Routine abdominal drainage versus no abdominal drainage for uncomplicated laparoscopic cholecystectomy

Abstract

Background

Laparoscopic cholecystectomy is the main method of treatment of symptomatic gallstones. Drains are used after laparoscopic cholecystectomy to prevent abdominal collections. However, drain use may increase infective complications and delay discharge.

Objectives

The aim is to assess the benefits and harms of routine abdominal drainage in uncomplicated laparoscopic cholecystectomy.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013.

Selection criteria

We included all randomised clinical trials comparing drainage versus no drainage after uncomplicated laparoscopic cholecystectomy irrespective of language and publication status.

Data collection and analysis

We used standard methodological procedures defined by The Cochrane Collaboration.

Main results

A total of 1831 participants were randomised to drain (915 participants) versus 'no drain' (916 participants) in 12 trials included in this review. Only two trials including 199 participants were of low risk of bias. Nine trials included patients undergoing elective laparoscopic cholecystectomy exclusively. One trial included patients undergoing laparoscopic cholecystectomy for acute cholecystitis exclusively. One trial included patients undergoing elective and emergency laparoscopic cholecystectomy, and one trial did not provide this information. The average age of participants in the trials ranged between 48 years and 63 years in the 10 trials that provided this information. The proportion of females ranged between 55.0% and 79.0% in the 11 trials that provided this information. There was no significant difference between the drain group (1/840) (adjusted proportion: 0.1%) and the 'no drain' group (2/841) (0.2%) (RR 0.41; 95% CI 0.04 to 4.37) in short‐term mortality in the ten trials with 1681 participants reporting on this outcome. There was no significant difference between the drain group (7/567) (adjusted proportion: 1.1%) and the 'no drain' group (3/576) (0.5%) in the proportion of patients who developed serious adverse events in the seven trials with 1143 participants reporting on this outcome (RR 2.12; 95% CI 0.67 to 7.40) or in the number of serious adverse events in each group reported by eight trials with 1286 participants; drain group (12/646) (adjusted rate: 1.5 events per 100 participants) versus 'no drain' group (6/640) (0.9 events per 100 participants); rate ratio 1.60; 95% CI 0.66 to 3.87). There was no significant difference in the quality of life between the two groups (one trial; 93 participants; SMD 0.22; 95% CI ‐0.19 to 0.63). The proportion of patients who were discharged as day‐procedure laparoscopic cholecystectomy seemed significantly lower in the drain group than the 'no drain' group (one trial; 68 participants; drain group (0/33) (adjusted proportion: 0.2%) versus 'no drain' group (11/35) (31.4%); RR 0.05; 95% CI 0.00 to 0.75). There was no significant difference in the length of hospital stay between the two groups (five trials; 449 participants; MD 0.22 days; 95% CI ‐0.06 days to 0.51 days). The operating time was significantly longer in the drain group than the 'no drain' group (seven trials; 775 participants; MD 5.00 minutes; 95% CI 2.69 minutes to 7.30 minutes). There was no significant difference in the return to normal activity and return to work between the groups in one trial involving 100 participants. This trial did not provide any information from which the standard deviation could be imputed and so the confidence intervals could not be calculated for these outcomes.

Authors' conclusions

There is currently no evidence to support the routine use of drain after laparoscopic cholecystectomy. Further well designed randomised clinical trials are necessary.

Plain language summary

Routine abdominal drainage versus no drainage for patients undergoing uncomplicated laparoscopic cholecystectomy

The liver produces bile which has many functions, including elimination of waste processed by the liver and digestion of fat. The bile is temporarily stored in the gallbladder (an organ situated underneath the liver) before it reaches the small bowel. Concretions in the gallbladder are called gallstones. Gallstones are present in about 5% to 25% of the adult western population. Between 2% and 4% become symptomatic in a year. The symptoms include pain related to the gallbladder (biliary colic), inflammation of the gallbladder (cholecystitis), obstruction to the flow of bile from the liver and gallbladder into the small bowel resulting in jaundice (yellowish discolourisation of the body usually most prominently noticed in the white of the eye, which turns yellow), bile infection (cholangitis), and inflammation of the pancreas, an organ which secretes digestive juices and harbours the insulin secreting cells which maintain blood sugar level (pancreatitis). Removal of the gallbladder (cholecystectomy) is currently considered the best treatment option for patients with symptomatic gallstones. This is generally performed by key‐hole surgery (laparoscopic cholecystectomy). Drain is a tube that is left inside the tummy to allow drainage of fluids to outside the tummy. Some surgeons have routinely drained after laparoscopic cholecystectomy because of the fear of collection of bile or blood requiring re‐operation. As the name indicates, the drain may drain out these collections to the exterior, thereby avoiding open surgery. However, routine use of drains may necessitate the patient to stay overnight or require drain removal after discharge both of which increase resource utilisation in this era of day surgery (where patients are admitted and discharged on the same day of surgery). The review authors set out to determine whether it is preferable to use routine drainage after laparoscopic cholecystectomy. A systematic search of medical literature was performed in order to identify studies which provided information on the above question. The authors obtained information from randomised trials only since such types of trials provide the best information if conducted well. Two authors independently identified the trials and collected the information.

A total of 1831 participants received drain (915 patients) versus 'no drain' (916 patients) in 12 trials included in this review. The decision of whether the patients received drain or not was determined by a method similar to toss of a coin. Only two trials including 199 patients were of low risk of bias (free from errors in study design that can result in wrong conclusions, leading to overestimation of benefits and to underestimation of harms of the drainage or no drainage). Nine of the 12 trials included patients who underwent planned operations. The average age of participants in the trials ranged between 48 years and 63 years in the 10 trials that provided this information. The proportion of females ranged between 55.0% and 79.0% in the 11 trials that provided this information. There was no significant or clinically important differences in the short‐term mortality, serious complications, quality of life, length of hospital stay, operating time, return to normal activity, or return to work in the trials that reported these outcomes. The proportion of patients who were discharged as day‐procedure laparoscopic cholecystectomy seemed significantly lower in the drain group than in the 'no drain' group in one trial of high risk of bias involving 68 participants. Currently, there is no evidence to support the use of drain after laparoscopic cholecystectomy. Further well‐designed randomised clinical trials are necessary.

Summary of findings

Summary of findings for the main comparison. Routine abdominal drain versus 'no drain' for laparoscopic cholecystectomy.

Routine abdominal drain versus 'no drain' for laparoscopic cholecystectomy
Patient or population: patients with laparoscopic cholecystectomy. Settings: secondary or tertiary. Intervention: drain. Comparison: no drain.
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	No drain	Drain
Mortality	2 per 1000	1 per 1000 (0 to 11)	RR 0.41 (0.04 to 4.37)	1681 (10 studies)	⊕⊝⊝⊝ very low1,2,3
Serious adverse events (proportion of patients)	5 per 1000	11 per 1000 (3 to 39)	RR 2.12 (0.67 to 6.40)	1143 (7 studies)	⊕⊝⊝⊝ very low1,2,3
Serious adverse events (number of events)	9 per 1000	15 per 1000 (6 to 36)	rate ratio 1.60 (0.66 to 3.87)	1286 (8 studies)	⊕⊝⊝⊝ very low1,2,3
Quality of life Psychosocial Adjustment To Illness Scale Self‐Report version (PAIS‐SR)		The mean quality of life in the intervention groups was 0.22 standard deviations higher (0.19 lower to 0.63 higher)		93 (1 study)	⊕⊝⊝⊝ very low1,4,5
Same day discharge	314 per 1000	16 per 1000 (0 to 236)	RR 0.05 (0 to 0.75)	68 (1 study)	⊕⊝⊝⊝ very low1,3
Hospital stay	The mean hospital stay in the control groups was 2.8 days	The mean hospital stay in the intervention groups was 0.22 higher (0.06 lower to 0.51 higher)		419 (4 studies)	⊕⊝⊝⊝ very low1,5
Operating time	The mean operating time in the control groups was 46 minutes	The mean operating time in the intervention groups was 5 higher (2.69 to 7.3 higher)		745 (6 studies)	⊕⊝⊝⊝ very low1,5
*The basis for the assumed risk is the mean control group risk across studies. 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.

