Abstract
Background
This is the second update of a Cochrane Review first published in 2013 and last updated in 2017.
Laparoscopic surgery is now widely performed to treat various abdominal diseases. Currently, carbon dioxide is the most frequently used gas for insufflation of the abdominal cavity (pneumoperitoneum). Although carbon dioxide meets most of the requirements for pneumoperitoneum, the absorption of carbon dioxide may be associated with adverse events. Therefore, other gases have been introduced as alternatives to carbon dioxide for establishing pneumoperitoneum.
Objectives
To assess the safety, benefits, and harms of different gases (e.g. carbon dioxide, helium, argon, nitrogen, nitrous oxide, and room air) used for establishing pneumoperitoneum in participants undergoing laparoscopic abdominal or gynaecological pelvic surgery.
Search methods
We searched CENTRAL, Ovid MEDLINE, Ovid Embase, four other databases, and three trials registers on 15 October 2021 together with reference checking, citation searching, and contact with study authors to identify additional studies.
Selection criteria
We included randomised controlled trials (RCTs) comparing different gases for establishing pneumoperitoneum in participants (irrespective of age, sex, or race) undergoing laparoscopic abdominal or gynaecological pelvic surgery under general anaesthesia.
Data collection and analysis
We used standard methodological procedures expected by Cochrane.
Main results
We included 10 RCTs, randomising 583 participants, comparing different gases for establishing pneumoperitoneum: nitrous oxide (four trials), helium (five trials), or room air (one trial) was compared to carbon dioxide. All the RCTs were single‐centre studies. Four RCTs were conducted in the USA; two in Australia; one in China; one in Finland; one in Iran; and one in the Netherlands. The mean age of the participants ranged from 27.6 years to 49.0 years.
Four trials randomised participants to nitrous oxide pneumoperitoneum (132 participants) or carbon dioxide pneumoperitoneum (128 participants). None of the trials was at low risk of bias. The evidence is very uncertain about the effects of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto odds ratio (OR) 2.62, 95% CI 0.78 to 8.85; 3 studies, 204 participants; very low‐certainty evidence), or surgical morbidity (Peto OR 1.01, 95% CI 0.14 to 7.31; 3 studies, 207 participants; very low‐certainty evidence). There were no serious adverse events related to either nitrous oxide or carbon dioxide pneumoperitoneum (4 studies, 260 participants; very low‐certainty evidence).
Four trials randomised participants to helium pneumoperitoneum (69 participants) or carbon dioxide pneumoperitoneum (75 participants) and one trial involving 33 participants did not state the number of participants in each group. None of the trials was at low risk of bias. The evidence is very uncertain about the effects of helium pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto OR 1.66, 95% CI 0.28 to 9.72; 3 studies, 128 participants; very low‐certainty evidence), or surgical morbidity (5 studies, 177 participants; very low‐certainty evidence). There were three serious adverse events (subcutaneous emphysema) related to helium pneumoperitoneum (3 studies, 128 participants; very low‐certainty evidence).
One trial randomised participants to room air pneumoperitoneum (70 participants) or carbon dioxide pneumoperitoneum (76 participants). The trial was at high risk of bias. There were no cardiopulmonary complications, serious adverse events, or deaths observed related to either room air or carbon dioxide pneumoperitoneum.
Authors' conclusions
The evidence is very uncertain about the effects of nitrous oxide, helium, and room air pneumoperitoneum compared to carbon dioxide pneumoperitoneum on any of the primary outcomes, including cardiopulmonary complications, surgical morbidity, and serious adverse events. The safety of nitrous oxide, helium, and room air pneumoperitoneum has yet to be established, especially in people with high anaesthetic risk.
Plain language summary
Different gases for insufflation of the abdominal cavity during keyhole abdominal surgery
Review question
What are the benefits and harms of various gases for insufflation (inflation with gas) of the abdominal (tummy) cavity to allow easier access to organs during laparoscopic (key‐hole) abdominal surgery?
Background
Laparoscopic surgery is now widely performed to treat various abdominal diseases. An ideal gas for insufflation of the abdominal cavity, increasing working, and viewing space, should be cheap, colourless, not flammable, inexplosive, easily removed by the body, and completely non‐toxic to participants. Currently, carbon dioxide is the most frequently used gas for this purpose. However, use of carbon dioxide may cause heart or lung complications. So, other gases have been suggested as alternatives to carbon dioxide.
Study characteristics
We searched for all relevant studies up to October 2021.
We identified 10 clinical trials with 583 participants, of which three trials (260 participants) compared nitrous oxide (laughing gas) with carbon dioxide, five trials (177 participants) compared helium with carbon dioxide, and one trial (146 participants) compared room air with carbon dioxide. Studies were conducted in the USA, Australia, China, Finland, Iran, and the Netherlands. The mean age of the participants in the trials ranged from 19 to 62 years.
Study funding sources
Two of 10 included studies were sponsored by non‐commercial grants. The other eight studies did not report funding sources.
Key results
We do not know whether nitrous oxide, helium, and room air are superior, equivalent, or inferior to carbon dioxide in the number of people with heart or lung complications, surgical complications, or serious unwanted events.
Because of the few participants included in the review, the safety of using nitrous oxide, helium, or room air is unknown.
Quality of the evidence
Overall, the quality of the evidence for the results is very low. Thus, future well‐designed trials examining complications, harms, quality of life, and pain are urgently needed.
Summary of findings
Background
This is the second update of a Cochrane Review first published in 2013 (Cheng 2013) and last updated in 2017 (Yu 2017).
Description of the condition
Laparoscopic surgery, which was originally developed in the 1910s, is now widely performed by general surgeons to treat various abdominal diseases (Ahmad 2019; Antoniou 2015; Birch 2016; Yu 2017), including diseases of the stomach, gallbladder, liver, pancreas, spleen, intestine, and kidney (Best 2016; Cheng 2012a; Dasari 2011; Deng 2020; Jaschinski 2018; Keus 2006; Kuhry 2008; Li 2018; Nabi 2016; Rao 2013; Riviere 2016; Sanabria 2013; Shin 2019).
The exact number of people undergoing laparoscopic surgery each year worldwide is unknown. Laparoscopic surgery offers various advantages over conventional open surgery, including less postoperative pain, smaller scars, shorter hospital stay, and a quicker recovery (Ahmad 2019; Antoniou 2015; Birch 2016). This method has become the gold standard for some abdominal procedures (e.g. laparoscopic cholecystectomy) (Gurusamy 2014; Keus 2006).
Description of the intervention
The first step in laparoscopic surgery is the establishment of pneumoperitoneum, including entry into the abdominal cavity and then insufflation of air or gas (Ahmad 2019; Birch 2016; Gurusamy 2014; Vilos 2017; Yu 2017), for facilitating adequate working and viewing space. Two common entry techniques are used: an open method (all layers of the abdominal wall are incised, and a trocar is inserted under direct vision), and a closed method (only the skin is incised, and a Veress needle is then inserted blindly into the abdominal cavity) (Ahmad 2019; la Chapelle 2015; Vilos 2017; Yu 2017). After entry into the abdominal cavity, gas is insufflated through the trocar (open method) or the Veress needle (closed method) to separate the abdominal wall from the internal organs (Ahmad 2019; Gurusamy 2014; Vilos 2017; Yu 2017). The pneumoperitoneum provides sufficient operating space to ensure adequate visualisation of camera and manipulation of instruments in the abdominal cavity (Gurusamy 2014; Vilos 2017; Yu 2017).
How the intervention might work
A pneumoperitoneum of 8 mmHg to 20 mmHg is created and pressure is maintained during laparoscopic surgery (Ahmad 2019; Gurusamy 2014; Vilos 2017). The ideal gas for establishing pneumoperitoneum should be cheap, colourless, non‐flammable, non‐explosive, easily excreted, and completely non‐toxic to participants (Peng 2018; Scott 2020). Carbon dioxide, which was introduced to create pneumoperitoneum in 1920s, is the most common gas used for insufflation currently (Cheng 2012b; Vilos 2017). Carbon dioxide is absorbed by the peritoneum, delivered directly to the lungs by the circulation (Eaton 2009; Sidler 2020), and is excreted by the lungs during respiratory exchange (Eaton 2009; Sidler 2020). Although carbon dioxide meets most of the requirements (e.g. low cost, non‐flammable, chemically stabile, and with high diffusion capacity with subsequent rapid absorption and excretion), it is not a perfect gas. The absorption of carbon dioxide causes hypercapnia and acidosis, which has to be avoided by hyperventilation (Gurusamy 2014; Sidler 2020; Vilos 2017). It is associated with various cardiopulmonary (heart and lung) complications, such as tachycardia, cardiac arrhythmias, and pulmonary oedema (Gurusamy 2014; Kabakchiev 2020; Vilos 2017). In addition, it may cause postoperative pain due to peritoneal irritation, and its use is associated with immunological impairment (Neuhaus 2001; Sidler 2020). Elderly people with cardiopulmonary diseases are more likely to experience these adverse events (Chen 2017; Vilos 2017).
Identifying an ideal insufflation gas to replace carbon dioxide has attracted the attention of some researchers in the era of laparoscopic surgery (Roberto Rodrigues Bicalho 2020; Scott 2020; Ypsilantis 2016). Various gases, such as helium, argon, nitrogen, nitrous oxide, and room air, have been introduced as alternatives to carbon dioxide to establish pneumoperitoneum (Rammohan 2011; Roberto Rodrigues Bicalho 2020; Scott 2020; Ypsilantis 2016). However, their uses are controversial. Helium and argon are inert gases that may offer some advantages over carbon dioxide (Roberto Rodrigues Bicalho 2020; Scott 2020). Nevertheless, they are less soluble than carbon dioxide, which might increase the risk of venous gas embolism (Richter 2012; Scott 2020). Nitrous oxide, also known as laughing gas, is a mild anaesthetic (Aboumarzouk 2011). It may reduce postoperative pain theoretically because of its anaesthetic and analgesic properties (Aboumarzouk 2011; Rammohan 2011). However, there have been some cases of explosion using electrocautery during laparoscopy, and the risk of explosion when using nitrous oxide insufflation remains controversial (Rammohan 2011; Scott 2020).
Why it is important to do this review
The use of other gases as alternatives to carbon dioxide for establishing pneumoperitoneum is controversial. Other gases (e.g. helium, argon, nitrogen, nitrous oxide, room air) may potentially offer some advantages over carbon dioxide, but it is also possible that they may have no benefit and may be associated with adverse events (Richter 2012; Scott 2020). Up to now, we have not been able to identify any systematic review or meta‐analysis assessing the different gases used to establish pneumoperitoneum during laparoscopic abdominal surgery. The last version of this review was published in 2017 (Yu 2017). Further randomised controlled trials (RCTs) evaluating different gases for establishing pneumoperitoneum during laparoscopic abdominal surgery have been published since the review, and these studies have now been assessed for inclusion and presented in this update.
Objectives
To assess the safety, benefits, and harms of different gases (e.g. carbon dioxide, helium, argon, nitrogen, nitrous oxide, room air) used for establishing pneumoperitoneum in participants undergoing laparoscopic general abdominal or gynaecological pelvic surgery.
Methods
Criteria for considering studies for this review
Types of studies
We included all RCTs (irrespective of sample size, language, or publication status) comparing different gases used for establishing pneumoperitoneum in participants undergoing laparoscopic abdominal surgery under general anaesthesia. We excluded studies on participants undergoing laparoscopic abdominal surgery under local/regional anaesthesia. We excluded quasi‐randomised trials (in which the allocation was performed on the basis of a pseudo‐random sequence, e.g. odd/even hospital number or date of birth, alternation), cluster randomised trials, and non‐randomised studies.
Types of participants
Participants (irrespective of age, sex, or race) who had undergone laparoscopic abdominal or gynaecological pelvic surgery (irrespective of elective or emergency procedure) under general anaesthesia.
Types of interventions
We included laparoscopic abdominal surgeries performed under standard pressure (12 mmHg to 16 mmHg) pneumoperitoneum with cold gas insufflation (Gurusamy 2014). We planned to assess the following gases for establishing pneumoperitoneum.
Nitrous oxide versus carbon dioxide.
Helium versus carbon dioxide.
Room (ambient) air versus carbon dioxide.
Argon versus carbon dioxide.
Nitrogen versus carbon dioxide.
Any other gas versus carbon dioxide.
Any other gas (except carbon dioxide) versus any other gas (except carbon dioxide).
Types of outcome measures
Primary outcomes
-
Complications (30 days; defined and graded by the Clavien‐Dindo complications classification system) (Clavien 2009).
Cardiopulmonary complications (defined by authors, e.g. arrhythmia, ischaemias, atelectasis, hypoxaemia, pneumothorax, pulmonary oedema).
Procedure‐related general complications (surgical morbidity).
Pneumoperitoneum‐related serious adverse events (30 days; defined by authors, e.g. gas embolism, subcutaneous emphysema, abdominal explosion).
Secondary outcomes
Mortality (30 days postoperatively).
Quality of life (30 days; any validated score).
Pain scores (seven days; graded by visual analogue scale (VAS) score (e.g. 0 cm to 10 cm).
Analgesia requirements (seven days).
Costs (30 days; e.g. costs of gases, hospital costs).
Cardiopulmonary changes (seven days; defined by authors, e.g. heart rate, blood pressure, blood pH, cardiac output, pulmonary compliance, peak airway pressure).
Reporting of the outcomes listed here was not an inclusion criterion for the review.
Search methods for identification of studies
We designed the search strategy with the help of Sys Johnsen (former Cochrane Information Specialist of the Cochrane Colorectal Cancer Group). Searches were conducted in October 2021 irrespective of language, year, or publication status.
Electronic searches
We searched the following electronic databases with no language or date of publication restrictions:
Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; 2021, Issue 10) (Appendix 1);
MEDLINE (Ovid) (1950 to October 2021) (Appendix 2);
Embase (Ovid) (1974 to October 2021) (Appendix 3);
Science Citation Index Expanded (Web of Science) (1970 to October 2021) (Appendix 4);
World Health Organization International Trials Registry Platform search portal (apps.who.int/trialsearch/) (October 2021);
ClinicalTrials.gov (www.clinicaltrials.gov/) (October 2021);
Chinese Biomedical Literature Database (CBM) (1978 to October 2021).
Searching other resources
Furthermore, we searched the following databases in October 2021:
Current Controlled Trials (www.controlled-trials.com/);
Chinese Clinical Trial Register (www.chictr.org/);
EU Clinical Trials Register (www.clinicaltrialsregister.eu/).
We searched the reference lists of identified studies and meeting abstracts via the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) (www.sages.org/), European Association for Endoscopic Surgery (EAES) (www.eaes-eur.org/), and Conference Proceedings Citation Index to explore further relevant clinical trials. We planned to communicate with the authors of included RCTs for further information in the review.
