholecystitis. We placed no restrictions on language, blinding, publication status, sample size, or whether the trials were adequately powered or not.

Types of participants

High-risk surgical patients with acute cholecystitis, that is, people with high-risk status (American Society of Anesthesiologists (ASA) Physical Status Classification III to V) with acute cholecystitis irrespective of the severity of acute cholecystitis. We accepted the revised Tokyo Guidelines for the diagnosis of acute cholecystitis (Yokoe 2012). The revised Tokyo guidelines is a modification of the Tokyo Guidelines for the diagnosis of acute cholecystitis (Hirota 2007; Yokoe 2012). If authors used other definitions for high-risk surgical patients (such as physiology scores) or acute cholecystitis, we included such trials and noted the definitions used by authors, and we planned subgroup analysis as appropriate.

Types of interventions

We included the following comparisons in high-risk surgical patients with acute cholecystitis.

  • Percutaneous cholecystostomy with antibiotic and supportive treatment followed by routine cholecystectomy versus antibiotic and supportive treatment and routine cholecystectomy. In this situation, percutaneous cholecystostomy is performed as a bridging treatment until the general health of the individual improves.

  • Percutaneous cholecystostomy with antibiotic and supportive treatment versus antibiotics and supportive treatment without routine cholecystectomy. In this situation, percutaneous cholecystostomy is performed in addition to the conservative treatment (antibiotics and supportive treatment).

  • Percutaneous cholecystostomy with supportive treatment (fluid management) without routine cholecystectomy versus routine cholecystectomy. In this situation, percutaneous cholecystostomy is offered as a replacement to cholecystectomy.

We accepted co-interventions if performed equally in both groups.

Types of outcome measures

Primary outcomes
  1. Mortality: all-cause mortality at 30 days and at maximal follow-up.

  2. Morbidity.

    1. Disease-related morbidity, such as cholecystitis, cholangitis, and pancreatitis.

    2. Intervention-related morbidity: only serious adverse events were considered. An adverse event was defined as any untoward medical occurrence that did or did not have a causal relationship with the treatment. A serious adverse event was defined according to the International Conference on Harmonisation - Good Clinical Practice guidelines (ICH-GCP 1997) as any event that increased mortality; was life-threatening; required inpatient hospitalisation; resulted in a persistent or significant disability; or any important medical event that might have jeopardised the patient or required intervention to prevent it.

    3. Surgery-related morbidity, such as injury to common bile duct, cholangitis, bile leak, biliary peritonitis, and wound infection.

  3. Quality of life (however defined by authors, ie, any questionnaire used by authors).

Secondary outcomes
  1. Conversion to open cholecystectomy (if routine laparoscopic cholecystectomy was attempted in both arms).

  2. Hospital stay.

    1. Total hospital stay.

    2. Intensive therapy unit stay.

  3. Costs.

Search methods for identification of studies

We searched the Cochrane Central Register of Controlled Trials (CENTRAL)(Issue 12 of 12, 2012) in The Cochrane Library, MEDLINE (1987 to December 2012), EMBASE (1987 to December 2012), and Science Citation Index Expanded (1987 to December 2012) (Royle 2003). We have given the search strategies with the time spans of the searches in Appendix 1. We also handsearched the references lists of identified trials.

Data collection and analysis

Selection of studies

Two review authors (KSG and MR) independently identified the trials for inclusion (Characteristics of included studies) and listed the excluded studies with the reasons for exclusion in the Characteristics of excluded studies table.

Data extraction and management

Two review authors (KSG and MR) independently extracted the following data from the trial report.

  1. Publication year and language of publication.

  2. Country in which the trial was conducted.

  3. Year in which the trial was conducted.

  4. Inclusion and exclusion criteria.

  5. Sample size.

  6. Population characteristics, such as age and sex ratio.

  7. ASA status.

  8. Biliary symptoms.

  9. Timing of intervention and control.

  10. Method of management of common bile duct stones (if present).

  11. Co-interventions.

  12. Method of access for cholecystectomy (open or laparoscopic cholecystectomy) (if performed).

  13. Outcomes.

  14. Risk of bias.

We sought any unclear or missing information by contacting the authors of the individual trials. If there was any doubt whether the trials shared the same participants, completely or partially (by identifying common authors and centres), we planned to contact the authors of the trials to clarify whether the trial report had been duplicated. However, we did not find any such trial. We resolved any differences in opinion through discussion.