¹ The trial(s) was (were) of high risk of bias.
 ² The confidence intervals overlapped 1 and either 0.75 or 1.25 or both.
 ³ The number of events in the intervention and control group was fewer than 300.
 ⁴ The confidence intervals overlapped 0 and minimal clinically important difference (0.25 for quality of life, 1 day for hospital stay, and 15 minutes for operating time). 
 ⁵ The total number of patients in the intervention and control group was fewer than 400.

Background

Description of the condition

About 5% to 25% of the adult western population have gallstones (GREPCO 1984; GREPCO 1988; Bates 1992; Halldestam 2004). The annual incidence of gallstones is about 1 in 200 people (NIH 1992). Only 2% to 4% of people with gallstones become symptomatic with biliary colic (pain), acute cholecystitis (inflammation), obstructive jaundice, or gallstone pancreatitis in a year (Attili 1995; Halldestam 2004). Cholecystectomy (removal of gallstones) is the preferred option in the treatment of symptomatic gallstones (Strasberg 1993). Every year, 1.5 million cholecystectomies are performed in the US and 60,000 in the UK (Dolan 2009; HES 2011). Approximately 80% of the cholecystectomies are performed laparoscopically (by key‐hole surgery) (Ballal 2009).

Description of the intervention

Routine drainage involves insertion of a drain into the abdominal cavity on completion of surgery. The drain is brought out usually through one of the ports (key‐hole) used for laparoscopic cholecystectomy. Surgical drains may either be open or closed. An open drain is when an artificial conduit is left in the wound to allow drainage of fluids to the exterior (eg, corrugated drain; Penrose drain; Yeates drain). Closed drains may either be suction drains (eg, Redon drain) or passive (gravity‐assisted) drains (eg, Robinson drain).

How the intervention might work

Some surgeons have routinely drained after laparoscopic cholecystectomy because of the fear of collection of bile or blood requiring open procedures (Hawasli 1992). As the name indicates, the drain may drain out these collections to the exterior, thereby avoiding open surgery following the laparoscopic surgery.

Why it is important to do this review

The routine use of a drain after laparoscopic cholecystectomy is of great importance in this era of day‐procedure laparoscopic cholecystectomy as the routine use of drains may necessitate the patient to stay overnight or require drain removal after discharge both of which increase resource utilisation. This is an update of our review published in 2007 (Gurusamy 2007b; Gurusamy 2007c).

Objectives

To assess the benefits and harms of routine abdominal drainage in uncomplicated laparoscopic cholecystectomy.

Methods

Criteria for considering studies for this review

Types of studies

We included only randomised controlled trials for benefits (irrespective of language, blinding, or publication status). We considered quasi‐randomised studies (where the method of allocating participants to a treatment are not strictly random, eg, date of birth, hospital record number, alternation) and non‐randomised studies for rare serious adverse events specifically related to drainage.

Types of participants

Patients who have undergone uncomplicated laparoscopic cholecystectomy. We did not include trials of patients who required complicated laparoscopic cholecystectomy as these would have involved a different group of patients.

Types of interventions

We included only trials comparing abdominal drainage and no drainage in laparoscopic cholecystectomy (irrespective of the type of the drain; timing of surgery; size and the number of ports; or abdominal lift or open, or closed method of induction of pneumoperitoneum).

Co‐interventions were allowed provided that they were used equally in the intervention arms.

Types of outcome measures

Primary outcomes

1. Short‐term mortality (30‐day mortality or in‐hospital mortality).

2. Adverse events are defined as any untoward medical occurrence not necessarily having a causal relationship with the treatment, but resulting in a dose reduction or discontinuation of treatment (ICH‐GCP 1996). Serious adverse events are defined as any event that would increase mortality; is life‐threatening; requires inpatient hospitalisation; results in a persistent or significant disability; or any important medical event which might have jeopardised the patient or requires intervention to prevent it. Examples of serious adverse events include reoperation for any reason including intra‐abdominal collections, bile leak requiring aspiration, etc. While bile duct injury falls under this category, the disability can be long term and hence this is considered separately.

3. Quality of life (however defined by authors).

Secondary outcomes

1. Hospital stay.

   1. Proportion discharged as day‐surgery.

   2. Length of hospital stay.

2. Operating time.

3. Return to normal activity.

4. Return to work.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until February 2013 (Royle 2003). We have given the search strategies in Appendix 1 with the time spans for the searches.

Searching other resources

We also searched the references of the identified trials to identify further relevant trials.

Data collection and analysis

Selection of studies

Review authors KG and RK or KS independently identified the trials for inclusion. We have listed the excluded studies with the reasons for the exclusion.

Data extraction and management

KG and RK independently extracted the following data.

1. Year and language of publication.

2. Country.

3. Year of study.

4. Inclusion and exclusion criteria.

5. Sample size.

6. Population characteristics such as age and sex ratio.

7. Details of intervention and control.

8. Co‐interventions.

9. Outcomes (listed above).

10. Risk of bias (described below).

Assessment of risk of bias in included studies

We independently assessed the risk of bias in the trials without masking 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 biased overestimation of beneficial intervention effects in randomised trials with high risk of bias (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savovic 2012; Savovic 2012a), we assessed the trials for the following risk of bias domains.

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 are 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: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

• Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.

• High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes were likely to be influenced by lack of blinding.

Blinding of outcome assessors

• Low risk of bias: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

• Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.

• High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes were likely to be influenced by lack of blinding.

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, has 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.

• Uncertain risk of bias: it is 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.

For‐profit bias

• Low risk of bias: the trial appears to be free of industry sponsorship or other kind of for‐profit support that may manipulate the trial design, conductance, or results of the trial. 

• Uncertain risk of bias: the trial may or may not be free of for‐profit bias as no information on clinical trial support or sponsorship is provided.

• High risk of bias: the trial is sponsored by the industry or has received other kind of for‐profit support.

We considered trials to have a low risk of bias if we assessed all the above domains as being at low risk of bias. In all other cases, the trials were considered to have a high risk of bias.

Measures of treatment effect

For binary outcomes, we calculated the risk ratio (RR) with 95% confidence interval (CI). We also planned to report the risk difference if it was different from the RR since risk difference allows meta‐analysis including trials with zero events in both groups. For continuous variables, we calculated the mean difference (MD) with 95% CI for hospital stay; and standardised mean difference (SMD) with 95% CI for variables such as quality of life. For count outcomes such as number of serious adverse events, we calculated the rate ratio with 95% confidence intervals.

