Anaesthetic regimens for day-procedure laparoscopic cholecystectomy

  • Review
  • Intervention

Authors


Abstract

Background

Day surgery involves admission of selected patients to hospital for a planned surgical procedure with the patients returning home on the same day. An anaesthetic regimen usually involves a combination of an anxiolytic, an induction agent, a maintenance agent, a method of maintaining the airway (laryngeal mask versus endotracheal intubation), and a muscle relaxant. The effect of anaesthesia may continue after the completion of surgery and can delay discharge. Various regimens of anaesthesia have been suggested for day-procedure laparoscopic cholecystectomy.

Objectives

To compare the benefits and harms of different anaesthetic regimens (risks of mortality and morbidity, measures of recovery after surgery) in patients undergoing day-procedure laparoscopic cholecystectomy.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 10, 2013), MEDLINE (PubMed) (1987 to November 2013), EMBASE (OvidSP) (1987 to November 2013), Science Citation Index Expanded (ISI Web of Knowledge) (1987 to November 2013), LILACS (Virtual Health Library) (1987 to November 2013), metaRegister of Controlled Trials (http://www.controlled-trials.com/mrct/) (November 2013), World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) portal (November 2013), and ClinicalTrials.gov (November 2013).

Selection criteria

We included randomized clinical trials comparing different anaesthetic regimens during elective day-procedure laparoscopic cholecystectomy (irrespective of language or publication status).

Data collection and analysis

Two authors independently assessed trials for inclusion and independently extracted the data. We calculated the risk ratio, rate ratio or mean difference with 95% confidence intervals based on intention-to-treat or available data analysis.

Main results

We included 11 trials involving 1069 participants at low anaesthetic risk. The sample size varied from 40 to 300 participants. We included 23 comparisons. All trials were at a high risk of bias. We were unable to perform a meta-analysis because there were no two trials involving the same comparison. Primary outcomes included perioperative mortality, serious morbidity and proportion of patients who were discharged on the same day. There were no perioperative deaths or serious adverse events in either group in the only trial that reported this information (0/60). There was no clear evidence of a difference in the proportion of patients who were discharged on the same day between any of the comparisons. Overall, 472/554 patients (85%) included in this review were discharged as day-procedure laparoscopic cholecystectomy patients. Secondary outcomes included hospital readmissions, health-related quality of life, pain, return to activity and return to work. There was no clear evidence of a difference in hospital readmissions within 30 days in the only comparison in which this outcome was reported. One readmission was reported in the 60 patients (2%) in whom this outcome was assessed. Quality of life was not reported in any of the trials. There was no clear evidence of a difference in the pain intensity, measured by a visual analogue scale, between comparators in the only trial which reported the pain intensity at between four and eight hours after surgery. Times to return to activity and return to work were not reported in any of the trials.

Authors' conclusions

There is currently insufficient evidence to conclude that one anaesthetic regimen for day-procedure laparoscopic cholecystectomy is to be preferred over another. However, the data are sparse (that is, there were few trials under each comparison and the trials had few participants) and further well designed randomized trials at low risk of bias and which are powered to measure differences in clinically important outcomes are necessary to determine the optimal anaesthetic regimen for day-procedure laparoscopic cholecystectomy, one of the commonest procedures performed in the western world.

Résumé scientifique

Schémas d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire

Contexte

La chirurgie ambulatoire implique l'admission à l'hôpital de patients sélectionnés pour une procédure chirurgicale planifiée avec les patients retournant à leur domicile le jour même. Un schéma d'anesthésie implique habituellement une combinaison d'anxiolytique, un agent d'induction, un agent d'entretien, une méthode maintenant les voies respiratoires (un masque laryngé par rapport à l'intubation endotrachéale), et un myorelaxant. L'effet de l'anesthésie peut se poursuivre après l'achèvement de la chirurgie et peut retarder la sortie d'hôpital. Différents schémas d'anesthésie ont été suggérés pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire.

Objectifs

Comparer les bénéfices et les préjudices des différents schémas d'anesthésie (risques de mortalité et de morbidité, les mesures de la récupération après la chirurgie) chez les patients subissant une cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL) dans la Bibliothèque Cochrane (numéro 10, 2013), MEDLINE (PubMed) (de 1987 à novembre 2013), EMBASE (OvidSP) (de 1987 à novembre 2013), Science Citation Index Expanded (ISI Web of Knowledge) (de 1987 à novembre 2013), LILACS (Virtual Health Library) (de 1987 à novembre 2013), metaRegister of Controlled Trials (http://www.controlled-trials.com/mrct) (novembre 2013), de l'Organisation Mondiale de la Santé (OMS) International Clinical Trials Registry Platform (ICTRP) de l'OMS (novembre 2013), et ClinicalTrials.gov (novembre 2013).

Critères de sélection

Nous avons inclus les essais cliniques randomisés comparant différents schémas d'anesthésie pendant la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire (indépendamment de la langue ou du statut de publication).

Recueil et analyse des données

Deux auteurs ont indépendamment évalué les essais à inclure et extrait les données de manière indépendante. Nous avons calculé le risque relatif, le rapport des taux ou la différence moyenne avec un intervalle de confiance à 95 % sur la base des analyses d'intention de traiter ou des données disponibles.

Résultats principaux

Nous avons inclus 11 essais portant sur 1 069 participants à faible risque anesthésique. La taille des échantillons variaient de 40 à 300 participants. Nous avons inclus 23 comparaisons. Tous les essais étaient à risque de biais élevé. Nous n'avons pas été en mesure de réaliser une méta-analyse, car il n'y avait pas deux essais portant sur la même comparaison. Les principaux critères de jugement incluaient la mortalité périopératoire, la morbidité grave et la proportion de patients libérés le jour même. Dans le seul essai ayant rendu compte de ces informations, il n'y avait dans aucun des groupes ni décès périopératoires, ni effets indésirables graves (0/60). Entre les diverses comparaisons, il n'y avait aucune preuve probante d'une différence dans la proportion de patients libérés le même jour. Dans l'ensemble, 472/554 patients (85 %) inclus dans cette revue sont sortis de l'hôpital suite à une cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire. Les critères de jugement secondaires incluaient les réadmissions à l'hôpital, la qualité de vie liée à la santé, la douleur, la reprise des activités et le retour au travail. Dans la seule comparaison qui rapportait ce résultat, il n'y avait aucune preuve probante d'une différence au niveau des réadmissions à l'hôpital dans les 30 jours. Une réhospitalisation a été signalée chez 60 patients (2 %) dans lesquelles ce résultat a été évalué. La qualité de vie n'était rapportée dans aucun des essais. Il n'y avait aucune preuve probante d'une différence au niveau de l'intensité de la douleur, mesurée par une échelle visuelle analogique, entre les comparateurs dans le seul essai qui rapportait l'intensité de la douleur 4 et 8 heures après la chirurgie. Les périodes de reprise des activités et du retour au travail n'étaient rapportées dans aucun des essais.

Conclusions des auteurs

Il n'existe actuellement pas suffisamment de preuves pour conclure qu'un schéma d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire soit préféré par rapport à un autre. Cependant, les données sont rares (il y avait peu d'essais pour chaque comparaison et les essais avaient peu de participants) et d'autres essais randomisés, bien conçus, à faible risque de biais et de puissance suffisante pour mesurer les différences dans les résultats cliniquement importants, sont nécessaires pour déterminer le meilleur schéma d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire, l'une des procédures les plus couramment réalisée dans le monde occidental.

Plain language summary

Anaesthetic regimens for day-procedure laparoscopic cholecystectomy

Background

Approximately 50 to 250 out of every 1000 adults in the western world have gallstones. Of every 100 people with gallstones, two to four people develop symptoms such as pain in the upper abdomen. This condition is treated by surgical removal of the gallbladder through 'keyhole surgery', a procedure that is known as laparoscopic cholecystectomy. It is possible to perform the operation and allow the patient to go home on the same day ('day surgery'). During surgery, the patient is given a range of medicines to provide lack of awareness of the procedure undertaken, reduce pain, and relax muscles (allowing the surgeon adequate access and vision). Together, this is called an anaesthetic regimen. Many different anaesthetic regimens have been suggested for use in day-procedure laparoscopic cholecystectomy. We sought to find the best anaesthetic regimen by performing a thorough search of the literature for randomized controlled trials, reported until November 2013.

Study characteristics

We included 11 trials involving 1069 patients in this review. Most participants in the trials had a low anaesthetic risk.

