Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy

  • Conclusions changed
  • Review
  • Intervention

Authors


Abstract

Background

A pneumoperitoneum of 12 to 16 mm Hg is used for laparoscopic cholecystectomy. Lower pressures are claimed to be safe and effective in decreasing cardiopulmonary complications and pain.

Objectives

To assess the benefits and harms of low pressure pneumoperitoneum compared with standard pressure pneumoperitoneum in people undergoing 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 to identify randomised trials,

using search strategies.

Selection criteria

We considered only randomised clinical trials, irrespective of language, blinding, or publication status for inclusion in the review.

Data collection and analysis

Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR), mean difference (MD), or standardised mean difference (SMD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available case analysis.

Main results

A total of 1092 participants randomly assigned to the low pressure group (509 participants) and the standard pressure group (583 participants) in 21 trials provided information for this review on one or more outcomes. Three additional trials comparing low pressure pneumoperitoneum with standard pressure pneumoperitoneum (including 179 participants) provided no information for this review. Most of the trials included low anaesthetic risk participants undergoing elective laparoscopic cholecystectomy. One trial including 140 participants was at low risk of bias. The remaining 20 trials were at high risk of bias. The overall quality of evidence was low or very low. No mortality was reported in either the low pressure group (0/199; 0%) or the standard pressure group (0/235; 0%) in eight trials that reported mortality. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%; seven trials; 394 participants; RR 3.00; 95% CI 0.14 to 65.90; very low quality evidence). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference between groups in the conversion to open cholecystectomy was imprecise (low pressure group 2/269, adjusted proportion 0.8%; standard pressure group 2/287, 0.7%; 10 trials; 556 participants; RR 1.18; 95% CI 0.29 to 4.72; very low quality evidence) and was compatible with an increase, a decrease, or no difference in the proportion of conversion to open cholecystectomy due to low pressure pneumoperitoneum. No difference in the length of hospital stay was reported between the groups (five trials; 415 participants; MD -0.30 days; 95% CI -0.63 to 0.02; low quality evidence). Operating time was about two minutes longer in the low pressure group than in the standard pressure group (19 trials; 990 participants; MD 1.51 minutes; 95% CI 0.07 to 2.94; very low quality evidence).

Authors' conclusions

Laparoscopic cholecystectomy can be completed successfully using low pressure in approximately 90% of people undergoing laparoscopic cholecystectomy. However, no evidence is currently available to support the use of low pressure pneumoperitoneum in low anaesthetic risk patients undergoing elective laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established. Further well-designed trials are necessary, particularly in people with cardiopulmonary disorders who undergo laparoscopic cholecystectomy.

Résumé scientifique

Pneumopéritoine provoqué par pression faible versus pression standard dans la cholécystectomie laparoscopique

Contexte

Un pneumopéritoine de 12 à 16 mm Hg est utilisé pour la cholécystectomie laparoscopique. Les pressions inférieures sont prétendument sûres et efficaces pour réduire les complications cardio-pulmonaires et la douleur.

Objectifs

Évaluer les bénéfices et les inconvénients du pneumopéritoine à faible pression par rapport au pneumopéritoine à pression standard chez les personnes subissant une cholécystectomie laparoscopique.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL) dans la Bibliothèque Cochrane, MEDLINE, EMBASE et Science Citation Index Expanded jusqu'à février 2013 pour identifier les essais randomisés, en utilisant diverses stratégies de recherche.

Critères de sélection

Nous avons uniquement pris en compte pour inclusion dans la revue les essais cliniques randomisés, indépendamment de la langue, de la mise en aveugle ou du statut de publication.

Recueil et analyse des données

Deux auteurs de la revue ont identifié les essais et extrait les données de manière indépendante. Nous avons calculé le risque relatif (RR), la différence moyenne (DM) ou la différence moyenne standardisée (DMS) avec intervalles de confiance (IC) à 95 % à l'aide de modèles à effets fixes et à effets aléatoires en utilisant le logiciel RevMan 5, sur la base de l'analyse des cas disponibles.

Résultats principaux

Un total de 1 092 participants assignés au hasard au groupe de pression faible (509 participants) et au groupe de pression standard (583 participants) dans 21 essais ont fourni des informations pour cette revue sur un ou plusieurs critères de jugement. Trois autres essais comparant le pneumopéritoine à faible pression au pneumopéritoine à pression standard (incluant 179 participants) n'ont pas fourni de données pour cette revue. La plupart des essais portaient sur des patients à faible risque anesthésique subissant une cholécystectomie laparoscopique élective. Un essai portant sur 140 participants était à faible risque de biais. Les 20 autres essais étaient à risque élevé de biais. La qualité globale des preuves était faible ou très faible. Aucune mortalité n'était rapportée, ni dans le groupe de pression faible (0/199 ; 0 %) ni dans le groupe de pression standard (0/235 ; 0 %), dans les huit essais qui rendaient compte de la mortalité. Un participant a présenté le critère de jugement d'événements indésirables graves (groupe de pression faible 1/179, 0,6 % ; groupe de de pression standard 0/215, 0 % ; sept essais ; 394 participants ; RR 3,00 ; IC à 95 % 0,14 à 65,90 ; preuves de très faible qualité). La qualité de vie, la reprise des activités normales et le retour au travail n'étaient rapportés dans aucun des essais. La différence entre les groupes dans le passage à une cholécystectomie ouverte était imprécise (groupe de pression faible 2/269, proportion ajustée 0,8 % ; groupe de pression standard 2/287, 0,7 % ; 10 essais ; 556 participants ; RR 1,18 ; IC à 95 % 0,29 à 4,72 ; preuves de très faible qualité) et était compatible avec une augmentation, une réduction ou aucune différence dans la proportion de conversion en cholécystectomie ouverte en raison du pneumopéritoine à faible pression. Aucune différence dans la durée du séjour à l'hôpital n'a été rapportée entre les groupes (cinq essais ; 415 participants ; DM -0,30 jours ; IC à 95 % -0,63 à 0,02 ; preuves de faible qualité). La durée opératoire était d'environ deux minutes de plus dans le groupe de pression faible que dans le groupe de pression standard (19 essais ; 990 participants ; DM 1,51 minutes ; IC à 95 % 0,07 à 2,94 ; preuves de très faible qualité).

Conclusions des auteurs

La cholécystectomie laparoscopique peut être menée à bien à l'aide d'une pression faible chez environ 90 % des personnes subissant une cholécystectomie laparoscopique. Cependant, aucune preuve n'est disponible à l'heure actuelle pour soutenir l'utilisation du pneumopéritoine à faible pression chez les patients à faible risque anesthésique subissant une cholécystectomie laparoscopique élective. La sécurité d'emploi du pneumopéritoine à faible pression doit encore être établie. D'autres essais bien conçus sont nécessaires, en particulier chez les personnes atteintes de troubles cardio-pulmonaires subissant une cholécystectomie laparoscopique.

Resumo

Pneumoperitônio de baixa pressão versus pneumoperitônio de pressão padrão na colecistectomia laparoscópica

Introdução

Um pneumoperitônio entre 12 a 16 mmhg é utilizado para realização da colecistectomia laparoscópica. Afirma-se que pressões mais baixas são mais seguras e eficazes na redução das complicações cardiopulmonares e da dor.

Objetivos

Avaliar as vantagens e desvantagens do pneumoperitônio de baixa pressão em comparação ao pneumoperitônio de pressão padrão em pessoas submetidas à colecistectomia laparoscópica.

Métodos de busca

As buscas foram realizadas nas seguintes bases de dados: Cochrane Central Register of Controlled Trials (CENTRAL) da The Cochrane Library, MEDLINE, EMBASE, e Science Citation Index Expanded até fevereiro de 2013, para identificar estudos randomizados,

usando as estratégias de busca.

Critério de seleção

Incluímos apenas ensaios clínicos randomizados, independentemente da língua, mascaramento ou status de publicação.

Coleta dos dados e análises

Dois autores desta revisão identificaram os estudos e extraíram os dados, independentemente. De acordo com a natureza dos dados, calculamos o risco relativo (RR), a diferença média (MD) ou a diferença média padronizada (SMD) com seus respectivos intervalos de confiança (IC) de 95%. Para as metanálises, usamos tanto o modelo de efeitos fixo quanto o de efeito aleatórios, usando o software o RevMan software 5, conforme apropriado.

Principais resultados

Identificamos 21 estudos que randomizaram 1.092 participantes para um grupo de baixa pressão (509 participantes) e um grupo de pressão padrão (583 participantes) e que apresentaram pelo menos um dos desfechos de interesse desta revisão. Identificamos 3 outros estudos comparando pneumoperitônio de baixa pressão com pneumoperitônio de pressão padrão (incluindo 179 participantes) que não forneceram dados passíveis de inclusão nesta revisão. A maioria dos estudos incluiu pacientes com baixo risco anestésico os quais foram submetidos à colecistectomia laparoscópica eletiva. Apenas 1 estudo (140 participantes) foi classificado como tendo baixo risco de viés. Os outros 20 estudos foram classificados como tendo um alto risco de viés. De modo geral, a qualidade da evidência foi baixa ou muito baixa. Apenas 8 estudos avaliaram mortalidade; não houve nenhum caso de morte no grupo de baixa pressão (0/199; 0%) nem no grupo de pressão padrão (0/235, 0%). Um participante apresentou um evento adverso grave (grupo de baixa pressão 1/179, 0,6%; grupo de pressão padrão 0/215, 0%; 7 estudos ;394 participantes; RR 3,00; IC 95% 0,14 a 65,90; evidência de qualidade muito baixa). Qualidade de vida, retorno da atividade normal e retorno ao trabalho não foram relatados em qualquer estudo. A diferença entre os grupos para conversão para colecistectomia aberta foi imprecisa: grupo de baixa pressão 2/287, proporção ajustada 0,8% versus grupo de pressão padrão 2/287, 0,7% (10 estudos, 556 participantes; RR 1,18; IC 95% 0,29 - 4,72; evidência de qualidade muito baixa). Esse resultado foi compatível com um aumento, uma diminuição ou nenhuma diferença na proporção de conversão para colecistectomia aberta, devido à baixa pressão do pneumoperitônio. Não houve diferença na duração de internação entre os grupos (5 estudos, 415 participantes; DM -0, 30 dias; 95% CI -0,63 a 0,02; evidência de baixa qualidade). O tempo operatório foi cerca de dois minutos mais longo no grupo de baixa pressão em comparação ao grupo de pressão padrão (19 estudos, 990 participantes; DM 1,51 minutos; 95% CI 0,07 a 2,94; evidência de qualidade muito baixa).

Conclusão dos autores

A colecistectomia laparoscópica pode ser realizada com sucesso utilizando pneumoperitônio com baixa pressão em cerca de 90% das pessoas submetidas à colecistectomia laparoscópica. No entanto, não há evidência atual disponível para apoiar o uso de pneumoperitônio de baixa pressão em pacientes de baixo risco anestésico submetidos à colecistectomia laparoscópica. A segurança do pneumoperitôneode baixa pressão ainda precisa ser estabelecida. São necessários mais estudos com desenhos adequados, especialmente em pessoas com doenças cardiopulmonares submetidas à colecistectomia laparoscópica.