Unit of analysis issues

The unit of analysis was the patient undergoing uncomplicated laparoscopic cholecystectomy, according to the result of randomisation.

Dealing with missing data

We performed an intention‐to‐treat analysis (Newell 1992) whenever possible for binary outcomes. For continuous outcomes, we used available‐case analysis. We imputed the standard deviation from P values according to the instructions given in the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2011) and used the median for the meta‐analysis when the mean was not available. If it was not possible to calculate the standard deviation from the P value or the CIs, we imputed the standard deviation as the highest standard deviation in the other trials included under that outcome, fully recognising that this form of imputation will decrease the weight of the trial for calculation of mean differences and bias the effect estimate to no effect in the case of standardised mean difference (Higgins 2011).

Assessment of heterogeneity

We examined the forest plot to visually assess heterogeneity. We used overlapping of CIs to assess the heterogeneity visually. We explored heterogeneity by the Chi² test, with significance set at a P value of 0.10, and measured the quantity of heterogeneity by the I² statistic (Higgins 2002).

Assessment of reporting biases

We planned to use a funnel plot to explore bias in the presence of at least 10 trials for the specific outcome (Egger 1997; Macaskill 2001). We planned to use asymmetry in the funnel plot of trial size against treatment effect to assess this bias. We also planned to use the linear regression approach described by Egger et al to determine the funnel plot asymmetry (Egger 1997).

Data synthesis

We performed the meta‐analyses according to the recommendations of The Cochrane Collaboration (Higgins 2011) and the Cochrane Hepato‐Biliary Group Module (Gluud 2013) using the software package Review Manager 5 (RevMan 2012). We planned to use a random‐effects model (DerSimonian 1986) and a fixed‐effect model (DeMets 1987). In the case of a discrepancy between the two models we planned to report both results; otherwise, we planned to report only the results from the fixed‐effect model. Since there was no discrepancy between the fixed‐effect and random‐effect models, we have reported the results from the fixed‐effect model.

Subgroup analysis and investigation of heterogeneity

We planned to perform the following subgroup analyses.

• Trials with low risk of bias compared to trials with high risk of bias.

• Drainage in emergency compared to elective laparoscopic cholecystectomy.

• Open compared to closed drains.

• Suction compared to closed passive drains.

• Trials that use routine antibiotic prophylaxis compared to those that do not use routine antibiotic prophylaxis.

We planned to perform the Chi² test for subgroup differences, setting a P value of 0.05 to identify any differences.

Sensitivity analysis

We performed a sensitivity analysis by excluding the trials in which means or standard deviations were imputed for the continuous outcomes.

Trial sequential analysis

We used trial sequential analysis to control for random errors due to sparse data and repetitive testing of the accumulating data (CTU 2011; Thorlund 2011). The underlying assumption of trial sequential analysis is that testing for significance may be performed each time a new trial is added to the meta‐analysis resulting in an increased risk of random errors (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010). We added the trials according to the year of publication, and if more than one trial was published in a year, we added the trials alphabetically according to the last name of the first author. We constructed the trial sequential monitoring boundaries on the basis of the required information size. These boundaries determine the statistical inference one may draw regarding the cumulative meta‐analysis that has not reached the required information size; if the trial sequential monitoring boundary is crossed before the required information size is reached, firm evidence may perhaps be established and further trials may turn out to be superfluous. On the other hand, if the boundary is not surpassed, it may be necessary to continue doing trials in order to detect or reject a certain intervention effect (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010).   

We applied trial sequential analysis (CTU 2011; Thorlund 2011) using a diversity‐analysed required sample size calculated from an alpha error of 0.05, a beta error of 0.20, a control event proportion obtained from the results of the meta‐analysis, and a relative risk reduction of 20% for binary primary outcomes and the observed diversity of the meta‐analysis (mortality and serious adverse events) with two or more trials to determine whether more trials are necessary on this topic (if the trial sequential monitoring boundary or the futility zone is crossed, then more trials may be unnecessary) (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010). Since trial sequential analysis cannot be performed for standardised mean difference, we did not plan to perform the trial sequential analysis for quality of life.

'Summary of findings' table

We have summarised the results of all the outcomes (with sufficient details to calculate the effect estimate and confidence intervals) in a 'Summary of findings' table prepared using GRADEPro 3.6 (http://ims.cochrane.org/revman/gradepro).

Results

Description of studies

Results of the search

We identified a total of 302 references through 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 = 6), MEDLINE (n = 114), EMBASE (n = 78), and Science Citation Index Expanded (n = 104). Trial authors provided one additional reference (Lucarelli 2012). We excluded 76 duplicates and 209 clearly irrelevant references through reading abstracts. The remaining 18 references were retrieved for further assessment. No references were identified through scanning reference lists of the identified randomised trials. We excluded five references for the reasons listed under the table 'Characteristics of excluded studies'. We identified two reports of the same trial (Nomdedeu 1997). In total, 12 randomised trials described in 13 publications fulfilled the inclusion criteria and provided data for the analyses (Thiebe 1994; Hawasli 1994; Nomdedeu 1997; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Picchio 2012). The reference flow is shown in Figure 1. Details including the sample size, post‐randomisation drop‐outs, patient characteristics, details of the intervention, and the outcomes reported in the trials are shown in 'Characteristics of included studies'.

1.

Study flow diagram.

Included studies

A total of 1889 participants were included in the 12 trials (Thiebe 1994; Hawasli 1994; Nomdedeu 1997; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Lucarelli 2012; Picchio 2012). There were 58 post‐randomisation drop‐outs in four trials (Thiebe 1994; Nursal 2003; Mrozowicz 2006; Georgiou 2011). In total, 1831 participants randomised to drain (915 participants) versus 'no drain' (916 participants) provided information for this review. The average age of participants in the trials ranged between 48 years and 63 years in the 10 trials that provided this information (Hawasli 1994; Nomdedeu 1997; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; Lucarelli 2012; Picchio 2012). The proportion of females ranged between 55.0% and 79.0% in the 11 trials that provided this information (Hawasli 1994; Nomdedeu 1997; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Lucarelli 2012; Picchio 2012).

One trial used open drain (Uchiyama 2007) and seven trials used closed drain (Hawasli 1994; Nomdedeu 1997; Nursal 2003; Mrozowicz 2006; Tzovaras 2009; Lucarelli 2012; Picchio 2012). This information was not available in four trials (Thiebe 1994; Capitanich 2005; Georgiou 2011; El‐Labban 2012). Four trials used suction drain (Hawasli 1994; Nomdedeu 1997; Nursal 2003; Picchio 2012) and five trials used passive drain (Thiebe 1994; Uchiyama 2007; Tzovaras 2009; El‐Labban 2012). This information was not available in four trials (Capitanich 2005; Mrozowicz 2006; Georgiou 2011; Lucarelli 2012).
 