Key results

There were no deaths or serious complications in the only trial that reported this information. Overall, 85% of patients (472/554) were discharged as day-procedure laparoscopic cholecystectomy patients and 2% of patients (1/60) required hospital readmission. The reasons for not discharging the patients as day-procedure patients were not described in detail in the trials. The reason for readmission was fever that developed in the patient and which subsequently settled on its own without any treatment. Quality of life was not reported in any of the trials. There was no clear evidence of a difference in the measures of pain intensity between any of the comparisons. Time to return to routine daily activity and to return to work were not reported in any of the trials. There is currently no evidence to support one anaesthetic regimen for day-procedure laparoscopic cholecystectomy over another.

Quality of evidence

All the trials had elements that tended to reduce our trust in the accuracy of the results. Few patients were included in each comparison resulting in a considerable chance of arriving at erroneous conclusions.

Future research

Randomized controlled trials designed to minimize the risk of arriving at wrong conclusions are necessary to determine the best anaesthetic regimen for day-procedure laparoscopic cholecystectomy, one of the commonest procedures performed in the western world.

Résumé simplifié

Schémas d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire

Contexte

Environ 50 à 250 sur 1 000 adultes dans le monde occidental souffrent de calculs biliaires. Sur 100 personnes souffrant de calculs biliaires, 2 à 4 patients développent des symptômes tels qu'une douleur dans le haut de l'abdomen. Cette affection est traitée par l'ablation chirurgicale de la vésicule biliaire à travers une chirurgie endoscopique, une procédure qui est connue sous le nom de cholécystectomie laparoscopique. Il est possible de procéder à l'opération et de permettre au patient de rentrer à son domicile le jour même (« chirurgie ambulatoire »). Pendant la chirurgie, le patient reçoit un éventail de médicaments pour fournir un manque de prise de conscience de la procédure, réduire la douleur et détendre les muscles (permettant au chirurgien un accès et une vision adéquats). Ensemble, cela se nomme un schéma d'anesthésie. De nombreux schémas d'anesthésie ont été suggérés pour utiliser dans la chirurgie ambulatoire de la cholécystectomie laparoscopique. Nous avons cherché à déterminer le meilleur schéma d'anesthésie par une recherche exhaustive de la littérature des essais contrôlés randomisés, rapportés jusqu'en novembre 2013.

Les caractéristiques de l'étude

Dans cette revue, nous avons inclus 11 essais portant sur 1 069 patients. La plupart des participants dans les essais présentaient un faible risque anesthésique.

Résultats principaux

Il n'y avait pas de décès ou de complications graves dans le seul essai ayant rendu compte de cette information. Dans l'ensemble, 85% des patients (472/554) rentraient à leur domicile suite à une chirurgie ambulatoire pour la cholécystectomie laparoscopique et 2% des patients (1/60) nécessitaient une réadmission à l'hôpital. Les raisons de ne pas autoriser les patients subissant une chirurgie ambulatoire à quitter l'hôpital n'étaient pas détaillées dans les essais. Les raisons de la réadmission étaient la fièvre développée chez le patient et qui par la suite disparaissait spontanément, sans traitement. La qualité de vie n'était rapportée dans aucun des essais. Il n'y avait aucune preuve probante d'une différence dans les mesures d'intensité de la douleur entre les comparaisons. Les délais de reprise des activités quotidiennes et du retour au travail n'étaient rapportés dans aucun des essais. Il n'existe actuellement aucune preuve permettant de recommander un schéma d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire par rapport à un autre.

Qualité des preuves

Tous les essais comportaient des éléments qui tendaient à réduire notre confiance dans l'exactitude des résultats. Dans chaque comparaison, peu de patients étaient inclus, entraînant un risque considérable de fournir des conclusions erronées.

Les recherches futures

Des essais contrôlés randomisés conçus pour minimiser le risque de conclusions erronées sont nécessaires pour déterminer le meilleur schéma d'anesthésie pour la cholécystectomie laparoscopique pratiquée en chirurgie ambulatoire, l'une des procédures les plus couramment réalisée dans le monde occidental.

Notes de traduction

Traduit par: French Cochrane Centre 15th June, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

Background

Description of the condition

Approximately 50 to 250 out of every 1000 adults in the western world have gallstones (Bates 1992GREPCO 1984GREPCO 1988; Halldestam 2004). 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 1995Halldestam 2004). Thus, 1 to 10 out of every 1000 adults in the western world develop symptoms related to gallstones every year. Regional differences exist in the cholecystectomy rates (Mjäland 1998). Every year, approximately 1.5 million cholecystectomies are performed in the US (Dolan 2009), which has a population of approximately 300 million people (US Census Bureau). Laparoscopic cholecystectomy is now the preferred method of cholecystectomy (Ballal 2009Dolan 2009; Harboe 2010). The procedure is usually performed as a day case, with minimal morbidity. However, deaths occur in the perioperative period (usually within 30 days) after laparoscopic cholecystectomy in about 0.1% to 0.5% of patients (Dolan 2009Giger 2011; Scollay 2011). The main predisposing factors for mortality are bile duct injury and elderly patients with co-morbidities (Giger 2011Scollay 2011). Day surgery is defined as the admission of selected patients to hospital for a planned surgical procedure and who return home on the same day (Department of Health 2002); it is a distinct entity from overnight stay cholecystectomy, which may sometimes be for less than 24 hours. Approximately 10% to 30% of patients scheduled for day-procedure laparoscopic cholecystectomy cannot be discharged as day-procedure patients (Gurusamy 2008; Vaughan 2013). Postoperative pain, nausea, and vomiting are the main reasons for failed hospital discharge in day-procedure and overnight-stay laparoscopic cholecystectomy patients (Gurusamy 2008; Vaughan 2013). Other reasons for failed hospital discharge include organizational issues, surgical procedure-related reasons such as conversion to open cholecystectomy or injury to the bile duct (Gurusamy 2008; Vaughan 2013).

Description of the intervention

An ideal anaesthetic regimen for day-procedure laparoscopic cholecystectomy is a safe anaesthetic that decreases anxiety, provides lack of awareness of the procedure undertaken, is short acting so that there is quick recovery of motor and cognitive functions, and has no adverse effects that can cause delay in discharge. In practice, anaesthesia for this procedure involves a combination of an induction agent, a maintenance agent, a method of maintaining the airway (laryngeal mask versus endotracheal intubation), a muscle relaxant and an intraoperative short acting opioid the effect of which is expected only during the operation. Thus, an anaesthetic regimen is a complex intervention with multiple components. Anaesthesia can be maintained by inhalational anaesthesia (usually after induction by an intravenous agent) or can be total intravenous anaesthesia when no inhalational anaesthesia is used for maintenance (Elcock 2002; Elliott 2003; White 2009a).

How the intervention might work

Different anaesthetic regimens have different patient acceptability and recovery profiles. For example, desflurane may have quicker recovery than sevoflurane but may be associated with more episodes of coughing (White 2009a). Sevoflurane was found to be associated with more cardiac and respiratory problems and nausea than isoflurane (Elcock 2002). Total intravenous anaesthesia (TIVA) by propofol induction and propofol maintenance is another possible anaesthetic regimen (Elliott 2003). The patient acceptability and recovery profiles may also vary depending upon pre-existing medical conditions that the patient may have. The best anaesthetic regimen is the one that has the fewest adverse effects that are important to the patient and which will enable the surgery to be completed as a day procedure.

Why it is important to do this review

Increasing the proportion of the people discharged as day patients for laparoscopic cholecystectomy has huge implications for the patient and the healthcare funder. There is currently no consensus on the anaesthetic regimen that is most suitable for day-patient laparoscopic cholecystectomy. There has been no systematic review on this topic. This review may help the formulation of day-patient anaesthetic regimens for laparoscopic cholecystectomy.

Objectives

To compare the benefits and harms of different anaesthetic regimens (risks of mortality and morbidity, measures of recovery after surgery) in patients undergoing day-procedure laparoscopic cholecystectomy.

Methods

Criteria for considering studies for this review

Types of studies

We included randomized clinical trials (RCTs) irrespective of blinding, language, publication status or sample size. We excluded quasi-randomized trials (for example, allocation by date of birth, day of the week, etc) and non-randomized studies since they do not take selection bias into account.

Types of participants

We included patients scheduled to undergo day-procedure laparoscopic cholecystectomy irrespective of the age of the patient and whether the procedure was carried out in a secondary or tertiary care setting. Thus, only patients undergoing elective laparoscopic cholecystectomy have been included in this review. We included studies enrolling patients with broader inclusion criteria but where the outcomes of individuals eligible for our study were reported separately.