Notas de tradução

Tradução do Centro Cochrane do Brasil (Marcos Aparecido Fernandes). Contato: tradutores@centrocochranedobrasil.org.br

Plain language summary

Low pressure pneumoperitoneum versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy

Background

The liver produces bile, which has many functions, including elimination of waste processed by the liver and digestion of fat. 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 within a year. 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 discolouration 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 that secretes digestive juices and harbours the insulin-secreting cells that 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). Laparoscopic cholecystectomy is generally performed by inflating the tummy with carbon dioxide gas to permit the organs and structures within the tummy to be viewed so that the surgery can be performed. The gas pressure used to inflate the tummy is usually 12 mm Hg to 16 mm Hg (standard pressure). However, this causes alterations in the blood circulation and may be detrimental. To overcome this, lower pressure has been suggested as an alternative to standard pressure. However, using lower pressure may limit the surgeon's view of the organs and structures within the tummy, possibly resulting in inadvertent damage to the organs or structures. The review authors set out to determine whether it is preferable to perform laparoscopic cholecystectomy using low pressure or standard pressure. A systematic search of medical literature was performed to identify studies that provided information on the above question. The review authors obtained information from randomised trials only because such types of trials provide the best information if conducted well. Two review authors independently identified the trials and collected the information.

Study characteristics

A total of 1092 patients were studied in 21 trials. Patients were assigned to a low pressure group (509 patients) or a standard pressure group (583 patients). The choice of treatment was determined by a method similar to the toss of a coin. Most of the trials included low surgical risk patients undergoing planned laparoscopic cholecystectomy.

Key results

Laparoscopic cholecystectomy could be completed successfully using low pressure in approximately 90% of people undergoing this procedure. No deaths were reported in either low pressure or standard pressure groups in eight trials that reported deaths (total of 434 patients in both groups). Seven trials with 394 patients described complications related to surgery. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference in the percentage of people undergoing conversion to open operation (from key-hole operation) between the low pressure group (2/269; 0.8%) and the standard pressure group (2/287; 0.7%) was imprecise. This was reported in 10 studies. No difference was noted in the length of hospital stay between the groups. Operating time was about two minutes longer (very low quality evidence) in the low pressure group than in the standard pressure group. Currently no evidence is available to support the use of low pressure pneumoperitoneum in low surgical risk patients undergoing planned laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established.

Quality of evidence

Only one trial including 140 participants was at low risk of bias (low chance of arriving at wrong conclusions because of study design). The remaining 20 trials were at high risk of bias (high chance of arriving at wrong conclusions because of trial design). The overall quality of evidence was very low.

Future research

Further well-designed trials are necessary, particularly in high surgical risk patients undergoing laparoscopic cholecystectomy.

Résumé simplifié

Pneumopéritoine provoqué par pression faible comparé au pneumopéritoine provoqué par pression standard dans la cholécystectomie laparoscopique

Contexte

Le foie produit la bile qui a de nombreuses fonctions, notamment l'élimination des déchets traités par le foie et la digestion des graisses. La bile est stockée temporairement dans la vésicule biliaire (un organe situé sous le foie) avant de parvenir à l'intestin grêle. Les concrétions dans la vésicule biliaire sont appelés calculs biliaires. Environ 5 % à 25 % de la population adulte occidentale ont des calculs biliaires. Entre 2 % et 4 % deviennent symptomatiques dans l'année. Les symptômes incluent la douleur liée à la vésicule biliaire (colique hépatique), l'inflammation de la vésicule biliaire (cholécystite), l'obstruction à l'écoulement de la bile du foie et de la vésicule biliaire dans l'intestin grêle entraînant un ictère (décoloration jaunâtre de l'organisme généralement principalement observée dans le blanc de l'œil, qui devient jaune), l'infection de la bile (angiocholite), et l'inflammation du pancréas, un organe sécrétant des fluides digestives et hébergeant les cellules productrices d'insuline qui maintiennent le niveau de sucre sanguin (pancréatite). L'ablation de la vésicule biliaire (cholécystectomie) est actuellement considérée comme la meilleure option de traitement pour les patients souffrant de calculs biliaires symptomatiques. Elle est généralement réalisée par chirurgie mini-invasive (cholécystectomie laparoscopique). Pour effectuer une cholécystectomie laparoscopique, le ventre est généralement gonflé avec du gaz carbonique pour permettre de voir les organes et les structures à l'intérieur de sorte de pouvoir opérer. La pression de gaz utilisée pour gonfler le ventre est généralement de 12 mm Hg à 16 mm Hg (pression standard). Cependant, cela entraîne des altérations de la circulation sanguine et peut être préjudiciable. Afin de surmonter ce problème, l'utilisation d'une pression plus faible a été proposée comme une alternative à la pression standard. Toutefois, l'utilisation d'une pression plus faible peut limiter la vue du chirurgien sur les organes et les structures dans le ventre, ce qui pourrait éventuellement entraîner des dommages par inadvertance à ces organes ou structures. Les auteurs de la revue ont cherché à déterminer s'il est préférable de réaliser une cholécystectomie laparoscopique à l'aide d'une pression faible ou de la pression standard. Une recherche systématique de la littérature médicale a été réalisée afin d'identifier des études fournissant des informations sur cette question. Les auteurs de la revue ont extrait des données uniquement à partir d'essais randomisés, car ce type d'essais fournissent les meilleures informations quand ils sont menés correctement. Deux auteurs de la revue ont de manière indépendante identifié les essais et recueilli les informations.

Caractéristiques des études

Un total de 1092 patients ont été étudiés dans 21 essais. Les patients ont été assignés à un groupe de pression faible (509 patients) ou à un groupe de pression standard (583 patients). Le choix du traitement a été déterminé par une méthode similaire au pile ou face. La plupart des essais portaient sur des patients à faible risque chirurgical subissant une cholécystectomie laparoscopique programmée.

Résultats principaux

La cholécystectomie laparoscopique a pu être menée à bien à l'aide d'une pression faible chez environ 90 % des personnes subissant cette procédure. Aucun décès n'a été rapporté dans les groupes de pression faible ou standard dans les huit essais ayant rendu compte des décès (un total de 434 patients dans les deux groupes). Sept essais avec 394 patients ont décrit les complications liées à la chirurgie. Un participant a présenté le critère de jugement d'événements indésirables graves (groupe de pression faible 1/179, 0,6 % ; groupe de pression standard 0/215, 0 %). La qualité de vie, la reprise des activités normales et le retour au travail n'étaient rapportés dans aucun des essais. La différence dans le pourcentage de personnes dont l'opération a dû être convertie (de chirurgie mini-invasive) en opération ouverte était imprécise entre le groupe de pression faible (2/269 ; 0,8 %) et le groupe de pression standard (2/287 ; 0,7 %). Ce critère était rapporté dans 10 études. Aucune différence n'était observée dans la durée d'hospitalisation entre les groupes. La durée opératoire était d'environ deux minutes de plus (preuves de qualité très faible) dans le groupe de pression faible que dans le groupe de pression standard. Aujourd'hui, il n'existe pas de preuves pour soutenir le recours au pneumopéritoine à faible pression chez les patients à faible risque chirurgical subissant une cholécystectomie laparoscopique programmée. La sécurité d'emploi du pneumopéritoine à faible pression doit encore être établie.

Qualité des preuves

Un seul essai portant sur 140 participants était à faible risque de biais (peu de chances d'arriver à des conclusions erronées en raison du plan d'étude). Les 20 autres essais étaient à risque élevé de biais (fortes chances d'arriver à des conclusions erronées en raison du plan d'étude). La qualité globale des preuves était très faible.

Recherches futures

D'autres essais bien conçus sont nécessaires, en particulier chez les patients à haut risque chirurgical subissant une cholécystectomie laparoscopique.

Notes de traduction

Traduit par: French Cochrane Centre 12th July, 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

Streszczenie prostym językiem

Porównanie odmy brzusznej niskociśnieniowej z normociśnieniową w cholecystektomii laparoskopowej

Wprowadzenie

Wątroba produkuje żółć, spełniającą wiele funkcji, takich jak usuwanie produktów przemiany materii z wątroby oraz trawienie tłuszczów. Żółć jest czasowo przechowywana w pęcherzyku żółciowym (narząd umiejscowiony pod wątrobą) zanim osiągnie jelito cienkie. Złogi w pęcherzyku żółciowym są nazywane kamieniami żółciowymi. Kamienie żółciowe są obecne u około 5% do 25% dorosłej populacji w krajach zachodnich. Od 2% do 4% chorych z kamicą żółciową rozwija w ciągu roku objawy. Objawy obejmują ból związany z pęcherzykiem żółciowym (kolka żółciowa), zapalenie pęcherzyka żółciowego, utrudnienie przepływu żółci z wątroby i pęcherzyka żółciowego do jelita cienkiego dające w wyniku żółtaczkę (żółtawe zabarwienie ciała zwykle najbardziej wyraźnie zauważalne w białkówce oka, która staje się żółta), zapalenie dróg żółciowych i zapalenie trzustki, organu, który wydziela soki trawienne i zawiera komórki wydzielające insulinę, które utrzymują poziom cukru we krwi. Usunięcie pęcherzyka żółciowego (cholecystektomia) obecnie uznaje się za najlepszą opcję terapeutyczną dla chorych z objawowymi kamieniami żółciowymi. Operacje jest zwykle wykonywana drogą laparoskopową. Cholecystektomię laparoskopową zwykle wykonuje się poprzez wypełnienie brzucha dwutlenkiem węgla celem uwidocznienia narządów i struktur brzucha aby umożliwić wykonanie zabiegu. Standardowe ciśnienie gazu wpompowywanego do brzucha wynosi od 12mm Hg do 16mm Hg. Jednakże takie ciśnienie powoduje zmiany w krążeniu krwi i może być szkodliwe. Aby przezwyciężyć te trudności, zasugerowano niższe ciśnienie jako alternatywę do ciśnienia standardowego. Stosowanie niższego ciśnienia może z drugiej strony ograniczać chirurgowi widoczność narządów i struktur w obrębie brzucha, co może spowodować większe ryzyko nieumyślnego uszkodzenia narządów i struktur. Celem autorów przeglądu było stwierdzenie, czy lepiej jest wykonywać cholecystektomię laparoskopową przy użyciu niskiego czy standardowego ciśnienia. Dokonano systematycznego wyszukiwania dostępnej literatury medycznej celem zidentyfikowania badań dostarczających informacji na temat powyższego zagadnienia. Autorzy przeglądu uzyskali informacje wyłącznie z badań z randomizacja, gdyż takie badania, pod warunkiem poprawnego ich przeprowadzenia, dostarczają najlepszych informacji. Dwóch autorów przeglądu niezależnie od siebie zidentyfikowało badania i zebrało informacje.

Charakterystyka badania

W 21 badaniach przebadano łącznie 1092 chorych. Pacjentów przypisano do grupy operowanych z zastosowaniem niskiego ciśnienia (509 chorych) lub grupy operowanych z zastosowaniem standardowego ciśnienia (583 chorych). Wybór metody leczenia określano stosując metodę podobną do rzutu monety. W większości badań udział brali pacjenci o niskim ryzyku operacyjnym poddawani planowej cholecystektomii laparoskopowej.