Assessment of risk of bias in included studies

Two review authors (KG and MR) assessed the risk of bias of the trials independently, without masking of the trial names. We followed the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), and the Cochrane Hepato-Biliary Group Module (Gluud 2013). Due to the risk of overestimation of intervention effects in randomised trials with high risk of bias (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savović 2012; Savović 2012a), we looked at the influence of different domains of risk of bias of the trials on the results by evaluating the risk of bias components in each trial (see below). If required, we sought further information from the study authors to assess the trials correctly.

Allocation sequence generation
  • Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice were adequate if performed by an independent person not otherwise involved in the trial.

  • Uncertain risk of bias: the method of sequence generation was not specified.

  • High risk of bias: the sequence generation method was not random.

Allocation concealment
  • Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomisation unit. The allocation sequence was unknown to the investigators (for example, if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).

  • Uncertain risk of bias: the method used to conceal the allocation was not described so that intervention allocations may have been foreseen in advance of, or during enrolment.

  • High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants and personnel
  • Low risk of bias: the trial was described as blinded, and the method of blinding of participants and personnel was described so that knowledge of allocation was adequately prevented during the trial.

  • Uncertain risk of bias: the trial was described as blinded, but the method of blinding was not described so that knowledge of allocation was possible during the trial.

  • High risk of bias, the trial was not blinded so that the allocation was known during the trial.

Blinding of outcome assessors
  • Low risk of bias: the trial was described as blinded, and the method of blinding of participants and personnel was described so that knowledge of allocation was adequately prevented during the trial.

  • Uncertain risk of bias: the trial was described as blinded, but the method of blinding was not described so that knowledge of allocation was possible during the trial.

  • High risk of bias, the trial was not blinded so that the allocation was known during the trial.

Incomplete outcome data
  • Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, had been employed to handle missing data.

  • Uncertain risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.

  • High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting
  • Low risk of bias: all outcomes were pre-defined and reported, or all clinically relevant and reasonably expected outcomes were reported. The trial was registered either on the www.clinicaltrials.gov web site or a similar register, or there was published protocol.

  • Uncertain risk of bias: it was unclear whether all pre-defined and clinically relevant and reasonably expected outcomes were reported.

  • High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported, and data on these outcomes were likely to have been recorded.

Vested interest bias
  • Low risk of bias (the trial was not conducted by any parties that might have conflicting interest (eg drug or drain or instrument manufacturer).

  • Uncertain risk of bias (the source of funding was not clear).

  • High risk of bias (the trial was not conducted by any parties that might have conflicting interest (eg drug or drain or instrument manufacturer).

Differential expertise bias
  • Low risk of bias (if the healthcare providers were experienced in performing the intervention and control).

  • Uncertain risk of bias (if the healthcare providers had completed their training in performing the intervention and control).

  • High risk of bias (the healthcare providers were clearly undergoing training during the trial).

We considered trials that were classified as low risk of bias in all the above domains as trials with low risk of bias. All other trials were considered as trials with high risk of bias.

Measures of treatment effect

For dichotomous variables, we planned to calculate the risk ratio (RR) with 95% confidence interval (CI). RR calculations did not include trials in which no events occurred in either group, whereas risk difference calculations do. We planned to report the risk difference if the results using this association measure were different from the RR. However, as there was only one trial for each comparison, we compared the groups using Fisher's exact test using Stata Intercooled version 10 rather than RR or risk difference. For continuous variables, we planned to calculate the mean difference (MD) with 95% CI for outcomes such as hospital stay, and standardised mean difference (SMD) with 95% CI for quality of life (where different scales might be used). For time-to-event outcomes such as survival at maximal follow-up, we planned to calculate the hazard ratio (HR) with 95% CI.

Unit of analysis issues

The unit of analysis was the high-risk surgical patient with acute calculous cholecystitis.

Dealing with missing data

We performed the analysis on an intention-to-treat basis (Newell 1992) whenever possible. Otherwise, we performed the available-patient analysis. We planned to impute the standard deviation from P values according to the instructions given in the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2011) and use the median for the meta-analysis when the mean was not available. We also planned to impute the standard deviation as the highest standard deviation in the other trials included under that outcome, if it was not possible to calculate the standard deviation from the P value or the CIs, fully recognising that this form of imputation would decrease the weight of the study for calculation of MDs and bias the effect estimate to no effect in case of SMD (Higgins 2011).

Assessment of heterogeneity

We planned to explore heterogeneity using the Chi2 test with significance set at P value = 0.10, and the quantity of heterogeneity was measured using the I2 statistic (Higgins 2002).

Assessment of reporting biases

We planned to use visual inspection of funnel plots to assess reporting bias (Egger 1997; Macaskill 2001). We also planned to perform the linear regression approach described by Egger 1997 to determine the funnel plot asymmetry.