Types of interventions

We included the comparison of one anaesthetic regimen with another. We considered an anaesthetic regimen as a combination of an induction agent, a maintenance agent, a method of maintaining the airway (laryngeal mask versus endotracheal intubation), a muscle relaxant and an intraoperative short acting opioid the effect of which is expected only during the operation. We included studies if at least one component of multiple components of the complex intervention was different between the comparison groups. We accepted comparisons of different methods of administration of the same agent (including route, frequency, or timing) or different doses of the same agent. We excluded studies in which a long acting opioid was used preoperatively or intraoperatively.

Types of outcome measures

Primary outcomes
  1. Perioperative mortality (during the operation or within 30 days of operation).

  2. Serious adverse events (perioperative morbidity such as bile duct injury, intra-abdominal collections requiring intervention or additional observations within 30 days). We used the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) definition of serious adverse events (ICH-GCP 1996). We defined serious adverse events as any event that would increase mortality; was life-threatening; required inpatient hospitalization; resulted in a persistent or significant disability; or any important medical event which might have jeopardized the patient or required intervention to prevent it (ICH-GCP 1996). We obtained this information and analysed it as a composite outcome.

  3. Proportion discharged the same day. We accepted the UK Department of Health definition of day surgery, that is, day surgery is the admission of selected patients to hospital for a planned surgical procedure, returning home on the same day (Department of Health 2002). We considered participants who were discharged on the same day as having developed the outcome even if they were re-admitted subsequently (either on the same day or a subsequent day). Such patients were included in the outcome 'hospital re-admissions related to surgery or anaesthesia used for surgery'.

Secondary outcomes
  1. Hospital readmissions related to surgery or anaesthesia used for surgery (within 30 days)

  2. Pain (visual analogue scale (VAS) scores at between four and eight hours). This is the time frame during which the majority of the day-procedure laparoscopic cholecystectomies are discharged (Gurusamy 2008; Vaughan 2013)

  3. Patient health-related quality of life (however defined by authors) within one week and at one month

  4. Return to normal activity (e.g., able to look after themselves)

  5. Return to work

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10, 2013) in The Cochrane Library, MEDLINE (PubMed) (1987 to November 2013), EMBASE (OvidSP) (1987 to November 2013), Science Citation Index Expanded (1987 to November 2013) (Royle 2003), and LILACS (1987 to November 2013). We have given the search strategies in Appendix 1 with the time spans for the searches.

Searching other resources

We searched the references of the identified trials to identify further relevant trials. We searched the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/) until November 2013. The meta-register includes the ISRCTN Register and National Institutes of Health (NIH) ClinicalTrials.gov register among other registers. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) portal and clinical.gov trial registers until November 2013. We searched the Euroanaesthesia (European Society of Anaesthesiology) and Anesthesiology (American Society of Anesthesiologists) Congress abstracts for the last three years. We contacted the authors of the trials included in the review to identify any previous unpublished trials.

Data collection and analysis

We performed the systematic review following the guidance in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Selection of studies

Two authors (JV and MN) independently identified the trials for inclusion. We have listed the excluded studies with the reasons for the exclusion in the Characteristics of excluded studies table. We resolved any differences through discussion.

Data extraction and management

Two authors (JV and MN) independently extracted the following data using a formal data extraction template (available on request):

  1. year and language of publication;

  2. country;

  3. year of conduct of the trial;

  4. inclusion and exclusion criteria;

  5. sample size;

  6. details of the anaesthetic regimen used;

  7. outcomes (described above);

  8. risk of bias (described below).

If authors reported visual analogue scores for pain (VAS) at different time points within the period of four to eight hours, we recorded the VAS at the latest time between four and eight hours. This is because the usual time for discharge of day-procedure laparoscopic cholecystectomy patients is between four and eight hours (Gurusamy 2008; Vaughan 2013). There are various ways of reporting pain at rest and during movements with unclear implications. The period for which patients mobilize to go to the toilet (at hospital and at home) and for transport (between hospital and home) are considerably shorter than the period that the patients spend resting, so we recorded pain at rest as the outcome of interest. With regards to quality of life, we planned to obtain the information from the 'global health' domain or a similar domain which gives a measure of overall health.

We sought any unclear or missing information by contacting the authors of the individual trials. If there was any doubt whether the trial reports shared the same patients, 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. We resolved any differences in opinion through discussion.

Assessment of risk of bias in included studies

We followed the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The risk of bias of the trials was assessed based on the following bias risk domains: random sequence generation, allocation concealment, blinding of participants and healthcare providers, blinding of outcome assessors, incomplete outcome data, and selective outcome reporting according to the assessment suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). In addition to the above domains, we assessed the 'vested interest bias' domain since sponsorship of a trial by a party who will benefit by the results of the trial leads to more favourable results and conclusions than sponsorship by other sources. This cannot be explained by the 'Risk of bias' domains suggested by the Cochrane Handbook for Systematic Reviews of Interventions (Lundh 2012). The vested interest bias domain was assessed as follows.

  • Low risk of bias (the trial was not performed or supported by any parties that might have conflicting interest, e.g., drug manufacturer).

  • Uncertain risk of bias (any conflicts of interest of the trialist or trial funder were not clear).

  • High risk of bias (the trial was performed or supported by parties that might have conflicting interests, e.g., drug manufacturer)

We considered trials which were classified as low risk of bias in all the above domains as low bias-risk trials.

Measures of treatment effect

For dichotomous variables, we calculated and reported the risk ratio (RR) with 95% confidence interval (CI). Risk ratio calculations do not include trials in which no event occurred in either of the groups whereas risk difference calculations do. We planned to report the risk difference if the results using this association measure led to different conclusions. For continuous variables, we calculated the mean difference (MD) with 95% CI for outcomes such as hospital stay, and planned to calculate the standardized mean difference (SMD) with 95% CI for quality of life (where different scales might be used).

Unit of analysis issues

The units of analysis were the patients about to undergo day-procedure laparoscopic cholecystectomy. For cluster randomized trials, we planned to include the information provided that the intervention effect was adjusted for the cluster effect. In the case of trials with three arms that could be included in the same meta-analysis, we planned to combine the intervention arms and compare the combined intervention group with control. We also planned to perform a sensitivity analysis in which we did not combine the intervention arms but split the control arm into two roughly equal halves (so that the participants were not included in the meta-analysis twice) in order to assess the impact of combining the intervention arms.

Dealing with missing data

We performed an intention-to-treat (ITT) analysis (Newell 1992) whenever possible. We imputed data for binary outcomes using various scenarios such as best-best scenario, worst-worst scenario, best-worst scenario, and worst-best scenario (Gurusamy 2009). In the best-best scenario, the outcomes of people with missing data were assumed to be good in both groups. In the best-worst scenario, the outcomes for people with missing data in the intervention group were assumed to be good, and assumed to be bad for those with missing data in the control group. The worst-best scenario is the opposite of the best-worst scenario, with the outcomes for people with missing data in the intervention group assumed to be bad, and assumed to be good for people with missing data in the control group. In the worst-worst scenario, the outcomes for people with missing data were assumed to be bad in both groups. We have reported the analysis of the best-best scenario for perioperative mortality, serious adverse events, and hospital readmissions since these outcomes are rare in day-procedure laparoscopic cholecystectomy; and the analysis of the worst-worst scenario for the proportion discharged on the same day since we did not anticipate the excluded participants to be discharged on the same day. We planned to report the other analyses if the conclusions would have changed if a different analysis was used. We imputed the data only when the post-randomization dropouts were less than 20% of the initial sample size (arbitrary choice).

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 Interventions (Higgins 2011), and we 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 CI, we planned to impute the standard deviation as the highest standard deviation in the other trials included under that outcome, fully recognizing that this form of imputation would decrease the weight of the study for calculation of mean differences and bias the effect estimate to no effect in the case of standardized mean differences (Higgins 2011). We imputed up to 20% of the values (arbitrary choice).

Assessment of heterogeneity

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 I2statistic (Higgins 2002).

Assessment of reporting biases

We planned to use visual asymmetry on a funnel plot to explore reporting bias (Egger 1997Macaskill 2001) in the presence of at least 10 trials. We planned to perform the linear regression approach described by Egger 1997 to determine the funnel plot asymmetry. We also considered selective reporting as evidence for reporting bias.