Kluczowe wyniki

Cholecystektomia laparoskopowa zakończyła się powodzeniem u około 90% chorych operowanych z wykorzystaniem niskiego ciśnienia. Nie odnotowano zgonów zarówno w grupie niskiego ciśnienia jak i standardowego ciśnienie w ośmiu badaniach, w których oceniano ryzyko zgonu (łącznie 434 chorych w obu grupach). W siedmiu badaniach oceniających 394 chorych oceniono powikłania pooperacyjne. Jeden chory doznał poważnych działań niepożądanych (grupa niskiego ciśnienia 1/179, 0,6%; grupa standardowego ciśnienia 0/215, 0%). W żadnym z badań nie oceniano jakości życia, czasu do powrotu do normalnej aktywności i powrotu do pracy. Różnica w odsetku osób poddanych konwersji do operacji metodą klasyczną (z operacji laparoskopowej) pomiędzy grupą niskiego ciśnienia (2/269; 0,8%), a grupą standardowego ciśnienia (2/287; 0,7%) było nieprecyzyjna. Zostało to odnotowane w 10 badaniach. Nie odnotowano różnicy pomiędzy grupami w długości pobytu w szpitalu. Czas operacji był o około 2 minuty dłuższy (bardzo niska jakość danych) w grupie z wykorzystaniem niskiego ciśnienia w porównaniu do grupy z wykorzystaniem standardowego ciśnienia. Obecnie brak jest dowodów na poparcie stosowania niskociśnieniowej odmy brzusznej u chorych niskiego ryzyka operacyjnego poddawanych planowej cholecystektomii laparoskopowej. Wskazane jest ustalenie poziomu bezpieczeństwa stosowania niskociśnieniowej odmy brzusznej.

Jakość ocenianych badań

Tylko jedno badanie obejmujące 140 chorych było obarczone małym ryzykiem błędu systematycznego (mała szansa błędnych wniosków wynikających ze sposobu przeprowadzenia badania). Pozostałych 20 badań było obarczonych dużym ryzykiem błędu systematycznego (duża szansa błędnych wniosków wynikających ze sposobu przeprowadzenia badania). Całościowa jakość badań była bardzo niska.

Kierunek przyszłych badań

Niezbędne są dalsze, dobrze zaplanowane badania z randomizacją, szczególnie dotyczące grupy pacjentów wysokiego ryzyka, u których wykonuje się laparoskopowe usunięcie pęcherzyka żółciowego.

Uwagi do tłumaczenia

Tlumaczenie: Mateusz Świerz, Redakcja: Andrzej L. Komorowski

Resumo para leigos

Uso do pneumoperitônio de baixa pressão comparado ao pneumoperitônio com pressão padrão durante colecistectomia laparoscópica

Introdução

O fígado produz a bile, que tem muitas funções, incluindo a eliminação de resíduos processados pelo fígado e a digestão de gordura. A bile é temporariamente armazenada na vesícula biliar (um órgão situado abaixo do fígado) antes de chegar ao intestino delgado. Algumas pessoas desenvolvem pedras (ou “cálculos” dentro da vesícula biliar. Cerca de 5% a 25% da população adulta ocidental têm cálculos biliares. Entre 2% a 4% das pessoas com cálculos biliares terão sintomas dentro de um ano. Os sintomas incluem cólica biliar, inflamação da vesícula biliar (colecistite) e obstrução do fluxo de bile do fígado e da vesícula biliar para o intestino delgado, resultando em icterícia (coloração amarelada do corpo, mais visível no branco do olho). Os cálculos biliares podem também causar infecção biliar (colangite) e inflamação do pâncreas (pancreatite), que é um órgão que secreta sucos digestivos e que tem células que produzem a insulina, responsável por equilibrar os níveis de açúcar no sangue. A cirurgia para extrair a vesícula biliar (colecistectomia) é considerada, atualmente, a melhor opção para tratar os pacientes que têm cálculos biliares sintomáticos. Essa cirurgia é geralmente realizada por via laparoscópica (colecistectomia laparoscópica). Para realizar uma colecistectomia laparoscópica, o médico precisa injetar um gás (o dióxido de carbono) dentro da barriga do paciente (isso é chamado de “pneumoperitônio”), para que ele possa ver os órgãos. Geralmente, a pressão do gás utilizado para distender a barriga fica entre 12 mm Hg e 16 mm Hg (pressão padrão). No entanto, essa pressão pode levar a alterações no fluxo sanguíneo e isso pode ser prejudicial. Para evitar este problema, a utilização de uma pressão mais baixa tem sido proposta como uma alternativa ao pneumoperitônio de pressão padrão. No entanto, o uso de uma pressão de gás menor pode limitar a visão que o cirurgião terá dos órgãos e estruturas dentro da barriga do paciente e isso pode levá-lo a causar danos aos órgãos ou estruturas inadvertidamente. Nesta revisão, os autores procuraram saber se é preferível realizar uma colecistectomia laparoscópica com pneumoperitônio de baixa pressão ou com a pressão padrão. Uma busca sistemática da literatura médica foi realizada para identificar estudos que tivessem informações sobre essa questão. Os autores desta revisão incluíram apenas ensaios clínicos randomizados porque tais estudos, quando são bem conduzidos, fornecem a melhor informação. Dois revisores identificaram os estudos e coletaram as informações independentemente.

Características dos estudos

A revisão incluiu 21 estudos com um total de 1.092 pacientes. Os pacientes desses estudos foram distribuídos em dois grupos: o de pneumoperitônio de baixa pressão (509 pacientes) ou o grupo de pressão padrão (583 pacientes). A escolha do grupo de tratamento foi determinada por sorteio usando um método semelhante ao lançamento de uma moeda. Na maioria dos estudos, os pacientes tinham um baixo risco cirúrgico e fizeram uma colecistectomia laparoscópica programada (ou seja, não eram cirurgias de urgência).

Principais resultados

A colecistectomia laparoscópica pôde ser concluída com sucesso usando o pneumoperitônio de baixa pressão em aproximadamente 90% das pessoas submetidas a esse procedimento. Oito estudos apresentaram dados sobre mortalidade e relataram que não houve nenhuma morte, nem nos grupos de baixa pressão e nem nos grupos de pressão padrão (434 pacientes em ambos os grupos). Sete ensaios clínicos com 394 pacientes descreveram complicações relacionadas à cirurgia. Um participante apresentou um evento adverso grave (1/179 grupo de baixa pressão, 0,6%; no grupo de pressão padrão, 0/215, 0%). Nenhum dos estudos apresentou dados sobre a qualidade de vida dos participantes, a retomada das atividades normais e o retorno ao trabalho. A diferença no percentual de pessoas cuja cirurgia teve de ser convertida da cirurgia laparoscópica para cirurgia aberta (onde o cirurgião faz um corte grande na barriga) foi pouco clara entre o grupo de baixa pressão (2/269, 0,8%) e o grupo de pressão padrão (2/287; 0,7%). Este desfecho foi relatado em 10 estudos. Não houve diferença na duração da internação dos pacientes nos grupos de pressão padrão ou baixa. A duração total da cirurgia foi cerca de dois minutos maior no grupo de baixa pressão do que no grupo de pressão padrão (evidência de qualidade muito baixa). Concluímos que, na atualidade, não há nenhuma evidência para apoiar o uso do pneumoperitônio de baixa pressão em pacientes de baixo risco cirúrgico submetidos à colecistectomia laparoscópica programada. A segurança do pneumoperitônio de baixa pressão ainda tem de ser estabelecida.

Qualidade da evidência

Apenas 1 estudo com 140 participantes foi classificado como tendo um baixo risco de viés, o que significa que existe pouca chance de as conclusões desse estudo estarem erradas por causa do desenho do estudo. Os outros 20 estudos foram classificados como tendo um alto risco de viés, o que significa que existe uma alta probabilidade de que as conclusões sejam incorretas por causa do desenho do estudo. A qualidade geral das evidências desta revisão sistemática foi classificada como sendo muito baixa.

Pesquisas futuras

São necessários mais estudos com desenhos adequados, especialmente envolvendo pacientes de alto risco cirúrgico submetidos à colecistectomia laparoscópica.

Notas de tradução

Tradução do Centro Cochrane do Brasil (Marcos Aparecido Fernandes). Contato: tradutores@centrocochranedobrasil.org.br

Summary of findings(Explanation)

Summary of findings for the main comparison. Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy
  1. 1The trial(s) was (were) at high risk of bias (two points).
    2The confidence intervals overlapped 1 and either 0.75 or 1.25 or both. Events in the intervention and control groups were fewer than 300 (two points).
    3Severe heterogeneity was noted by the I2 and the lack of overlap of confidence intervals (two points).

Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy
Patient or population: patients undergoing laparoscopic cholecystectomy.
Settings: secondary or tertiary.
Intervention: low pressure pneumoperitoneum.
Comparison: standard pressure pneumoperitoneum.
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Assumed riskCorresponding risk
Control Intervention
MortalityNo mortality in either groupnot estimable

434

(8 studies)

⊕⊝⊝⊝
very low 1,2
Serious adverse events 3 per 1000 8 per 1000
(0 to 167)
RR 3
(0.14 to 65.9)
394
(7 studies)
⊕⊝⊝⊝
very low 1,2
Conversion to open cholecystectomy 7 per 1000 8 per 1000
(2 to 33)
RR 1.18
(0.29 to 4.72)
556
(10 studies)
⊕⊝⊝⊝
very low 1,2
Hospital stayThe mean hospital stay in the control groups was
2 days
The mean hospital stay in the intervention groups was
0.3 lower
(0.63 lower to 0.02 higher)
 415
(5 studies)
⊕⊝⊝⊝
very low 1,3
Operating timeThe mean operating time in the control groups was
55 minutes
The mean operating time in the intervention groups was
1.51 higher
(0.07 to 2.94 higher)
 990
(19 studies)
⊕⊕⊝⊝
low 1
*The basis for the assumed risk is the mean control group risk for conversion to open cholecystectomy. Although we planned to use the mean control group risk for serious adverse events also, we could not do so because no serious adverse events were reported in the control group. Overall serious adverse events in both groups were used as the control group risk. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

About 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 one 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 within a year (Attili 1995; Halldestam 2004). Cholecystectomy (removal of the gallbladder) is the preferred option in the treatment of symptomatic gallstones (Strasberg 1993). Every year, more than 0.5 million cholecystectomies are performed in the US and 60,000 in the UK (Dolan 2009; HES 2011). Approximately 80% of cholecystectomies are performed laparoscopically (by key-hole surgery) (Ballal 2009). Biliary colic (pain in the right upper abdomen lasting longer than half an hour) is one of the symptoms related to gallstones (Berger 2000) and is the most common indication for cholecystectomy (Glasgow 2000).

Description of the intervention

Traditionally, one of the first steps in laparoscopic cholecystectomy is the creation of pneumoperitoneum (Russell 1993) using carbon dioxide (CO2) through a Veress needle (Casati 1997) or through a port (hole) (Alijani 2004) in the abdominal wall. Traditionally, the pressure used is around 15 mm Hg (Russell 1993). The created pneumoperitoneum allows visualisation and manipulation of instruments inside the abdominal cavity. Increased intra-abdominal pressure due to the pneumoperitoneum causes several cardiopulmonary changes. The increased intra-abdominal pressure increases the absorption of CO2, causing hypercapnia and acidosis, which must be avoided by hyperventilation (Henny 2005). It also pushes the diaphragm upwards, decreasing pulmonary compliance (Alijani 2004; Henny 2005), and increases the peak airway pressure (Galizia 2001; Alijani 2004). Increased intra-abdominal pressure increases the venous return due to blood compressed out of the splanchnic vasculature (Henny 2005). Pneumoperitoneum also increases systemic vascular resistance (Galizia 2001; Mertens 2004) and pulmonary vascular resistance (Galizia 2001). Carbon dioxide pneumoperitoneum predisposes to cardiac arrhythmias (Egawa 2006). During the early phase of pneumoperitoneum, cardiac output is reduced (Galizia 2001; Alijani 2004) by decreasing venous return (Neudecker 2002). Although these cardiorespiratory changes may be tolerated by healthy adults with adequate cardiopulmonary reserve, people with cardiopulmonary diseases may not tolerate these cardiopulmonary changes. About 17% of patients undergoing laparoscopic cholecystectomy have an American Society of Anesthesiologists (ASA) status of III or IV (Giger 2006; ASA 2007). Abdominal wall lift, using a special device (eg, Laparolift (Egawa 2006), Laparo-tensor (Alijani 2004)) introduced through a port in the abdominal wall, has been used to decrease the cardiopulmonary changes and has been considered in a different review (Gurusamy 2012). Helium insufflation is an alternative to CO2 insufflation (Neuhaus 2001) and has been reported to have little or no effect on pulmonary function in pigs (Junghans 1997). However, concerns about the solubility of helium in the blood and hence the risk of gas embolism have precluded its routine use in humans (Neuhaus 2001).