Data synthesis

Meta-analysis

We planned to perform the meta-analyses using Review Manager 5.2 (RevMan 2012). We planned to use a random-effects model (DerSimonian 1986) and a fixed-effect model (DeMets 1987). In case of discrepancy between the two models, we planned to report both results; otherwise, we planned to report the results of the fixed-effect model.

Trial sequential analysis

We planned to use the trial sequential analysis to control for random errors due to sparse data and repetitive testing of the accumulating data for the primary outcomes (CTU 2011; Thorlund 2011). We planned to add the trials according to the year of publication, and if more than one trial was published in a year, add the trials in alphabetical order according to the last name of the first author. We planned to construct the trial sequential monitoring boundaries on the basis of the required information size (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010).

We planned to apply trial sequential analysis (CTU 2011; Thorlund 2011) using a required sample size calculated from an alpha error of 0.05, a beta error of 0.20, a control group proportion obtained from the results, and a relative risk reduction of 20% for binary outcomes with two or more trials to determine whether more trials are necessary on this topic (if the trial sequential monitoring boundary and the required information size is reached or the futility zone is crossed, then more trials are unnecessary) (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010). For hospital stay, the required sample size was calculated from an alpha error of 0.05, a beta error of 0.20, the variance estimated from the meta-analysis results of low risk of bias trials, and a minimal clinically relevant difference of one day. Trial sequential analysis cannot be performed for rate ratios and standardised mean difference. So, we did not plan to perform trial sequential analysis for number of adverse events, quality of life, costs.

Since there was only trial for each comparison, we did not perform trial sequential analyses.

Subgroup analysis and investigation of heterogeneity

We planned the following subgroup analyses.

  • Trials with low risk of bias (adequate methodology) compared to trials with high risk of bias (unclear or inadequate methodology).

  • Different ASA status.

  • Different definitions used for high-risk surgical patients.

  • Different definitions used for acute cholecystitis.

  • Different severity of acute cholecystitis (according to revised Tokyo Guidelines) (Hirota 2007; Yokoe 2012)

  • Patients with common bile duct stones compared to those without common bile duct stones.

  • Different methods of management of common bile duct stones in the control group.

  • Open and laparoscopic cholecystectomy.

We did not perform any of these analyses because we found an insufficient number of trials.

Sensitivity analysis

We planned to perform a sensitivity analysis by imputing data for binary outcomes using various scenarios such as best-worse case scenario, worse-best case scenario, best-case scenario, and worst-case scenario (Gurusamy 2009; Gluud 2013). We planned to perform a sensitivity analysis by excluding the trials in which the mean and the standard deviation were imputed.

Results

Description of studies

Results of the search

We identified 753 bibliographic references through the electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register and The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (n = 37), MEDLINE (n = 510), EMBASE (n = 114), and Science Citation Index Expanded (n = 92). We identified no references through scanning reference lists of the identified randomised trials. We excluded 117 duplicates and 629 clearly irrelevant references through reading abstracts. We selected seven references for further assessment. We excluded four references (three studies) for the reasons listed in the Characteristics of excluded studies table. One reference was of an ongoing trial (Kortram 2012). We included two references of two completed randomised clinical trials in the review (Hatzidakis 2002; Akyürek 2005). The reference flow is shown in Figure 1. The details of the population characteristics, the groups to which the participants were randomised, and the outcomes reported by individual trials are shown in the Characteristics of included studies table.

Figure 1.

Study flow diagram.

Included studies

Both trials included people with an APACHE II score (Acute Physiology and Chronic Health Evaluation II) of 12 or above, which indicates a greater than 10% predicted risk of in-hospital mortality (Hatzidakis 2002; Akyürek 2005). One trial included people with calculous cholecystitis (Akyürek 2005). The other trial included people with calculous or acalculous cholecystitis (Hatzidakis 2002). We used only the information available on the people with calculous cholecystitis in this trial for this review. The sample sizes were 86 people (Hatzidakis 2002) and 70 people (Akyürek 2005). Akyürek 2005 reported that the mean age of participants was 62 years and 67.1% were women. Hatzidakis 2002 did not report the mean age or percentage of women.

In one trial, percutaneous cholecystostomy (performed within eight hours of referral to the surgeon) followed by early laparoscopic cholecystectomy (within 96 hours when patient status improved) was compared with conservative treatment with delayed laparoscopic cholecystectomy (performed eight weeks after the symptoms settled) (Akyürek 2005). In the other trial, percutaneous cholecystostomy (performed within 24 hours of referral) was compared with conservative management (Hatzidakis 2002). Cholecystectomy was not routinely performed either in people with calculous cholecystitis or acalculous cholecystitis in this trial. The conservative management in both of these trials included broad-spectrum antibiotics and supportive treatment for both arms. There were no trials comparing percutaneous cholecystostomy versus cholecystectomy.