 Nine trials mentioned that they included patients undergoing elective laparoscopic cholecystectomy or excluded patients with acute cholecystitis (Thiebe 1994; Hawasli 1994; Nomdedeu 1997; Capitanich 2005; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Picchio 2012). One trial included patients with acute cholecystitis exclusively (Lucarelli 2012). One trial mentioned that it included patients with or without acute cholecystitis (Nursal 2003). This information was not available in one trial (Mrozowicz 2006). Nine trials reported that the drain was brought out through the port (Hawasli 1994; Nomdedeu 1997; Nursal 2003; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; Lucarelli 2012; Picchio 2012). This information was not available in the remaining three trials (Thiebe 1994; Capitanich 2005; El‐Labban 2012). The drain was usually removed in about 24 hours (Hawasli 1994; Nursal 2003; Mrozowicz 2006; Tzovaras 2009; Lucarelli 2012; Picchio 2012), about 42 hours (Uchiyama 2007), or when the drain fluid was less than 50 mL/day (Nomdedeu 1997) in the trials that reported the duration of the drain. Seven trials reported that antibiotic prophylaxis was used (Nomdedeu 1997; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Lucarelli 2012). This information was not available in the remaining five trials (Thiebe 1994; Hawasli 1994; Nursal 2003; Capitanich 2005; Picchio 2012).

Risk of bias in included studies

Two trials were of low risk of bias (Capitanich 2005; Picchio 2012). The remaining trials were of high risk of bias (Thiebe 1994; Hawasli 1994; Nomdedeu 1997; Nursal 2003; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Lucarelli 2012). The summary of the risk of bias in each domain and the risk of bias in each domain in each trial are shown in Figure 2 and Figure 3.

2.

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

3.

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

Eight trials were at low risk of bias due to adequate allocation generation (Hawasli 1994; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Georgiou 2011; Lucarelli 2012; Picchio 2012). Five trials were at low risk of bias due to adequate allocation concealment (Nomdedeu 1997; Nursal 2003; Capitanich 2005; Lucarelli 2012; Picchio 2012). Three trials were at low risk of bias due blinding of patients and personnel (Capitanich 2005; Lucarelli 2012; Picchio 2012). Four trials were at low risk of bias due to blinding of outcome assessors (Nursal 2003; Capitanich 2005; Lucarelli 2012; Picchio 2012). There were no post‐randomisation drop‐outs in three trials (Capitanich 2005; Lucarelli 2012; Picchio 2012). These three trials were at low risk of bias due to incomplete outcome data (Capitanich 2005; Picchio 2012). Seven trials reported mortality and morbidity and were considered to be at low risk of bias to selective outcome reporting (Nursal 2003; Capitanich 2005; Uchiyama 2007; Tzovaras 2009; El‐Labban 2012; Lucarelli 2012; Picchio 2012). Three trials were considered to be at low risk of for‐profit bias (Nursal 2003; Capitanich 2005; Picchio 2012).

Effects of interventions

See: Table 1

The results are summarised in Table 1.

Short‐term mortality

Ten trials reported this outcome (Thiebe 1994; Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Lucarelli 2012; Picchio 2012). There was no significant difference in the short‐term mortality between the drain group (1/840) (0.1%) versus the 'no drain' group (2/841) (0.2%) (RR 0.41; 95% CI 0.04 to 4.37) (Analysis 1.1). Since there were no events in eight of the nine trials (Thiebe 1994; Nursal 2003; Capitanich 2005; Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Picchio 2012), the issue of random‐effects model versus fixed‐effect model does not arise. There was no change in results by using the risk difference. A trial sequential analysis showed that the accrued sample size was less than 1% of the diversity‐adjusted required sample size (352,564 participants) and so trial sequential boundaries could not be drawn (Figure 4).

1.1. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 1 Mortality.

4.

Trial sequential analysis of mortality 
 The diversity‐adjusted required information size (DARIS) was calculated to 352,564 patients, based on the proportion of patients in the control group with the outcome of 0.2%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing 1651 patients in the 10 trials, only 0.47% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, not even the conventional boundaries were crossed by the cumulative Z‐curve.

Serious adverse events

Seven trials reported the proportion of participants who developed serious adverse events (Nursal 2003; Capitanich 2005; Uchiyama 2007; Tzovaras 2009; El‐Labban 2012; Lucarelli 2012; Picchio 2012). There was no significant difference in the proportion of patients who developed serious adverse events between the drain group (7/567) (1.1%) versus the 'no drain' group (3/576) (0.5%) (RR 2.17; 95% CI 0.49 to 9.62) (Analysis 1.2). There was no change in results by using the random‐effects model or risk difference. A trial sequential analysis showed that the accrued sample size was less than 1% of the diversity‐adjusted required sample size (175,965) and so trial sequential boundaries could not be drawn (Figure 5). None of these serious adverse events were reoperations for intra‐abdominal collections. Three of the serious adverse events were reoperation for bleeding (two in the drain group and one in the 'no drain' group) (Tzovaras 2009; Picchio 2012).

1.2. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 2 Serious adverse events (proportion of patients).

5.

Trial sequential analysis of serious adverse events 
 The diversity‐adjusted required information size (DARIS) was calculated to 175,965 patients, based on the proportion of patients in the control group with the outcome of 0.4%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing 1113 patients in the seven trials, only 0.63% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, not even the conventional boundaries were crossed by the cumulative Z‐curve.

Eight trials reported the number of serious adverse events in each group (Nursal 2003; Capitanich 2005; Mrozowicz 2006; Uchiyama 2007; Tzovaras 2009; El‐Labban 2012; Lucarelli 2012; Picchio 2012). There was no significant difference in the number of serious adverse events between the drain group (12/646) (1.5 events per 100 participants) versus the 'no drain' group (6/640) (0.9 events per 100 participants) (rate ratio 1.60; 95% CI 0.66 to 3.87) (Analysis 1.3). There was no change in results by using the random‐effects model.

1.3. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 3 Serious adverse events (number).

Quality of life

Only one trial reported quality of life (Capitanich 2005). There was no significant difference in the quality of life between the two groups (SMD 0.22; 95% CI ‐0.19 to 0.63) (Analysis 1.4). Since only one trial reported this outcome, the issue of random‐effects model versus fixed‐effect model does not arise.

1.4. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 4 Quality of life.

Hospital stay

Only one trial reported the proportion of patients who were discharged as day‐procedure laparoscopic cholecystectomy (Hawasli 1994). The proportion of patients who were discharged as day‐procedure laparoscopic cholecystectomy was significantly lower in the drain group (0/33) (0%) versus the 'no drain' group (11/35) (31.4%) (RR 0.05; 95% CI 0.00 to 0.75) (Analysis 1.5). Since only one trial reported this outcome, the issue of random‐effects model versus fixed‐effect model does not arise. There was no change in interpretation results by using the risk difference.

1.5. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 5 Same day discharge.

Four trials reported the length of hospital stay (Nomdedeu 1997; Mrozowicz 2006; Uchiyama 2007; Picchio 2012). There was no significant difference in the length of hospital stay between the two groups (MD 0.22 days; 95% CI ‐0.06 to 0.51) ( (Analysis 1.6). There was no change in results by using the random‐effects model. Either the mean or the standard deviation or both were imputed in three trials (Nomdedeu 1997; Mrozowicz 2006; Uchiyama 2007). Excluding these trials from the analysis did not alter the results.

1.6. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 6 Hospital stay.