How the intervention might work

Lower pressure may decrease the effects of pneumoperitoneum. However, the safety of low pressure pneumoperitoneum has not been established.

Why it is important to do this review

In our previous version of the review, we found evidence from trials with high risk of bias showing that low pressure pneumoperitoneum decreased pain scores (Gurusamy 2009). However, pain scores are unvalidated surrogate outcomes for pain in people undergoing laparoscopic cholecystectomy, and several Cochrane systematic reviews have demonstrated that pain scores can be decreased with no clinical implications in people undergoing laparoscopic cholecystectomy (Gurusamy 2014a; Gurusamy 2014b; Gurusamy 2014c). In addition, no study has evaluated the level of pain scores that people undergoing laparoscopic cholecystectomy or any other elective or emergency operation consider as important. The minimal clinically important difference in pain scores has also not been established in people undergoing laparoscopic cholecystectomy or any other elective or emergency operation. This update of our previous review includes results from trials that became available since the time of our last review.

Objectives

To assess the benefits and harms of low pressure pneumoperitoneum compared with standard pressure pneumoperitoneum in patients undergoing laparoscopic cholecystectomy.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomised clinical trials that compared different pressures of pneumoperitoneum in participants undergoing laparoscopic cholecystectomy (irrespective of language, blinding, publication status, or sample size, or whether the trials were adequately powered). We did not consider randomised trials that compared abdominal wall lift in combination with pneumoperitoneum versus pneumoperitoneum alone. Such trials were included in the review in which abdominal lift and pneumoperitoneum were compared (Gurusamy 2012).

We excluded quasi-randomised trials (ie, trials in which the method of allocating participants to a treatment were not strictly random, for example, date of birth, hospital record number, or alternation).

Types of participants

Patients undergoing laparoscopic cholecystectomy (elective or emergency) for any reason (symptomatic gallstones, acalculous cholecystitis, gallbladder polyp, or any other condition) using four ports, at least two of 10 mm or larger and the remaining two of 5 mm or larger (which is generally considered as standard laparoscopic cholecystectomy). We excluded trials in which fewer ports or smaller ports were used, as the safety of such procedures has not been established (Gurusamy 2013; Gurusamy 2014d). We applied no restriction based on the type of anaesthesia used provided that the same type of anaesthesia was used in both groups.

Types of interventions

Trials comparing low pressure (less than 12 mm Hg) versus standard pressure (12 to 16 mm Hg) pneumoperitoneum. We excluded any trials using pressure greater than 16 mm Hg. The definitions of standard (12 mm Hg to 16 mm Hg) and low (less than 12 mm Hg) were chosen arbitrarily and were based on general belief and the review authors' opinions. No universal definitions are available for standard and low.

Types of outcome measures

Primary outcomes
  1. Mortality (30-day or in-hospital mortality).

  2. Serious adverse events: defined as any events that would increase mortality; are life-threatening; require inpatient hospitalisation; or result in persistent or significant disability; or any important medical events that might have jeopardised the participant or required intervention for prevention. All other adverse events were considered non-serious (ICH-GCP 1997). Combining outcomes of different severity can result in wrong conclusions about the safety and effectiveness of an intervention (Cordoba 2010), and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) recommends that an exhaustive list of all outcomes should not be included—only important outcomes that are important to patients or health policy-makers; therefore we included only serious adverse events rather than all adverse events.

  3. Quality of life.

Secondary outcomes
  1. Conversion to open cholecystectomy.

  2. Hospital stay.

    1. Proportion discharged as day procedure.

    2. Length of hospital stay.

  3. Return to normal activity.

  4. Return to work.

  5. Operating time.

We also collected information on the successful completion of low pressure laparoscopic cholecystectomy.

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 (Royle 2003). We have provided the search strategies in Appendix 1 along with the time span for the searches. Searches were conducted until February 2013.

Searching other resources

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

Data collection and analysis

Selection of studies

KSG and JV independently identified the trials for inclusion. We have listed the excluded studies along with the reasons for exclusion.

Data extraction and management

KSG and JV 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 2012). Based on 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; Savović 2012; Savović 2012a), we assessed the trials for the following risk of bias domains.

Allocation sequence generation
  1. Low risk of bias: Sequence generation was achieved using a 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.

  2. Uncertain risk of bias: The method of sequence generation was not specified.

  3. High risk of bias: The sequence generation method was not random.

Allocation concealment
  1. 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 (eg, if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).

  2. 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.

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

Blinding of participants, personnel, and outcome assessors
  1. Low risk of bias: Blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

  2. Uncertain risk of bias: Information was insufficient to allow assessment of whether blinding was likely to induce bias on the results.

  3. High risk of bias: No blinding or incomplete blinding was provided, and assessment of outcomes was likely to be influenced by lack of blinding.

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

  2. Uncertain risk of bias: Information was insufficient to allow assessment of whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.

  3. High risk of bias: The results were likely to be biased because of missing data.

Selective outcome reporting
  1. Low risk of bias: All outcomes were predefined and reported, or all clinically relevant and reasonably expected outcomes were reported.

  2. Uncertain risk of bias: It is unclear whether all predefined and clinically relevant and reasonably expected outcomes were reported. 

  3. 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
  1. Low risk of bias: The trial appears to be free of industry sponsorship or other kinds of for-profit support that may lead to manipulatiion of trial design, conductance, or results. 

  2. 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.

  3. High risk of bias: The trial is sponsored by the industry or has received other kinds of for-profit support.

We considered trials to have a low risk of bias if we assessed all of 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 the conclusions would have changed by using risk difference, because 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 as well as standardised mean difference (SMD) with 95% CI for variables such as quality of life.

Unit of analysis issues

The unit of analysis was the participant undergoing laparoscopic cholecystectomy.

Dealing with missing data

We performed an intention-to-treat analysis (Newell 1992) when possible for binary outcomes. For continuous outcomes, we used available-case analysis in the presence of missing data unless the study authors reported an intention-to-treat analysis based on an appropriate method of imputation of data such as multiple imputation. We planned to use intention-to-treat analysis if such analysis was available. We imputed the standard deviation from P values according to 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 would decrease the weight of the trial for calculation of mean differences and would bias the effect estimate to no effect in the case of standardised mean differences (Higgins 2011).

Assessment of heterogeneity

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

Assessment of reporting biases

We used a funnel plot to explore bias in the presence of at least 10 trials for the outcome (Egger 1997; Macaskill 2001). We used asymmetry in the funnel plot of trial size against treatment effect to assess this bias. We also used 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 2012), using the software package Review Manager 5 (RevMan 2012). We used a random-effects model (DerSimonian 1986) and a fixed-effect model (DeMets 1987). In the case of a discrepancy between the two models, we have reported both results; otherwise, we have reported only the results from the fixed-effect model.

Subgroup analysis and investigation of heterogeneity

We planned to perform the following subgroup analyses.

  1. Trials with low risk of bias versus trials with high risk of bias.

  2. Different gases used for pneumoperitoneum.

  3. Different pressures used for pneumoperitoneum (borderline low 10 mm Hg to 11 mm Hg; moderately low 7 mm Hg to 9 mmHg; and very low up to 6 mm Hg). This was defined arbitrarily again based on general belief and on review authors' opinions because no universal definitions are available.

  4. Elective versus emergency cholecystectomy.

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

Sensitivity analysis

We planned to perform a sensitivity analysis by excluding the trials in which medians or standard deviations were imputed for continuous outcomes.

Trial sequential analysis

We planned to use trial sequential analysis to control for random errors due to sparse data and repetitive testing of 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. We planned to add the trials according to the year of publication, and if more than one trial was published in a year, we planned to add the trials alphabetically according to the last name of the first author. We planned to construct 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 to detect or reject a certain intervention effect (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009, Wetterslev 2009; Thorlund 2010).   

We planned to apply trial sequential analysis (CTU 2011; Thorlund 2011) using a diversity-adjusted required information size (DARIS) calculated from an alpha error of 0.05, a beta error of 0.20, a control event proportion obtained from the results, and a relative risk reduction of 20% for binary outcomes with two or more trials to determine whether more trials on this topic are necessary. Trial sequential analysis cannot be performed for standardised mean difference. So, we did not plan to perform a trial sequential analysis for quality of life. For hospital stay, return to normal activity, and return to work, we planned to calculate the DARIS from an alpha error of 0.05, a beta error of 0.20, the variance estimated from the meta-analysis results of low risk of bias trials (if available), and a minimal clinically relevant difference of one day. For operating time, we planned to calculate the DARIS using a minimal clinically relevant difference of 15 minutes, with remaining parameters the same as for hospital stay.

Summary of findings table

We have summarised the results of all outcomes 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 1057 bibliographic references through electronic searches of The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (n = 202), MEDLINE (n = 240), EMBASE (n = 233), and Science Citation Index Expanded (n = 382). We excluded 465 duplicates and 555 clearly irrelevant references through reading abstracts. Thirty-eight references were retrieved for further assessment. One reference was identified through contacting experts in the field. No references were identified by scanning reference lists of the identified randomised trials. We excluded 12 references of 11 studies for the reasons listed under the table ‘Characteristics of excluded studies’. Twenty-six references of 24 randomised clinical trials were included in the review. Twenty-one randomised clinical trials provided data for this review. The reference flow is shown in Figure 1. The details of population characteristics, pressure used for pneumoperitoneum, and outcomes reported by individual trials are shown in the table ‘Characteristics of included studies’.

Figure 1.

Study flow diagram.

Included studies

A total of 1277 participants were randomly assigned in the 24 trials included in this review (Pier 1994; Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2002; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Kandil 2010; Topal 2011; Eryilmaz 2012). However, only 21 trials including 1092 participants provided information for this review and further description about participants and interventions (Pier 1994; Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). Participants were randomly assigned to the low pressure group (509 participants) and the standard pressure group (583 participants) in the 21 trials (Pier 1994; Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). The average age of participants ranged between 42 years and 58 years in the 19 trials that provided this information (Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). The proportion of female participants ranged between 21.7% and 100% in the 19 trials that provided this information (Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). Twenty trials included only participants undergoing elective laparoscopic cholecystectomy (Pier 1994; Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). It was not clear whether participants undergoing emergency laparoscopic cholecystectomy were included in one trial (Polat 2003). Eleven trials clearly stated that they included only ASA I or II (low anaesthetic risk) participants (Pier 1994; Dexter 1999; Barczynski 2003; Perrakis 2003; Sefr 2003; Basgul 2004; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). One trial included ASA I to III participants (Koc 2005). This information was not available for the remaining nine trials (Unbehaum 1995; Wallace 1997; Polat 2003; Celik 2004; Ibraheim 2006; Joshipura 2009; Kanwer 2009; Torres 2009; Topal 2011). All 21 trials used carbon dioxide pneumoperitoneum (Pier 1994; Unbehaum 1995; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011).