Risk of bias in included studies

Both trials had high risk of bias. The assessments of the different domains of risk of bias in each trial are shown in Figure 2. Further information on the reason for classification is stated in the 'Risk of bias' table. The proportion of trials that were at low risk of bias in each domain is shown in Figure 3.

Figure 2.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Figure 3.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Effects of interventions

See: Summary of findings for the main comparison Intervention versus control for high-risk surgical patients with acute calculous cholecystitis

The main results are summarised in Table 1. The primary outcomes are also summarised in the Summary of findings for the main comparison.

Table 1. Summary of results
  1. CI: confidence interval; CoT: conservative treatment; LC: delayed laparoscopic cholecystectomy; MD: mean difference; PCLC: percutaneous cholecystostomy followed by early laparoscopic cholecystectomy; PeC: percutaneous cholecystostomy.
    * = statistically significant at P value < 0.05.

Study nameInterventionControl30-day mortalityOverall morbidityQuality of lifeTotal hospital stayConversion to open cholecystectomyCosts
Akyürek 2005PCLC
(n = 37)
LC
(n = 33)
0 versus 11 versus 2Not reported.(MD -9.90 days; 95% CI -12.31 to -7.49)*2/31 versus 4/30(MD -1123.00 USD; 95% CI -1336.60 to -909.40)*
Hatzidakis 2002PeC
(n = 44)
CoT
(n = 42)
6 versus 76 versus 3Not reported.Not reported.Not reported.Not reported.

Percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy

Thirty-one of the 37 participants underwent percutaneous cholecystostomy followed by early laparoscopic cholecystectomy in the intervention group (Akyürek 2005). Four of the remaining six participants underwent percutaneous cholecystostomy followed by successful delayed laparoscopic cholecystectomy. The remaining two participants refused surgery after undergoing percutaneous cholecystostomy. The long-term outcomes of these two participants were not reported.

Thirty of the 33 participants underwent delayed laparoscopic cholecystectomy in the control group. One participant died before delayed laparoscopic cholecystectomy could be performed, and two participants refused surgery and were well after 13 months. While the excluded participants were included for the outcome 'mortality', they were excluded from all the other outcomes.

Mortality

There was no significant difference in mortality between the two groups (0/37 percutaneous cholecystostomy plus early laparoscopic cholecystectomy versus 1/33 delayed laparoscopic cholecystectomy; Fisher's exact test: P value = 0.47).

Morbidity
Disease-related morbidity

There was no significant difference in the development of pancreatitis between the groups (0/31 percutaneous cholecystostomy plus early laparoscopic cholecystectomy versus 2/30 delayed laparoscopic cholecystectomy; Fisher's exact test: P value = 0.24). There were no other disease-related morbidities, such as recurrent acute cholecystitis, obstructive jaundice, or cholangitis, in either group.

Procedure-related morbidity

There was one bile leak from the gallbladder requiring drainage following percutaneous cholecystostomy. Since the procedure was only performed in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group, this is not relevant in the delayed laparoscopic cholecystectomy group. Therefore, overall, the procedure-related morbidity was 1/31 with percutaneous cholecystostomy plus early laparoscopic cholecystectomy versus 0/30 with delayed laparoscopic cholecystectomy (Fisher's exact test: P value = 1.00).

Surgery-related morbidity

There were no major morbidities related to surgery in either group (Fisher's exact test: P value = 1.00).

Overall morbidity

There was no significant difference in the overall morbidity between the two groups (1/31 percutaneous cholecystostomy plus early laparoscopic cholecystectomy versus 2/30 delayed laparoscopic cholecystectomy; Fisher's exact test: P value = 0.61).

Quality of life

Quality of life was not reported in the trial.

Conversion to open cholecystectomy

There was no significant difference in the proportion of participants requiring conversion to open cholecystectomy between the two groups (2/31 percutaneous cholecystostomy plus early laparoscopic cholecystectomy versus 4/30 delayed laparoscopic cholecystectomy; Fisher's exact test: P value = 0.43).

Total hospital stay

The mean total hospital stay was significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group (MD -9.90 days; 95% CI -12.31 to -7.49).

Total costs

The mean total costs were significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group (MD -1123.00 USD; 95% CI -1336.60 to -909.40).

Percutaneous cholecystostomy with conservative treatment versus conservative treatment

Nine of the 44 participants underwent delayed cholecystectomy in the percutaneous cholecystostomy with conservative treatment group. Seven of the 42 participants underwent delayed cholecystectomy in the conservative treatment only group (Hatzidakis 2002).