Data collection and analysis
We conducted the systematic review according to guidelines of the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2021) and Methodological Expectations of Cochrane Intervention Reviews (Chandler 2020).
Selection of studies
After completing the searches, we merged the search results using the software package Endnote X7 (reference management software) and removed duplicate records. Two review authors (YX, CY) independently scanned the title and abstract of every record identified by the search for inclusion. We retrieved the full text for further assessment if the inclusion criteria were unclear from the abstract. We included eligible studies irrespective of whether they reported the measured outcome data. We detected duplicate publications by identifying common authors, centres, details of the interventions, numbers of participants, and baseline data (Lefebvre 2021). We excluded papers that did not meet the inclusion criteria and listed the reasons for their exclusion. A third review author (DY) resolved any discrepancy between the two review authors by discussion.
Data extraction and management
We used a standard data collection form to record study characteristics and outcome data, which had been piloted on at least one study in the review. Two review authors (CN, GJ) extracted the following study characteristics from included studies.
Methods: study design, total duration of study and run in, number of study centres and location, study setting, withdrawals, date of study.
Participants: number of participants, mean age, age range, gender, severity of condition, diagnostic criteria, inclusion criteria, exclusion criteria.
Interventions: intervention, comparison.
Outcomes: primary and secondary outcomes specified and collected, time points reported.
Notes: funding for trial, notable conflicts of interest of trial authors.
Two review authors (CN, GJ) independently extracted outcome data from included studies. We resolved disagreements by consensus or by involving a third review author (DY). One review author (CN) copied the data from the data collection form into Review Manager 5 (Review Manager 2020). We double‐checked that the data were entered correctly by comparing the study reports with the data presented in the systematic review. A second review author (GJ) cross‐checked study characteristics for accuracy against the trial reports.
Assessment of risk of bias in included studies
Two review authors (BL, ZL) independently assessed the risk of bias in the included trials, using the Cochrane's RoB 1 for randomised trials (Chapter 8, Higgins 2017). We assessed risk of bias for the following domains:
random sequence generation;
allocation concealment;
blinding of participants and personnel;
blinding of outcome assessment;
incomplete outcome data;
selective reporting bias;
other sources of bias (baseline imbalances).
We judged each domain as low risk, high risk, or unclear risk of bias according to the criteria used in Cochrane's RoB 1 (see Appendix 5) (Chapter 8.5.d, Higgins 2017). We considered a trial at low risk of bias if we assessed the trial at low risk of bias across all domains. Otherwise, we considered trials at unclear risk of bias or at high risk of bias regarding one or more domains at high risk of bias. We resolved any difference in opinion by discussion. In case of disagreements, consensus was reached by discussion with a third review author (CY).
We presented the results of the risk of bias in two figures (a risk of bias graph and a risk of bias summary) generated by Review Manager 5 (Review Manager 2020).
Assessment of bias in conducting the systematic review
We conducted the review according to the published protocol (Lu 2012), and reported any deviations from that protocol in the Differences between protocol and review section of the review.
Measures of treatment effect
We performed the meta‐analysis using Review Manager 5 (Review Manager 2020). For dichotomous outcomes, we calculated risk ratio (RR) with 95% confidence interval (CI) (Deeks 2021). In case of rare events (e.g. mortality, serious adverse events), we calculated the Peto odds ratio (Peto OR) (Deeks 2021). For continuous outcomes, we calculated the mean difference (MD) with 95% CI (Deeks 2021). For continuous outcomes with different measurement scales in different RCTs, we calculated the standardised mean difference (SMD) with 95% CI (Deeks 2021).
Where a trial reported multiple arms, we included only the relevant arms. If two comparisons (e.g. drug A versus placebo and drug B versus placebo) had to be entered into the same meta‐analysis, we halved the control group to avoid double counting.
Unit of analysis issues
The unit of analysis was the individual participant. We excluded cluster RCTs in this review. We identified no relevant cross‐over trials for inclusion in this review. For review updates, we planned to only include data from the first period of treatment (e.g. before crossover).
Dealing with missing data
We contacted the original investigators to request further information in case of missing data. If there was no reply, we used only the available data in the analyses. We also performed 'best‐case'/'worst‐case' scenario analyses to take into account missing data. We did this by changing missing data to having an event ('worst/best‐case' scenario) and then to not having an event ('best/worst‐case' scenario) in a sensitivity analysis to investigate the impact of missing data on meta‐analysis results.
Assessment of heterogeneity
We described heterogeneity in the data using the Chi2 test (Deeks 2021). We considered a P value less than 0.05 to be statistically significant heterogeneity (Deeks 2021). We also used the I2 statistic to measure the quantity of heterogeneity. In case of statistical heterogeneity or clinical heterogeneity (or both), we performed the meta‐analysis but interpreted the result cautiously and planned to investigate potential sources to the heterogeneity.
Assessment of reporting biases
We planned to perform and examine a funnel plot to explore possible publication biases. However, as the number of trials included in each comparison was fewer than 10, we did not produce any funnel plots (Sterne 2017).
Data synthesis
We performed the meta‐analysis using Review Manager 5 (Review Manager 2020). For all analyses, we examined both fixed‐effect and random‐effects models. We reported only the fixed‐effect model results according to the protocol when there was no discrepancy between the two models. In case of discrepancy between the two models, we reported both results.
Subgroup analysis and investigation of heterogeneity
We planned to perform the following subgroup analysis; however, due to too few included trials for each outcome analysis, these were not conducted.
Trials with low risk of bias versus trials with high risk of bias.
The type of operation (laparoscopic surgery of stomach, gallbladder, liver, pancreas, spleen, intestine, kidney, etc.).
People with high anaesthetic risk (e.g. people with cardiopulmonary disease; American Society of Anesthesiologists (ASA) status III or IV) versus people with low anaesthetic risk (e.g. people without cardiopulmonary disease; ASA status I or II).
Sensitivity analysis
We performed the following sensitivity analysis.
Changing between worst/best‐case scenario analysis (the events happened in the experimental group but did not happen in the control group for missing participants) and best/worst‐case scenario analysis (the events happened in the control group but did not happen in the experimental group for missing participants) for missing data.
If the results did not change, they were considered robust.
We also planned to perform the following two sensitivity analyses; however, as all included trials had a high or unclear risk of bias and low numbers of participants, these could not be conducted.
Excluding trials with a high or unclear risk of bias.
Excluding RCTs with small sample sizes.
Trial sequential analysis
We performed trial sequential analysis (TSA) for the primary outcomes if possible. TSA aims to reduce the risk of random error in the setting of repetitive testing of accumulating data, thereby improving the reliability of conclusions (Brok 2008; Wetterslev 2008; Wetterslev 2009). The required information size was calculated on the basis of a risk ratio reduction (RRR) of 20% (Brok 2008; Wetterslev 2008; Wetterslev 2009). The results of the trials were presented as a cumulative Z‐curve. The trial sequential monitoring boundaries were constructed and the diversity‐adjusted required information size calculated with a type 1 error of 5% and a type 2 error of 20% (Brok 2008; Wetterslev 2008; Wetterslev 2009). TSA was not adjusted for heterogeneity because the estimate of the heterogeneity parameter may be unreliable. The results were presented as a graph with the cumulative meta‐analysis results entered. The TSA shows firm evidence of intervention effects (or no intervention effects) if the cumulative Z‐curve crosses the monitoring boundaries; it also shows that additional trials may be needed if the boundaries are not crossed (Brok 2008; Wetterslev 2008; Wetterslev 2009). TSA was performed using Trial Sequential Analysis software (TSA 2011).
Summary of findings and assessment of the certainty of the evidence
We evaluated the certainty of the evidence using the GRADE approach for the following outcomes (Schünemann 2009): cardiopulmonary complications, procedure‐related general complications (surgical morbidity), pneumoperitoneum‐related serious adverse events, mortality, quality of life, pain scores, analgesia requirements, and costs.
We presented the certainty of the evidence in summary of findings tables for the following comparisons.
Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum.
Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum.
Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum.
Judgements about the certainty of the evidence (high, moderate, low, or very low) were justified, documented, and incorporated into the reporting of results for each outcome. The certainty of the evidence was downgraded by one level (serious concern) or two levels (very serious concerns) applying to each of the following five reasons listed: risk of bias; inconsistency (unexplained heterogeneity, inconsistency of results); indirectness (indirect population, intervention, control, outcomes); imprecision (wide CIs, single trials); and publication bias.
Results
Description of studies
See: Characteristics of included studies; Characteristics of excluded studies; and Characteristics of studies awaiting classification tables.
Results of the search
In this updated review, we identified 3644 records through the electronic searches of CENTRAL (797 records), MEDLINE (Ovid) (436 records), Embase (Ovid) (832 records), Science Citation Index Expanded (Web of Science) (1514 records), and Chinese Biomedical Literature Database (CBM) (65 records). Of the 3644 records, 2269 records had already been assessed for the second version of this updated review (2269 records prior to 2016 and 336 duplicates). Of the remaining 1039 records, we excluded 1037 clearly irrelevant records through reading titles and abstracts. We retrieved the remaining two records for further assessment (Asgari 2011; Bergstrom 2015). We included Asgari 2011. Bergstrom 2015 was a conference abstract. We contacted the original investigators for further information necessary for assessment, but received no feedback. Therefore, this study is awaiting classification.
In total, this updated review included 10 RCTs. The study flow diagram is shown in Figure 1.
1.
Study flow diagram.
Included studies
In the last published version of this review from 2017, we included nine RCTs, published between 1993 and 2015 (Aitola 1998; Bongard 1993; Gu 2015; Lipscomb 1993; Naude 1996; Neuhaus 2001; O'Boyle 2002; Sietses 2002; Tsereteli 2002). In this update, we identified one additional RCT (Asgari 2011), giving 10 included RCTs (including 583 participants). Details of the RCTs are shown in the Characteristics of included studies table. Four RCTs compared nitrous oxide pneumoperitoneum with carbon dioxide pneumoperitoneum (Aitola 1998; Asgari 2011; Lipscomb 1993; Tsereteli 2002). Five RCTs compared helium pneumoperitoneum with carbon dioxide pneumoperitoneum (Bongard 1993; Naude 1996; Neuhaus 2001; O'Boyle 2002; Sietses 2002). One RCT compared room (ambient) air pneumoperitoneum with carbon dioxide pneumoperitoneum (Gu 2015). All the RCTs were single‐centre studies. Studies were conducted in the USA (Bongard 1993; Lipscomb 1993; Naude 1996; Tsereteli 2002), Australia (Neuhaus 2001; O'Boyle 2002), China (Gu 2015), Finland (Aitola 1998), Iran (Asgari 2011), and the Netherlands (Sietses 2002). Three RCTs reported the number of surgeons, which was one or two in those studies (Aitola 1998; Lipscomb 1993; Tsereteli 2002). Nine RCTs reported the mean age of the included participants (Aitola 1998; Asgari 2011; Bongard 1993; Gu 2015; Lipscomb 1993; Naude 1996; O'Boyle 2002; Sietses 2002; Tsereteli 2002). The mean age of the participants ranged from 27.6 years to 49.0 years. Eight RCTs reported the sex distribution of the included participants (Aitola 1998; Asgari 2011; Bongard 1993; Gu 2015; Lipscomb 1993; Naude 1996; O'Boyle 2002; Tsereteli 2002). The mean proportion of women varied between 45.5% and 100%. Participants underwent various elective laparoscopic general abdominal or gynaecological pelvic procedures (e.g. cholecystectomy, fundoplication (antireflux surgery), hernia repair, tubal ligation). The outcomes measured were complications, pneumoperitoneum‐related serious adverse events, cardiopulmonary changes, pain scores, hospital costs, and mortality. Two RCTs were funded by non‐commercial grants. The other eight RCTs did not report funding sources. None of the RCTs reported the conflicts of interest.
Excluded studies
We excluded 10 studies. One RCT included participants who underwent laparoscopic pelvic surgery performed by gynaecology surgeons under local anaesthesia (Lipscomb 1994). Two RCTs focused on diagnostic laparoscopy performed under local anaesthesia (Minoli 1982; Sharp 1982). None of the other excluded studies were RCTs (Fernández‐Cruz 1998; McMahon 1994; Neuberger 1996; O'Connor 2017; Ooka 1993; Rammohan 2011; Zheng 2014).
Studies awaiting classification
One study was reported in a conference abstract (Bergstrom 2015). The study did not report further information on the study design, inclusion criteria, or exclusion criteria. We received no reply from the authors on email contact. Therefore, we assessed this study as awaiting classification (see Characteristics of studies awaiting classification table).
Risk of bias in included studies
The risk of bias of the included studies is shown in Figure 2 and Figure 3. None of the included trials was at low risk of bias.
2.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation was at low risk of bias in two trials where participants were randomised using computer‐generated numbers (Bongard 1993; Lipscomb 1993), and unclear risk of bias in eight trials (Aitola 1998; Asgari 2011; Gu 2015; Naude 1996; Neuhaus 2001; O'Boyle 2002; Sietses 2002; Tsereteli 2002). Allocation concealment was at low risk of bias in two trials that used sealed opaque envelopes to conceal the allocations (Neuhaus 2001; O'Boyle 2002), and unclear risk of bias in the remaining eight studies (Aitola 1998; Asgari 2011; Bongard 1993; Gu 2015; Lipscomb 1993; Naude 1996; Sietses 2002; Tsereteli 2002).
Blinding
Blinding of participants and personnel was at low risk of bias in one trial (Asgari 2011), unclear risk of bias in six trials (Aitola 1998; Gu 2015; Lipscomb 1993; Neuhaus 2001; O'Boyle 2002; Sietses 2002), and high risk of bias in three trials (Bongard 1993; Naude 1996; Tsereteli 2002). Blinding of outcome assessment was at low risk of bias in six trials (Aitola 1998; Asgari 2011; Lipscomb 1993; Neuhaus 2001; O'Boyle 2002; Tsereteli 2002), and unclear risk of bias in four trials (Bongard 1993; Gu 2015; Naude 1996; Sietses 2002).
Incomplete outcome data
There were no postrandomisation dropouts in four trials (Asgari 2011; Gu 2015; Lipscomb 1993; Neuhaus 2001). Although there were seven dropouts (6.4%) in two trials, the data were analysed on an intention‐to‐treat basis (Bongard 1993; O'Boyle 2002). There were three dropouts (2.1%) in two trials (Aitola 1998; Tsereteli 2002). The attrition rate may be too low to represent a source of bias in both trials (Aitola 1998; Tsereteli 2002). These eight trials were considered at low risk of attrition bias. There were eight dropouts (16.3%) in the other two trials (Naude 1996; Sietses 2002), but the data were not analysed on an intention‐to‐treat basis. Thus, both trials were at high risk of attrition bias (Naude 1996; Sietses 2002). The reasons for the dropouts were reported in the Characteristics of included studies table.