Interventions

The types of low pressure used in the different trials were as follows.

In the remaining two trials, the pressure used was 8 to 10 mm Hg (Unbehaum 1995; Celik 2004).

In one trial, the trocar was inserted at standard pressure and the operation was performed under low pressure (Joshipura 2009).

Risk of bias in included studies

The risk of bias of all trials included in the review is shown in Figure 2. The risk of bias in individual trials is shown in Figure 3. Nine trials had low risk of bias in the allocation sequence generation domain (Wallace 1997; Dexter 1999; Barczynski 2003; Sefr 2003; Hasukic 2005; Chok 2006; Kanwer 2009; Sandhu 2009; Celik 2010). Eleven trials had low risk of bias in the allocation concealment domain (Dexter 1999; Barczynski 2002; Barczynski 2003; Perrakis 2003; Sefr 2003; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Joshipura 2009; Sandhu 2009). Three trials had low risk of bias in the blinding of participants, personnel, and outcome assessors domain (Wallace 1997; Joshipura 2009; Sandhu 2009). Ten trials had low risk of bias due to missing outcome data (Wallace 1997; Barczynski 2002; Barczynski 2003; Perrakis 2003; Sefr 2003; Celik 2004; Hasukic 2005; Chok 2006; Joshipura 2009; Sandhu 2009). Seven trials had low risk of bias due to selective outcome reporting (Wallace 1997; Dexter 1999; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). Four trials had low risk of bias in the for-profit bias domain (Barczynski 2002; Chok 2006; Kanwer 2009; Sandhu 2009). Only one trial was considered to be at low risk of bias (Sandhu 2009).

Figure 2.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 3.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Effects of interventions

See: Summary of findings for the main comparison Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy

The results are summarised in Summary of findings for the main comparison.

Mortality

Mortality was reported in eight trials (Wallace 1997; Dexter 1999; Perrakis 2003; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). No mortality was reported in either the low pressure group (0/199; 0%) or the standard pressure group (0/235; 0%). As no mortality was reported in either group, we were unable to use the control group proportion for calculation of the required information size of the trial sequential analysis. Instead, we used a proportion of 0.2% in the control group based on data from approximately 30,000 patients included in a database in Switzerland (Giger 2011). The proportion of information accrued was only 0.12% of the DARIS, and so the trial sequential monitoring boundaries were not drawn (Figure 4). The cumulative Z-curve does not cross the conventional statistical boundaries.

Figure 4.

Trial sequential analysis of mortality
The diversity-adjusted required information size (DARIS) was calculated to 352,564 participants, based on the proportion of participants in the control group with the outcome of 0.2%, for a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accrual of 434 participants in the eight trials, only 0.12% of the DARIS has been reached. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). 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 (dotted red line) were crossed by the cumulative Z-curve.

Serious adverse events

Serious adverse events were reported in seven trials (Wallace 1997; Dexter 1999; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). No significant difference was noted in the proportions of participants with serious adverse events between the low pressure group (1/179; 0.6%) and the standard pressure group (0/215; 0%) (RR 3.00, 95% CI 0.14 to 65.90) (Analysis 1.1). As only serious adverse events were reported in only one trial, the issue of fixed-effect model versus random-effects model does not arise. As no serious adverse events were reported in the control group, we used the overall proportions in both groups as the control group proportion for performing trial sequential analysis. The proportion of information accrued was only 0.14% of the DARIS, and so the trial sequential monitoring boundaries were not drawn (Figure 5). The cumulative Z-curve does not cross the conventional statistical boundaries.

Figure 5.

Trial sequential analysis of serious adverse events
The diversity-adjusted required information size (DARIS) was calculated to 281,924 participants, based on the proportion of participants in the control group with the outcome of 0.25%, for a relative risk reduction of 20%, an alpha of 5%, a beta of 20% and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accrual of 394 participants in the seven trials, only 0.14% 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 (dotted red line) were crossed by the cumulative Z-curve.

Quality of life

Quality of life was not reported in any of the trials.

Conversion to open cholecystectomy

Conversion to open cholecystectomy was reported in 10 trials (Dexter 1999; Barczynski 2003; Perrakis 2003; Sefr 2003; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Sandhu 2009; Celik 2010). No significant difference in the conversion to open cholecystectomy was observed between the low pressure group (2/269; 0.7%) and the standard pressure group (2/287; 0.7%) (RR 1.18, 95% CI 0.29 to 4.72) (Analysis 1.2). The trial sequential analysis revealed that the proportion of information accrued was only 0.55% of the DARIS, and so the trial sequential monitoring boundaries were not drawn (Figure 6). The cumulative Z-curve does not cross the conventional statistical boundaries.

Figure 6.

Trial sequential analysis of conversion to open cholecystectomy
The diversity-adjusted required information size (DARIS) was calculated to 100,279 participants, based on the proportion of participants in the control group with the outcome of 0.70%, for a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z-curve (blue line). After accrual of 556 participants in the 10 trials, only 0.55% 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 (dotted red line) were crossed by the cumulative Z-curve.

Hospital stay

None of the trials reported the proportion discharged as day-procedure laparoscopic cholecystectomy. Length of hospital stay was reported in five trials (Unbehaum 1995; Wallace 1997; Barczynski 2003; Joshipura 2009; Sandhu 2009). Hospital stay was statistically shorter in the low pressure group than in the standard pressure group by the fixed-effect model (MD -0.27 days, 95% CI -0.36 to -0.17) (Analysis 1.3). This difference was not clinically significant. No significant difference was noted between the groups using the random-effects model (MD -0.30 days, 95% CI -0.63 to 0.02). No imputation of mean or standard deviation was performed, and so the sensitivity analysis was not performed. The trial sequential analysis suggested that it is unlikely that future trials will demonstrate any significant difference in length of hospital stay between low pressure groups and standard pressure groups as the cumulative Z-curve has crossed the DARIS but does not cross the conventional statistical boundaries (Figure 7).

Figure 7.

Trial sequential analysis of hospital stay
The diversity-adjusted required information size (DARIS) was 183 participants based on a minimal relevant difference (MIRD) of one day, a variance (VAR) of 0.47, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 91.83%. Neither the conventional statistical boundaries (dotted red line) nor the trial sequential monitoring boundaries (red line) are crossed by the cumulative Z-curve (blue line), although the DARIS has been reached. The findings are consistent with no significant difference in length of hospital stay between low pressure and standard pressure pneumoperitoneum with low risk of random errors.

Return to normal activity

None of the trials reported this outcome.

Return to work

None of the trials reported this outcome.

Operating time

Operating time was reported in 19 trials (Pier 1994; Wallace 1997; Dexter 1999; Barczynski 2003; Perrakis 2003; Polat 2003; Sefr 2003; Basgul 2004; Celik 2004; Hasukic 2005; Koc 2005; Chok 2006; Ibraheim 2006; Joshipura 2009; Kanwer 2009; Sandhu 2009; Torres 2009; Celik 2010; Topal 2011). Operating time was about two minutes longer in the low pressure group than in the standard pressure group (MD 1.51 minutes, 95% CI 0.07 to 2.94) (Analysis 1.4). No change in results was noted when the random-effects model was used. The mean or the standard deviation or both were imputed in five trials (Wallace 1997; Dexter 1999; Perrakis 2003; Torres 2009; Celik 2010). Excluding these trials from the analysis did not alter the results. The trial sequential analysis revealed that the DARIS has been crossed. The conventional statistical boundaries were crossed by a cumulative Z-curve favouring standard pressure pneumoperitoneum. Findings were consistent with low pressure pneumoperitoneum resulting in longer operating time compared with standard pressure pneumoperitoneum with low risk of random errors (Figure 8).

Figure 8.

Trial sequential analysis of operating time
The diversity-adjusted required information size (DARIS) was 37 participants based on a minimal relevant difference (MIRD) of 15 minutes, a variance (VAR) of 258.34, an alpha (a) of 5%, a beta (b) of 20%, and a diversity (D2) of 0%. The conventional statistical boundaries (dotted red line) are crossed by the cumulative Z-curve (blue line) after the fourth trial. The trial sequential monitoring boundary (red line) is crossed by the cumulative Z-curve after the second trial. The findings are consistent with low pressure pneumoperitoneum associated with a longer operating time than standard pressure pneumoperitoneum with low risk of random errors.

Successful completion of low pressure laparoscopic cholecystectomy

Successful completion of low pressure laparoscopic cholecystectomy was reported in nine trials (Wallace 1997; Barczynski 2003; Perrakis 2003; Chok 2006; Ibraheim 2006; Joshipura 2009; Kanwer 2009; Sandhu 2009; Celik 2010). The median proportion of successful completion of low pressure laparoscopic cholecystectomy was 90%, with a range between 71.4% and 100%.

Subgroup analysis

Only one of the trials was at low risk of bias (Sandhu 2009). So this subgroup analysis was not performed. The remaining subgroup analyses were not performed because of the few trials included in the subgroups for the primary outcomes.

Reporting bias

Reporting bias could be assessed for conversion to open cholecystectomy and operating time. Visual inspection of the funnel plot and Egger's linear regression method of assessment of the funnel plot revealed no evidence of reporting bias (conversion to open cholecystectomy: P value 0.50; operating time: P value 0.07).

Discussion

Summary of main results

This review compared the safety and effectiveness of low pressure pneumoperitoneum versus standard pressure pneumoperitoneum. No mortality was noted in either group in the eight trials that reported mortality (Wallace 1997; Dexter 1999; Perrakis 2003; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). Serious adverse events were reported in seven trials only (Wallace 1997; Dexter 1999; Hasukic 2005; Chok 2006; Karagulle 2008; Sandhu 2009; Celik 2010). No statistically significant difference was seen in the proportion of participants with serious adverse events between the low pressure group (1/179; 0.6%) and the standard pressure group (0/215; 0%). Conversion to open cholecystectomy was reported in 10 trials (Dexter 1999; Barczynski 2003; Perrakis 2003; Sefr 2003; Chok 2006; Ibraheim 2006; Karagulle 2008; Joshipura 2009; Sandhu 2009; Celik 2010). In many of these trials, the reason for conversion and the outcomes of participants who underwent conversion to open cholecystectomy were not reported (Barczynski 2003; Perrakis 2003; Sefr 2003; Ibraheim 2006; Joshipura 2009). A small proportion of participants who underwent conversion to open cholecystectomy (and for whom the reason for conversion or the outcome was not available) may have been converted to open cholecystectomy because of procedure-related injuries such as injuries to the viscera or bile duct. This possibility has not been ruled out in this review. In addition, the confidence intervals of serious adverse events are wide, and significant increases or decreases in complications due to low pressure pneumoperitoneum cannot be ruled out. Hence, no conclusion can be made about the safety of low pressure pneumoperitoneum.

The potential benefit of using low pressure pneumoperitoneum is reduced cardiopulmonary complications. However, even in trials that reported morbidity, no cardiopulmonary complications were described. This is likely to be due to inclusion of only low anaesthetic risk participants in the trials, as well as the low overall incidence of cardiopulmonary complications (0.5% in a case series of 400 patients, 70% of whom were low anaesthetic risk patients) (Dexter 1997). Information on whether low pressure could be beneficial in patients with cardiopulmonary disease is not available from the trials included in this review and requires investigation in further trials.

Operating time was two minutes longer in the low pressure group, and this finding is not clinically significant. Hospital stay was not different between the two groups using the random-effects model. Although the fixed-effect model showed significantly shorter hospital stay in the low pressure group than in the standard pressure group, this difference is not clinically significant.