Data synthesis

We planned to pool the results of the trials even if there were differences in the doses administered, the route of administration, or other components of the anaesthetic regimen. With regards to comparison of the differences in the doses, we anticipated summarizing the data in direct meta-analysis as we did not expect two or more trials to compare the same difference in the doses. However, we planned to include such trials for mixed-treatment meta-analysis provided that at least one of the arms was connected to the network (that is, at least one of the arms in the trial comparing two or more treatments had been included as one of the arms in another trial performing a different comparison). With regards to the comparison of the differences in the routes of administration, we planned to pool the results even if there were differences in the dose administered or another component of the anaesthetic regimen. We did not use statistical heterogeneity to determine whether to pool the results. We planned to perform the meta-analyses using the software package RevMan 5.1 and following the recommendations of The Cochrane Collaboration (Higgins 2011). We planned to use both a random-effects model (DerSimonian 1986) and a fixed-effect model (DeMets 1987) meta-analysis. In the case of a discrepancy between the two models we planned to report both results; otherwise we planned to report the results of the random-effects model.

We planned to use a mixed-treatment comparison to assess the consistency between the direct and indirect effect estimates (Salanti 2008). We planned to perform this with the WinBUGS version 1.4.3 using the Bayesian method.

Subgroup analysis and investigation of heterogeneity

We planned to perform the following subgroup analyses in the presence of at least two trials in each subgroup (an arbitrary decision since we consider that information from one trial included under a subgroup is subject to significant risk of false positive and false negative error in a 'test for subgroup differences'). We planned to perform a sensitivity analysis in such a situation.

  • Trials including only American Society of Anesthesiologists (ASA) Physical Status 1 or 2 participants (normal healthy patients or patients with mild systemic disease) versus those including ASA Physical Status 3 (patients with severe systemic disease).

We planned to use the 'test for subgroup differences' to identify the differences between subgroups.

We also planned to explore heterogeneity using meta-regression in the presence of at least 10 trials in a meta-analysis.

Sensitivity analysis

We planned to perform a sensitivity analysis by excluding trials with high risk of bias. We performed a sensitivity analysis by imputing data for binary outcomes using various scenarios such as a best-best scenario, worst-worst scenario, best-worst scenario, and worst-best scenario (Gurusamy 2009). We planned to perform a sensitivity analysis by excluding the trials in which the mean and the standard deviation were imputed. We also planned to perform a sensitivity analysis in which we did not combine the intervention arms in trials with three arms but split the control arm into two roughly equal halves (so that the participants were not included in the meta-analysis twice) in order to assess the impact of combining the intervention arms.

Summary of findings

We used the principles of the GRADE system (Guyatt 2008) to assess the quality of the body of evidence associated with each of the outcomes in our review (serious adverse events, proportion discharged as day-procedure patients, hospital readmissions, pain (VAS), patient quality of life, return to normal activity, return to work) and planned to construct a 'Summary of findings' (SoF) table using the GRADE software. The GRADE approach appraises the quality of a body of evidence based on the extent to which one can be confident that an estimate of effect or association reflects the item being assessed. The quality measure of a body of evidence considers within study risk of bias (methodological quality), the directness of the evidence, heterogeneity of the data, precision of effect estimates, and risk of publication bias.

Results

Description of studies

Results of the search

We identified a total of 1643 references through the electronic searches of the Cochrane Hepato-Biliary Group Controlled Trials Register and Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (n = 44), MEDLINE (n = 419), EMBASE (n = 108), Science Citation Index Expanded (n = 753), mRCT (n = 212), WHO ICTRP (n = 30), and ClinicalTrials.gov (n = 37). We have shown the flow of references in Figure 1. We excluded 289 duplicates and 1324 clearly irrelevant references through reading the abstracts. We could not retrieve one reference identified from a search of the ICTRP as there was no publication (Nostdahl 2011). We retrieved 29 references for further assessment. No references were identified through scanning reference lists of the identified randomized trials. Of the 29 references, we excluded 18 references for the reasons listed under the table Characteristics of excluded studies. In total, 11 publications describing 11 randomized trials fulfilled the inclusion criteria.

Figure 1.

Study flow diagram.

Included studies

All the 11 trials were completed trials and could provide data for the analyses (Collard 2007; Damen 2004; Erk 2007; Grundmann 2001; Habib 2004; Lauwick 2008; Mathisen 1999; Paventi 2002; Raeder 1998; Song 1998; Wallden 2006). Details of the trials are shown in the table Characteristics of included studies. The trials featured comparisons of different anaesthetic regimens for day-case laparoscopic cholecystectomy. Some trials included more than one comparison. There were a total of 23 comparisons featuring 1069 participants.

Excluded studies

We excluded 16 studies. The reasons for exclusion are listed in the Characteristics of excluded studies table.

Risk of bias in included studies

The risk of bias is summarized in the risk of bias graph (Figure 2) and risk of bias summary (Figure 3). All the trials were at high risk of bias as seen in Figure 3. The reasons for classification of the risk of bias are provided in the table Characteristics of included studies.

Figure 2.

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

Figure 3.

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

Allocation

Two trials had adequate random sequence generation (18%) (Lauwick 2008; Wallden 2006). Two trials had adequate allocation concealment (18%) (Collard 2007; Lauwick 2008).

Blinding

One trial demonstrated adequate blinding of participants and personnel (9%) (Damen 2004). One trial demonstrated adequate blinding of outcome assessors (9%) (Habib 2004).

Incomplete outcome data

Five trials (45%) reported no post-randomization dropouts (Grundmann 2001; Mathisen 1999; Paventi 2002; Raeder 1998; Song 1998).

Selective reporting

No trials were free from bias due to selective reporting.

Other potential sources of bias

Three trials (27%) demonstrated no vested interest bias (Lauwick 2008; Song 1998; Wallden 2006).

Effects of interventions

Only one trial was included under each of the comparisons. Meta-analysis was therefore not performed for any of the comparisons.

Mortality

There was no mortality in the only trial that explicitly reported mortality (Raeder 1998). This trial compared propofol infusion (30 participants) versus desflurane for maintenance (30 participants) (Raeder 1998). Induction of anaesthesia was achieved with fentanyl and propofol. Endotracheal intubation was performed using vecuronium as the muscle relaxant in this trial (Raeder 1998). Alfentanil was used when systolic blood pressure and heart rate increased by more than 30% from baseline value (Raeder 1998).

In the remaining trials, although short-term mortality was not reported explicitly, we could infer that there was no perioperative mortality based on the number of patients included in the other outcomes.

Serious adverse events

One trial featuring one comparison reported serious adverse events (Raeder 1998). This trial compared propofol infusion (30 participants) versus desflurane (30 participants) (Raeder 1998). The other aspects of the anaesthetic regimen used in this trial are provided in the outcome 'mortality'. No serious adverse events were reported in this comparison.

Proportion discharged same day

Six trials featuring 13 comparisons reported same day discharge (Collard 2007; Damen 2004; Lauwick 2008; Paventi 2002; Raeder 1998; Song 1998). There were no significant differences in the proportion of patients discharged as day-surgery patients between the groups in any of these comparisons, as shown below.

  • Intermittent doses of fentanyl for induction and throughout the surgery versus continuous infusion of esmolol for induction and throughout the surgery: 57 participants (Collard 2007) (RR 0.89; 95% CI 0.77 to 1.03).

  • Intermittent doses of fentanyl for induction and throughout the surgery versus continuous infusion of remifentanil for induction and throughout the surgery: 55 participants (Collard 2007) (RR 0.89; 95% CI 0.77 to 1.03).

  • Continuous infusion of esmolol for induction and throughout the surgery versus continuous infusion of remifentanil for induction and throughout the surgery: 58 participants (Collard 2007) (RR 1.00; 95% CI 0.94 to 1.07).

  • Remifentanil for induction and maintenance versus sufentanil for induction and maintenance: 70 participants (Damen 2004) (RR 0.81; 95% CI 0.60 to 1.11).

  • Fentanyl on induction and intravenous lidocaine on induction and throughout the surgery versus fentanyl on induction: 49 participants (Lauwick 2008) (RR 1.05; 95% CI 0.91 to 1.21).

  • Remifentanil versus sevoflurane: 40 participants (Paventi 2002) (RR 1.13; 95% CI 0.86 to 1.46).

  • Propofol versus desflurane: 60 participants (Raeder 1998) (RR 1.00; 95% CI 0.94 to 1.07).

  • 1% to 4% sevoflurane maintenance versus 1% to 4% sevoflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure: 126 participants (Song 1998) (RR 0.97; 95% CI 0.82 to 1.16).

  • 1% to 4% sevoflurane maintenance versus 2% to 8% desflurane maintenance: 122 participants (Song 1998) (RR 0.97; 95% CI 0.81 to 1.15).

  • 1% to 4% sevoflurane maintenance versus 2% to 8% desflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure: 126 participants (Song 1998) (RR 0.99; 95% CI 0.83 to 1.19).