Selective reporting
None of the studies provided a study protocol. There was a study registration for one trial (Asgari 2011), but this registration was done retrospectively after trial conduct. Selective reporting was at low risk of bias in six trials where the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events) (Aitola 1998; Asgari 2011; Bongard 1993; Neuhaus 2001; O'Boyle 2002; Tsereteli 2002). The other four trials failed to include results for key outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events) that would be expected to have been reported for such studies (Gu 2015; Lipscomb 1993; Naude 1996; Sietses 2002). Thus, we considered these four trials to be high risk of selective reporting (Gu 2015; Lipscomb 1993; Naude 1996; Sietses 2002).
Other potential sources of bias
Three trials presented considerable baseline imbalance, thus we considered these at high risk of bias (Bongard 1993; Lipscomb 1993; Naude 1996).
Effects of interventions
See: Table 1; Table 2; Table 3
Summary of findings 1. Nitrous oxide versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery.
| Nitrous oxide versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery | ||||||
|
Patient or population: people undergoing laparoscopic general abdominal or gynaecological pelvic surgery under general anaesthesia Setting: secondary and tertiary care Intervention: nitrous oxide pneumoperitoneum Comparison: carbon dioxide pneumoperitoneum | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with carbon dioxide pneumoperitoneum | Risk with nitrous oxide pneumoperitoneum | |||||
|
Cardiopulmonary complications Follow‐up: 0–1 month |
29 per 1000 | 79 per 1000 (21 to 286) | Peto OR 2.62 (0.78 to 8.85) | 204 (3 studies) | ⊕⊝⊝⊝ Very lowa,b | — |
|
Procedure‐related general complications (surgical morbidity) Follow‐up: 0–1 month |
19 per 1000 | 19 per 1000 (3 to 110) | Peto OR 1.01 (0.14 to 7.31) | 207 (3 studies) | ⊕⊝⊝⊝ Very lowa,b | — |
|
Pneumoperitoneum‐related serious adverse events Follow‐up: 0–1 month |
See comment | See comment | Not estimable | 260 (4 studies) | ⊕⊝⊝⊝ Very lowb,c | None of the studies reported any pneumoperitoneum‐related serious adverse events. |
|
Mortality Follow‐up: 0–1 month |
See comment | See comment | Not estimable | 260 (4 studies) | ⊕⊝⊝⊝ Very lowb,c | None of the studies reported any deaths. |
| Quality of life | None of the studies reported quality of life. | |||||
|
Pain scores (first postoperative day) VAS, lower score indicates less pain. Scale: 0–10 cm Follow‐up: 1 day |
The mean pain scores (first postoperative day) in the carbon dioxide pneumoperitoneum group was 3.50 cm | The mean pain scores (first postoperative day) in the nitrous oxide pneumoperitoneum group was 0.90 cm lower (2.10 lower to 0.30 higher) | MD −0.90 (−2.10 to 0.30) | 64 (1 study) | ⊕⊝⊝⊝ Very lowc,d,e | 2 studies reported lower pain scores in the nitrous oxide group compared with the carbon dioxide group at various time points on the first postoperative day (Aitola 1998; Tsereteli 2002). Neither trial reported the standard deviation for pain scores on the VAS scale. The other study reported no difference in the pain scores using McGill pain questionnaire between groups (Lipscomb 1993). We were unable to use the data from these 3 studies in meta‐analysis for the reasons given above. |
|
Analgesia requirements Follow‐up: 1 week |
The mean analgesia requirement in the carbon dioxide pneumoperitoneum was 54.4 mg of oxycodone and 2.0 tablets/24 hours of ibuprofen | The mean analgesia requirement in the nitrous oxide pneumoperitoneum was 0.65 standard deviations (moderate effect) lower (0.90 lower to 0.39 lower) | SMD −0.65 (moderate effect) (−0.90 to −0.39) | 257 (4 studies) | ⊕⊝⊝⊝ Very lowc,d,f | — |
| Costs | None of the studies reported costs. | |||||
| *The basis for the assumed risk is the mean comparison group proportion in the studies. The risk in the intervention group (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; MD: mean difference; OR: odds ratio; RR: risk ratio; SMD: standardised mean difference; VAS: visual analogue scale. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aDowngraded two levels for very serious risk of bias: all included studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel. bDowngraded two levels for very serious imprecision: small sample size, few events, and wide confidence intervals that included both potential benefit and potential harm from the intervention. cDowngraded two levels for very serious risk of bias: three studies with unclear risk of bias for random sequence generation; all included studies with unclear risk of bias for allocation concealment; one study with high risk of bias for blinding of participants and personnel; one study with high risk of bias for selective reporting and baseline imbalance. dDowngraded one level for serious imprecision: small sample size. eDowngraded one level for serious inconsistency: three different laparoscopic operations and results of one study are not in agreement with the other three studies. fDowngraded one level for serious inconsistency: substantial heterogeneity (I2 = 80%).
Summary of findings 2. Helium versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery.
| Helium versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery | ||||||
|
Patient or population: people undergoing laparoscopic general abdominal or gynaecological pelvic surgery under general anaesthesia Setting: secondary and tertiary care Intervention: helium pneumoperitoneum Comparison: carbon dioxide pneumoperitoneum | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with carbon dioxide pneumoperitoneum | Risk with helium pneumoperitoneum | |||||
|
Cardiopulmonary complications Follow‐up: 0–1 month |
30 per 1000 | 44 per 1000 (10 to 183) | Peto OR 1.66 (0.28 to 9.72) | 128 (3 studies) | ⊕⊝⊝⊝ Very lowa,b | — |
|
Procedure‐related general complications (surgical morbidity) Follow‐up: 0–1 month |
See comment | See comment | Not estimable | 177 (5 studies) | ⊕⊝⊝⊝ Very lowb,c |
None of the studies reported any significant procedure‐related general complications in either group. |
|
Pneumoperitoneum‐related serious adverse events Follow‐up: 0–1 month |
0 per 1000 | 44 per 1000 (0 to 0) | Peto OR 8.28 (0.86 to 80.03) | 128 (3 studies) | ⊕⊝⊝⊝ Very lowa,b | — |
|
Mortality Follow‐up: 0–1 month |
See comment | See comment | Not estimable | 177 (5 studies) | ⊕⊝⊝⊝ Very lowb,c | None of the studies reported any deaths. |
| Quality of life | None of the studies reported quality of life. | |||||
|
Pain scores (first postoperative day) Visual analogue scale, lower score indicates less pain. Scale: 0–10 cm Follow‐up: 1 day |
The mean pain scores (first postoperative day) in the carbon dioxide pneumoperitoneum was 3.01 cm | The mean pain scores (first postoperative day) in the helium pneumoperitoneum was 0.49 cm higher (0.28 lower to 1.26 higher) | MD 0.49 (−0.28 to 1.26) | 108 (2 studies) | ⊕⊕⊝⊝ Lowd,e | — |
|
Analgesia requirements (morphine mg) Follow‐up: 2 days |
The mean analgesia requirements (morphine) in the carbon dioxide pneumoperitoneum was 36.6 mg | The mean analgesia requirements (morphine) in the helium pneumoperitoneum was 12 mg higher (4.44 higher to 19.56 higher) | MD 12.00 (4.44 to 19.56) | 90 (1 study) | ⊕⊝⊝⊝ Very lowd,e,f | 2 trials (108 participants) reported analgesia requirements (Neuhaus 2001; O'Boyle 2002). Results of O'Boyle 2002 presented here. The other study including 18 participants reported no difference in the number of participants requiring analgesia (morphine) between the groups (Neuhaus 2001). |
| Costs | None of the studies reported costs. | |||||
| *The basis for the assumed risk is the mean comparison group proportion in the studies. The risk in the intervention group (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; MD: mean difference; OR: odds ratio; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aDowngraded two levels for very serious risk of bias: two studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel and baseline imbalance. bDowngraded two levels for very serious imprecision: small sample size, few events, and wide confidence intervals that included both potential benefit and potential harm from the intervention. cDowngraded two levels for very serious risk of bias: four studies with unclear risk of bias for random sequence generation; three studies with unclear risk of bias for allocation concealment; two studies with high risk of bias for blinding of participants and personnel, incomplete outcome data, selective reporting, and baseline imbalance. dDowngraded one level for serious imprecision (small sample size). eDowngraded one level for serious risk of bias: two studies with high risk of bias for random sequence generation and blinding of participants and personnel. fDowngraded one level for serious inconsistency: two different laparoscopic operations and results of one study were not in agreement with the other study.
Summary of findings 3. Room air versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery.
| Room air versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery | ||||||
|
Patient or population: people undergoing laparoscopic general abdominal or gynaecological pelvic surgery under general anaesthesia Setting: secondary and tertiary care Intervention: room air pneumoperitoneum Comparison: carbon dioxide pneumoperitoneum | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with carbon dioxide pneumoperitoneum | Risk with room air pneumoperitoneum | |||||
|
Cardiopulmonary complications Follow‐up: 1 month |
See comment | See comment | Not estimable | 146 (1 study) | ⊕⊝⊝⊝ Very lowa,b | Trial did not report any cardiopulmonary complications. |
| Procedure‐related general complications (surgical morbidity) | The study did not report procedure‐related general complications. | |||||
|
Pneumoperitoneum‐related serious adverse events Follow‐up: 1 month |
See comment | See comment | Not estimable | 146 (1 study) | ⊕⊝⊝⊝ Very lowa,b | Trial did not report any pneumoperitoneum‐related serious adverse events. |
|
Mortality Follow‐up: 1 month |
See comment | See comment | Not estimable | 146 (1 study) | ⊕⊝⊝⊝ Very lowa,b | The study did not report any deaths. |
| Quality of life | The study did not report quality of life. | |||||
|
Pain scores (first postoperative day) Visual analogue scale, lower score indicates less pain. Scale: 0–10 cm Follow‐up: 1 day |
The mean pain scores (first postoperative day) in the carbon dioxide pneumoperitoneum was 2.60 cm | The mean pain scores (first postoperative day) in the room air pneumoperitoneum was 0.80 cm lower (1.15 lower to 0.45 lower) | MD −0.80 (−1.15 to −0.45) | 146 (1 study) | ⊕⊝⊝⊝ Very lowa,b | — |
| Analgesia requirements | The study did not report analgesia requirements. | |||||
|
Hospital costs (CNY) Follow‐up: 1 month |
The mean hospital costs in the carbon dioxide pneumoperitoneum was CNY 12,012.00 | The mean hospital costs in the room air pneumoperitoneum was CNY 2667.00 lower (3275.68 lower to 2058.32 lower) | MD −2667.00 (−3275.68 to −2058.32) | 146 (1 study) | ⊕⊝⊝⊝ Very lowa,b | — |
| *The basis for the assumed risk is the mean comparison group proportion in the studies. The risk in the intervention group (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; CNY: Chinese Yuan; MD: mean difference. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
aDowngraded two levels for very serious risk of bias: unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting. bDowngraded one level for serious imprecision (small sample size).
1. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum
Four trials with 260 participants compared nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (Aitola 1998; Asgari 2011; Lipscomb 1993; Tsereteli 2002). See Table 1.
1.1. Primary outcomes
1.1.1. Cardiopulmonary complications (Analysis 1.1)
Three trials (204 participants) reported cardiopulmonary complications (Aitola 1998; Asgari 2011; Tsereteli 2002). Overall, there were 11 cases of cardiopulmonary complications: eight in the nitrous oxide group and three in the carbon dioxide group. The evidence is very uncertain about the effect of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto OR 2.62, 95% CI 0.78 to 8.85; P = 0.12; Analysis 1.1). There was clinical heterogeneity because the three trials performed quite different laparoscopic operations (cholecystectomy versus foregut surgery). This finding was downgraded to very low certainty due to very serious risk of bias (all included studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel) and very serious imprecision (small sample size, few events, and wide CIs that included both potential benefit and potential harm from the intervention).
1.1. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications
1.1.2. Procedure‐related general complications (surgical morbidity) (Analysis 1.2)
Three trials (207 participants) reported surgical morbidity (Aitola 1998; Asgari 2011; Tsereteli 2002). Overall, there were four cases of procedure‐related general complications: two in the nitrous oxide group versus two in the carbon dioxide group. The evidence is very uncertain about the effect of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on surgical morbidity (Peto OR 1.01, 95% 0.14 to 7.31; P = 0.99; Analysis 1.2). There was clinical heterogeneity because the three trials performed quite different laparoscopic operations (cholecystectomy versus foregut surgery). This finding was downgraded to very low certainty due to very serious risk of bias (all included studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel) and serious imprecision (small sample size, few events, and wide confidence CIs that included both potential benefit and potential harm from the intervention).
1.2. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Procedure‐related general complications
1.1.3. Pneumoperitoneum‐related serious adverse events
None of the trials reported any pneumoperitoneum‐related serious adverse events. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (three studies with unclear risk of bias for random sequence generation; all included studies with unclear risk of bias for allocation concealment; one study with high risk of bias for blinding of participants and personnel; one study with high risk of bias for selective reporting and baseline imbalance) and very serious imprecision (small sample size and few events).
1.2. Secondary outcomes
1.2.1. Mortality
None of the trials reported any deaths. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (three studies with unclear risk of bias for random sequence generation; all included studies with unclear risk of bias for allocation concealment; one study with high risk of bias for blinding of participants and personnel; one study with high risk of bias for selective reporting and baseline imbalance) and very serious imprecision (small sample size and few events).
1.2.2. Quality of life
None of the trials reported quality of life.
1.2.3. Pain scores (Analysis 1.3)
One trial (64 participants undergoing laparoscopic cholecystectomy) reported pain scores on the first postoperative day (Asgari 2011). The pain scores (VAS scale of 1 cm to 10 cm with lower numbers indicating less pain) was 2.6 cm in the nitrous oxide group versus 3.5 cm in the carbon dioxide group. The evidence is very uncertain about the effect of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on the pain scores (MD −0.90 cm, 95% −2.10 to 0.30; P = 0.30; Analysis 1.3). Two trials (140 participants undergoing laparoscopic cholecystectomy or foregut surgery) reported pain scores at various time points on the first postoperative day (Aitola 1998; Tsereteli 2002). Both trials reported lower pain scores (about 1 cm on a VAS scale of 0 cm to 10 cm with lower numbers indicating less pain) in the nitrous oxide group compared with the carbon dioxide group at various time points on the first postoperative day (Aitola 1998; Tsereteli 2002). However, as neither trial reported the standard deviation (SD) for pain scores, we did not perform a meta‐analysis (Aitola 1998; Tsereteli 2002). Another trial (53 participants undergoing laparoscopic tubal ligation) reported pain scores on the first postoperative day using the McGill Pain Questionnaire (0 cm to 5 cm with lower numbers indicating less pain). The pain scores was 1.4 cm in the nitrous oxide group versus 1.0 cm in the carbon dioxide group (Lipscomb 1993). There was clinical heterogeneity because the trials performed quite different laparoscopic operations (cholecystectomy, foregut surgery, and tubal ligation). This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (three studies with unclear risk of bias for random sequence generation; all included studies with unclear risk of bias for allocation concealment; one study with high risk of bias for blinding of participants and personnel; one study with high risk of bias for selective reporting and baseline imbalance), serious inconsistency (three different laparoscopic operations and results of one study are not in agreement with the other three studies) and serious imprecision (small sample size).