Thus no clinical benefit of low pressure pneumoperitoneum is apparent, and information about its safety is lacking.

Overall completeness and applicability of evidence

Most of the trials included low anaesthetic risk participants undergoing elective laparoscopic cholecystectomy. So the findings of this review are applicable only to low anaesthetic risk patients undergoing elective laparoscopic cholecystectomy.

Quality of the evidence

Only one of the included trials was assessed as having low risk of bias, although it is possible to perform trials with low risk of bias for this comparison as compared with many other comparisons in surgery for which it is not possible to perform trials with low risk of bias (Sandhu 2009). The quality of the evidence is low or very low, as shown in Summary of findings for the main comparison. However, this is the best quality evidence available on this topic.

Potential biases in the review process

We performed a thorough search of the literature. However, some trials may not have been reported by the researchers because of the lack of benefit associated with low pressure pneumoperitoneum. However, this would not have affected the conclusions of this review in that we do not recommend low pressure pneumoperitoneum unless future trials demonstrate clinical benefit.

Agreements and disagreements with other studies or reviews

We agree with the findings of our previous version that the safety of low pressure pneumoperitoneum has not been established (Gurusamy 2009).

Authors' conclusions

Implications for practice

Laparoscopic cholecystectomy can be completed successfully using low pressure in approximately 90% of people undergoing laparoscopic cholecystectomy. However, currently no evidence is available to support the use of low pressure pneumoperitoneum. The safety of low pressure pneumoperitoneum has yet to be established.

Implications for research

Further trials with low risk of bias are required for elective laparoscopic cholecystectomy, laparoscopic cholecystectomy in patients with acute cholecystitis, and laparoscopic cholecystectomy in patients with cardiopulmonary disorders.

Future trials need to be designed according to the SPIRIT guidelines (www.spirit-statement.org/) and conducted and reported in accordance with the CONSORT statement (www.consort-statement.org).

Acknowledgements

To the Cochrane Hepato-Biliary Group for the support provided.

Peer Reviewers: Yogesh Puri, UK; Rutger Schols, The Netherlands.
Contact Editor: Steffano Trastulli, Italy.

K Samraj who identified trials and extracted data for the previous version of this review.

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

Comparison 1. Low pressure versus standard pressure pneumoperitoneum
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Serious adverse events7394Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.14, 65.90]
2 Conversion to open cholecystectomy10556Risk Ratio (M-H, Fixed, 95% CI)1.18 [0.29, 4.72]
3 Hospital stay5415Mean Difference (IV, Random, 95% CI)-0.30 [-0.63, 0.02]
4 Operating time19990Mean Difference (IV, Fixed, 95% CI)1.51 [0.07, 2.94]
Analysis 1.1.

Comparison 1 Low pressure versus standard pressure pneumoperitoneum, Outcome 1 Serious adverse events.

Analysis 1.2.

Comparison 1 Low pressure versus standard pressure pneumoperitoneum, Outcome 2 Conversion to open cholecystectomy.

Analysis 1.3.

Comparison 1 Low pressure versus standard pressure pneumoperitoneum, Outcome 3 Hospital stay.

Analysis 1.4.

Comparison 1 Low pressure versus standard pressure pneumoperitoneum, Outcome 4 Operating time.

Appendices

Appendix 1. Search strategies

DatabasePeriod of SearchSearch Strategy
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Wiley)Issue 1, 2013#1 MeSH descriptor Cholecystectomy, Laparoscopic explode all trees
#2 (laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*) AND cholecystectom*
#3 (#1 OR #2)
#4 MeSH descriptor Pneumoperitoneum, Artificial explode all trees
#5 MeSH descriptor Insufflation explode all trees
#6 MeSH descriptor Abdominal Wall explode all trees
#7 pneumoperitoneum OR insufflation OR "abdominal wall lift" OR gasless
#8 (#4 OR #5 OR #6 OR #7)
#9 (#3 AND #8)
MEDLINE (PubMed)1987 to February 2013(laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*) AND (cholecystectom* OR cholecystectomy, laparoscopic[MeSH]) AND (pneumoperitoneum OR Pneumoperitoneum, Artificial[MeSH] OR insufflation OR insufflation[MeSH] OR "abdominal wall lift" OR Abdominal Wall[MeSH] OR gasless) 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]) AND humans [mh])
EMBASE (Ovid SP)1987 to February 20131 exp CROSSOVER PROCEDURE/
2 exp DOUBLE BLIND PROCEDURE/
3 exp SINGLE BLIND PROCEDURE/
4 exp RANDOMIZED CONTROLLED TRIAL/
5 (((RANDOM* or FACTORIAL* or CROSSOVER* or CROSS) and OVER*) or PLACEBO* or (DOUBL* and BLIND*) or (SINGL* and BLIND*) or ASSIGN* or ALLOCAT* or VOLUNTEER*).af.
6 1 or 2 or 3 or 4 or 5
7 (laparoscop* or coelioscop* or celioscop* or peritoneoscop*).af.
8 "cholecystectom*".af.
9 8 and 7
10 exp Cholecystectomy/
11 exp Laparoscopic Surgery/
12 11 and 10
13 9 or 12
14 (pneumoperitoneum or insufflation or "abdominal wall lift" or gasless).af.
15 exp Pneumoperitoneum/
16 exp Abdominal Wall/
17 16 or 15 or 14
18 6 and 13 and 17
Science Citation Index Expanded (Web of Knowledge)1987 to February 2013#1 TS=(laparoscop* OR coelioscop* OR celioscop* OR peritoneoscop*)
#2 TS=(cholecystectom*)
#3 TS=(pneumoperitoneum OR insufflation OR "abdominal wall lift" OR gasless)
#4 TS=(random* OR blind* OR placebo* OR meta-analysis)
#5 #4 AND #3 AND #2 AND #1

What's new

DateEventDescription
29 March 2013AmendedAuthor list: Kurinchi Selvan Gurusamy, Jessica Vaughan, Brian R Davidson.
29 March 2013New citation required and conclusions have changed

The methods of the review have been revised according to version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

The conclusions now read: "There is currently no evidence to support the use of low pressure pneumoperitoneum. The safety of low pressure pneumoperitoneum has to be established. Further well-designed trials are necessary". The conclusions in the published 2009 version read: "Low pressure pneumoperitoneum appears effective in decreasing pain after laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established".

19 February 2013New search has been performedThe search was updated, and nine new trials were included (Karagulle 2008; Kanwer 2009; Sandhu 2009; Joshipura 2009; Torres 2009; Kandil 2010; Celik 2010; Topal 2011; Eryilmaz 2012).

History

Protocol first published: Issue 1, 2008
Review first published: Issue 2, 2009

DateEventDescription
29 October 2008AmendedConverted to new review format.

Contributions of authors

KS Gurusamy wrote the review, assessed the trials for inclusion, and extracted data on included trials. J Vaughan identified trials and extracted data on included trials for this version. BR Davidson provided advice on improving the review.

Declarations of interest

None known.

Sources of support

Internal sources

  • None, Other.

External sources

  • None, Other.

Differences between protocol and review

Differences between first and second versions

The methods of the review have been revised according to version 5.1.0 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This resulted in a change in outcomes and in risk of bias. Outcomes related to pain scores were excluded from the revised version, as the clinical implication of reduction in pain is not clear. A clinically significant reduction in pain score is likely to result in shorter hospital stay, earlier return to normal activity, and earlier return to work, all of which have been included in the revised version.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Barczynski 2002

MethodsRandomised clinical trial
Participants

Country: Poland.
Number randomly assigned: 20.
Postrandomisation dropouts: zero (0%).

Revised sample size: 20.
Mean age: 46 years.
Females: 11 (55%).

Inclusion criteria:
Laparoscopic cholecystectomy due to uncomplicated symptomatic gallstones.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 10).
Group 2: standard pressure 12 mm Hg (n = 10).
OutcomesNone of the outcomes of interest for this review were reported.
NotesThrough their replies in February 2008, the authors of the trial confirmed that this trial was different from Barczynski 2003. Additional attempts to contact the trial authors in March 2013 were unsuccessful.
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: "... randomised (closed envelope method) to either LP or SP pneumoperitoneum groups..."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Low riskQuote: "This work was supported by the grant BBN-501/KL/456/L from Jagiellonian University College of Medicine."

Barczynski 2003

MethodsRandomised clinical trial.
Participants

Country: Poland.
Number randomly assigned: 148.
Postrandomisation dropouts: zero.

Revised sample size: 148.
Mean age: 48 years.
Females: 129 (87.2%).

Inclusion criteria:
1. Uncomplicated, symptomatic cholelithiasis.
2. ASA I or II.
3. Age > = 18 years.

Exclusion criteria:
1. Pregnancy and lactation.
2. Previous extensive abdominal surgery.
3. Prolonged administration of NSAIDs or other analgesics.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 74).
Group 2: standard pressure 12 mm Hg (n = 74).
OutcomesThe outcomes reported were conversion to open cholecystectomy, quality of life, hospital stay, and operating time.
NotesThrough their replies in February 2008, the authors of the trial confirmed that this trial was different from Barczynski 2003. Additional attempts to contact the trial authors in March 2013 were unsuccessful.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: “The randomization was based on each patient receiving a sealed envelope containing a random number selected from the table assigning the given individual to one of two groups).”
Allocation concealment (selection bias)Low riskQuote: “The randomization was based on each patient receiving a sealed envelope containing a random number selected from the table assigning the given individual to one of two groups).”
Blinding (performance bias and detection bias)
All outcomes
High risk

Quote: “Neither the patients nor the nurses knew the relevant group assignment.”

Comment: Assessor blinding of primary outcomes such as surgical morbidity was not performed, and so the blinding is inadequate in this trial.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Basgul 2004

MethodsRandomised clinical trial.
Participants

Country: Turkey.
Number randomly assigned: 22.
Postrandomisation dropouts: not stated.
Revised sample size: 22.

Mean age: 49 years.
Females: 10 (45.5%).

Inclusion criteria:
1. Undergoing laparoscopic cholecystectomy.
2. Adults.
3. ASA grade I or II.

Exclusion criteria:
1. Endocrine or immune system disorders.
2. Malignant or chronic inflammatory disease.
3. Marked obesity
4. Acute cholecystitis.
5. Kidney or liver disorders.
6. Patients on immunosuppressive treatment.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure10 mm Hg (n = 11).
Group 2: standard pressure 14 to 15 mm Hg (n = 11).
OutcomesThe outcome reported was operating time.
NotesAttempts to contact the trial authors in February 2008 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Celik 2004

MethodsRandomised clinical trial.
Participants

Country: Turkey.
Number randomly assigned: 100.
Postrandomisation dropouts: zero.
Revised sample size: 100.

Mean age: 42 years.
Females: 81 (81%).

Inclusion criteria:
Elective laparoscopic cholecystectomy.