  • 1% to 4% sevoflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure versus 2% to 8% desflurane maintenance: 124 participants (Song 1998) (RR 0.99; 95% CI 0.84 to 1.18).

  • 1% to 4% sevoflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure versus 2% to 8% desflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure: 128 participants (Song 1998) (RR 1.02; 95% CI 0.86 to 1.21).

  • 2% to 8% desflurane maintenance versus 2% to 8% desflurane maintenance and 0.5 mg/kg intravenous propofol at skin closure: 124 participants (Song 1998) (RR 1.02; 95% CI 0.86 to 1.22).

The other aspects of the anaesthetic regimens in these trials apart from the comparisons are as follows.

Collard 2007: induction of anaesthesia was achieved with propofol and the treatment that was used for comparison. Endotracheal intubation was performed using rocuronium as muscle relaxant in this trial and the patients received the same muscle relaxant as required. Anaesthesia maintenance was with desflurane to maintain systolic blood pressure within 20% of baseline, whereas the treatment used for comparison was administered to keep the heart rate within 20% of baseline.

Damen 2004: induction of anaesthesia was achieved with propofol and the treatment that was used for comparison. Endotracheal intubation was performed using rocuronium as muscle relaxant in this trial and the patients received the same muscle relaxant as required. Anaesthesia maintenance was with the treatment used for comparison and propofol to ensure that systolic blood pressure was between 80 mm Hg and less than 15 mm higher than baseline and the heart rate was between 50 and 90 beats per minute.

Lauwick 2008: induction of anaesthesia was achieved with propofol and the treatment that was used for comparison. Endotracheal intubation was performed using rocuronium as muscle relaxant in this trial and the patients received the same muscle relaxant as required. Anaesthesia maintenance was with desflurane to ensure that systolic blood pressure and heart rate were within 20% of baseline.

Paventi 2002: induction of anaesthesia was achieved with propofol and remifentanil. Endotracheal intubation was performed using cisatracurium as muscle relaxant in this trial. Anaesthesia maintenance was with the treatment used for comparison to ensure that medium blood pressure was within 25% of the baseline values.

Raeder 1998: the other aspects of the anaesthetic regimen used in this trial were as mentioned in the outcome 'mortality'.

Song 1998: induction of anaesthesia was achieved with propofol and fentanyl. Endotracheal intubation was performed using rocuronium as muscle relaxant in this trial and the patients received the same muscle relaxant as required. Anaesthesia maintenance was with the treatment used for comparison and fentanyl to ensure that systolic blood pressure increase was less than 30% of baseline and heart rate was less than 100 beats per minute.

Hospital readmissions

One trial featuring one comparison reported hospital readmissions (Raeder 1998). This trial compared propofol infusion (30 participants) versus desflurane (30 participants) (Raeder 1998). The other aspects of the anaesthetic regimen used in this trial are as mentioned in the outcome 'mortality'. The only patient who required readmission developed fever after one week, which settled spontaneously (Raeder 1998). There was no significant difference in the hospital readmission rates in this comparison (rate ratio 3.00; 95% CI 0.13 to 70.83).

Pain

One trial featuring three comparisons reported pain (Mathisen 1999). In this trial, pre-emptive ketamine was compared with postoperative ketamine and placebo. Induction of anaesthesia was achieved with propofol and fentanyl (Mathisen 1999). Endotracheal intubation was performed using vecuronium as muscle relaxant in this trial and the patients received the same muscle relaxant as required. Anaesthesia maintenance was with propofol and fentanyl. Alfentanil was used when systolic blood pressure and heart rate increased by more than 20% from baseline value (Mathisen 1999).

There was no significant difference in VAS scores between the any of the comparisons as shown below.

  • Pre-emptive ketamine versus placebo: 40 participants (Mathisen 1999) (MD 0.00 mm; 95% CI -6.69 to 6.69).

  • Postoperative ketamine versus placebo: 40 participants (Mathisen 1999) (MD - 5.20 mm; 95% CI -11.89 to 1.49).

  • Pre-emptive ketamine versus postoperative ketamine: 40 participants (Mathisen 1999) (MD 5.20 mm; 95% CI -1.49 to 11.89).

Health-related quality of life

None of the trials reported quality of life.

Return to activity

None of the trials reported return to activity.

Return to work

None of the trials reported return to work.

Variations in meta-analysis and effect estimate

Since there was a maximum of one trial included in each comparison, the issue of fixed-effect and random-effects models did not arise. There was no change in the results by calculating the risk difference rather than the risk ratio.

Sensitivity analysis

Please see Appendix 2.

Subgroup analyses

All the trials were at high risk of bias, so we did not perform any subgroup analysis.

Funnel plot

We did not construct a funnel plot as there were under 10 trials included in each comparison.

Network meta-analysis

The trials were very heterogeneous in many of the aspects of anaesthesia. It was not possible to create a network, so network meta-analysis was not performed.

Discussion

Summary of main results

This systematic review compared the safety and effectiveness of different anaesthetic regimens for day-procedure laparoscopic cholecystectomy. We were unable to perform a meta-analysis because there were no two trials involving the same comparison. This is likely to reflect the very large number of possible regimens available for testing. In one small trial, there was no observed short-term all-cause mortality or serious adverse events. There was no clear evidence of a difference in the proportion discharged on the same day, number of readmissions, or visual analogue pain scores between any of the interventions compared in this review. Health-related quality of life, return to activity, and return to work were not reported in any of the trials.

Overall completeness and applicability of evidence

This review included patients undergoing elective day-procedure laparoscopic cholecystectomy, which is the predominant desired management choice for symptomatic gallstones. Hence this review is applicable to most patients undergoing the procedure. The review includes mostly patients of low anaesthetic risk and is applicable only for such patients.

There was no short-term all-cause mortality in any of the comparisons. This is expected because of the low mortality rates in laparoscopic cholecystectomy, 0.1% to 0.5% of patients (Dolan 2009; Giger 2011; Scollay 2011) and because the trials included in this review recruited patients who were fit for day-procedure laparoscopic cholecystectomy. Such patients are likely have a low operative risk and hence are likely to survive any complications if they developed. There were no significant differences in serious adverse events in the only comparison that reported this outcome (Raeder 1998). On average, less than 1% of patients undergoing ambulatory anaesthesia have serious adverse events (Chung 1999) and less than 1% of patients undergoing laparoscopic cholecystectomy have serious adverse events (Duca 2003). Although the proportion of patients with serious adverse events during or after day-procedure laparoscopic cholecystectomy is not known, it is likely to be less than 1% based on the above information. So, the sample size included in the trials may be too small to detect a difference in the severe adverse events. To detect a 0.2% decrease (20% relative risk reduction) in severe adverse events after day-procedure laparoscopic cholecystectomy, from 1% to 0.8%, in carefully selected patients undergoing day-procedure laparoscopic cholecystectomy with a false positive error of 5% and a false negative error of 20% (power of 80%) one needs approximately 70,000 patients. It is unlikely that a trial including 70,000 patients undergoing day-procedure laparoscopic cholecystectomy will be conducted.

There were no significant differences in the proportion of patients discharged as day-procedure laparoscopic cholecystectomy patients in any of the comparisons. Overall, approximately 85% of patients (472/554) included in this review were discharged as day-procedure laparoscopic cholecystectomy patients. This is similar to the proportion of patients who were discharged as day-procedure laparoscopic cholecystectomy patients in a previous Cochrane review assessing the safety and effectiveness of day-procedure laparoscopic cholecystectomy (Gurusamy 2008; Vaughan 2013). However, it must be noted that the number of patients included in the trials is small. To detect a 10% increase in day-procedure laparoscopic cholecystectomy patients, from 80% to 90%, in such carefully selected patients with a false positive error of 5% and a false negative error of 20% (power of 80%) one needs approximately 440 patients. None of the trials included in this review included 440 or more patients. So, the lack of difference in the proportion of patients discharged as day-procedure laparoscopic cholecystectomy patients that was observed in the trials may be due to lack of evidence of effect rather than lack of effect. Further adequately powered randomized controlled trials are necessary.

There was no significant difference in the hospital readmissions within 30 days in the only comparison in which this outcome was reported. One readmission was reported in the 60 patients (2% of patients) in whom this outcome was assessed.