Operating time

Six trials reported operating time (Hawasli 1994; Mrozowicz 2006; Uchiyama 2007; Georgiou 2011; El‐Labban 2012; Picchio 2012). The operating time was significantly longer in the drain group than the 'no drain' group (MD 5.00 minutes; 95% CI 2.69 to 7.30) (Analysis 1.7). The results did not change by using the random‐effects model. Either the mean or the standard deviation or both were imputed in four trials (Hawasli 1994; Mrozowicz 2006; Georgiou 2011; El‐Labban 2012). Excluding these four trials from the analysis showed that there was no significant difference in the operating time between the two groups (MD 2.67 minutes; 95% CI ‐2.91 to 8.25).

1.7. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 7 Operating time.

Return to normal activity

Only one trial reported the return to normal activity (Hawasli 1994). This trial did not provide any information from which the standard deviation could be imputed. The authors of the trial stated that there was no significant difference in the return to normal activity between the two groups (5.1 days on average in the drain group versus 5.2 days on average in the 'no drain' group) (Hawasli 1994) (Analysis 1.8).

1.8. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 8 Return to normal activity.

Return to normal activity
Study	Mean in drain group	Mean in 'no drain' group	Statistical significance at P value of 0.05
Hawasli 1994	5.1 days (50 participants)	5.2 days (50 participants)	Not significant

Return to work

Only one trial reported the return to work (Hawasli 1994). This trial did not provide any information from which the standard deviation could be imputed. The authors of the trial stated that there was no significant difference in the return to normal activity between the two groups (7.6 days on average in the drain group versus 7.2 days on average in the 'no drain' group) (Hawasli 1994) (Analysis 1.9).

1.9. Analysis.

Comparison 1 Drain versus 'no drain', Outcome 9 Return to work.

Return to work
Study	Mean in drain group	Mean in 'no drain' group	Statistical significance at P value of 0.05
Hawasli 1994	7.6 days (50 participants)	7.2 days (50 participants)	Not significant

Subgroup analyses

We did not perform any subgroup analysis since none, one, or a maximum of two trials would have been included for each subgroup for these subgroup analyses. This would have resulted in high possibility of false positive and false negative results and so was avoided.

Reporting bias

We did not use a funnel plot because fewer than 10 trials were included under each outcome.

Discussion

Summary of main results

This review has shown no significant advantage of using a drain after laparoscopic cholecystectomy. The main reasons for using routine abdominal drainage after laparoscopic cholecystectomy is to decrease the complications such as intra‐abdominal collections that require treatment and to detect bile leak, thereby decreasing the overall mortality and morbidity associated with laparoscopic cholecystectomy. However, the proportion of patients who develop these complications are less than 0.5% as indicated in this review. In order to detect a clinically relevant difference (say a relative risk reduction of 20%), more than 150,000 participants are required. The total number of participants included in this review was only 1801 participants. Thus, the absence of significant difference between the two groups may either be due to lack of effect or lack of evidence of effect. Although there was insufficient participants to identify clinically relevant differences in mortality and morbidity, one would have expected longer hospital stay in the 'no drain' group if the morbidity was higher. However, there was no significant difference in the length of hospital stay between the two groups. One can consider the confidence intervals to be narrow since the confidence intervals did not overlap 1 or ‐1 day as the minimal clinically relevant difference for hospital stay is one day. On the other hand, the proportion of patients who were discharged as day‐procedure laparoscopic cholecystectomy seemed lower in the drain group than the 'no drain' group in the only trial that reported this outcome (Hawasli 1994). These findings suggest that the possibility of shorter hospital stay in the drain group versus the 'no drain' group (and hence a lower mortality and morbidity in the drain group compared to the 'no drain' group) may be unlikely.

The operating time was significantly longer in the drain group than the 'no drain' group but the difference was only five minutes, which does not appear to be clinically significant or result in increased resource utilisation. However, drain use may result in increased resource utilisation in a different way. Most of the trials in which the duration of drain was reported retained the drain for about 24 hours. This would mean that the patient has to either stay in hospital until the drain is removed or has to go home with the drain necessitating drain removal by a visit to the hospital on the next day or a community nurse visiting the patient at home on the next day. This clearly involves additional resource utilisation. Considering that there is no evidence for any benefit for the drain, this additional resource utilisation does not appear to be justified.

Overall completeness and applicability of evidence

Most of the trials included in this review included only adult patients undergoing elective laparoscopic cholecystectomy (nine of the twelve trials). So, this review is applicable only in adult patients undergoing elective laparoscopic cholecystectomy. However, it must be pointed out that there is no evidence to suggest that the rationale for drain use is any different in children or in patients undergoing emergency laparoscopic cholecystectomy (one trial showed that there was no evidence for any benefit from drain use in patients undergoing laparoscopic cholecystectomy for acute cholecystitis (Lucarelli 2012)).

Quality of the evidence

Only two trials were of low risk of bias (Capitanich 2005; Picchio 2012). The overall quality of the evidence was very low as indicated in Table 1. Moreover, as stated, we only obtained a very small proportion of the diversity‐adjusted required information size. However, it must be noted that this is the best evidence available currently.

Potential biases in the review process

We performed a thorough search of literature. However, we cannot rule out trials not being reported because of lack of benefit of drain use. This is unlikely to affect our conclusions. We imputed the mean and standard deviation when these were not available. Excluding the trials in which such imputation was performed did not alter the conclusions. Overall, the evidence from this review can be considered the best available evidence on this topic.

Agreements and disagreements with other studies or reviews

Our conclusions are largely in agreement with our previous version (Gurusamy 2007b). Drain use seems unnecessary for open cholecystectomy also and may even be harmful (Gurusamy 2007a).

Authors' conclusions

Implications for practice.

Currently, there is no evidence to support the use of drains after laparoscopic cholecystectomy.

Implications for research.

Further randomised clinical trials are needed to compare drain use in laparoscopic cholecystectomy performed for acute cholecystitis.Trials need to be conducted and reported according to the SPIRIT (http://www.spirit‐statement.org) and the CONSORT Statements (www.consort‐statement.org).

What's new

Date	Event	Description
14 June 2013	New citation required and conclusions have changed	The methods were revised in line with the version 5.1.0 of the Cochrane Handbook for Systematic Reviews of Interventions. We included only routine drainage versus no routine drainage for this review. Hence, the conclusions changed from "Drain use after elective laparoscopic cholecystectomy increases wound infection rates and delays hospital discharge. We could not find evidence to support the use of drain after laparoscopic cholecystectomy" into "There is currently no evidence to support the routine use of drain after laparoscopic cholecystectomy".
14 June 2013	Amended	One additional trial was sent by a peer reviewer and with the new trial by Lucarelli 2012 et al, a total of six new trials were included in this update. Thus, the total number of included trials in this review is 12.
28 March 2013	Amended	Rahul Koti joined the review group and the review authors are as follows: Kurinchi Selvan Gurusamy, Rahul Koti, Brian R Davidson.
27 February 2013	New search has been performed	The searches were updated in February 2013. Five new trials were included (Uchiyama 2007; Tzovaras 2009; Georgiou 2011; El‐Labban 2012; Picchio 2012).