Mortality

There was no significant difference in mortality between the two groups (6/44 percutaneous cholecystostomy with conservative treatment versus 7/42 conservative treatment only; Fisher's exact test: P value = 0.77).

Morbidity
Disease-related morbidity

One participant in the percutaneous cholecystostomy with conservative treatment group and three participants in the conservative treatment only group developed recurrent acute cholecystitis over a 12-month follow-up period (1/44 percutaneous cholecystostomy with conservative treatment group versus 3/42 conservative treatment only group; Fisher's exact test: P value = 0.35). There were no other disease-related morbidities, such as pancreatitis, obstructive jaundice, or cholangitis, in either group.

Procedure-related morbidity

Four participants underwent re-operations due to procedure-related complications. Three participants underwent surgery for catheter dislodgement, and one participant underwent surgery for recurrent abdominal wall abscess at the percutaneous cholecystostomy site. This abscess contained a gallstone as the nidus for infection. Since the procedure was only performed in the percutaneous cholecystostomy with conservative treatment group, this is not relevant in the conservative treatment only group. Therefore, overall procedure-related morbidity was 4/44 with percutaneous cholecystostomy versus 0/42 with conservative treatment (Fisher's exact test: P value = 0.12).

Surgery-related morbidity

Twelve of 44 participants in the percutaneous cholecystostomy with conservative treatment group (nine elective and three emergency) underwent cholecystectomy (nine elective and three emergency) and 7/42 participants in the conservative treatment only underwent cholecystectomy (all elective). There was one death in the percutaneous cholecystostomy with conservative treatment group after the person underwent emergency cholecystectomy for failed percutaneous cholecystostomy (1/12 or 8.3%). Surgery-related morbidity in the conservative treatment only group was not reported.

Overall morbidity

There was no significant difference in the overall morbidity between the two groups (6/44 percutaneous cholecystostomy with conservative treatment group versus 3/42 conservative treatment only group; Fisher's exact test: P value = 0.49).

Conversion to open cholecystectomy

The number of participants who underwent laparoscopic cholecystectomy was not reported in this trial. Therefore, we were unable to calculate the proportion of participants who underwent conversion to open cholecystectomy.

Other outcomes

Total hospital stay, quality of life, and total costs were not reported in this trial.

Variations in statistical analysis

Since we did not calculate the RR for either of the trials, we did not calculate the risk difference. Since there was only one trial for each comparison, we could not perform a meta-analysis or trial sequential analyses.

Trial sequential analysis

We did not perform trial sequential analysis as there was only one trial in each comparison.

Subgroup analysis

We did not perform a subgroup analysis because we found an insufficient number of trials.

Reporting bias exploration

We did not assess reporting bias by funnel plot because we found an insufficient number of trials.

Discussion

Summary of main results

This review has shown that there is a considerable lack of information on surgical treatment of high-risk surgical patients with acute cholecystitis. The treatment options included in this review include percutaneous cholecystostomy followed by routine early laparoscopic cholecystectomy, percutaneous cholecystostomy alone (with definitive treatment in only selected patients), delayed laparoscopic cholecystectomy, conservative treatment (antibiotic treatment and supportive treatment) with definitive treatment in selected patients, and conservative treatment with routine cholecystectomy. There does not seem to be much controversy regarding whether the patient needs antibiotic therapy and supportive treatment such as fluid and electrolytes management, and these interventions were not the focus of this review. The controversy appears to be whether definitive treatment by cholecystectomy is necessary and whether any additional procedure such as percutaneous cholecystostomy is necessary in the early phase of treatment.

The issue of whether definitive treatment by cholecystectomy is needed in high-risk surgical patients with acute cholecystitis cannot be assessed directly as there have been no randomised clinical trials addressing this issue. However, there appears to be some indirect evidence that definitive treatment by cholecystectomy is useful from the trials that are included in this review. In one of the trials, some participants whose medical condition improved after percutaneous cholecystostomy worsened and died in the absence of any planned definitive treatment performed routinely (Hatzidakis 2002). Other indirect evidence that definitive treatment with cholecystectomy may be beneficial is from a Cochrane review that assessed whether prophylactic cholecystectomy is beneficial in people with common bile duct stones with gallbladder in-situ (McAlister 2007). This review found that prophylactic cholecystectomy decreased mortality in people with common bile duct stones (including high-risk patients) even after clearance of the common bile duct by endoscopic sphincterotomy (McAlister 2007). Thus, it appears that routine cholecystectomy may be indicated in high-risk surgical patients as a definitive treatment. There is currently no information available on whether it is better to do cholecystectomy laparoscopically or by open method in this group of patients (Keus 2006a; Keus 2006b; Keus 2006c; Keus 2010).