Exclusion criteria:
1. Cholangitis, acute cholecystitis, or pancreatitis.
2. Cardiovascular and renal diseases.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm Hg or 10 mm Hg (n = 40).
Group 2: standard pressure 12 mm Hg or 14 mm Hg or 16 mm Hg (n = 60).
OutcomesThe outcome reported was operating time.
NotesAttempts to contact the trial authors in February 2008 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Celik 2010

MethodsRandomised clinical trial.
ParticipantsCountry: Turkey.
Number randomly assigned: 64.
Postrandomisation dropouts: four (6.3%).
Revised sample size: 60.
Average age: 44 years.
Females: 60 (100%).
Successful completion of low pressure laparoscopic cholecystectomy: 20/23 (87.0%)
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Female patients with cholelithiasis.
Exclusion criteria:
1. American Society of Anesthesiologists physical status grade III or IV.
2. Age younger than 18 years or older than 65 years.
3. Inability to understand the research questionnaire.
4. Having endoscopic retrograde cholangiopancreatography intervention in last 30 days.
5. Undergoing acute cholecystitis attack.
6. Pregnancy.
7. Patients with co-morbidities like hepatic, renal, endocrine, and immunologic diseases, which can cause chronic pain.
8. Patients who had been using opioids or tranquilising medications for longer than one week before the surgery.
9. Patients with history of drug abuse.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm Hg (n = 20).
Group 2: standard pressure 12 mm or 14 mm Hg (n = 40).
OutcomesOutcomes reported were mortality, morbidity, and operating time.
Notes

Attempts to contact the trial authors in March 2013 were unsuccessful.

Reasons for postrandomisation dropouts: conversion to open cholecystectomy (one in standard pressure); pericholecystic adhesions (two in low pressure); and increase in pressure from low pressure group to standard pressure group (the participant who underwent conversion to open cholecystectomy was included for conversion to open cholecystectomy but was excluded from other outcomes).

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "After induction of anesthesia, patients were randomized prospectively into three groups by computer generation."
Allocation concealment (selection bias)Unclear riskComment: This information was not available.
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Unclear riskComment: This information was not available.

Chok 2006

MethodsRandomised clinical trial.
Participants

Country: China.
Number randomly assigned: 40.
Postrandomisation dropouts: zero.
Revised sample size: 40.

Mean age: 47 years.
Females: 24 (60%).

Inclusion criteria:
1. Symptomatic cholelithiasis with or without complications.
2. Elective outpatient cholecystectomy.
3. ASA I or II.
4. Age < 70 years.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 20).
Group 2: standard pressure 12 mm Hg (n = 20).
OutcomesOutcomes reported were mortality, morbidity, conversion to open cholecystectomy, and operating time.
NotesTrial authors provided additional information in February 2008 and March 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "The random sequence is from random number table (author replies)."
Allocation concealment (selection bias)Low riskQuote: "Randomization was performed preoperatively at the pre-anesthetic clinic by drawing consecutive sealed and numbered envelopes by an independent third party (author replies)."
Blinding (performance bias and detection bias)
All outcomes
High risk

Quote: "A preset questionnaire was completed on postoperative days 1 and 3 through telephone by the nursing staff, who were blinded to the randomization results (author replies)."

Comment: Assessor blinding of primary outcomes was not performed, and so the blinding is inadequate in this trial.

Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Low riskQuote: "This study was funded by the Tung Wah Group of Hospitals (TWGHs) Research Fund-Research Project."

Dexter 1999

MethodsRandomised clinical trial.
Participants

Country: United Kingdom.
Number randomly assigned: 23.
Postrandomisation dropouts: three (13%).
Revised sample size: 20.

Mean age: 52 years.
Females: 13 (65%).

Inclusion criteria:
1. Elective laparoscopic cholecystectomy.
2. ASA I or II.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 10).
Group 2: standard pressure 15 mm Hg (n = 10).
OutcomesOutcomes reported were mortality, morbidity, and conversion to open cholecystectomy.
Notes

Postrandomisation dropouts: two in low pressure group because of cross-over; one in standard pressure group because of conversion to open cholecystectomy.

Trial authors provided additional information in February 2008. Additional attempts to contact the trial authors in March 2013 were unsuccessful.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Randomisation was by computer (author replies)."
Allocation concealment (selection bias)Low riskQuote: "The randomisation was drawn when the patient entered the anaesthetic room, by contacting a third person with the envelopes (author replies)."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Three postrandomisation dropouts were reported. These were excluded from the analysis.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Unclear riskComment: This information was not available.

Eryilmaz 2012

MethodsRandomised clinical trial.
ParticipantsCountry: Turkey.
Number randomly assigned: 43.
Postrandomisation dropouts: not stated.
Revised sample size: 43.
Average age: 51 years.
Females: 26 (60.5%).
Successful completion of low-pressure laparoscopic cholecystectomy: not stated.
Intraoperative cholangiogram: not stated.
Inclusion criteria:
ASA physical status I or II patients undergoing elective laparoscopic cholecystectomy.
Exclusion criteria:
1. Patients with liver failure.
2. Coagulopathy.
3. Known allergy to medications.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 20).
Group 2: standard pressure 14 mm Hg (n = 23).
OutcomesNone of the outcomes included in this review were reported in this trial.
NotesAttempts to contact the trial authors in March 2013 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Hasukic 2005

MethodsRandomised clinical trial.
Participants

Country: Bosnia.
Number randomly assigned: 50.
Postrandomisation dropouts: not stated.
Revised sample size: 50.

Mean age: 43 years.
Females: 45 (90%).

Inclusion criteria:
1. Uncomplicated symptomatic cholelithiasis.
2. ASA I or II.
3. Age >= 18 years.
4. No history of previous liver disease.
5. Normal values on preoperative liver function tests.

Exclusion criteria:
1. Concomitant common bile duct exploration.
2. Acute cholecystitis.
3. Pregnancy and lactation.
4. Previous extensive abdominal surgery.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 25).
Group 2: standard pressure 14 mm Hg (n = 25).
OutcomesOutcomes reported were mortality, morbidity, and operating time.
NotesTrial authors provided additional information in February 2008 and April 2013.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComment: "The randomization was based on sealed envelopes containing random numbers selected from the table (author replies)."
Allocation concealment (selection bias)Low riskQuote: "Every patient admitted to the hospital for cholecystectomy who met the inclusive criteria for the study received a sealed envelope with the written method: standard pressure or low pressure. Stated envelopes were opened immediately before laparoscopic cholecystectomy" (author replies).
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Low risk

Quote: "The clinical study was performed at the clinic without financial support outside of the University Clinical Center."

.

Ibraheim 2006

MethodsRandomised clinical trial.
Participants

Country: Saudi Arabia.
Number randomly assigned: 20.
Postrandomisation dropouts: not stated.
Revised sample size: 20.

Mean age: 49 years.
Females: 14 (70%).

Inclusion criteria:
Elective laparoscopic cholecystectomy.

Exclusion criteria:
1. Respiratory or coronary artery disease.
2. Coagulopathy.
3. Body mass index > 30.
4. Previous gastric surgery.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 6 to 8 mm Hg (n = 10).
Group 2: standard pressure 12 to 14 mm Hg (n = 10).
OutcomesOutcomes reported were conversion to open cholecystectomy and operating time.
NotesAttempts to contact the trial authors in February 2008 were unsuccessful.
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: "They were randomly allocated using a sealed envelope method to one of two study groups..."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Joshipura 2009

MethodsRandomised clinical trial.
ParticipantsCountry: India.
Number randomly assigned: 26.
Postrandomisation dropouts: zero (0%).
Revised sample size: 26.
Average age: 57 years.
Females: 11 (42.3%).
Successful completion of low pressure laparoscopic cholecystectomy: 10/14 (71.4%).
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Patients with uncomplicated symptomatic gall stones were included in the study.
Exclusion criteria:
1. Patients with complicated gall stone disease like pyocele or gangrene of gall bladder, acute gall stone pancreatitis, and gall stone with common bile duct stone.
2. History of cholangitis.
3. Gall bladder carcinoma.
4. Patients with previous history of upper abdominal surgery.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm Hg (trocar insertion at 12 mm Hg) (n = 14).
Group 2: standard pressure 12 mm Hg (n = 12).
OutcomesOutcomes reported were operating time and hospital stay.
NotesAttempts to contact the trial authors in March 2013 were unsuccessful.
Reasons for postrandomisation dropouts: not stated.
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: "Patients were randomized to either HPLC or LPLC group just before starting surgery by a picking up closed envelope randomly by a nurse not involved in this study."
Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Patients were blinded about their group to avoid bias in postoperative period whereas considering the visual analog scale for pain. Operating surgeons were also blinded about set pressure, as they had to scale at the end of surgery about the vision, space for dissection, and surgical space while doing the suction. However, it was allowed to ‘‘increase the pressure’’ without un-blinding if surgeon found difficulty in getting adequate space for dissection but it was recorded as a conversion."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Kandil 2010

MethodsRandomised clinical trial.
ParticipantsCountry: Egypt.
Number randomly assigned: 116.
Postrandomisation dropouts: 16 (13.8%).
Revised sample size: 100.
Average age: 42 years.
Females: 62 (62%).
Successful completion of low pressure laparoscopic cholecystectomy: not stated clearly.
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Patients who were treated for gall bladder stone (either elective or having acute cholecystitis).
Exclusion criteria:
1. Age > 80 years.
2. History of upper laparotomy.
3. Hemorrhagic tendency due to cirrhosis.
4. American Society of Anesthesiology grade of III or higher.
5. Patients refused to give informed consent.
6. Patients in whom the laparoscopic procedure was converted to open cholecystectomy or from low to high pressure. 
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm or 10 mm Hg (n = 50).
Group 2: standard pressure 12 mm Hg or 14 mm Hg (n = 50).
OutcomesNone of the outcomes included in this review were reported in this trial.
NotesAttempts to contact the trial authors in March 2013 were unsuccessful.
Reasons for postrandomisation dropouts: The laparoscopic procedure was converted to open cholecystectomy (two), refused to give informed consent (one), history of upper laparotomy (three), Grade III by American Society of Anesthesiology (two), the laparoscopic procedure was converted from low to higher pneumoperitoneum pressure (four), and participants had cirrhotic liver (four).
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Kanwer 2009

MethodsRandomised clinical trial.
ParticipantsCountry: India.
Number randomly assigned: 60.
Postrandomisation dropouts: five (8.3%).
Revised sample size: 55.
Average age: not stated.
Females: not stated.
Successful completion of low pressure laparoscopic cholecystectomy: 27/30 (90%).
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Patients with uncomplicated symptomatic gall stone disease tagged for laparoscopic cholecystectomy.
Exclusion criteria:
Patients with acute cholecystitis and with complications of gall stone disease like gall bladder perforation, empyema, and common bile duct stone. 
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 27).
Group 2: standard pressure 14 mm Hg (n = 28).
OutcomesOutcomes reported were mortality and operating time.
NotesTrial authors provided additional information in March 2013.
Reasons for postrandomisation dropouts: conversion to open cholecystectomy (two in standard pressure group) and conversion to standard pressure (from low pressure group).
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Patients were randomised into two groups using a random number table."
Allocation concealment (selection bias)Unclear riskQuote: "Sealed envelope method (author replies)."
Comment: Further details were not available.
Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "No blinding (author replies)."
Comment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as morbidity were not reported.
For-profit bias?Low riskQuote: "Institute funded (author replies)."

Karagulle 2008

MethodsRandomised clinical trial.
ParticipantsCountry: Turkey.
Number randomly assigned: 45.
Postrandomisation dropouts: one (2.2%).
Revised sample size: 44.
Average age: 47 years.
Females: 37 (84.1%).
Successful completion of low pressure laparoscopic cholecystectomy: not stated.
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Patients with ASA I or II with symptomatic cholelithiasis.
Exclusion criteria:
1. Patients who had acute cholecystitis.
2. Previous upper abdominal surgery.
3. Systemic or connective tissue diseases.
4. Using tobacco and/or had lung diseases (obstructive, restrictive, or both).
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm Hg (n = 14).
Group 2: standard pressure 12 mm Hg or 15 mm Hg (n = 30).
OutcomesOutcomes reported were mortality, morbidity, and conversion to open cholecystectomy.
NotesAttempts to contact the trial authors in March 2013 were unsuccessful.
Reasons for postrandomisation dropouts: conversion to open cholecystectomy (one in low pressure group). This participant was included for conversion to open cholecystectomy but was excluded from other outcomes.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Unclear riskComment: This information was not available.