Appendices

Appendix 1. Search Strategies

Database	Period	Search strategy used
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Wiley)	Issue 1, 2013.	#1 laparoscop$ or celioscop$ or coelioscop$ or abdominoscop$ or peritoneoscop$ in All Fields in all products #2 cholecystecto* or colecystecto* in All Fields in all products #3 MeSH descriptor Cholecystectomy, Laparoscopic explode all trees in MeSH products #4 MeSH descriptor Drainage explode all trees in MeSH products #5 drain* in All Fields in all products #6 (( #1 AND #2 ) OR #3) AND ( #4 OR #5 )
MEDLINE (Pubmed)	January 1987 to February 2013.	((((laparoscop* or celioscop* or coelioscop* or abdominoscop* or peritoneoscop*) AND (cholecystecto* or colecystecto*)) OR "Cholecystectomy, Laparoscopic"[MeSH]) AND ("Drainage"[MeSH] OR drain*)) AND (randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double‐blind method [mh] OR single‐blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR (placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp]) NOT (animals [mh] NOT human [mh])) AND ("1987"[PDAT] : "3000"[PDAT])
EMBASE (OvidSP)	January 1987 to February 2013.	1. exp crossover‐procedure/ or exp double‐blind procedure/ or exp randomized controlled trial/ or single‐blind procedure/ 2. (((((random* or factorial* or crossover* or cross over* or cross‐over* or placebo* or double*) adj blind*) or single*) adj blind*) or assign* or allocat* or volunteer*).af. 3. 1 or 2 4. (laparoscop* or celioscop* or coelioscop* or abdominoscop* or peritoneoscop*).af. 5. exp laparoscopy/ or exp laparoscopic surgery/ 6. 4 or 5 7. (cholecystect* or colecystect*).af. 8. exp cholecystectomy/ 9. 7 or 8 10. drain*.af. 11. exp drain/ 12. exp surgical drainage/ 13. 10 or 11 or 12 14. 3 and 6 and 9 and 13
Science Citation Index Expanded (Web of Knowledge)	January 1987 to February 2013.	#1 TS=(laparoscop* OR celioscop* OR coelioscop* OR abdominoscop* OR peritoneoscop*) #2 TS=(cholecystecto* OR colecystecto*) #3 TS=drain* #4 TS=(random* OR blind* OR placebo* OR meta‐analysis) #5 #1 AND #2 AND #3 AND #4

Data and analyses

Comparison 1. Drain versus 'no drain'.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mortality	10	1681	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.04, 4.37]
2 Serious adverse events (proportion of patients)	7	1143	Risk Ratio (M‐H, Fixed, 95% CI)	2.12 [0.61, 7.40]
3 Serious adverse events (number)	8	1286	Rate Ratio (Fixed, 95% CI)	1.60 [0.66, 3.87]
4 Quality of life	1		Std. Mean Difference (IV, Fixed, 95% CI)	Totals not selected
5 Same day discharge	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
6 Hospital stay	5	449	Mean Difference (IV, Fixed, 95% CI)	0.22 [‐0.06, 0.50]
7 Operating time	7	775	Mean Difference (IV, Fixed, 95% CI)	4.97 [2.70, 7.25]
8 Return to normal activity			Other data	No numeric data
9 Return to work			Other data	No numeric data

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Capitanich 2005.

Methods	Randomised clinical trial
Participants	Country: Argentina. Number randomised: 93. Post‐randomisation drop‐outs: 0 (0%). Revised sample size: 93. Average age: 52 years. Females: 55 (59.1%). Drains brought through: not stated. Duration of drain: not stated. Prophylactic antibiotics: not stated. Inclusion criteria Elective laparoscopic cholecystectomy. Exclusion criteria 1. Emergency cholecystectomy. 2. Jaundice. 3. Injury to cystic artery. 4. Choledocholithiasis. 5. Sclerotic gallbladder. 6. Loss to follow‐up.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 40). Further details: Not stated. Group 2: no drain (n = 53).
Outcomes	The outcomes reported were mortality, morbidity, and quality of life.
Notes	Attempts were made to contact the authors in September 2006 and March 2013. Authors provided replies in September 2006 and March 2013. Reasons for post‐randomisation drop‐outs: not stated.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The random sequence was generated by a random number table (author replies)".
Allocation concealment (selection bias)	Low risk	Quote: "The allocation of patients was made with sealed envelopes. The envelopes were opened once the criteria of inclusion were met. That is: after the extraction of the gallbladder and before the conclusion of the procedure (author replies) ".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "patients and healthcare were blinded (author replies)".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The outcomes were recorded by a non involved staff member (author replies)".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported
For‐profit bias	Low risk	Quote: "We did not receive funding support (author replies)".

El‐Labban 2012.

Methods	Randomised clinical trial
Participants	Country: Egypt. Number randomised: 160. Post‐randomisation drop‐outs: not stated. Revised sample size: 160. Average age: not stated Females: 116 (72.5%). Drains brought through: not stated. Duration of drain: not stated. Prophylactic antibiotics: Cefuroxime 750 mg one dose. Inclusion criteria American Society of Anesthesiologists (ASA) I, II, and III patients admitted to undergo elective laparoscopic cholecystectomy. Exclusion criteria 1. Age > 70 years. 2. Did not have acute cholecystitis, cholangitis, or pancreatitis. 3. Did not have any contraindication for the laparoscopic approach. 4. Did not require common bile duct exploration or any other additional procedure. 5. Refused to enter the study. 6. Converted to open surgery. 7. Patients with chronic liver disease or bleeding tendency.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 80). Further details: Passive drain. Group 2: no drain (n = 80).
Outcomes	The outcomes reported were mortality, morbidity, and operating time.
Notes	Attempts were made to contact the authors in March 2013. No replies were received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: This information was not available.
Allocation concealment (selection bias)	Unclear risk	Quote: "Although entrance into the trial was decided before surgery, the randomisation arm was only notified to the operating team after the completion of cholecystectomy and just before closure of the wounds using sealed envelopes in blocks of 20". Comment: Further details were not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: This information was not available.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Georgiou 2011.

Methods	Randomised clinical trial
Participants	Country: Cyprus and Greece. Number randomised: 130. Post‐randomisation drop‐outs: 14 (10.8%). Revised sample size: 116. Average age: 51 years. Females: 79 (68.1%). Drains brought through: port. Duration of drain: drain kept for at least 24 hours; kept longer if bile drained. Prophylactic antibiotics: Cefuroxime 750 mg one dose on induction. Inclusion criteria Patients admitted for elective cholecystectomy. Exclusion criteria 1. Patients with acute cholecystitis and empyema of gallbladder. 2. Patients who underwent exploration of the common bile duct.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 63). Further details: Polythene drain ‐ no further details. Group 2: no drain (n = 53).
Outcomes	The outcomes reported were mortality and operating time.
Notes	Attempts were made to contact the authors in March 2013. No replies were received. Reasons for post‐randomisation drop‐outs: inflammation was noticed during operation (groups not stated).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "in patients selected by draw".
Allocation concealment (selection bias)	Unclear risk	Quote: "in patients selected by draw". Comment: Further details were not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: There were post‐randomisation drop‐outs.
Selective reporting (reporting bias)	High risk	Comment: Important outcomes such as morbidity were not adequately reported
For‐profit bias	Unclear risk	Comment: This information was not available.

Hawasli 1994.