Pain scores (VAS scores) at between four and eight hours were significantly lower, by different levels, in three comparisons. None of the trials that reported a significant difference in the pain scores reported the proportion of patients discharged as day-procedure laparoscopic cholecystectomy patients. The impact of this decrease in pain scores in terms of improving the patient experience is also not clear as none of the trials reported the quality of life of patients. The minimal clinically significant difference in the pain scores varies between 9 mm and 18 mm (Kelly 1998; Kelly 2001; Kendrick 2005; Singer 1998; Todd 1996) in a visual analogue score (VAS) scale of 10 cm. There has been no such study in the postoperative setting.

None of the trials reported return to normal activity. Quicker return to normal activity will decrease the number of work days lost by the patients and potentially their carers.

Quality of the evidence

The overall quality of the evidence was very low. All the trials were at a high risk of bias. Blinding of patients, healthcare providers and assessors was not reported in many of the trials. Alongside this, many studies did not report the important primary outcomes, potentially resulting in selective outcome reporting. Some trials had a significant proportion of post-randomization dropouts, introducing potential missing outcome data bias.

In order to reduce the risk of bias, blinding needs to be performed. Depending upon the intervention, it may not always be possible to blind the anaesthetists involved in the patients' care although placebo or an unidentifiable intervention and control may be used, if appropriate, in some circumstances. It is generally possible to blind the patients and the outcome assessors to the groups. Care should also be taken to ensure that the person in charge of discharging the patient or assessing whether the patient has a serious adverse event is blinded to the groups. Post-randomization dropouts could be reduced by performing the randomization on the day of surgery (enrolment can be done earlier), thereby reducing the risk of missing outcome bias. There is no justification for loss to follow-up, at least for the proportion discharged as day-procedure patients, since this outcome is usually measured within four to eight hours.

Each comparison contained only one trial and these trials included few participants and few outcome measures. This increases the risks of type I as well as type II errors (random errors). The consistency of the findings could not be assessed because of the inclusion of only one trial under each comparison.

Potential biases in the review process

We followed the guidance from the Cochrane Handbook for Systematic Reviews of Interventions for this review. There were no language, publication status, or sample size restrictions. Two authors independently selected trials for inclusion thereby minimizing the errors during selection. However, there may be many unpublished trials. We are unable to assess publication bias because of the inclusion of few trials in this review.

We have used median for the analysis when the mean was not available and imputed the standard deviation from P values according to the formulae stated in the Cochrane Handbook for Systematic Reviews of Interventions. This imputation of standard deviation may have introduced bias. However, the alternative to this approach is to ignore the available information which would have introduced an even greater bias. Besides, sensitivity analysis demonstrated no difference in the significance of results with and without imputed values.

Agreements and disagreements with other studies or reviews

There have been no previous reviews on the anaesthetic regimens in day-surgery laparoscopic cholecystectomy. A systematic review of anaesthetic regimens in all day surgeries suggested that recovery was earlier with desflurane and sevoflurane compared with isoflurane, but there was no significant difference in readiness to be discharged between the different anaesthetic regimens (Gupta 2004). This review also found that there were no major differences in the safety profile of different anaesthetic agents (Gupta 2004).

Authors' conclusions

Implications for practice

There is currently insufficient evidence to recommend one anaesthetic regimen for day-procedure laparoscopic cholecystectomy over another.

Implications for research

Further well designed randomized trials with low risk of bias and enrolling about 500 patients as a minimum are necessary to measure differences in clinically important outcomes, such as the proportion of people discharged as day cases, in order to determine the optimal anaesthetic regimen for day-procedure laparoscopic cholecystectomy. Furthermore, cost-effectiveness assessment and outcomes such as quality of life and time to return to work after cholecystectomy should be incorporated in such trials.

Acknowledgements

We would like to thank the Cochrane Anaesthesia Review Group for their support, in particular Mathew Zachrias and Mike Bennett (content editors), Nathan Pace (statistical editor), Kwok M Ho, Preethy Mathew and Mark Skues (peer-referees) and Anne Lyddiatt (consumer referee), and Orla Ní Ógáin and Toby Lasserson (Editors, Cochrane Editorial Unit), for their suggestions to improve the text. We would also like to thank the authors who provided additional information.

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 for identification of studies

DatabasePeriod of SearchSearch Strategy
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane LibraryIssue 10, 2013.

#1 laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*
#2 cholecystectom*
#3 MeSH descriptor Cholecystectomy, Laparoscopic explode all trees
#4 (( #1 AND #2 ) OR #3)
#5 MeSH descriptor Day Care explode all trees 
#6 MeSH descriptor Ambulatory Surgical Procedures explode all trees 
#7 MeSH descriptor Ambulatory Care explode all trees

#8 day?case* OR day?surgery OR day?care OR day?stay OR day?procedure OR ambulatory OR out?patient OR (an?esth* near regimen*)

#9 #5 OR #6 OR #7 OR #8
#10 #4 AND #9

MEDLINE (PubMed)1987 to November 2013.(((laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*) AND (cholecystectom*)) OR “cholecystectomy, laparoscopic”[MeSH]) AND ("Ambulatory Surgical Procedures"[Mesh] OR "Day Care"[Mesh] OR "Ambulatory Care"[Mesh] OR (day case) OR day-case OR (day surgery) or day-surgery OR (day care) OR day-care OR (day stay) OR day-stay OR (day procedure) OR day-procedure OR ambulatory OR outpatient OR out-patient OR (an?esth* AND regimen*)) AND ((randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [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 November 2013.1. (laparoscop* or coelioscop* or celioscop* or peritoneoscop*).af.
2. exp laparoscopic surgery/
3. 1 or 2
4. cholecystectom*.af.
5. exp cholecystectomy/
6. 4 or 5
7. (day?case* OR day?surgery OR day?care OR day?stay OR day?procedure OR ambulatory OR outpatient OR out-patient OR (an?esth* adj3 regimen*)).af.
8. exp ambulatory care/
9. 7 or 8
10. 3 and 6 and 9
11. exp crossover-procedure/ or exp double-blind procedure/ or exp randomized controlled trial/ or single-blind procedure/
12. (random* or factorial* or crossover* or placebo*).af.
13. 11 or 12
14. 10 and 13
Science Citation Index Expanded (ISI Web of Knowledge)1987 to November 2013.#1 TS=(laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*)
#2 TS=(cholecystectom*)
#3 TS=((day case) OR day-case OR (day surgery) or day-surgery OR (day care) OR day-care OR (day stay) OR day-stay OR (day procedure) OR day-procedure OR ambulatory OR outpatient OR out-patient) OR TS=(an?esth* SAME regimen*)
#4 TS=(random* OR rct* OR crossover OR masked OR blind* OR placebo* OR meta-analysis OR systematic review* OR meta-analys*)
#5 #4 AND #3 AND #2 AND #1
LILACS (Virtual Health Library)1987 to November 2013.(laparoscop$ OR coelioscop$ OR celioscop$ OR peritoneoscop$) AND (cholecystectom$) AND ((day case) OR day-case OR (day surgery) or day-surgery OR (day care) OR day-care OR (day stay) OR day-stay OR (day procedure) OR day-procedure OR ambulatory OR outpatient OR out-patient or (anaesthetic$ regimen$) or (anesthetic regimen$))
metaRegister of Controlled Trials (http://www.controlled-trials.com/mrct/)November 2013(laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*) AND (cholecystectom*)
WHO International Clinical Trials Registry Platform (ICTRP) portal (http://apps.who.int/trialsearch/)November 2013

Three searches were used and results combined.

1. laparoscop* AND cholecystectom* AND day*

2. laparoscop* AND cholecystectom* AND ambulatory

3. laparoscop* AND cholecystectom* AND out*

ClinicalTrials.govNovember 2013

Four searches were used and results combined.

1. laparoscopic cholecystectomy AND day

2. laparoscopic cholecystectomy AND ambulatory

3. laparoscopic cholecystectomy AND outpatient

4. laparoscopic cholecystectomy AND out-patient

Appendix 2. Sensitivity analysis

As we did not perform any meta-analysis in this review, formal sensitivity analysis was not appropriate. We have, however, investigated the potential effect of missing data in the individual study reports where there were missing data. Four of the 11 trials included in this systematic review had post-randomization dropouts (Collard 2007; Damen 2004; Lauwick 2008; Wallden 2006). In these groups, a sensitivity analysis was performed for the binary outcome (same day discharge) to investigate best and worst outcomes. With regards to the number of people discharged on the same day, imputation of outcomes by the worst-best scenario significantly favoured the control in four comparisons (Collard 2007; Damen 2004). When the outcomes were imputed according to the best-best scenario, worst-worst scenario and best-worst scenario, the results showed no significant difference from the results in the absence of imputation.

In one trial (Mathisen 1999), the standard deviation was imputed. Since this was the only trial that provided data we did not perform a sensitivity analysis.