One trial reported a shorter total hospital stay and lower costs in people undergoing percutaneous cholecystostomy followed by early laparoscopic cholecystectomy (Akyürek 2005). Although the authors of this trial excluded six people in the percutaneous cholecystostomy group because the patients were still ill (inclusion of these participants would have resulted in a longer mean total hospital stay and hence an increased cost in the percutaneous cholecystostomy group), the authors of this trial excluded three people in the control group. Of these three people, one person developed multiorgan failure, which would have resulted in an increase in the cost of the control group also (the impact that this participant had on hospital stay cannot be determined from the information available).

There was no significant difference in the outcomes between percutaneous cholecystostomy with conservative treatment versus conservative treatment alone.

Overall completeness and applicability of evidence

This review is applicable only for the high-risk surgical patients with calculous cholecystitis.

Quality of the evidence

The risk of bias in both trials was high. We were unable to assess the consistency of the findings because of the presence of only one trial assessing two different comparisons. Thus, the evidence has to be interpreted with caution. Overall, the evidence is of very low quality as shown in Summary of findings for the main comparison. However, it must be noted that this is the best level of evidence that is available currently.

Further adequately powered trials with low risk of bias are necessary. To identify a reduction in mortality from 10% (the mean mortality in the control arm in the two trials included in this review) to 5% with a type I error of 0.05 and type II error of 0.20, at least 435 participants are required in each arm (PS Power and Sample Size Program version 3). The need for funding such a trial can be assessed by performing a "value of information analysis" (Griffin 2008).

Potential biases in the review process

We followed the Cochrane Handbook for Systematic Reviews of Interventions for this review (Higgins 2011). We did not blind the trials when extracting data or assessing the risk of bias and low risk of play of chance, but these procedures were done independently and in duplicate. There were no language, publication status, or sample size restrictions. Thus, we minimised the bias due to selection of trials. In spite of an extensive search of literature, there is a possibility of publication bias. Because of the few trials included in this review with few participants and outcomes, there is a high risk of random errors.

Agreements and disagreements with other studies or reviews

There have been no other systematic reviews or meta-analyses on this topic.

Authors' conclusions

Implications for practice

Based on current available evidence, we are unable to determine the role of percutaneous cholecystostomy in the clinical management of high-risk surgical patients with acute cholecystitis.

Implications for research

There is a need for adequately powered randomised clinical trials of low risk of bias on this issue. Future trials should be designed according to the SPIRIT Statement (SPIRIT 2013), and be conducted and reported based on the CONSORT Statement (Moher 2010; Schulz 2010).

Acknowledgements

To The Cochrane Hepato-Biliary Group for the support that they have provided.

Review
Peer Reviewers: Karl Sondenaa, Norway; Malte Schmidt, Norway; A McKay, Canada; Taylor S Riall, USA; Jean Marc Regimbeau; France.
Contact Editor: Christian Gluud, Denmark.

This project was funded by the National Institute for Health Research.
Disclaimer of the Department of Health: "The views and opinions expressed in the review are those of the authors and do not necessarily reflect those of the National Institute for Health Research (NIHR), National Health Services (NHS), or the Department of Health".

Data and analyses

Download statistical data

This review has no analyses.