Methods	Randomised clinical trial
Participants	Country: USA. Number randomised: 100. Post‐randomisation drop‐outs: not stated. Revised sample size: 100. Average age: 52 years. Females: 79 (79%). Drains brought through: port. Duration of drain: not stated. Prophylactic antibiotics: not stated. Inclusion criteria Elective uncomplicated laparoscopic cholecystectomy. Exclusion criteria 1. Acute cholecystitis. 2. Required cholangiogram. 3. Complicated procedure.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 50). Further details: 19 Fr J vac drain. Group 2: no drain (n = 50).
Outcomes	The outcomes reported were proportion discharged as day‐surgery, operating time, return to activity, and return to work.
Notes	Attempts were made to contact the authors in April 2007 and March 2013. No replies were received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A computer‐generated randomized schedule was used to randomly enter these patients into either group".
Allocation concealment (selection bias)	Unclear risk	Comment: This information was not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: This information was not available.
Selective reporting (reporting bias)	High risk	Comment: Important outcomes such as mortality and morbidity were not reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Lucarelli 2012.

Methods	Randomised clinical trial
Participants	Country: Italy. Number randomised: 30. Post‐randomisation drop‐outs: 0 (0%). Revised sample size: 30. Average age: 63 years. Females: 20 (66.7%). Drains brought through: port Duration of drain: drain removed after 24 hours unless indicated by blood or bile drainage Prophylactic antibiotics: Augmentin 1 g 8 hourly (duration not stated) Inclusion criteria 1. Patients with acute cholecystitis. 2. 18 years or older. Exclusion criteria 1. Symptoms present for > 1 week. 2. Gangrenous or emphysematous cholecystitis was present. 3. Previous upper abdominal surgery. 4. Significant medical diseases that rendered them unfit for laparoscopic surgery 5. Coexisting common bile duct stones with ductal dilatation, acute cholangitis, or acute pancreatitis.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 15). Further details: 5.7 mm multiporous drain connected to a 500 ml reservoir. Group 2: no drain (n = 15).
Outcomes	The outcomes reported were mortality, morbidity, hospital stay, and operating time.
Notes	Attempts were made to contact the authors in June 2013. No replies were received. Reasons for post‐randomisation drop‐outs: not stated.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was computer generated,…".
Allocation concealment (selection bias)	Low risk	Quote: "Randomization was computer generated, using numbered and sealed envelopes, which were opened in the operating room at the end of surgery before drain fixation to the skin".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "In group B, after the surgeon inserted the drain, a nurse of the operating room pulled out the drain outside the port, shortened the tube, and fixed the end to the skin with a tape after blocking the tip with a bead. All drains in both groups were connected to a 500‐mL reservoir. This way, the operator, the patients, and the assessors were blinded to the intervention".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "In group B, after the surgeon inserted the drain, a nurse of the operating room pulled out the drain outside the port, shortened the tube, and fixed the end to the skin with a tape after blocking the tip with a bead. All drains in both groups were connected to a 500‐mL reservoir. This way, the operator, the patients, and the assessors were blinded to the intervention".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported
For‐profit bias	Unclear risk	Comment: This information was not available.

Mrozowicz 2006.

Methods	Randomised clinical trial
Participants	Country: Poland. Number randomised: 150. Post‐randomisation drop‐outs: 7 (4.7%). Revised sample size: 143. Average age: 58 years. Females: 112 (78.3%). Drains brought through: port. Duration of drain: drain removed after 24 hours unless indicated by blood or bile drainage. Prophylactic antibiotics: prophylactic antibiotics were used but details were not provided. Inclusion criteria Symptomatic cholelithiasis. Exclusion criteria 1. Conversion to open surgery. 2. Obstructive jaundice. 3. Peritonitis. 4. Suspicion of cancer. 5. Intra‐operative injury. 6. Intra‐operative haemorrhage.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 79). Further details: closed drain but not clear whether this was passive drain or suction drain. Group 2: no drain (n = 64).
Outcomes	The outcomes reported were mortality, morbidity, hospital stay, and operating time.
Notes	Attempts were made to contact the authors in March 2013. No replies were received. Reasons for post‐randomisation drop‐outs: conversion to open cholecystectomy (1 in intervention group and 6 in control group).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients fulfilling the inclusion criteria were randomly assigned to the study (without drainage) or control (with drainage) groups, according to a computer‐based randomization list".
Allocation concealment (selection bias)	Unclear risk	Comment: This information was not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: There were post‐randomisation drop‐outs.
Selective reporting (reporting bias)	High risk	Comment: While mortality and complications were reported, the severity of the complications in each group were not reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Nomdedeu 1997.

Methods	Randomised clinical trial
Participants	Country: Spain. Number randomised: 50. Post‐randomisation drop‐outs: not stated. Revised sample size: 50. Average age: 52 years. Females: 35 (70%). Drains brought through: port. Duration of drain: drain removed when the drainage was less than 50 ml in 24 hours. Prophylactic antibiotics: Three doses of 1 g of cefazolin sodium administered one hour before surgery and at 8 and 16 hours of surgery, Inclusion criteria Symptomatic gallstones. Exclusion criteria 1. Cholecystitis. 2. Coagulopathy. 3. Abnormal cholangiogram. 4. Conversion to open cholecystectomy. 5. Biliary colic with jaundice and/or fever. 6. Gallbladder rupture during surgery. 7. Liver disease.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 25). Further details: 16 Fr Jackson suction drain. Group 2: no drain (n = 25).
Outcomes	The outcome reported was hospital stay.
Notes	Attempts were made to contact the authors in April 2007 and March 2013. No replies were received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: This information was not available.
Allocation concealment (selection bias)	Low risk	Comment: This information was not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: This information was not available.
Selective reporting (reporting bias)	High risk	Comment: Important outcomes such as mortality and morbidity were not reported
For‐profit bias	Unclear risk	Comment: This information was not available.

Nursal 2003.

Methods	Randomised clinical trial
Participants	Country: Turkey. Number randomised: 85. Post‐randomisation drop‐outs: 16 (18.8%). Revised sample size: 69. Average age: 50 years. Females: 51 (73.9%). Drains brought through: port. Duration of drain: drain removed after 24 hours. Prophylactic antibiotics: not stated. Inclusion criteria 1. ASA grade I and II. 2. Gallstones with or without acute cholecystitis. Exclusion criteria 1. Patients who were converted to open surgery. 2. Refused laparoscopic cholecystectomy. 3. Refused to give informed consent. 4. Given medications other than the standard anaesthesia protocol.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 35). Further details: 6 Fr suction drain. Group 2: no drain (n = 34).
Outcomes	The outcomes reported were mortality and morbidity.
Notes	Attempts were made to contact the authors in April 2007 and March 2013. Authors provided replies in March 2013. Reasons for post‐randomisation drop‐outs: conversion to open cholecystectomy (7); requiring additional medications (8); and missing information (1) (groups not stated).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The random sequence was computer‐generated (author replies)".
Allocation concealment (selection bias)	Low risk	Quote: "The allocation was concealed by the department secretary in a separate file accessible only to her, secured by a password only she knows (author replies)".
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "The drains in the control group were sealed and concealed but were still connected to the reservoir….Patients were blinded, the surgeons were not (author replies)".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The drains in the control group were sealed and concealed but were still connected to the reservoir . The outcome assessors were blinded (author replies)".
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: There were post‐randomisation drop‐outs.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported
For‐profit bias	Low risk	Quote: "Baskent University funded the study (author replies)".

Picchio 2012.