Contributions of authors

Conceiving the review: K Gurusamy (KG); BR Davidson (BRD)

Co-ordinating the review: KG

Undertaking manual searches: KG, Jessica Vaughan (JV)

Screening search results: KG, JV

Organizing retrieval of papers: JV

Screening retrieved papers against inclusion criteria: JV, Myura Nagendran (MN)

Appraising quality of papers: JV, MN

Abstracting data from papers: JV, MN

Writing to authors of papers for additional information: JV

Providing additional data about papers: JV

Obtaining and screening data on unpublished studies: JV

Data management for the review: JV

Entering data into Review Manager (RevMan 5.1): JV

RevMan statistical data: JV

Other statistical analysis not using RevMan: not applicable

Interpretation of data: JV, KG

Statistical inferences: JV, KG

Writing the review: JV, KG

Securing funding for the review: KG, BRD

Performing previous work that was the foundation of the present study: not applicable

Guarantor for the review (one author): KG

Person responsible for reading and checking review before submission: JV, MN, J Cooper (JC), BRD, KG

Declarations of interest

Jessica Vaughan: none known

Myura Nagendran: none known

Jacqueline Cooper: none known

Brian R Davidson: none known

Kurinchi Selvan Gurusamy: none known

Sources of support

Internal sources

  • None, Not specified.

External sources

  • National Insitute for Health Research (NIHR), UK.

    NIHR is the health research wing of the UK Government. It part funds Dr K Gurusamy's salary and funds all the materials needed for the preparation of this review.

Differences between protocol and review

  1. A different data extraction form was used to extract data. However, all the relevant information stated in the protocol (Gurusamy 2012) and the previous data extraction form was obtained.

  2. Minor modifications have been made to meet the MECIR recommendations. These modifications were related to the reporting of the review rather than the conduct of the review.

  3. Two new authors have been added (Jessica Vaughan and Myura Nagendran).

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Collard 2007

MethodsRandomized clinical trial
ParticipantsCountry: Canada
Number randomized: 95
Post-randomization dropouts: 10 (6%)
Revised sample size: 85
Average age: 50 years
Females: 36 (63.2%)
Inclusion criteria
1. Age between 18 years and 85 years
2. ASA physical status I and II
Exclusion criteria
1. History of hepatic, renal, or cardiac failure
2. Organ transplant
3. Diabetes
4. Morbid obesity (body mass index > 40)
5. Chronic use of opioids or beta adrenergic antagonists
known asthma or reactive airway disease
severe mental impairment
allergy to local anaesthetics
inability to comprehend pain assessment
Interventions

Participants were randomly assigned to three groups
Group 1: intermittent doses of fentanyl (n = 27)
Group 2: continuous infusion of esmolol (5 to 15 μg/kg/minute) with no supplementary opioids (n = 30)

Group 3: continuous infusion of remifentanil (0.1 to 0.5 μg/kg/minute) (n=28)

OutcomesThe outcome reported was same day discharge
NotesReply from author: Brown sealed envelopes used for allocation concealment, blinding of patients and participants was done, funding came from internal sources.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Low riskQuote: Brown sealed envelopes used
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: Participants were blinded

Comment: Further details were not available

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk

Quote: Outcome assessors were blinded

Comment: Further details were not available

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear risk

Quote: funding came from internal sources

Comment: Further details were not available

Damen 2004

MethodsRandomized clinical trial
ParticipantsCountry: Netherlands
Number randomized: 82
Post-randomization dropouts: 12 (14.6%)
Revised sample size: 70
Average age: 44 years
Females: 52 (74.3%)
Inclusion criteria
1. ASA I or II
2. Reading and writing capabilities in Dutch
3. Adequate home care by a responsible, vested adult
4.Willingness to be discharged the same day
5. Willingness to keep a diary for one week
Exclusion criteria
1. Cardio- or pulmonopathy
2. Urgent procedure (e.g., cholecystitis)
3. Known allergic reactions to one of the anaesthetics
4. Previous UGI or biliary tract surgery
5. Signs of choledochal duct stones
6. Inadequate home care
InterventionsParticipants were randomly assigned to two groups
Group 1: remifentanil used in anaesthetic protocol (n = 35)
Group 2: sufentanil used in anaesthetic protocol (n = 35)
OutcomesThe outcome reported was same day discharge
Notes Attempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: selection from blind envelope

Comment: Further details were not available

Allocation concealment (selection bias)Unclear risk

Quote: selection from blind envelope

Comment: Further details were not available

Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote: The patient and surgeon were not informed
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Erk 2007

MethodsRandomized clinical trial
ParticipantsCountry: Turkey
Number randomized: 300
Post-randomization dropouts: not stated
Revised sample size: 300
Average age: 51 years
Females: 102 (51%)
Inclusion criteria
1. ASA status I, II or III
Exclusion criteria
1. Motion sickness
2. History of postoperative nausea and vomiting
3. Obesity
4. Menstruation
Interventions

Participants were randomly assigned to three groups
Group 1: anaesthesia maintained with propofol infusion (6mg/kg/hour) (n = 100)
Group 2: anaesthesia maintained with sevoflurane infusion (to maintain 1.3 MAC value) (n = 100)

Group 3: anaesthesia maintained with desflurane infusion (to maintain 1.3 MAC value) (n=100)

OutcomesNo outcomes of interest were reported
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: Further details were not available
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: This information was not available
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Grundmann 2001

MethodsRandomized clinical trial
ParticipantsCountry: Germany
Number randomized: 50
Post-randomization dropouts: 0 (0%)
Revised sample size: 50
Average age: 48 years
Females: 36 (72%)
Inclusion criteria
1. ASA status I to II
2. 23 to 65 years
3. History of symptomatic cholelithasis
Exclusion criteria
1. Alcohol or drug abuse
2. Morbid obesity
3. Cardiac, pulmonary, hepatic or renal disease
4. Pregnancy
5. Contraindications to any of the drugs used
InterventionsParticipants were randomly assigned to two groups
Group 1: remifentanil/propofol based anaesthesia (n = 25)
Group 2: remifentanil/desflurane based anaesthesia (n = 25)
OutcomesNo outcomes of interest were reported
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Habib 2004

MethodsRandomized clinical trial
ParticipantsCountry: USA
Number randomized: 60
Post-randomization dropouts: 0 (0%)
Revised sample size: 60
Average age: 44 years
Females: 48 (80%)
Inclusion criteria
1. ASA status I-III
Exclusion criteria
1. Antiemetic or glucosteroid use 24h before surgery
2. Pregnancy
3. Allergy to drugs included in trial
4. Obesity
5. Mental retardation
6. Psychiatric illness
InterventionsParticipants were randomly assigned to two groups
Group 1: Multimodal PONV prophylaxis incorporating TIVA with propofol and a combination of ondansetron and droperidol (n = 30)
Group 2: ondansetron and droperidol in the presence of a isoflurane/nitrous oxide based anaesthetic (n = 30)
OutcomesNo outcomes of interest were reported
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskQuote: "Randomization was achieved using a sealed envelope technique and was prepared by independent personnel not associated with the study (pp78)"
Comment: Further details were not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: "Data were collected by an independent research nurse who was unaware of the patients' randomization (pp78)"
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Lauwick 2008

MethodsRandomized clinical trial
ParticipantsCountry: Canada
Number randomized: 50
Post-randomization dropouts: 1 (2%)
Revised sample size: 49
Average age: 52 years
Females: 33 (67.3%)
Inclusion criteria
1. Age 18 to 85 years
2. ASA status < III
Exclusion criteria
1. History of hepatic, renal or cardiac failure
2. History of organ transplant
3. Diabetes
4. Morbid obesity (body mass index > 40 kg/m2)
5. Chronic use of opioids
6. Allergy to local anaesthetics
7. Inability to comprehend pain assessment
InterventionsParticipants were randomly assigned to two groups
Group 1: fentanyl 1.5 μg/kg and a bolus of lidocaine 1.5 mg/kg followed by a continuous infusion of lidocaine 2 mg/kg/hour following induction of anaesthesia (n = 25)
Group 2: fentanyl 1.5 μg/kg following induction of anaesthesia (n = 24)
OutcomesThe outcome reported was same day discharge
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: Computer-generated randomization schedule
Allocation concealment (selection bias)Low riskQuote: Allocation concealment was achieved by placing the randomization sequence for each subject in sequentially numbered sealed brown envelopes
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available
Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk

Quote: Patients were transferred to the PACU where the blood pressure, pulse, respiration and temperature were monitored and recorded by nurses who were blinded to the randomization sequence