Appendices

Appendix 1. Search strategies

DatabasePeriod of searchSearch strategy
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Wiley)Issue 12, 2012.#1 MeSH descriptor Frail Elderly explode all trees
#2 MeSH descriptor Aged, 80 and over explode all trees
#3 MeSH descriptor Geriatrics explode all trees
#4 Elder* OR geriatric OR old* OR octogenarian OR octogenarians OR nonagenarian OR nonagenarians OR centenarian OR centenarians OR debilitat*
#5 (high or poor) AND (surg* or anaesthe* OR anesthe*) AND risk
#6 (#1 OR #2 OR #3 OR #4 OR #5)
#7 MeSH descriptor Cholecystitis, Acute explode all trees
#8 cholecystitis OR colecystitis OR colecistitis*
#9 (#7 OR #8)
#10 (#6 AND #9)
MEDLINE (PubMed)1987 to December 2012.((Elder* OR geriatric OR old* OR octogenarian OR octogenarians OR nonagenarian OR nonagenarians OR centenarian OR centenarians OR "Frail Elderly"[MeSH] OR "Aged, 80 and over"[MeSH] OR "Geriatrics"[MeSH] OR debilitat* OR ((high or poor) AND (surg* OR anaesthe* OR anesthe*) AND risk))) AND (cholecystitis OR colecystitis OR colecistitis* OR “cholecystitis, acute”[MeSH]) AND ((randomised controlled trial [pt] OR controlled clinical trial [pt] OR randomised [tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab] OR trial [tiab] OR groups [tiab]) NOT (animals [mh] NOT humans [mh]))
EMBASE (OvidSP)1987 to December 2012.1 (Elder* OR geriatric OR old* OR octogenarian OR octogenarians OR nonagenarian OR nonagenarians OR centenarian OR centenarians OR debilitat*).af.
2 exp elderly care/ or exp geriatric care/ or exp geriatric patient/ or exp aging/
3 (high OR poor).af.
4 ((surg* OR anaesthe* OR anesthe*) AND (risk)).af
5 exp surgical risk/
6 4 or 5
7 3 AND 6
8 1 OR 2 OR 7
9 (cholecystitis OR colecystitis OR colecistitis*).af.
10 exp acute cholecystitis/
11 9 OR 10
12 8 AND 11
13 exp crossover-procedure/ or exp double-blind procedure/ or exp randomised controlled trial/ or single-blind procedure/
14 (random* or factorial* or crossover* or placebo*).af.
15 13 OR 14
16 12 AND 15
Science Citation Index Expanded (Web of Science)1987 to December 2012.#1 TS=(Elder* OR geriatric OR old* OR octogenarian OR octogenarians OR nonagenarian OR nonagenarians OR centenarian OR centenarians OR debilitat*)
#2 TS=((high or poor) AND (surg* or anaesthe* OR anesthe*) AND risk)
#3 #2 OR #1
#4 TS=(cholecystitis OR colecystitis OR colecistitis*)
#5 TS=(random* OR rct* OR crossover OR masked OR blind* OR placebo* OR meta-analysis OR systematic review* OR meta-analys*)
#6 #5 AND #4 AND #3

Contributions of authors

KS Gurusamy wrote the review, assessed the trials for inclusion, and extracted data on included trials. M Rossi independently assessed the trials for inclusion and extracted data on included trials. BR Davidson critically commented on the review and provided advice for improving the review.

Y Kumar was included in the protocol as the person who would extract the data. However, Y Kumar was unable to extract the data.

Declarations of interest

The authors of this review (KS Gurusamy and BR Davidson) are involved in the design of a trial involving a new device that has the potential to be used in high-risk surgical patients.

Sources of support

Internal sources

  • Department of Surgery, University College London, UK.

External sources

  • None, Not specified.

Differences between protocol and review

  1. The comparisons included were restricted to percutaneous cholecystostomy for high-risk surgical patients with acute cholecystitis based on advice from the Co-ordinating Editor.

  2. The outcomes were classified into primary outcomes and secondary outcomes based on guidelines from the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

  3. Conversion to open cholecystectomy was added as one of the secondary outcomes in trials in which routine laparoscopic cholecystectomy was attempted as this has cost implications.

  4. The mean costs in each intervention group of the trial were also included as one of the outcomes.

  5. The 'Risk of bias' domains were revised in line with the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

  6. The age for elderly participants has been removed as inclusion criteria for participants based on comments from peer reviewers.

Notes

The protocol of this review has the title "Methods of management of high-risk surgical patients with acute cholecystitis". The review title has been changed to "Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis" because of the revised inclusion criteria.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Akyürek 2005

MethodsRandomised clinical trial.
ParticipantsCountry: Turkey.
Sample size: 70.
Post-randomisation dropout(s): 9 (12.9%).
Revised sample size: 61.
Females: 47 (67.1%).
Mean age: 61.6 years.
ASA III: 13 (18.6%).
ASA IV: 25 (35.7%).
ASA V: 23 (32.9%).
Calculous cholecystitis: 70 (100%).
Inclusion criteria:
High-risk surgical patients (APACHE II score 12 or more) with acute calculous cholecystitis.
InterventionsThe participants were randomised to the following groups.
Group 1 (intervention): percutaneous cholecystostomy with laparoscopic cholecystectomy (n = 37).
Further details: percutaneous cholecystostomy (transhepatic mostly; ultrasound guided) was performed within 8 hours of referral. Early laparoscopic cholecystectomy was performed within 96 hours if percutaneous cholecystostomy was successful and if the participant's APACHE II score was less than 12. Broad-spectrum antibiotics were used.
Group 2 (control): laparoscopic cholecystectomy (n = 33).
Further details: broad-spectrum antibiotic treatment followed by laparoscopic cholecystectomy after 8 weeks of full recovery.
OutcomesThe outcomes reported were mortality, disease-related morbidity, surgery-related morbidity, procedure-related morbidity, hospital stay, and costs.
NotesWe tried to contact the study author in August 2010.