1.3. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)
1.2.4. Analgesia requirements (Analysis 1.4)
Four trials (257 participants) reported analgesia requirements. The trials used different measurement scales (milligrams versus tablets per 24 hours); therefore we calculated an SMD. Analgesia requirements (oxycodone or ibuprofen) in the nitrous oxide group was less compared to the carbon dioxide group, but the evidence is very uncertain (SMD −0.65, 95% CI −0.90 to −0.39; P < 0.00001; Analysis 1.4). In addition, there was clinical heterogeneity because the four trials performed quite different laparoscopic operations (cholecystectomy, foregut surgery, and tubal ligation). Consequently, this finding was downgraded to very low‐certainty evidence due to very serious risk of bias (three studies with unclear risk of bias for random sequence generation; all included studies with unclear risk of bias for allocation concealment; one study with high risk of bias for blinding of participants and personnel; and one study with high risk of bias for selective reporting and baseline imbalance), serious imprecision (small sample size), and serious inconsistency (substantial heterogeneity I2 = 80%).
1.4. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Analgesia requirements
1.2.5. Costs
None of the trials reported costs.
1.2.6. Cardiopulmonary changes (Analysis 1.5; Analysis 1.6)
One trial (100 participants) reported cardiopulmonary changes (Tsereteli 2002). The evidence is very uncertain about the effect of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on the following cardiopulmonary parameter changes (the differences between the start of pneumoperitoneum and the end of pneumoperitoneum) between the groups: heart rate change (MD −0.60 beats/minute, 95% CI −4.13 to 2.93; P = 0.74), mean arterial pressure change (MD −3.80 mmHg, 95% CI −7.90 to 0.30; P = 0.07), oxygen saturation change (MD 0%, 95% CI −0.39 to 0.39; P = 1.00), and peak airway pressure change (MD −0.30 cmH2O, 95% CI −2.17 to 1.57; P = 0.75) (Analysis 1.5). There were no other cardiopulmonary changes reported.
1.5. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Cardiopulmonary changes
One trial (64 participants) reported cardiopulmonary parameters (Asgari 2011). The evidence is very uncertain about the effect of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on heart rate, mean arterial pressure, or oxygen saturation at the start or end of pneumoperitoneum (Analysis 1.6).
1.6. Analysis.
Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 6: Cardiopulmonary parameters
These findings were downgraded to very low‐certainty evidence due to very serious risk of bias (all included studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for performance bias), serious imprecision (small sample size), and indirectness of the outcome (surrogate outcome).
2. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum
Five trials (177 participants) reported helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (Bongard 1993; Naude 1996; Neuhaus 2001; O'Boyle 2002; Sietses 2002). Four trials randomised participants to helium pneumoperitoneum (69 participants) or carbon dioxide pneumoperitoneum (75 participants) (Bongard 1993; Naude 1996; Neuhaus 2001; O'Boyle 2002; Sietses 2002), and one trial involving 33 participants did not state the number of participants in each group (Sietses 2002). See Table 2.
2.1. Primary outcomes
2.1.1. Cardiopulmonary complications (Analysis 2.1)
Three trials (128 participants) reported cardiopulmonary complications (Bongard 1993; Neuhaus 2001; O'Boyle 2002). Overall, there were five cases of cardiopulmonary complications: three in the helium group and two in the carbon dioxide group. The evidence is very uncertain about the effect of helium pneumoperitoneum compared to carbon dioxide pneumoperitoneum on cardiopulmonary complications (Peto OR 1.66, 95% CI 0.28 to 9.72; P = 0.57; Analysis 2.1). There was clinical heterogeneity because the three trials performed quite different laparoscopic operations (cholecystectomy, fundoplication, and gastrointestinal surgery). This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (two studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel and baseline imbalance) and very serious imprecision (small sample size, few events, and wide CIs that included both potential benefit and potential harm from the intervention).
2.1. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications
2.1.2. Procedure‐related general complications (surgical morbidity)
None of the trials reported any significant procedure‐related general complications. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (four studies with unclear risk of bias for random sequence generation; three studies with unclear risk of bias for allocation concealment; two studies with high risk of bias for blinding of participants and personnel, incomplete outcome data, selective reporting, and baseline imbalance) and serious imprecision (small sample size and few events).
2.1.3. Pneumoperitoneum‐related serious adverse events (Analysis 2.2)
Three trials (128 participants) reported serious adverse events (Bongard 1993; Neuhaus 2001; O'Boyle 2002). There were three serious adverse events (subcutaneous emphysema) related to pneumoperitoneum; three in the helium group and none in the carbon dioxide group. The evidence is very uncertain about the effect of helium pneumoperitoneum compared to carbon dioxide pneumoperitoneum on the Peto OR for pneumoperitoneum‐related serious adverse events (Peto OR 8.28, 95% CI 0.86 to 80.03; P = 0.07; Analysis 2.2). There was clinical heterogeneity because the three trials performed quite different laparoscopic operations. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (two studies with unclear risk of bias for random sequence generation and allocation concealment; one study with high risk of bias for blinding of participants and personnel and baseline imbalance) and very serious imprecision (small sample size, few events, and wide CIs that included both potential benefit and potential harm from the intervention).
2.2. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Pneumoperitoneum‐related serious adverse events
2.2. Secondary outcomes
2.2.1. Mortality
None of the trials reported any deaths. This finding was downgraded to very low‐certainty evidence due to serious risk of bias (four studies with unclear risk of bias for random sequence generation; three studies with unclear risk of bias for allocation concealment; two studies with high risk of bias for blinding of participants and personnel, incomplete outcome data, selective reporting, and baseline imbalance) and serious imprecision (small sample size and few events).
2.2.2. Quality of life
None of the trials reported quality of life.
2.2.3. Pain scores (shoulder or abdominal pain) (Analysis 2.3)
Two trials (108 participants) reported pain scores (Neuhaus 2001; O'Boyle 2002). The evidence suggests that helium pneumoperitoneum results in little to no difference in the first postoperative day pain scores (graded by VAS on a scale of 0 cm to 10 cm, with lower numbers indicating less pain) compared to carbon dioxide pneumoperitoneum (MD 0.49 cm, 95% CI −0.28 to 1.26; P = 0.21; Analysis 2.3). There was clinical heterogeneity because the two trials performed quite different laparoscopic operations. This finding was downgraded to low‐certainty evidence due to serious risk of bias (two studies with unclear risk of bias for random sequence generation and blinding of participants and personnel) and serious imprecision (small sample size).
2.3. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)
2.2.4. Analgesia requirements (Analysis 2.4; Analysis 2.5)
Two trials (108 participants) reported analgesia requirements (Neuhaus 2001; O'Boyle 2002). One trial reported the amount of analgesia consumed (O'Boyle 2002). The overall analgesic (morphine) consumption was higher in the helium group than the carbon dioxide group (MD 12.00 mg, 95% CI 4.44 to 19.56; P = 0.002; Analysis 2.4). One trial reported the number of participants requiring analgesia (Neuhaus 2001). There was no difference in analgesia (morphine) requirements between the helium group (3/8; 37.5%) and carbon dioxide group (9/10; 90%) (Analysis 2.5). However, the trial was underpowered with only 18 participants (very low‐certainty evidence). There was clinical heterogeneity because the two trials performed quite different laparoscopic operations. This finding was downgraded to very low‐certainty evidence due to serious risk of bias (two studies with unclear risk of bias for random sequence generation and blinding of participants and personnel), serious inconsistency (two different laparoscopic operations and results of one study are not in agreement with the other study), and serious imprecision (small sample size).
2.4. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Analgesia requirements (morphine mg)
2.5. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Number of participants requiring analgesia
2.2.5. Costs
None of the trials reported costs.
2.2.6. Cardiopulmonary changes (Analysis 2.6)
Two trials (34 participants) reported blood pH (Bongard 1993; Naude 1996). There was no difference between the groups in blood pH at the start of pneumoperitoneum (MD 0.01, 95% CI −0.01 to 0.04; P = 0.30). However, the blood pH was higher in the helium group compared with the carbon dioxide group at the middle of pneumoperitoneum (MD 0.08, 95% CI 0.06 to 0.11; P < 0.00001) and the end of pneumoperitoneum (MD 0.10, 95% CI 0.06 to 0.14; P < 0.00001). Three trials (52 participants) reported partial pressure of carbon dioxide (Bongard 1993; Naude 1996; Neuhaus 2001). There was no difference between the groups in partial pressure of carbon dioxide at the start of pneumoperitoneum (MD 0.31 mmHg, 95% CI −1.79 to 2.40; P = 0.78) or the middle of pneumoperitoneum (MD −0.84 mmHg, 95% CI −3.70 to 2.02; P = 0.56). However, the partial pressure of carbon dioxide was lower in the helium group than the carbon dioxide group at the end of pneumoperitoneum (MD −12.78 mmHg, 95% CI −16.78 to −8.77; P < 0.00001). There was clinical heterogeneity because the included trials performed quite different laparoscopic operations. These findings were downgraded to very low‐certainty evidence due to very serious risk of bias (two studies with unclear risk of bias for random sequence generation and allocation concealment; two studies with high risk of bias for blinding of participants and personnel and baseline imbalance; one study with high risk of bias for incomplete outcome data and selective reporting), serious imprecision (small sample size), and indirectness of the outcome (surrogate outcome).
3. Room (ambient) air pneumoperitoneum versus carbon dioxide pneumoperitoneum
One trial (146 participants) reported room (ambient) air pneumoperitoneum versus carbon dioxide pneumoperitoneum (Gu 2015). See Table 3.
3.1. Primary outcomes
3.1.1. Cardiopulmonary complications
The trial did not report any cardiopulmonary complications. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting) and serious imprecision (small sample size).
3.1.2. Procedure‐related general complications (surgical morbidity)
The trial did not report surgical morbidity.
3.1.3. Pneumoperitoneum‐related serious adverse events
The trial did not report any pneumoperitoneum‐related serious adverse events. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting) and serious imprecision (small sample size for such a rare outcome).
3.2. Secondary outcomes
3.2.1. Mortality
The trial did not report any deaths. This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting) and serious imprecision (small sample size for such a rare outcome).
3.2.2. Quality of life
The trial did not report quality of life.
3.2.3. Pain scores (Analysis 3.3)
Room air pneumoperitoneum may reduce the first postoperative day pain scores (graded by VAS on a scale of 0 cm to 10 cm with lower numbers indicating less pain) compared to carbon dioxide pneumoperitoneum, but the evidence is very uncertain (MD −0.80 cm, 95% CI −1.15 to −0.45; P < 0.00001). This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting) and serious imprecision (small sample size).
3.2.4. Analgesia requirements
The trial did not report analgesia requirements.
3.2.5. Costs (Analysis 3.4)
Room air pneumoperitoneum may reduce the total hospital costs compared to carbon dioxide pneumoperitoneum, but the evidence is very uncertain (MD −CNY 2667.00, 95% CI −3275.68 to −2058.32; equivalent to approximately USD 308 to USD 490 in November 2020; P < 0.00001). This finding was downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting) and serious imprecision (small sample size).
3.2.6. Cardiopulmonary changes (Analysis 3.5)
There was no difference between groups in heart rate at the start of pneumoperitoneum (MD −0.10 beats/minute, 95% CI −3.11 to 2.91; P = 0.95). However, heart rate was lower in the room air group compared with the carbon dioxide group in the middle of pneumoperitoneum (MD −7.30 beats/minute, 95% CI −9.78 to −4.82; P < 0.00001) and the end of pneumoperitoneum (MD −8.70 beats/minutes, 95% CI −11.72 to −5.68; P < 0.00001) (Analysis 3.5).
3.5. Analysis.
Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Cardiopulmonary parameters
There was no difference between groups in blood systolic pressure or partial pressure of carbon dioxide at the start, middle, or end of pneumoperitoneum (all very low‐certainty evidence).
All these findings were downgraded to very low‐certainty evidence due to very serious risk of bias (unclear risk of bias for random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment; high risk of bias for selective reporting), serious imprecision (small sample size), and indirectness of the outcome (surrogate outcome).
4. Reporting bias
We did not perform funnel plots to assess reporting biases because the number of included studies in each comparison was fewer than 10. The study by Bergstrom 2015 could not be included in the present review, as results were published only as a conference abstract. However, as this study had only 30 participants, the unavailability of full study results was not considered a source of potential publication bias.
5. Subgroup analysis
None of the planned subgroup analyses was performed due to the limited number of included trials for each outcome.
6. Sensitivity analysis
We performed worst/best‐case scenario and best/worst‐case scenario analyses for the outcomes cardiopulmonary complications, procedure‐related general complications (surgical morbidity), pneumoperitoneum‐related serious adverse events, and mortality to assess the impact of missing data for 13 postrandomisation dropouts across five trials (Analysis 4.1; Analysis 4.2; Analysis 4.3; Analysis 4.4; Analysis 5.1; Analysis 5.2; Analysis 5.3; Analysis 5.4; Analysis 6.1; Analysis 6.2; Analysis 6.3; Analysis 6.4; Analysis 7.1; Analysis 7.2; Analysis 7.3; Analysis 7.4). Results are presented in Table 4. Assigning death or no death to all missing participants in the helium versus carbon dioxide pneumoperitoneum comparison altered the conclusion drawn, confirming that the low mortality rate and small numbers of participants were insufficient to reliably assess this outcome. The other three outcomes (cardiopulmonary complications, procedure‐related general complications, and pneumoperitoneum‐related serious adverse events) also changed by assigning event or no event to all missing participants in the helium versus carbon dioxide pneumoperitoneum comparison.