Comment: Further details were not available

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasLow riskQuote: This work was supported by internal funds, Department of anaesthesia, McGill University Health Centre

Mathisen 1999

MethodsRandomized clinical trial
ParticipantsCountry: Norway
Number randomized: 60
Post-randomization dropouts: 0 (0%)
Revised sample size: 40
Average age: 49 years
Females: 49 (81.7%)
Inclusion criteria
1. ASA grade I or II
Interventions

Participants were randomly assigned to three groups
Group 1: pre-emptive 1mg/kg ketamine after induction of anaesthesia. Postoperative saline (n = 20)
Group 2: pre-emptive saline after induction of anaesthesia. Postoperative 1mg/kg ketamine (n= 20)

Group 3: placebo. Saline pre-emptively and postoperatively (n = 20)

OutcomesThe outcome reported was pain
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: The hospital pharmacy prepared the drugs in identical ampoules marked with patient number and injection number in a randomized, double-blind manner

Comment: Further details were not available

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Paventi 2002

MethodsRandomized clinical trial
ParticipantsCountry: Italy.
Number randomized: 40
Post-randomization dropouts: 0 (0%)
Revised sample size: 40
Average age: 32 years
Females: not stated
Inclusion criteria
1. ASA status I-II
2. BMI >30
Exclusion criteria
1. Cardiovascular or pulmonary pathology
2. Diabetes
3. Liver or renal failure
4. Drug or alcohol abuse
InterventionsParticipants were randomly assigned to two groups
Group 1: Remifentanil infusion from 0.25 to 2 µg/kg/min to maintain medium pressure values which are within 25% of baseline (n = 20)
Group 2: Sevoflurane from 0.3% to 3% (n = 20).
OutcomesThe outcome reported was same day discharge
Notes Attempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasUnclear riskComment: This information was not available

Raeder 1998

MethodsRandomized clinical trial
ParticipantsCountry: Norway.
Number randomized: 60
Post-randomization dropouts: 0 (0%)
Revised sample size: 60
Average age: not stated
Females: 51 (85%)
Inclusion criteria
1. ASA grade I to III
2. Age > 18 years
Exclusion criteria
1. Contraindications for any of the drugs in the study
InterventionsParticipants were randomly assigned to two groups
Group 1: anaesthesia maintained by propofol infusion 10 mg/kg/hour for the first 10 min, reduced to 8 mg/kg/hour for the rest of the procedure (n = 30)
Group 2: anaesthesia maintained by desflurane initially at 1 MAC (e.g. 6%), further adjusted to keep haemodynamic parameters within 30% of baseline values (n = 30)
OutcomesThe outcomes reported were serious adverse events, same day discharge, and readmission to hospital
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskComment: This information was not available
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available
Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk

Quote: The patients were immediately transferred to the recovery unit and further registrations were done by a study nurse blinded as to which method of anaesthesia had been used

Comment: Further details were not available

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasHigh risk

Quote: The Ullevaal University Foundation had received a $10,000 grant at the start of the study from Pharmacia, the distributor of desflurane in Norway

Comment: The trial was funded by a party with vested interest in the results

Song 1998

MethodsRandomized clinical trial
ParticipantsCountry: USA
Number randomized: 250
Post-randomization dropouts: 0 (0%)
Revised sample size: 250
Average age: 32 years
Females: 126 (100%)
Inclusion criteria
1. Age 18-65
2. ASA status I or II
3. Female scheduled for laparoscopic cholecystectomy
Exclusion criteria
1. History of post-operative nausea and vomiting, motion sickness or gastroesophageal dysfunction
2. Received antiemetic drugs within 24 hours of anaesthesia
3. Nausea or vomiting in preceding 24 hours
4. Patient more than twice their ideal body weight
Interventions

Participants were randomly assigned to four groups

Group 1: 1-4% sevoflurane maintenance and 5ml IV saline at skin closure (n = 62)

Group 2: 1-4% sevoflurane maintenance and 0.5mg/kg IV propofol at skin closure (n = 64)

Group 3: 2-8% desflurane maintenance and 5ml IV saline at skin closure (n = 60)

Group 4: 2-8% desflurane maintenance and 0.5mg/kg IV propofol at skin closure (n = 64)

OutcomesThe outcome reported was same day discharge
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: Based on a computer-generated random number
Allocation concealment (selection bias)Unclear riskComment: This information was not available
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: Single-blinded

Comment: Further details were not available

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskQuote: All the postoperative assessments were made by an independent "blinded" observer who was unaware of the primary maintenance anaesthetic and prophylactic antiemetic therapy
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasLow riskQuote: Supported in part by the Ambulatory anaesthesia Research Foundation (AARF; Dr Paul White, President and CEO). The AARF has not received corporate funding since 1988, and no corporate funds were used to support this study

Wallden 2006

  1. a

    ASA = American Society of Anesthesiologists

    BMI  = body mass index

    IV = intravenous

    MAC = minimum alveolar concentration

    PACU = postanaesthesia care unit

MethodsRandomized clinical trial
ParticipantsCountry: Sweden
Number randomized: 50
Post-randomization dropouts: 5 (10%)
Revised sample size: 45
Average age: 45 years
Females: 36 (80%)
Inclusion criteria
1. ASA grade I to II
Exclusion criteria
1. Conversion to open cholecystectomy
2. Procedure takes longer than 150 minutes
InterventionsParticipants were randomly assigned to two groups
Group 1: total intravenous anaesthesia with propofol/remifentanil/rocuronium (n= 24)
Group 2: inhalational opioid-free anaesthesia with sevoflurane/rocuronium (n= 21)
OutcomesNo outcomes of interest were reported
NotesAttempts were made to contact the corresponding author in April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: An independent nurse prepared all the sealed envelopes from of a computer-generated table before the study started
Allocation concealment (selection bias)Unclear risk

Quote: by the use of sealed envelopes

Comment: Further details were not available

Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote: There was no blinding in the study
Blinding of outcome assessment (detection bias)
All outcomes
High riskQuote: There was no blinding in the study
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomization dropouts
Selective reporting (reporting bias)High riskComment: Some important outcomes which will generally be assessed were not reported
Vested interest biasLow riskQuote: This study was supported by grants from Örebro County Council, Örebro, and Emil Andersson’s Fund for Medical Research, Sundsvall

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Aceto 2003Surgery was not ambulatory
Bilen 2003Surgery was not ambulatory
Blobner 1994Surgery was not ambulatory
Boldt 1998Separate data was not available for laparoscopic cholecystectomy
Calvo-Soto 2009Surgery was not ambulatory
Ding 2011Not a pharmaceutical intervention, trial investigates acupuncture. Does not meet inclusion criteria of this review
Elcock 2002Separate data was not available for laparoscopic cholecystectomy
Fanelli 2006Surgery was not ambulatory
Galindo 2008Surgery was not ambulatory
Graziola 2005Surgery was not ambulatory
Imbelloni 2011Surgery was not ambulatory
Ji 2011Surgery was not ambulatory
Khan 1997Did not meet inclusion criteria
Palomba 1994Surgery was not ambulatory
Stevanovic 2008Surgery was not ambulatory
Suttner 1999Article retracted
van Delden 2002Surgery was not ambulatory
Yang 2004Separate data were not available for laparoscopic cholecystectomy

Characteristics of studies awaiting assessment [ordered by study ID]

Nostdahl 2011

  1. a

    NSAID = non-steroidal anti-inflammatory drugs

MethodsRandomized controlled trial
Participants

Inclusion criteria

  1. Patients scheduled for day-surgery laparoscopic cholecystectomy

  2. The patient is able to read and comprehend Norwegian language

  3. The patient is cognitive adequate and able to fill in survey forms

  4. The patient has read and signed patient information form

Exclusion criteria

  1. Serious illness (ASA 3-4)

  2. Pregnancy or suspected pregnancy

  3. Breastfeeding women

  4. Contraindications to use of NSAIDs

  5. Serious allergic reaction to anaesthetics

  6. Allergy towards egg, soya or peanuts

  7. Known or suspected malignant hyperthermia or porphyria

  8. Fatigue-related diagnosis

  9. Recently received adjuvant therapy (chemotherapy, radiotherapy)

  10. Severe chronic pain

InterventionsDesflurane versus propofol
Outcomes

Primary outcome:

Incidence and severity of fatigue after anaesthesia based on propofol or desflurane
Secondary outcome:

Incidence and severity of postoperative nausea after anaesthesia based on propofol or desflurane

NotesThe recruiting status of the study is not known. There is no record of this study in Pubmed. None of the outcomes relevant for this systematic review are included in this study.

Ancillary