Reason for post-randomisation dropout(s): 6 participants in the intervention group were not fit to undergo laparoscopic cholecystectomy within 96 hours. Of these, 4 participants underwent laparoscopic cholecystectomy as delayed procedure. 2 participants refused delayed procedure also. 2 participants in the control group refused surgery and were well after 13 months of follow-up. 1 participant in the control group died. These participants were excluded from the analysis by the study authors but were included for the outcome 30-day mortality.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "After informed consent was obtained, patients were assigned by simple random sampling using a random number table to one of the treatment arms".
Allocation concealment (selection bias)Unclear risk Comment: this information was not available.
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: this information was not available - probably unblinded.
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: this information was not available - probably unblinded.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: there were post-randomisation dropouts.
Selective reporting (reporting bias)Low riskComment: important primary outcomes that would be expected to be measured in such trials were reported.
Free from vested interest bias?Unclear riskComment: this information was not available.
Free from differential expertise bias?Unclear riskQuote: "A specialized interventional radiologist team performed all procedures".
Comment: the prior experience in performing the procedure was not stated.

Hatzidakis 2002

  1. a

    An APACHE II score (Acute Physiology and Chronic Health Evaluation II score) of 12 indicates a greater than 10% predicted risk of in-hospital mortality.

    ASA: American Society of Anesthesiologists; CO: conservative treatment; CT: computerised tomogram; PC: percutaneous cholecystostomy; US: ultrasound.

MethodsRandomised clinical trial.
ParticipantsCountry: Greece.
Sample size: 86.
Post-randomisation dropout(s): not stated.
Revised sample size: 86.
Females: not stated.
Mean age: not stated.
ASA III: not stated.
ASA IV: not stated.
ASA V: not stated.
Calculous cholecystitis: 86 (100%).
Inclusion criteria:
High-risk surgical patients (APACHE II score 12 or more) with acute cholecystitis.
InterventionsThe participants were randomised to the following groups.
Group 1: percutaneous cholecystostomy with antibiotic (n = 44).
Further details: percutaneous cholecystostomy (first 17 participants CT scan guided then ultrasound guided; transhepatic or transperitoneal approach) within 24 hours of referral in combination with broad-spectrum antibiotics.
Group 2: antibiotic (n = 42).
Further details: broad-spectrum antibiotics.
OutcomesThe outcomes reported were mortality, procedure-related morbidity, and disease-related morbidity.
NotesWe tried to contact the study author in August 2010. We did not receive any replies.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote: "Patients were randomly assigned into two groups by drawing a playing card. Black cards sent the patients to the CO group (n = 60), where conservative treatment was administered, whereas red cards sent patients to the group (n = 63) for percutaneous cholangiogram".
Comment: there is no predefined random sequence. This allows the random sequence to be changed.
Allocation concealment (selection bias)High riskQuote: "Patients were randomly assigned into two groups by drawing a playing card. Black cards sent the patients to the CO group (n = 60), where conservative treatment was administered, whereas red cards sent patients to the group (n = 63) for percutaneous cholangiogram".
Comment: there is no predefined random sequence. This is similar to an open allocation system.
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: this information was not available - probably unblinded.
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: this information was not available - probably unblinded.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: this information was not available.
Selective reporting (reporting bias)High riskComment: surgery-related morbidity in the conservative treatment group was not reported.
Free from vested interest bias?Unclear riskComment: this information was not available.
Free from differential expertise bias?High riskQuote: "After gaining experience, we moved from CT- to US-guided PCs that were completed in a much shorter operation time and with less discomfort for the patients. After the introduction of the locking pigtails, which were initially not available, no further catheter dislodgment was noted".
Comment: the trial was performed before the learning curve was complete.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Nikonov 2008Not a randomised clinical trial.
Tazawa 2003Not a randomised clinical trial.
Vetrhus 2003This randomised clinical trial excluded high-risk surgical patients.

Characteristics of ongoing studies [ordered by study ID]

Kortram 2012

Trial name or titleAcute Cholecystitis in High Risk Surgical Patients: Percutaneous Cholecystostomy versus Laparoscopic Cholecystectomy (CHOCOLATE Trial)
MethodsRandomised clinical trial
ParticipantsHigh-risk patients with acute calculous cholecystitis
InterventionsPercutaneous cholecystostomy versus laparoscopic cholecystectomy
OutcomesMortality, complications, and need for re-intervention
Starting date1 February 2011
Contact informationDjamila Boerma (d.boerma@antoniusziekenhuis.nl)
Notes 

Ancillary