4.1. Analysis.
Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 1: Cardiopulmonary complications
4.2. Analysis.
Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 2: Procedure‐related general complications
4.3. Analysis.
Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 3: Pneumoperitoneum‐related serious adverse events
4.4. Analysis.
Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 4: Mortality
5.1. Analysis.
Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 1: Cardiopulmonary complications
5.2. Analysis.
Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 2: Procedure‐related general complications
5.3. Analysis.
Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 3: Pneumoperitoneum‐related serious adverse events
5.4. Analysis.
Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 4: Mortality
6.1. Analysis.
Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 1: Cardiopulmonary complications
6.2. Analysis.
Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 2: Procedure‐related general complications
6.3. Analysis.
Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 3: Pneumoperitoneum‐related serious adverse events
6.4. Analysis.
Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 4: Mortality
7.1. Analysis.
Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 1: Cardiopulmonary complications
7.2. Analysis.
Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 2: Procedure‐related general complications
7.3. Analysis.
Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 3: Pneumoperitoneum‐related serious adverse events
7.4. Analysis.
Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 4: Mortality
1. Sensitivity analysis by changing between worst‐case scenario analysis and best‐case scenario analysis for missing data.
| Changing between worst‐case scenario analysis and best‐case scenario analysis for missing data | |||
| Outcomes | Risk ratio (95% CI) | ||
| Main analysis | Worst/best‐case | Best/worst‐case | |
| Nitrous oxide vs carbon dioxide | |||
| Cardiopulmonary complications | Peto OR 2.62 (0.78 to 8.85) | Peto OR 3.16 (1.03 to 9.69) | Peto OR 1.66 (0.54 to 5.12) |
| Procedure‐related general complications (surgical morbidity) | Peto OR 1.01 (0.14 to 7.31) | Peto OR 2.01 (0.40 to 10.20) | Peto OR 0.51 (0.10 to 2.60) |
| Pneumoperitoneum‐related serious adverse events | No events | Peto OR 7.46 (0.47 to 119.30) |
Peto OR 0.14 (0.01 to 2.19) |
| Mortality | No events | Peto OR 7.46 (0.47 to 119.30) |
Peto OR 0.14 (0.01 to 2.19) |
| Helium vs carbon dioxide | |||
| Cardiopulmonary complications | Peto OR 1.66 (0.28 to 9.72) | Peto OR 4.66 (1.43 to 15.15) | Peto OR 1.66 (0.28 to 9.72) |
| Procedure‐related general complications/surgical morbidity | No events | Peto OR 8.89 (1.94 to 40.64) | Peto OR 0.12 (0.01 to 2.07) |
| Pneumoperitoneum‐related serious adverse events | Peto OR 8.28 (0.86 to 80.03) |
Peto OR 9.19 (2.56 to 33.01) |
Peto OR 8.28 (0.86 to 80.03) |
| Mortality | No events | Peto OR 8.89 (1.94 to 40.64) |
Peto OR 0.12 (0.01 to 2.07) |
CI: confidence interval; Peto OR: Peto odds ratio, which was calculated for rare events (mortality, serious adverse events).
TSA of nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum for cardiopulmonary complications is shown in Figure 4. The TSA graph showed that the cumulative Z‐curve did not cross the naive 5% statistical boundaries. The analysis showed a diversity‐adjusted required information size of 3781 participants (the number of participants needed to reach firm evidence of an intervention effect of 20% RRR). The number of participants included corresponded to only a small fraction (5.4%) of the diversity‐adjusted required information size; therefore, the trial sequential boundaries could not be drawn. TSA of nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum for surgical morbidity is shown in Figure 5. The TSA graph showed that the cumulative Z‐curve did not cross the naive 5% statistical boundaries. The analysis showed a required information size of 3919 participants (the number of participants needed to reach firm evidence of an intervention effect of 20% RRR). The number of participants included corresponded to only a small fraction (5.3%) of the diversity‐adjusted required information size; therefore, the trial sequential boundaries could not be drawn. Accordingly, we lack evidence to conclude equivalence of nitrous oxide and carbon dioxide pneumoperitoneum.
4.
Trial sequential analysis of nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum for cardiopulmonary complications. Analysis was performed with an event rate of 2.9% (Pc) in the control group, a risk ratio reduction of 20%, alpha 5%, beta 20%, and observed diversity 0%. The accrued sample size was so small that the trial sequential boundaries could not be drawn. The cumulative Z‐curve did not cross the naive 5% statistical boundaries (red horizontal lines). The results showed that the observed diversity‐adjusted required information size was 3781 participants, corresponding to 5.4% of the total sample size in the included trials. Accordingly, the meta‐analysis did not support or refute an intervention effect as data were too few.
5.
Trial sequential analysis of nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum for surgical morbidity. Analysis was performed with an event rate of 2.8% (Pc) in the control group, a risk ratio reduction of 20%, alpha 5%, beta 20%, and observed diversity 0%. The cumulative Z‐curve did not cross the naive 5% statistical boundaries (red horizontal lines). The results showed that the observed diversity adjusted required information size was 3919 participants, corresponding to 5.3% of the total sample size in the included trials. Accordingly, the meta‐analysis did not support or refute an intervention effect as data were too few.
TSA of helium pneumoperitoneum versus carbon dioxide pneumoperitoneum for cardiopulmonary complications is shown in Figure 6. The TSA graph showed that the cumulative Z‐curve did not cross the naive 5% statistical boundaries. The analysis showed a diversity‐adjusted required information size of 3651 participants (the number of participants needed to reach firm evidence of an intervention effect of 20% RRR). The number of participants included corresponded to only a small fraction (3.5%) of the diversity‐adjusted required information size; therefore, the trial sequential boundaries could not be drawn. TSA of helium pneumoperitoneum versus carbon dioxide pneumoperitoneum for serious adverse events is shown in Figure 7. The TSA graph showed that the cumulative Z‐curve did not cross the naive 5% statistical boundaries. The analysis showed a diversity‐adjusted required information size of 4793 participants (the number of participants needed to reach firm evidence of an intervention effect of 20% RRR). The number of participants included corresponded to only 2.7% of the diversity‐adjusted required information size; therefore, the trial sequential boundaries could not be drawn. Accordingly, we lack evidence to conclude equivalence of helium and carbon dioxide pneumoperitoneum.
6.
Trial sequential analysis of helium pneumoperitoneum versus carbon dioxide pneumoperitoneum for cardiopulmonary complications. Analysis was performed with an event rate of 3.0% (Pc) in the control group, a risk ratio reduction of 20%, alpha 5%, beta 20%, and observed diversity 0%. The cumulative Z‐curve did not cross the naive 5% statistical boundaries (red horizontal lines). The results showed that the observed diversity adjusted required information size was 3651 participants, corresponding to 3.5% of the total sample size in the included trials. Accordingly, the meta‐analysis did not support or refute an intervention effect as data were too few.
7.
Trial sequential analysis of helium pneumoperitoneum versus carbon dioxide pneumoperitoneum for serious adverse events. Analysis was performed with an event rate of 2.3% (Pc) in the control group, a risk ratio reduction of 20%, alpha 5%, beta 20%, and observed diversity 0%. The cumulative Z‐curve did not cross the naive 5% statistical boundaries (red horizontal lines). The results showed that the observed diversity adjusted required information size was 4793 participants, corresponding to 2.7% of the total sample size in the included trials. Accordingly, the meta‐analysis did not support or refute an intervention effect as data were too few.
Discussion
Summary of main results
Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum
Four studies with 260 participants contributed data to the primary outcomes of this review. The evidence is very uncertain about the effects of nitrous oxide pneumoperitoneum compared to carbon dioxide pneumoperitoneum on any of the primary outcomes, such as cardiopulmonary complications or surgical morbidity. There were no serious adverse events or deaths related to the use of nitrous oxide or carbon dioxide pneumoperitoneum. Three trials showed lower pain scores (a difference of about 1 cm on a VAS scale of 1 cm to 10 cm with lower numbers indicating less pain) in nitrous oxide pneumoperitoneum at various time points on the first postoperative day. However, we do not consider 1 cm on a VAS scale to be clinically significant as this difference is less than the minimum important clinical difference (Katz 2015; Parker 2013; Todd 1996). The benefits for nitrous oxide pneumoperitoneum were lower analgesia requirements, but the evidence was very uncertain.
The safety of nitrous oxide pneumoperitoneum is another major concern for patients, laparoscopic surgeons, and healthcare funders. Exposure to nitrous oxide may be harmful to laparoscopic surgeons because nitrous oxide has an anaesthetic effect. This review included four trials with 132 participants undergoing nitrous oxide pneumoperitoneum. Although none of the trials reported any serious adverse events in the nitrous oxide group, they did not have the statistical power to establish the safety of nitrous oxide pneumoperitoneum. The TSA showed an information size of more than 3700 participants is needed to reach firm evidence for primary outcomes. As this review included only four trials with 260 participants for this comparison, there is lack of evidence to support or refute the effectiveness or safety of nitrous oxide pneumoperitoneum compared with carbon dioxide pneumoperitoneum.
Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum
Four studies with 144 people contributed data to the primary outcomes of this review. The evidence is very uncertain about the effects of helium pneumoperitoneum compared to carbon dioxide pneumoperitoneum on any of the primary outcomes, such as cardiopulmonary complications or surgical morbidity. There were three serious adverse events related to helium pneumoperitoneum. Although there were fewer cardiopulmonary changes in the helium pneumoperitoneum group, this did not translate into any clinical benefit.
In contrast to other gases used for creating a pneumoperitoneum, helium is an inert gas that has extremely low reactivity with other substances. The safety of helium pneumoperitoneum is also an important outcome for patients, laparoscopic surgeons, and healthcare funders. This review included four trials with 69 participants undergoing helium pneumoperitoneum. Three of the four trials reported a total of three serious adverse events related to pneumoperitoneum in the helium group. The adverse events were various subcutaneous emphysemas (e.g. scrotal, facial, and cervical emphysema). Although the meta‐analysis did not demonstrate any evidence of differences in pneumoperitoneum‐related serious adverse events between helium and carbon dioxide pneumoperitoneum, it also did not have the statistical power to establish the safety of helium pneumoperitoneum. The TSA showed an information size of more than 3600 participants needed to reach firm evidence for primary outcomes. As this review included only four trials with 144 participants in this comparison, there is a lack of evidence to support or refute the effectiveness or safety of helium pneumoperitoneum compared with carbon dioxide pneumoperitoneum.
Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum
One study with 146 people contributed data to the primary outcomes of this review. There were no cardiopulmonary complications or serious adverse events related to either room air or carbon dioxide pneumoperitoneum. The study showed lower pain scores (a difference of about 1 cm on a VAS scale of 1 cm to 10 cm with lower numbers indicating less pain) in room air pneumoperitoneum during the first postoperative day. However, we do not consider 1 cm on a VAS scale to be clinically significant as this difference is less than the minimum important clinical difference (Katz 2015; Parker 2013; Todd 1996). The benefits for room air pneumoperitoneum were fewer total hospital costs (about USD 380) but the evidence is very uncertain.
Hospital cost is an important outcome for healthcare funders. The trial showed decreased total hospital costs in the room air group; this could be due to a shorter duration of hospitalisation in the room air group (2.5 days) than in the carbon dioxide group (3.2 days), less analgesia requirements in the room air group, or both. In addition, the cost of carbon dioxide cylinders and carbon dioxide insufflators may be higher than the cost of room air insufflators.
The safety of room air pneumoperitoneum is another major concern for patients, laparoscopic surgeons, and healthcare funders because of the risk of air embolism (Ikechebelu 2005). This review included one trial with 70 participants undergoing room air pneumoperitoneum. Although the trial did not report any serious adverse events in the room air group, it did not have the statistical power to establish the safety of room air pneumoperitoneum. Accordingly, there is a lack evidence to support or refute the effectiveness or safety of room air pneumoperitoneum compared with carbon dioxide pneumoperitoneum.
Overall completeness and applicability of evidence
Only 24 participants in two trials (12.6%) had high anaesthetic risk (ASA III or IV) (O'Boyle 2002; Tsereteli 2002). Of the remaining trials, three trials excluded participants with ASA III or IV (Aitola 1998; Bongard 1993; Sietses 2002); and five trials did not report ASA status (Asgari 2011; Gu 2015; Lipscomb 1993; Naude 1996; Neuhaus 2001). Thus, the results of this review are primarily applicable in ASA I or ASA II patients undergoing various laparoscopic abdominal surgeries under general anaesthesia. However, this review involved only 583 participants and lacked sufficient power to support or refute any gas for establishing pneumoperitoneum. Thus, further trials on this topic are urgently needed.
Quality of the evidence
Overall, the certainty of the evidence was very low for the outcomes for which we could assess the certainty of evidence (Table 1; Table 2; Table 3). The major reason for downgrading the certainty of evidence was serious or very serious risk of bias in the trials. One of the major sources of bias was lack of blinding. Lack of blinding might introduce detection bias and performance bias. Blinding of healthcare providers, participants, and outcome assessors can be achieved with appropriate study design. Another major source of bias was incomplete outcome data. A total of 13/269 (4.8%) participants were excluded from the analysis for various reasons in five trials (Aitola 1998; Bongard 1993; Naude 1996; O'Boyle 2002; Tsereteli 2002). Only two trials analysed the data on an intention‐to‐treat basis (Bongard 1993; O'Boyle 2002). In addition, sensitivity analysis by changing between worst‐case scenario analysis and best‐case scenario analysis for missing data revealed that some results changed in the helium pneumoperitoneum versus carbon dioxide pneumoperitoneum comparison.
We further downgraded the certainty of evidence due to indirectness of the outcomes in trials (e.g. surrogate outcomes such as cardiopulmonary changes). We also downgraded the certainty of evidence due to imprecision; the review included only 583 participants in total, with the actual number included in specific outcomes being less than this since not all studies reported all the outcomes in each comparison; the number of participants included corresponded to only a small fraction of the required information size in all TSAs. There was also clinical heterogeneity among the included trials. As a result of these factors, the CIs for the majority of outcomes were wide, indicating that the estimates of effects obtained were based on an insufficient amount of information, reducing the certainty of the evidence. The trials included under each comparison were too few to assess publication bias.
Potential biases in the review process
There were several unavoidable potential biases of note in the review process.
First, this review involved only 583 participants and therefore, was too underpowered to detect differences reliably for the rarer outcomes, such as serious adverse events (e.g. gas embolism, abdominal explosion).
Second, when we contacted the original investigators to request further information, there were no replies.
Third, we were unable to explore publication bias because of the few trials included in each comparison.
Agreements and disagreements with other studies or reviews
The systematic review (a clinical practice guideline) by Neudecker and colleagues (Neudecker 2002) included two trials (Aitola 1998; Bongard 1993), which were included in this review. Neudecker and colleagues concluded that using insufflation gases such as nitrous oxide, helium, or argon appears to reduce pain, but they did not feel that this justified a general recommendation for the use of these gases. Our review agrees with their conclusion on nitrous oxide pneumoperitoneum, that the effectiveness or safety (or both) of nitrous oxide pneumoperitoneum have not been established. However, our review did not observe a reduction in pain with helium pneumoperitoneum. Furthermore, the authors of two trials comparing nitrous oxide pneumoperitoneum with carbon dioxide pneumoperitoneum recommended nitrous oxide pneumoperitoneum for prolonged laparoscopic surgery in people with chronic cardiopulmonary diseases (Aitola 1998; Tsereteli 2002); our review did not agree with the conclusions of the trial authors. Due to the lack of evidence, we conclude that further assessment for ASA III or ASA IV patients is required.