Koc 2005

MethodsRandomised clinical trial.
Participants

Country: Turkey.
Number randomly assigned: 53.
Postrandomisation dropouts: three (5.7%).
Revised sample size: 50.

Mean age: 47 years.
Females: 41 (82%).
Inclusion criteria:

1. Elective laparoscopic cholecystectomy for symptomatic gall stones.
2. ASA I to III.
Exclusion criteria:

1. Acute cholecystitis or acute pancreatitis.
2. Common bile duct exploration or another surgical procedure.
3. Treatment with drugs that influence neurohormonal parameters.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 25).
Group 2: standard pressure 15 mm Hg (n = 25).
OutcomesThe outcome reported was operating time.
Notes

Reason for postrandomisation dropout: conversion to open cholecystectomy
(group not stated).

Attempts to contact the trial authors in February 2008 were unsuccessful.

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: "...patients were randomized to low- or high-pressure pneumoperitoneum groups by closed envelope method in the operating room prior to surgery."
Blinding (performance bias and detection bias)
All outcomes
High risk

Quote: "...a short-form MGQ (SF-MGQ) was obtained from all patients by a research assistant who was blind to the group allocation of the patients."

Comment: Assessor blinding of primary outcomes was not performed, and so the blinding is inadequate in this trial.

Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Three postrandomisation dropouts were due to conversion to open cholecystectomy.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Perrakis 2003

MethodsRandomised clinical trial.
Participants

Country: Greece.
Number randomly assigned: 40.
Postrandomisation dropouts: zero.
Revised sample size: 40.

Mean age: 57 years.
Females: 30 (75%).

Inclusion criteria:
1. Elective laparoscopic cholecystectomy.
2. ASA I or II.

Exclusion criteria:
1. Regular analgesic medication.
2. Extensive upper abdominal incision.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 mm Hg (n = 20).
Group 2: standard pressure 15 mm Hg (n = 20).
OutcomesOutcomes reported were mortality, conversion to open cholecystectomy, and operating time.
NotesAttempts to contact the trial authors in February 2008 were unsuccessful.
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: "Randomization was performed preoperatively using envelopes with random numbers."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Pier 1994

MethodsRandomised clinical trial.
Participants

Country: Germany.
Number randomly assigned (included for this review): 22.
Postrandomisation dropouts: not stated.
Revised sample size: 22.

Mean age: not stated.
Females: not stated.

Inclusion criteria:
1. Elective laparoscopic cholecystectomy.
2. Age > 18 years.
3. ASA I or II.

Exclusion criteria:
Conversion to open cholecystectomy.

Interventions

Participants were randomly assigned to different pressures of pneumoperitoneum.

Group 1: low pressure < 9 mm Hg (n = 12).
Group 2: standard pressure 14 to 16 mm Hg (n = 10).
Two other groups (high pressure > 18 mm Hg and standard pressure 14 to 16 mm Hg with Argon gas) were excluded from this review.

OutcomesThe outcome reported was operating time.
NotesAttempts to contact the trial authors in February 2008 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Polat 2003

MethodsRandomised clinical trial.
Participants

Country: Turkey.
Number randomly assigned: 24.
Postrandomisation dropouts: not stated.
Revised sample size: 24.

Mean age: 48 years.
Females: 11 (45.8%).

Inclusion criteria:
Laparoscopic cholecystectomy for symptomatic cholelithiasis.

Exclusion criteria:
Patients with metabolic, endocrine, hepatic, or renal disease.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 12).
Group 2: standard pressure 15 mm Hg (n = 12).
OutcomesThe outcome reported was operating time.
NotesAttempts to contact the study authors in February 2008 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Sandhu 2009

MethodsRandomised clinical trial.
ParticipantsCountry: Thailand.
Number randomly assigned: 140.
Postrandomisation dropouts: zero (0%).
Revised sample size: 140.
Average age: 55 years.
Females: 111 (79.3%).
Successful completion of low pressure laparoscopic cholecystectomy: 68/70 (97.1%).
Intraoperative cholangiogram: not stated.
Inclusion criteria:
1. Adults with American Society of Anesthesiologists (ASA) physical status grade I or II.
2. Undergoing elective laparoscopic cholecystectomy for benign gall bladder.
Exclusion criteria:
1. Patients younger than 18 years.
2. Those who refused to give consent.
3. Inability to understand the research questionnaire.
4. Pregnancy.
5. Patients who were found to require additional procedures at surgery.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7 mm Hg (n = 70).
Group 2: standard pressure 14 mm Hg (n = 70).
OutcomesOutcomes reported were mortality, morbidity, conversion to open cholecystectomy, operating time, and hospital stay.
NotesStudy authors provided additional information in March 2013.
Reasons for postrandomisation dropouts: not stated.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "After induction of anesthesia, patients were randomized prospectively by computer generation."
Allocation concealment (selection bias)Low riskQuote: "Put a coded card (label pressure 7 mmHg or 14 mmHg as prospectively randomized by computer generation) in an opaque, sealed, and sequentially numbered envelope. Then open the envelope before surgery by surgeon (author replies)."
Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "both the patients and healthcare providers were blinded. The outcome assessors were blinded as well (author replies)."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Low riskQuote: "This study was not supported by any funding sources. We used our own budget (author replies)."

Sefr 2003

MethodsRandomised clinical trial.
Participants

Country: Czech Republic.
Number randomly assigned: 30.
Postrandomisation dropouts: zero.
Revised sample size: 30.

Mean age: 54 years.
Females: 23 (76.7%).

Inclusion criteria:
1. Laparoscopic cholecystectomy for uncomplicated symptomatic gall stone disease.
2. ASA I or II.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 15).
Group 2: standard pressure 15 mm Hg (n = 15).
OutcomesOutcomes reported were conversion to open cholecystectomy and operating time.
NotesThe study authors provided additional information in February 2008. Additional attempts to contact the study authors in March 2013 were unsuccessful.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "Randomization was achieved by computerized random-number generation."
Allocation concealment (selection bias)Low riskQuote: "the allocation was done by a third party - university dept. of statistics (author replies)."
Blinding (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Topal 2011

MethodsRandomised clinical trial.
ParticipantsCountry: Turkey.
Number randomly assigned: 60.
Postrandomisation dropouts: not stated.
Revised sample size: 60.
Average age: 42 years.
Females: 13 (21.7%).
Successful completion of low pressure laparoscopic cholecystectomy: not stated.
Intraoperative cholangiogram: not stated.
Inclusion criteria:
1. Patients who underwent laparoscopic surgery for non-complicated cholelithiasis.
Exclusion criteria:
1. Patients with preexisting coagulation derangement.
2. Acute cholecystitis, cholangitis, or other acute inflammation.
3. Current or recent (six months) acute pancreatitis.
4. Haematological disorders.
5. Anticoagulant treatment.
6. Current or recent (six months) thromboembolic disorders.
7. Renal, hepatic, rheumatic, or vascular disease.
8. Recent (six months) surgery.
9. Current or recent (three years) malignancy.
10. Pregnancy.
11. Positive family history for coagulation disorders.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 10 mm Hg (n = 20).
Group 2: standard pressure 13 mm or 16 mm Hg (n = 40).
OutcomesThe outcome reported was operating time.
NotesAttempts to contact the study authors in March 2013 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Torres 2009

MethodsRandomised clinical trial.
ParticipantsCountry: Poland.
Number randomly assigned: 40.
Postrandomisation dropouts: not stated.
Revised sample size: 40.
Average age: 49 years.
Females: 28 (70%).
Successful completion of low pressure laparoscopic cholecystectomy: not stated.
Intraoperative cholangiogram: not stated.
Inclusion criteria:
Patients with cholelithiasis and indications for surgical treatment.
Exclusion criteria:
1. No symptoms of acute cholecystitis.
2. Diabetes.
3. Body mass index.
4. Above 36 kg/m2.
5. Autoimmunological diseases.
InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 6 to 8 mm Hg (n = 20).
Group 2: standard pressure 12 to 14 mm Hg (n = 20).
OutcomesThe outcome reported was operating time.
NotesAttempts to contact the trial authors in March 2013 were unsuccessful.
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 (performance bias and detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: This information was not available.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Unbehaum 1995

MethodsRandomised clinical trial.
Participants

Country: Germany.
Number randomly assigned: 71.
Postrandomisation dropouts: 10 (14.1%).
Revised sample size: 61.

Mean age: 47 years.
Females: 44 (72.1%).

Inclusion criteria:
1. Elective laparoscopic cholecystectomy.
2. Symptomatic gall stones.

Exclusion criteria:
1. Conversion to open cholecystectomy.
2. Requirement for other procedures.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 8 to 10 mm Hg (n = 30).
Group 2: standard pressure 14 to 16 mm Hg (n = 31).
OutcomesThe outcome reported was hospital stay.
Notes

Reason for postrandomisation dropouts was not stated.

We were unable to contact the trial authors in December 2008.

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 (performance bias and detection bias)
All outcomes
Unclear riskQuote: "Die Vorlage der Analog skalzt erfolgte im Blindversuch, das heißt durch eine Person, der nicht bekannt war, welcher der beiden Versuchsgrttppen der Patient zugeordnet worden war" (Translation: pain scores were recorded by a person who was not aware of patient groups).
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: Postrandomisation dropouts were reported.
Selective reporting (reporting bias)High riskComment: Important outcomes such as mortality and morbidity were not reported.
For-profit bias?Unclear riskComment: This information was not available.

Wallace 1997

MethodsRandomised clinical trial.
Participants

Country: United Kingdom.
Number randomly assigned: 40.
Postrandomisation dropouts: zero.
Revised sample size: 40.

Mean age: 58 years.
Females: 30 (75%).

Inclusion criteria:
Laparoscopic cholecystectomy for uncomplicated symptomatic gall stone disease.

InterventionsParticipants were randomly assigned to different pressures of pneumoperitoneum.
Group 1: low pressure 7.5 mm Hg (n = 20).
Group 2: standard pressure 15 mm Hg (n = 20).
OutcomesOutcomes reported were mortality, morbidity, hospital stay, and operating time.
NotesAttempts to contact the study authors in February 2008 were unsuccessful.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComment: "Randomization was by computerized random-number generation."
Allocation concealment (selection bias)Unclear riskComment: This information was not available.
Blinding (performance bias and detection bias)
All outcomes
Low riskComment: "the patient, investigator and senior registrar who discharged the patients were blind to the operating insufflation pressure."
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: No postrandomisation dropouts were reported.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported.
For-profit bias?Unclear riskComment: This information was not available.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Barczynski 2004Study of effect of saline washout during low pressure laparoscopic cholecystectomy.
Beqiri 2012Neither the number of ports nor the size of the ports was reported in this trial.
Brokelman 2006The size of the ports was not stated.
Esmat 2006Quasi-randomised trial (systematic randomisation).
Giraudo 2001Neither the number of ports nor the size of the ports was reported in this trial.
Morino 1998Neither the number of ports nor the size of the ports was reported in this trial.
Parikh 2009Not a randomised clinical trial.
Sandoval-Jimenez 2009The size of ports in the control group was not stated.
Sarli 2000Quasi-randomised trial (randomisation by drawing cards labelled A and B).
Tou 2004Comment on an included trial (Sefr 2003).
Yasir 2012Neither the number of ports nor the size of the ports was reported in this trial.

Ancillary