Methods	Randomised clinical trial
Participants	Country: Italy, Nigeria. Number randomised: 106. Post‐randomisation drop‐outs: 0 (0%). Revised sample size: 106. Average age: 48 years. Females: 82 (77.4%). Drains brought through: port. Duration of drain: drain removed after 24 hours unless indicated by blood or bile drainage. Prophylactic antibiotics: not stated. Inclusion criteria 1. Patients undergoing elective laparoscopic cholecystectomy. 2. Aged 18 years and older. Exclusion criteria 1. Patients with acute cholecystitis, cholangitis, or pancreatitis. 2. Intraoperative common bile duct exploration or any other additional procedure were performed.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 53). Further details: suction drain. Group 2: no drain (n = 53).
Outcomes	The outcomes reported were mortality, morbidity, hospital stay, and operating time.
Notes	Attempts were made to contact the authors in March 2013. Authors provided replies in March 2013. Reasons for post‐randomisation drop‐outs: not stated.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was computer generated, using numbered and sealed envelopes, which were opened in the operating room at the end of surgery before drain fixation to the skin".
Allocation concealment (selection bias)	Low risk	Quote: "Randomization was computer generated, using numbered and sealed envelopes, which were opened in the operating room at the end of surgery before drain fixation to the skin".
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "In group B, after the surgeon inserted the drain, a nurse of the operatory room pulled out the drain outside the port, shortened the tube, and fixed the end to the skin with a tape after blocking the tip with a bead. All drains in both groups were connected to a 500‐mL closed suction reservoir. This way, the operator, the patients, and the assessors were blinded to the intervention".
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "In group B, after the surgeon inserted the drain, a nurse of the operatory room pulled out the drain outside the port, shortened the tube, and fixed the end to the skin with a tape after blocking the tip with a bead. All drains in both groups were connected to a 500‐mL closed suction reservoir. This way, the operator, the patients, and the assessors were blinded to the intervention".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: There were no post‐randomisation drop‐outs.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported.
For‐profit bias	Low risk	Quote: "The study received a grant from the Sapienza University of Rome (author replies)".

Thiebe 1994.

Methods	Randomised clinical trial
Participants	Country: Germany. Number randomised: 300. Post‐randomisation drop‐outs: 21 (7%). Revised sample size: 279. Average age: not stated Females: not stated Drains brought through: not stated. Duration of drain: not stated. Prophylactic antibiotics: not stated. Inclusion criteria Laparoscopic cholecystectomy. Exclusion criteria 1. Patients who were converted to open surgery. 2. Liver bed bleeding. 3. Acute cholecystitis.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 131). Further details: silicon gravity drain. Group 2: no drain (n = 148).
Outcomes	The outcomes reported were mortality.
Notes	Attempts were made to contact the authors in April 2007 and March 2013. No replies were received. Reasons for post‐randomisation drop‐outs: conversion to open cholecystectomy (10); drain used because of acute cholecystitis or bleeding from liver bed (6); drain removed during recovery phase (3); reason for drop‐out not stated (2); groups were not stated.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: This information was not available.
Allocation concealment (selection bias)	Unclear risk	Comment: This information was not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: There were post‐randomisation drop‐outs.
Selective reporting (reporting bias)	High risk	Comment: Important outcomes such as morbidity were not reported adequately. Although the authors mention the number of complications, the severity of the complications was not reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Tzovaras 2009.

Methods	Randomised clinical trial
Participants	Country: Greece. Number randomised: 565. Post‐randomisation drop‐outs: not stated. Revised sample size: 565. Average age: 56 years. Females: 393 (69.6%). Drains brought through: port. Duration of drain: drain removed after 24 hours unless indicated by blood or bile drainage. Prophylactic antibiotics: prophylactic antibiotics (single standard dose) were used but details were not provided. Inclusion criteria American Society of Anesthesiologists (ASA) I, II, and III patients undergoing elective laparoscopic cholecystectomy. Exclusion criteria 1. Did not have acute cholecystitis, cholangitis, or pancreatitis. 2. Did not have any contraindication for the laparoscopic approach. 3. Did not require common bile duct exploration or any other additional procedure.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 284). Further details: 4 mm corrugated silicone drain draining into a colostomy bag without suction. Group 2: no drain (n = 281).
Outcomes	The outcomes reported were mortality and morbidity.
Notes	Attempts were made to contact the authors in March 2013. No replies were received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: This information was not available.
Allocation concealment (selection bias)	Unclear risk	Quote: "Although entrance into the trial was decided before surgery, the randomization arm was only notified to the operating team after the completion of cholecystectomy and just before closure of the wounds using sealed envelopes in blocks of 20". Comment: Further details were not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: This information was not available.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Uchiyama 2007.

Methods	Randomised clinical trial
Participants	Country: Japan. Number randomised: 120. Post‐randomisation drop‐outs: not stated. Revised sample size: 120. Average age: 55 years. Females: 66 (55%). Drains brought through: port. Duration of drain: drain removed after 42 hours. Prophylactic antibiotics: Sulbactam/cefoperazone combination three times:30 min before the operation, 4 hours after the operation, and on the day after the operation. Inclusion criteria 1. Patients with cholecystolithiasis or gallbladder polyp undergoing laparoscopic cholecystectomy. 2. Under 80 years old. 3. Provision of informed consent (in writing) to participate in this study. Exclusion criteria 1. Patients with acute cholecystitis and choledocholithiasis. 2. Patients with a history of upper laparotomy. 3. Patients with severe complications, including cardiopulmonary disease or a hemorrhagic tendency due to cirrhosis.
Interventions	Participants were randomly assigned to two groups. Group 1: drain (n = 60). Further details: 8 mm open Penrose drain. Group 2: no drain (n = 60).
Outcomes	The outcomes reported were mortality, morbidity, hospital stay, and operating time.
Notes	Attempts were made to contact the authors in March 2013. No replies were received.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The subjects were allocated to each treatment group on the completion of LC, according to the allocation table".
Allocation concealment (selection bias)	Unclear risk	Quote: "The subjects were allocated to either group A or group B, using an equal number of blind envelopes". Comment: Further details were not available.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: This information was not available.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: This information was not available.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: This information was not available.
Selective reporting (reporting bias)	Low risk	Comment: Important outcomes such as mortality and morbidity were reported.
For‐profit bias	Unclear risk	Comment: This information was not available.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abbott 2001	Performed in other laparoscopic procedures and not in laparoscopic cholecystectomy.
Alexander 1987	Performed in other laparoscopic procedures and not in laparoscopic cholecystectomy.
Mrsic 1997	Not a randomised clinical trial.
Tsimoyiannis 1998	Some patients who were randomised were replaced by other new patients who were allocated to the same group as the patients originally included.
Tsimoyiannis 1998b	In this study where the main outcome measures were pain, nausea, and vomiting, the drain group received other interventions, such as intraperitoneal normal saline or bupivacaine instillation.

Differences between protocol and review

Differences between first version and second version

The methods of revised according to the version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This included revision of the outcomes and the risk of bias in the trials.

Contributions of authors

K Gurusamy is the lead author and identified the trials for inclusion; extracted the data for some trials and wrote the review. R Koti independently assessed the trials for inclusion and extracted data on included trials for the update. BR Davidson critically commented on the review and suggested improvements.

Sources of support

Internal sources

• NIHR, UK.

  This update is funded by NINHR, UK

External sources

• No sources of support supplied

Declarations of interest

None known.

New search for studies and content updated (conclusions changed)