Authors' conclusions
Implications for practice.
The evidence is very uncertain about the effects of nitrous oxide, helium, and room air pneumoperitoneum compared to carbon dioxide pneumoperitoneum on any of the primary outcomes, including cardiopulmonary complications, surgical morbidity, and serious adverse events. The safety of nitrous oxide, helium, and room air pneumoperitoneum has yet to be established, especially in people with high anaesthetic risk.
Implications for research.
Further trials with sufficient sample size are needed to compare various gases (e.g. nitrous oxide, helium, argon, nitrogen, room air) with carbon dioxide under standard pressure pneumoperitoneum with cold gas insufflation for people with high anaesthetic risk. Future trials should include outcomes such as complications, serious adverse events, quality of life, and pain. There is a lack of data for low‐income settings. It is important to work out if cheaper and more available gases than carbon dioxide can be used to facilitate laparoscopic abdominal surgery. Further randomised controlled trials performed in low‐income countries are necessary to confirm or refute the findings of this review.
What's new
| Date | Event | Description |
|---|---|---|
| 15 October 2021 | New citation required and conclusions have changed | Searches updated 15 October 2021. One new RCT with 64 participates identified and included in analyses. Review updated accordingly with one new RCT included. Author byline changed. |
History
Protocol first published: Issue 1, 2012 Review first published: Issue 1, 2013
| Date | Event | Description |
|---|---|---|
| 14 June 2017 | New citation required but conclusions have not changed | Searches updated 24 September 2016, and review updated accordingly with one new RCT included. Author byline changed. This updated review furthermore included Trial Sequential Analysis (TSA) for the primary outcome for improving the reliability of conclusions. |
Notes
None.
Acknowledgements
We would like to thank Cochrane Colorectal Group editorial office, Dr Kristoffer Andresen and Ms Malene Agnete Højland, who assisted in the development of the updated review, and Dr Sys Johnsen and Dr Sara Hallum, who developed the search strategy. We would also like to thank editors and peer referees for valuable comments to this updated review. We would also like to thank Anne Lawson for copy editing the review.
Finally, we would like to thank the contribution of authors of the previous version of this review: including Dr Tianwu Yu, Dr Yao Cheng, Dr Xiaomei Wang, Dr Bing Tu, Dr Nansheng Cheng, Dr Jianping Gong, and Dr Lian Bai.
Appendices
Appendix 1. Cochrane Central Register of Controlled Trials (CENTRAL) search strategy
#1 MeSH descriptor: [Surgical Procedures, Minimally Invasive] explode all trees
#2 MeSH descriptor: [Laparoscopy] explode all trees
#3 MeSH descriptor: [Video‐Assisted Surgery] explode all trees
#4 (laparoscop* or coelioscop* or celioscop* or peritoneoscop* or minimally invasive or video assisted surgery)
#5 (#1 or #2 or #3 or #4)
#6 MeSH descriptor: [Carbon Dioxide] explode all trees
#7 MeSH descriptor: [Nitrogen Oxides] explode all trees
#8 MeSH descriptor: [Nitrogen] explode all trees
#9 MeSH descriptor: [Argon] explode all trees
#10 MeSH descriptor: [Helium] explode all trees
#11 (gas* or carbon dioxide or CO2 or nitrous oxide or laughing gas or N2O or nitrogen or N2 or helium or argon)
#12 (#6 or #7 or #8 or #9 or #10 or #11)
#13 MeSH descriptor: [Pneumoperitoneum] explode all trees
#14 (pneumoperitoneum*)
#15 (#13 or #14)
#16 (#5 and #12 and #15)
Appendix 2. MEDLINE (Ovid) search strategy
1. exp Surgical Procedures, Minimally Invasive/
2. exp Laparoscopy/
3. exp Video‐Assisted Surgery/
4. (laparoscop* or coelioscop* or celioscop* or peritoneoscop* or minimally invasive or video assisted surgery).mp.
5. 1 or 2 or 3 or 4
6. exp Carbon Dioxide/
7. exp Nitrogen Oxides/
8. exp Nitrogen/
9. exp Argon/
10. exp Helium/
11. (gas* or carbon dioxide or CO2 or nitrous oxide or laughing gas or N2O or nitrogen or N2 or helium or argon).mp.
12. 6 or 7 or 8 or 9 or 10 or 11
13. exp Pneumoperitoneum/
14. pneumoperitoneum*.mp.
15. 13 or 14
16. 5 and 12 and 15
17. randomized controlled trial.pt.
18. controlled clinical trial.pt.
19. randomized.ab.
20. placebo.ab.
21. clinical trial as topic.sh.
22. randomly.ab.
23. trial.ti.
24. 17 or 18 or 19 or 20 or 21 or 22 or 23
25. exp animals/ not humans.sh.
26. 24 not 25
27. 16 and 26
Appendix 3. Embase (Ovid) search strategy
1. exp minimally invasive surgery/
2. exp laparoscopy/
3. (laparoscop* or coelioscop* or celioscop* or peritoneoscop* or minimally invasive or video assisted surgery).mp.
4. 1 or 2 or 3
5. exp carbon dioxide/
6. exp nitrous oxide/
7. exp nitrogen/
8. exp argon/
9. exp helium/
10. exp gas/
11. (gas* or carbon dioxide or CO2 or nitrous oxide or laughing gas or N2O or nitrogen or N2 or helium or argon).mp.
12. 5 or 6 or 7 or 8 or 9 or 10 or 11
13. exp pneumoperitoneum/
14. pneumoperitoneum*.mp.
15. 13 or 14
16. 4 and 12 and 15
17. CROSSOVER PROCEDURE.sh
18. DOUBLE‐BLIND PROCEDURE.sh
19. SINGLE‐BLIND PROCEDURE.sh
20. (crossover* or cross over*).ti,ab.
21. placebo*.ti,ab.
22. (doubl* adj blind*).ti,ab.
23. allocate*.ti,ab.
24. trial.ti.
25. RANDOMIZED CONTROLLED TRIAL.sh.
26. random*.ti,ab.
27. 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26
28. (exp animal/ or exp invertebrate/ or animal.hw or nonhuman/) not (exp human/ or human cell/ or (human or humans or man or men or wom?n).ti.)
29. 27 not 28
30. 16 and 29
Appendix 4. Science Citation Index Expanded search strategy
#1 Topic=(laparoscop* or coelioscop* or celioscop* or peritoneoscop* or minimally invasive or video assisted surgery)
#2 Topic=(gas* or carbon dioxide or CO2 or nitrous oxide or laughing gas or N2O or nitrogen or N2 or helium or argon)
#3 Topic=(pneumoperitoneum*)
#4 Topic=(randomized or randomised or controlled or trial or clinical or placebo or clinical or randomly or trial)
#5 (#4 AND #3 AND #2 AND #1)
Appendix 5. Criteria for judging risk of bias in the 'Risk of bias' assessment tool
|
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence. | |
| Criteria for a judgement of 'low risk' of bias. | The investigators described a random component in the sequence generation process such as:
aMinimisation may be implemented without a random element, and this is considered to be equivalent to being random. |
| Criteria for the judgement of 'high risk' of bias. | The investigators described a non‐random component in the sequence generation process. Usually, the description would involve some systematic, non‐random approach, e.g.:
Other non‐random approaches happen much less frequently than the systematic approaches mentioned above and tend to be obvious. They usually involve judgement or some method of non‐random categorisation of participants, e.g.:
|
| Criteria for the judgement of 'unclear risk' of bias. | Insufficient information about the sequence generation process to permit judgement of 'low risk' or 'high risk.' |
|
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment. | |
| Criteria for a judgement of 'low risk' of bias. | Participants and investigators enrolling participants could not have foreseen assignment because 1 of the following, or an equivalent method, was used to conceal allocation:
|
| Criteria for the judgement of 'high risk' of bias. | Participants or investigators enrolling participants could possibly have foreseen assignments and thus introduced selection bias, such as allocation based on:
|
| Criteria for the judgement of 'unclear risk' of bias. | Insufficient information to permit judgement of 'low risk' or 'high risk.' This is usually the case if the method of concealment was not described or not described in sufficient detail to allow a definite judgement; e.g. if the use of assignment envelopes was described, but it remained unclear whether envelopes were sequentially numbered, opaque and sealed. |
|
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study. | |
| Criteria for a judgement of 'low risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'high risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'unclear risk' of bias. | Any 1 of the following:
|
|
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors. | |
| Criteria for a judgement of 'low risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'high risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'unclear risk' of bias. | Any 1 of the following:
|
|
Incomplete outcome data Attrition bias due to amount, nature, or handling of incomplete outcome data. | |
| Criteria for a judgement of 'low risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'high risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'unclear risk' of bias. | Any 1 of the following:
|
|
Selective reporting Reporting bias due to selective outcome reporting. | |
| Criteria for a judgement of 'low risk' of bias. | Any of the following:
|
| Criteria for the judgement of 'high risk' of bias. | Any 1 of the following:
|
| Criteria for the judgement of 'unclear risk' of bias. | Insufficient information to permit judgement of 'low risk' or 'high risk'. It is likely that the majority of studies will fall into this category. |
|
Other bias Bias due to problems not covered elsewhere in the table. | |
| Criteria for a judgement of 'low risk' of bias. | Study appeared free of other sources of bias. |
| Criteria for the judgement of 'high risk' of bias. | There was ≥ 1 important risk of bias; e.g. the study:
|
| Criteria for the judgement of 'unclear risk' of bias. | There may be a risk of bias, but there was either:
|
Data and analyses
Comparison 1. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1.1 Cardiopulmonary complications | 3 | 204 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.62 [0.78, 8.85] |
| 1.2 Procedure‐related general complications | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.01 [0.14, 7.31] |
| 1.3 Pain scores (cm) (first postoperative day) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | ‐0.90 [‐2.10, 0.30] |
| 1.4 Analgesia requirements | 4 | 257 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.65 [‐0.90, ‐0.39] |
| 1.4.1 Oxycodone (mg) | 2 | 140 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐1.07 [‐1.42, ‐0.71] |
| 1.4.2 Ibuprofen (tablets/24 hours) | 1 | 53 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.16 [‐0.70, 0.38] |
| 1.4.3 Analgesia use (mg/kg) | 1 | 64 | Std. Mean Difference (IV, Fixed, 95% CI) | ‐0.25 [‐0.74, 0.24] |
| 1.5 Cardiopulmonary changes | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.5.1 Heart rate change (beats/minute) | 1 | 100 | Mean Difference (IV, Fixed, 95% CI) | ‐0.60 [‐4.13, 2.93] |
| 1.5.2 Mean arterial pressure change (mmHg) | 1 | 100 | Mean Difference (IV, Fixed, 95% CI) | ‐3.80 [‐7.90, 0.30] |
| 1.5.3 Oxygen saturation change (%) | 1 | 100 | Mean Difference (IV, Fixed, 95% CI) | 0.00 [‐0.39, 0.39] |
| 1.5.4 Peak airway pressure change (cmH2O) | 1 | 100 | Mean Difference (IV, Fixed, 95% CI) | ‐0.30 [‐2.17, 1.57] |
| 1.6 Cardiopulmonary parameters | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.6.1 Heart rate (beats/minute) (start) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | ‐0.50 [‐7.55, 6.55] |
| 1.6.2 Heart rate (beats/minute) (end) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | 1.30 [‐7.14, 9.74] |
| 1.6.3 Mean arterial pressure (mmHg) (start) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | ‐5.50 [‐13.46, 2.46] |
| 1.6.4 Mean arterial pressure (mmHg) (end) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | 2.90 [‐4.24, 10.04] |
| 1.6.5 Oxygen saturation (%) (start) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐0.60, 0.80] |
| 1.6.6 Oxygen saturation (%) (end) | 1 | 64 | Mean Difference (IV, Fixed, 95% CI) | ‐0.30 [‐1.52, 0.92] |
Comparison 2. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 2.1 Cardiopulmonary complications | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.66 [0.28, 9.72] |
| 2.2 Pneumoperitoneum‐related serious adverse events | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 8.28 [0.86, 80.03] |
| 2.3 Pain scores (cm) (first postoperative day) | 2 | 108 | Mean Difference (IV, Fixed, 95% CI) | 0.49 [‐0.28, 1.26] |
| 2.4 Analgesia requirements (morphine mg) | 1 | 90 | Mean Difference (IV, Fixed, 95% CI) | 12.00 [4.44, 19.56] |
| 2.5 Number of participants requiring analgesia | 1 | 18 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.42 [0.17, 1.04] |
| 2.6 Cardiopulmonary parameters | 3 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 2.6.1 Blood pH (start) | 2 | 34 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.01, 0.04] |
| 2.6.2 Blood pH (middle) | 3 | 52 | Mean Difference (IV, Fixed, 95% CI) | 0.08 [0.06, 0.11] |
| 2.6.3 Blood pH (end) | 2 | 34 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [0.06, 0.14] |
| 2.6.4 Partial pressure of carbon dioxide (mmHg) (start) | 2 | 34 | Mean Difference (IV, Fixed, 95% CI) | 0.31 [‐1.79, 2.40] |
| 2.6.5 Partial pressure of carbon dioxide (mmHg) (middle) | 3 | 52 | Mean Difference (IV, Fixed, 95% CI) | ‐0.84 [‐3.70, 2.02] |
| 2.6.6 Partial pressure of carbon dioxide (mmHg) (end) | 2 | 34 | Mean Difference (IV, Fixed, 95% CI) | ‐12.78 [‐16.78, ‐8.77] |
2.6. Analysis.
Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 6: Cardiopulmonary parameters
Comparison 3. Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 3.1 Cardiopulmonary complications | 1 | 146 | Risk Ratio (M‐H, Fixed, 95% CI) | Not estimable |
| 3.2 Pneumoperitoneum‐related serious adverse events | 1 | 146 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Not estimable |
| 3.3 Pain scores (cm) (first postoperative day) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐0.80 [‐1.15, ‐0.45] |
| 3.4 Hospital costs (CNY) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐2667.00 [‐3275.68, ‐2058.32] |
| 3.5 Cardiopulmonary parameters | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 3.5.1 Heart rate (beats/minute) (start) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐0.10 [‐3.11, 2.91] |
| 3.5.2 Heart rate (beats/minute) (middle) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐7.30 [‐9.78, ‐4.82] |
| 3.5.3 Heart rate (beats/minute) (end) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐8.70 [‐11.72, ‐5.68] |
| 3.5.4 Blood systolic pressure (mmHg) (start) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐1.00 [‐5.12, 3.12] |
| 3.5.5 Blood systolic pressure (mmHg) (middle) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | 2.80 [‐0.44, 6.04] |
| 3.5.6 Blood systolic pressure (mmHg) (end) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐2.00 [‐5.42, 1.42] |
| 3.5.7 Partial pressure of carbon dioxide (mmHg) (start) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐0.20 [‐1.39, 0.99] |
| 3.5.8 Partial pressure of carbon dioxide (mmHg) (middle) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | ‐0.30 [‐1.37, 0.77] |
| 3.5.9 Partial pressure of carbon dioxide (mmHg) (end) | 1 | 146 | Mean Difference (IV, Fixed, 95% CI) | 0.10 [‐1.43, 1.63] |
3.1. Analysis.
Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications
3.2. Analysis.
Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Pneumoperitoneum‐related serious adverse events
3.3. Analysis.
Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)
3.4. Analysis.
Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Hospital costs (CNY)
Comparison 4. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 4.1 Cardiopulmonary complications | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 3.16 [1.03, 9.69] |
| 4.2 Procedure‐related general complications | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 2.01 [0.40, 10.20] |
| 4.3 Pneumoperitoneum‐related serious adverse events | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 7.46 [0.47, 119.30] |
| 4.4 Mortality | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 7.46 [0.47, 119.30] |
Comparison 5. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 5.1 Cardiopulmonary complications | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.66 [0.54, 5.12] |
| 5.2 Procedure‐related general complications | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.51 [0.10, 2.60] |
| 5.3 Pneumoperitoneum‐related serious adverse events | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.14 [0.01, 2.19] |
| 5.4 Mortality | 3 | 207 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.14 [0.01, 2.19] |
Comparison 6. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data).
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 6.1 Cardiopulmonary complications | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 4.66 [1.43, 15.15] |
| 6.2 Procedure‐related general complications | 4 | 144 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 8.89 [1.94, 40.64] |
| 6.3 Pneumoperitoneum‐related serious adverse events | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 9.19 [2.56, 33.01] |
| 6.4 Mortality | 4 | 144 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 8.89 [1.94, 40.64] |
Comparison 7. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data.
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 7.1 Cardiopulmonary complications | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.66 [0.28, 9.72] |
| 7.2 Procedure‐related general complications | 4 | 144 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.12 [0.01, 2.07] |
| 7.3 Pneumoperitoneum‐related serious adverse events | 3 | 128 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 8.28 [0.86, 80.03] |
| 7.4 Mortality | 4 | 144 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.12 [0.01, 2.07] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Aitola 1998.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: Finland, single‐centre Study dates: not reported Number of operating surgeons: 2 Number randomised: 40 Postrandomisation dropout: 1 (2.5%) Intention‐to‐treat‐analysis: no Description of sample size calculation: no Mean age: 48.0 years Females: 32 (66.7%) ASA I or II: 40 (100%) ASA III or IV: 0 (0%) Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: 12–14 mmHg Participants randomly assigned to 2 groups Group 1: nitrous oxide pneumoperitoneum (n = 20) Group 2: carbon dioxide pneumoperitoneum (n = 20) |
|
| Outcomes | Complications, adverse events, cardiopulmonary changes (heart rate, blood pressure, blood pH, partial pressure of carbon dioxide, and mean end‐tidal carbon dioxide), pain, analgesia requirements, operative time, and total gas volume. | |
| Notes | 1 postrandomisation dropout in nitrous oxide group. Reason for postrandomisation dropout: 1 participant developed a painful port‐site rectus sheath haematoma. Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "Neither the nurse nor the patient knew which gas was used". Comment: it was not clear that the surgeon and other clinical staff were adequately blinded. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "The same anesthesiologist, who was blinded to the pneumoperitoneum gas used, took care of the anaesthesia of all the patients. The evaluation of postoperative pain was made on a double‐blind, controlled basis by a trained nurse". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "The only patient who developed a postoperative complication was excluded from the pain analysis". Comment: 1 postrandomisation dropout may be too low an attrition rate to represent a source of bias. |
| Selective reporting (reporting bias) | Low risk | Comment: the study protocol was not available, but it was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
Asgari 2011.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: Iran, single‐centre Study dates: not reported Number of operating surgeons: not reported Number randomised: 64 Postrandomisation dropout: 0 (0%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 40 years Females: 57 (89.1%) ASA I or II: 64 (100%) ASA III or IV: 0 (0%) Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: 12–14 mmHg Participants randomly assigned to 2 groups Group 1: nitrous oxide pneumoperitoneum (n = 32) Group 2: carbon dioxide pneumoperitoneum (n = 32) |
|
| Outcomes | Complications, cardiopulmonary changes (heart rate, blood pressure, oxygen saturation, mean end‐tidal carbon dioxide, and mean minute ventilation), pain, analgesia requirements | |
| Notes | Funding source: not reported Declarations of interest: not reported |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)". |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: no postrandomisation dropouts. |
| Selective reporting (reporting bias) | Low risk | Comment: a study registration was available for 1 study (Asgari 2011), but this registration was done retrospectively after trial conduct. It was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
Bongard 1993.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: USA, single‐centre Study dates: August 1991 to October 1991 Number of operating surgeons: not reported Number randomised: 20 Postrandomisation dropout: 1 (5%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: yes Mean age: 34.4 years Females: 17 (85%) ASA I or II: 20 (100%) ASA III or IV: 0 (0%) Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: 15 mmHg Participants randomly assigned to 2 groups Group 1: helium pneumoperitoneum (n = 10) Group 2: carbon dioxide pneumoperitoneum (n = 10) |
|
| Outcomes | Complications, adverse events, cardiopulmonary changes (heart rate, blood pressure, blood pH, partial pressure of carbon dioxide, bicarbonate concentration, and end‐tidal carbon dioxide), and duration of pneumoperitoneum | |
| Notes | 1 postrandomisation dropout in helium group. Reason for postrandomisation dropout: conversion to open surgery. Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "A computer‐generated code was used to randomise the insufflating agent used". |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "The operating surgeon and anesthesiologist were informed of the randomisation result preoperatively". |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "Patient No. 9 (helium) was converted to an open procedure when the intraoperative cholangiogram showed multiple stones in a dilated common bile duct. The end values for this patient were recorded immediately before celiotomy incision at 110 minutes". |
| Selective reporting (reporting bias) | Low risk | Comment: the study protocol was not available, but it was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | High risk | Quote: "The average weight of the helium group was significantly greater (P<0.02)". |
Gu 2015.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: China, single‐centre Study dates: February 2012 to February 2014 Number of operating surgeons: not reported Number randomised: 146 Postrandomisation dropout: 0 (0%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 44.7 years Females: 83 (56.8%) ASA I or II: not reported ASA III or IV: not reported Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: 12–14 mmHg Participants randomly assigned to 2 groups Group 1: room air pneumoperitoneum (n = 70) Group 2: carbon dioxide pneumoperitoneum (n = 76) |
|
| Outcomes | Complications, adverse events, cardiopulmonary changes (heart rate, blood pressure, partial pressure of carbon dioxide), pain, hospital costs, and duration of hospitalisation | |
| Notes | Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: no information provided. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: no postrandomisation dropouts. |
| Selective reporting (reporting bias) | High risk | Comment: the study protocol was not available, and the study report failed to include results for a key outcome (surgical morbidity) that would be expected to have been reported for such a study. |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
Lipscomb 1993.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: USA, single‐centre Study dates: not reported Number of operating surgeons: 0 Number randomised: 53 Postrandomisation dropout: 0 (0%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 27.6 years Females: 53 (100%) ASA I or II: not reported ASA III or IV: not reported Inclusion criteria:
Exclusion criteria: not reported |
|
| Interventions | Pneumoperitoneum: pressure not reported Participants randomly assigned to 2 groups Group 1: nitrous oxide pneumoperitoneum (n = 29) Group 2: carbon dioxide pneumoperitoneum (n = 24) |
|
| Outcomes | Pain, analgesia requirements, and operative time | |
| Notes | Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were prospectively randomised using computer‐generated numbers". |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: no information provided. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "All data collection was by individuals blinded to the type of gas used". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: no postrandomisation dropouts. |
| Selective reporting (reporting bias) | High risk | Comment: the study protocol was not available, and the study report failed to include results for key outcomes (e.g. cardiopulmonary complications, surgical morbidity) that would be expected to have been reported for such a study. |
| Other bias | High risk | Quote: "There was a significant difference between the two groups in weight (P=0.004)". |
Naude 1996.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: USA, single‐centre Study dates: not reported Number of operating surgeons: not reported Number randomised: 16 Postrandomisation dropout: 2 (12.5%) Intention‐to‐treat‐analysis: no Description of sample size calculation: no Mean age: 34.5 years Females: 16 (100%) ASA I or II: not reported ASA III or IV: not reported Inclusion criteria:
Exclusion criteria: not reported |
|
| Interventions | Pneumoperitoneum: pressure not reported Participants randomly assigned to 2 groups Group 1: helium pneumoperitoneum (n = 8) Group 2: carbon dioxide pneumoperitoneum (n = 8) |
|
| Outcomes | Cardiopulmonary changes (blood pH and partial pressure of carbon dioxide), operative time, and hormone changes (e.g. adrenaline, noradrenaline, cortisol) | |
| Notes | 2 postrandomisation dropouts in carbon dioxide group. Reason for postrandomisation dropout: not reported. Main outcome in trial was hormone changes. Outcomes of interest for this review were blood pH and partial pressure of carbon dioxide. Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "The operating surgeon and the anesthesiologist were notified of the patient's assignment". |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: 2 postrandomisation dropouts. |
| Selective reporting (reporting bias) | High risk | Comment: the study protocol was not available, and the study report failed to include results for key outcomes (e.g. cardiopulmonary complications, serious adverse events) that would be expected to have been reported for such a study. |
| Other bias | High risk | Quote: "There was a significant age difference between the helium and CO2 group". |
Neuhaus 2001.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: Australia, single‐centre Study dates: not reported Number of operating surgeons: not reported Number randomised: 18 Postrandomisation dropout: 0 Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: not reported Females: not reported ASA I or II: not reported ASA III or IV: not reported Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: pressure not reported Participants randomly assigned to 2 groups Group 1: helium pneumoperitoneum (n = 8) Group 2: carbon dioxide pneumoperitoneum (n = 10) |
|
| Outcomes | Complications, adverse events, cardiopulmonary changes (blood pH and partial pressure of carbon dioxide), pain, analgesia requirements, operative time, and total gas volume | |
| Notes | Funding source: Olympus/Gastroenterological Society of Australia Postgraduate Scholarship in Endoscopic Research and Royal Adelaide Hospital Special Purposes Fund. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Low risk | Quote: "All participants gave informed consent, and were randomised in the operating theatre by opening one of 20 previously sealed opaque envelopes". |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "The patients and the investigators were all blinded to which insufflation gas had been used". Comment: it was not clear that the surgeon and other clinical staff were adequately blinded. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "The patients and the investigators were all blinded to which insufflation gas had been used". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: no postrandomisation dropouts. |
| Selective reporting (reporting bias) | Low risk | Comment: the study protocol was not available, but it was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
O'Boyle 2002.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: Australia, single‐centre Study dates: January 2000 to November 2000 Number of operating surgeons: not reported Number randomised: 90 (to groups 1 and 2) Postrandomisation dropout: 6 (6.7%) Intention‐to‐treat‐analysis: yes Description of sample size calculation: no Mean age: 49.0 years Females: 58 (64%) ASA I or II: 82 (91.1%) ASA III or IV: 8 (8.9%) Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: pressure not reported Participants (n = 173) were randomly assigned to 4 groups Group 1: helium pneumoperitoneum (n = 43) Group 2: carbon dioxide pneumoperitoneum (n = 47) Group 3: carbon dioxide pneumoperitoneum with saline lavage (n = 43). We planned to combine groups to create a single pair‐wise comparison for trials with multiple intervention groups. However, the saline lavage may decrease postoperative pain after laparoscopic surgery, which may be a confounding factor when we assess the effect of helium pneumoperitoneum on postoperative pain scores. Thus, this group was not included in the review. Group 4: helium pneumoperitoneum with saline lavage (n = 40). This group was also not included in the review. |
|
| Outcomes | Complications, adverse events, pain, analgesia requirements, operative time, hospital stay, and total gas volume | |
| Notes | There were 6 postrandomisation dropouts in the helium alone group. Reason for postrandomisation dropout: conversion to open surgery. Funding source: National Health and Medical Research Council of Australia. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Low risk | Quote: "Randomisation was performed by opening a sealed envelope for each patient in the operating theatre". |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Quote: "The operating surgeon was not aware of the gas chosen until anaesthesia had commenced, and patients were blinded to the gas used throughout the study". Comment: it was not clear that the surgeon and other clinical staff were adequately blinded. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "Post‐operative assessment was also performed by a blinded investigator". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "All data analysis was performed on an intention‐to‐treat basis. Where conversion to an open procedure was necessary, patients remained in their original allocated group". |
| Selective reporting (reporting bias) | Low risk | Comment: the study protocol was not available, but it was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
Sietses 2002.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: Netherlands, single‐centre Study dates: not reported Number of operating surgeons: not reported Number randomised: 33 Postrandomisation dropout: 6 (18.2%) Intention‐to‐treat‐analysis: no Description of sample size calculation: no Mean age: 49.0 years Females: not reported ASA I or II: 33 (100%) ASA III or IV: 0 (0%) Inclusion criteria:
Exclusion criteria:
|
|
| Interventions | Pneumoperitoneum: pressure not reported Participants (n = 33) were randomly 3 groups Group 1: helium pneumoperitoneum (n = not reported) Group 2: carbon dioxide pneumoperitoneum (n = not reported) Group 3: abdominal wall lift (n = not reported) |
|
| Outcomes | Peripheral white blood cell, C‐reactive protein, interleukin‐6, and HLA‐DR (human leukocyte antigen – antigen D related) expression | |
| Notes | Reason for 6 postrandomisation dropouts: conversion to open surgery (n = 2, 1 from the helium group and 1 from the carbon dioxide group) and conversion from abdominal wall lift to carbon dioxide pneumoperitoneum (n = 4). All 6 excluded from the protocol. Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Comment: no information provided. |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | Comment: no information provided. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: no information provided. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: 6 postrandomisation dropouts. |
| Selective reporting (reporting bias) | High risk | Comment: the study protocol was not available, and the study report failed to include results for key outcomes (e.g. cardiopulmonary complications, serious adverse events) that would be expected to have been reported for such a study. |
| Other bias | Low risk | Comment: study appeared free of other sources of bias. |
Tsereteli 2002.
| Study characteristics | ||
| Methods | Randomised controlled trial | |
| Participants | Country: USA, single‐centre Study dates: March 1999 to November 2000 Number of operating surgeons: 1 Number randomised: 103 Postrandomisation dropout: 3 (2.8%) Intention‐to‐treat‐analysis: no Description of sample size calculation: yes Mean age: 47.5 years Females: 35 (45.5%) ASA I or II: 84 (84%) ASA III or IV: 16 (16%) Inclusion criteria:
Exclusion criteria: not reported |
|
| Interventions | Pneumoperitoneum: pressure not reported Participants randomly assigned to 2 group Group 1: nitrous oxide pneumoperitoneum (n = 51) Group 2: carbon dioxide pneumoperitoneum (n = 52) |
|
| Outcomes | Complications, adverse events, cardiopulmonary changes (heart rate, blood pressure, oxygen saturation, peak inspiratory pressure, mean end‐tidal carbon dioxide, and mean minute ventilation), pain, analgesia requirements, operative time, duration of pneumoperitoneum, and hospital stay | |
| Notes | 2 postrandomisation dropouts in carbon dioxide group. Reason for postrandomisation dropout: 1 participant was converted from laparoscopic surgery to laparotomy, and 1 participant demonstrated an oesophageal leak, which required thoracotomy to repair and extended hospital stay to 15 days. 1 postrandomisation dropout in nitrous oxide group. Reason for postrandomisation dropout: participant had repeat laparoscopy on postoperative day 1 because of herniation of fundoplication. Funding source: not reported. Declarations of interest: not reported. |
|
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Comment: no information provided. |
| Allocation concealment (selection bias) | Unclear risk | Quote: "Patients were randomised after induction of general anaesthesia by an envelope drawing". Comment: not reported if the envelope was sealed. |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Quote: "Patients and anesthesiologists were blinded to the pneumoperitoneum gas used until the patient was discharged from the hospital. Although an attempt was made to blind the surgeon to the insufflating gas, differences in insufflation apparatus made this difficult". Comment: the surgeon was not blinded adequately. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "Pain assessor (ZT) was blinded to the pneumoperitoneum gas used until the patient was discharged from the hospital". |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: 3 postrandomisation dropouts may be too low an attrition rate to represent a source of bias. |
| Selective reporting (reporting bias) | Low risk | Comment: the study protocol was not available, but it was clear that the published reports included all expected outcomes (e.g. cardiopulmonary complications, surgical morbidity, serious adverse events). |
| Other bias | Low risk | Comment: study appears free of other sources of bias. |
ASA: American Society of Anesthesiologists; n: number of participants.
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Fernández‐Cruz 1998 | Non‐randomised study. |
| Lipscomb 1994 | Laparoscopic pelvic surgery performed by gynaecology surgeons under local anaesthesia. |
| McMahon 1994 | Non‐randomised study. |
| Minoli 1982 | Diagnostic laparoscopy performed under local anaesthesia. |
| Neuberger 1996 | Non‐randomised study. |
| O'Connor 2017 | Non‐randomised study. |
| Ooka 1993 | Non‐randomised study. |
| Rammohan 2011 | Non‐randomised study. |
| Sharp 1982 | Diagnostic laparoscopy performed under local anaesthesia. |
| Zheng 2014 | Non‐randomised study. |
Characteristics of studies awaiting classification [ordered by study ID]
Bergstrom 2015.
| Methods | Randomised controlled trial? |
| Participants | Country: Sweden Number of participants: 30 Mean age: not reported Females: not reported ASA I or II: not reported ASA III or IV: not reported Inclusion criteria: elective laparoscopic cholecystectomy Exclusion criteria: not reported |
| Interventions | Pneumoperitoneum: pressure not reported Participants randomly assigned to 2 groups Group 1: helium pneumoperitoneum (n = 15) Group 2: carbon dioxide pneumoperitoneum (n = 15) |
| Outcomes | Peritoneal pH, peritoneal fibrinolytic components, and peritoneal fibrinolytic capacity |
| Notes | Conference abstract. It needs further classification because we could not judge whether it is a true randomised controlled trial from the abstract. |
Differences between protocol and review
We excluded cluster randomised controlled trials in the review stage because we did not expect to find any studies of this type.
We evaluated the certainty of evidence using the GRADE approach and applied the trial sequential analysis (TSA) approach for improving the reliability of conclusions, which we had not stated in the protocol.
We were unable to perform subgroup analysis or explore publication bias because of the few trials included in each comparison.
We intended to exclude people who underwent laparoscopic pelvic surgery performed by gynaecologic surgeons in the protocol stage. However, we included these participants in the review stage according to the peer reviewers' suggestions because pelvic surgery is a type of abdominal surgery.
We excluded studies on people undergoing laparoscopic abdominal surgery under local anaesthesia in the review stage because laparoscopic abdominal surgeries are always performed under general anaesthesia nowadays.
Room air versus carbon dioxide has now been included specifically as a comparison.
We contacted the original investigators to request further information. We obtained additional information from two studies (Asgari 2011; Gu 2015). However, there was no reply in other cases.
Contributions of authors
All authors in this updated review fulfilled the following four criteria:
substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND
drafting the work or revising it critically for important intellectual content; AND
final approval of the version to be published; AND
agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Sources of support
Internal sources
-
Chongqing Medical University, China
This review was supported by National Natural Science Foundation of China (Grant No. 81701950, 82172135), Medical Research Projects of Chongqing (Grant No. 2018MSXM132), and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University (Grant No. KY2019Y002).
-
National Key R&D Program, China
Research and Application Demonstration of Information Technology for Food Safety Social Co‐governance (Foundation：2017YFC1602000).
External sources
-
New Source of support, Other
No sources of support provided
Declarations of interest
XY: none.
YC: none.
NC: none.
JG: none.
LB: none.
LZ: none.
YD: none.
Edited (conclusions changed)
References
References to studies included in this review
Aitola 1998 {published data only}
- Aitola P, Airo I, Kaukinen S, Ylitalo P.Comparison of N2O and CO2 pneumoperitoneums during laparoscopic cholecystectomy with special reference to postoperative pain. Surgical Laparoscopy Endoscopy 1998;8(2):140-4. [PubMed] [Google Scholar]
Asgari 2011 {published data only}
- Asgari M, Ahmadzadeh M, Akhoundzadeh R, Pourmehdi Z, Dorostan N.A randomized clinical trial, comparing nitrous oxide and carbon dioxide for producing pneumoperitoneum in laparoscopic cholecystectomy. Iranian Journal of Surgery 2011;19(3):1930. [Google Scholar]
- NCT01512511.Comparing nitrous oxide and carbon dioxide for laparoscopic cholecystectomy. clinicaltrials.gov/ct2/show/NCT01512511 (first received 15 January 2012).
Bongard 1993 {published data only}
- Bongard FS, Pianim NA, Leighton TA, Dubecz S, Davis IP, Lippmann M, et al.Helium insufflation for laparoscopic operation. Surgery Gynecology & Obstetrics 1993;177(2):140-6. [PubMed] [Google Scholar]
Gu 2015 {published data only}
- Gu Y, Wu W.Clinical application value of air insufflation medium under laparoscopic cholecystectomy [空气膨腹介质下腹腔镜胆囊切除术的临床应用价值]. Chinese and Foreign Medical Research 2015;13(1):8-9. [Google Scholar]
Lipscomb 1993 {published data only}
- Lipscomb GH, Stovall TG, Summitt RL Jr, Ling FW.The effect of nitrous oxide and carbon dioxide pneumoperitoneum on post laparoscopy tubal ligation pain. Journal of Gynecologic Surgery 1993;9(3):175-8. [Google Scholar]
Naude 1996 {published data only}
- Naude GP, Ryan MK, Pianim NA, Klein SR, Lippmann M, Bongard FS.Comparative stress hormone changes during helium versus carbon dioxide laparoscopic cholecystectomy. Journal of Laparoendoscopic Surgery 1996;6(2):93-8. [DOI] [PubMed] [Google Scholar]
Neuhaus 2001 {published data only}
- Neuhaus SJ, Watson DI, Ellis T, Lafullarde T, Jamieson GG, Russell WJ.Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study. ANZ Journal of Surgery 2001;71(8):447-52. [DOI] [PubMed] [Google Scholar]
O'Boyle 2002 {published data only}
- O'Boyle CJ, deBeaux AC, Watson DI, Ackroyd R, Lafullarde T, Leong JY, et al.Helium vs carbon dioxide gas insufflation with or without saline lavage during laparoscopy. Surgical Endoscopy 2002;16(4):620-5. [DOI] [PubMed] [Google Scholar]
Sietses 2002 {published data only}
- Sietses C, von Blomberg ME, Eijsbouts QA, Beelen RH, Berends FJ, Cuesta MA.The influence of CO2 versus helium insufflation or the abdominal wall lifting technique on the systemic immune response. Surgical Endoscopy 2002;16(3):525-8. [DOI] [PubMed] [Google Scholar]
Tsereteli 2002 {published data only}
- Tsereteli Z, Terry ML, Bowers SP, Spivak H, Archer SB, Galloway KD, et al.Prospective randomized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery. Journal of the American College of Surgeons 2002;195(2):173-9. [DOI] [PubMed] [Google Scholar]
References to studies excluded from this review
Fernández‐Cruz 1998 {published data only}
- Fernández-Cruz L, Sáenz A, Taurá P, Sabater L, Astudillo E, Fontanals J.Helium and carbon dioxide pneumoperitoneum in patients with pheochromocytoma undergoing laparoscopic adrenalectomy. World Journal of Surgery 1998;22(12):1250-5. [DOI] [PubMed] [Google Scholar]
Lipscomb 1994 {published data only}
- Lipscomb GH, Summitt RL Jr, McCord ML, Ling FW.The effect of nitrous oxide and carbon dioxide pneumoperitoneum on operative and postoperative pain during laparoscopic sterilization under local anesthesia. Journal of the American Association of Gynecologic Laparoscopists 1994;2(1):57-60. [DOI] [PubMed] [Google Scholar]
McMahon 1994 {published data only}
- McMahon AJ, Baxter JN, Murray W, Imrie CW, Kenny G, O'Dwyer PJ.Helium pneumoperitoneum for laparoscopic cholecystectomy: ventilatory and blood gas changes. British Journal of Surgery 1994;81(7):1033-6. [DOI] [PubMed] [Google Scholar]
Minoli 1982 {published data only}
- Minoli G, Terruzzi V, Spinzi GC, Benvenuti C, Rossini A.The influence of carbon dioxide and nitrous oxide on pain during laparoscopy: a double-blind, controlled trial. Gastrointestinal Endoscopy 1982;28(3):173-5. [DOI] [PubMed] [Google Scholar]
Neuberger 1996 {published data only}
- Neuberger TJ, Andrus CH, Wittgen CM, Wade TP, Kaminski DL.Prospective comparison of helium versus carbon dioxide pneumoperitoneum. Gastrointestinal Endoscopy 1996;43(1):38-41. [DOI] [PubMed] [Google Scholar]
O'Connor 2017 {published data only}
- O'Connor Z, Faniriko M, Thelander K, O'Connor J, Thompson D, Park A.Laparoscopy using room air insufflation in a rural African jungle hospital: the Bongolo hospital experience, January 2006 to December 2013. Surgical Innovation 2017;24(3):264-7. [DOI] [PubMed] [Google Scholar]
Ooka 1993 {published data only}
- Ooka T, Kawano Y, Kosaka Y, Tanaka A.Blood gas changes during laparoscopic cholecystectomy – comparative study of N2O pneumoperitoneum and CO2 pneumoperitoneum. Masui. The Japanese Journal of Anesthesiology 1993;42(3):398-401. [PubMed] [Google Scholar]
Rammohan 2011 {published data only}
- Rammohan A, Manimaran AB, Manohar RR, Naidu RM.Nitrous oxide for pneumoperitoneum: no laughing matter this! A prospective single blind case controlled study. International Journal of Surgery (London, England) 2011;9(2):173-6. [DOI] [PubMed] [Google Scholar]
Sharp 1982 {published data only}
- Sharp JR, Pierson WP, Brady CE 3rd.Comparison of CO2- and N2O-induced discomfort during peritoneoscopy under local anesthesia. Gastroenterology 1982;82(3):453-6. [PubMed] [Google Scholar]
Zheng 2014 {published data only}
- Zheng J, Peng Y, Zhong L, Mo C, He L.Comparing room air and carbon dioxide pneumoperitoneum in laparoscopic cholecystectomy [空气与二氧化碳气腹腹腔镜胆囊切除术的比较]. Chinese Journal of Minimally Invasive Surgery 2014;5(14):389-92. [Google Scholar]
References to studies awaiting assessment
Bergstrom 2015 {published data only}
- Bergstrom M, Park PO, Falk P, Haglind E, Holmdahl L.Clinical evaluation of peritoneal acidification and fibrinolytic response during laparoscopy comparing CO2 and helium. Surgical Endoscopy and Other Interventional Techniques 2015;29:S527. [Google Scholar]
Additional references
Aboumarzouk 2011
- Aboumarzouk OM, Agarwal T, Syed Nong Chek SA, Milewski PJ, Nelson RL.Nitrous oxide for colonoscopy. Cochrane Database of Systematic Reviews 2011, Issue 8. Art. No: CD008506. [DOI: 10.1002/14651858.CD008506.pub2] [DOI] [PubMed] [Google Scholar]
Ahmad 2019
- Ahmad G, Gent D, Henderson D, O'Flynn H, Phillips K, Watson A.Laparoscopic entry techniques. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No: CD006583. [DOI: 10.1002/14651858.CD006583.pub5] [DOI] [PubMed] [Google Scholar]
Antoniou 2015
- Antoniou SA, Antoniou GA, Antoniou AI, Granderath FA.Past, present, and future of minimally invasive abdominal surgery. Journal of the Society of Laparoendoscopic Surgeons 2015;13(29):e2015.00052. [DOI] [PMC free article] [PubMed] [Google Scholar]
Best 2016
- Best LM, Mughal M, Gurusamy KS.Laparoscopic versus open gastrectomy for gastric cancer. Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No: CD011389. [DOI: 10.1002/14651858.CD011389.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]
Birch 2016
- Birch DW, Dang JT, Switzer NJ, Manouchehri N, Shi X, Hadi G, et al.Heated insufflation with or without humidification for laparoscopic abdominal surgery. Cochrane Database of Systematic Reviews 2016, Issue 10. Art. No: CD007821. [DOI: 10.1002/14651858.CD007821.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Brok 2008
- Brok J, Thorlund K, Gluud C, Wetterslev J.Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. Journal of Clinical Epidemiology 2008;61(8):763-9. [DOI] [PubMed] [Google Scholar]
Chandler 2020
- Chandler J, Lasserson T, Higgins JP, Tovey D, Thomas J, Flemyng E, et al.Standards for the planning, conduct and reporting of updates of Cochrane Intervention Reviews. In: Higgins JP, Lasserson T, Chandler J, Tovey D, Thomas J, Flemyng E, et al. Methodological Expectations of Cochrane Intervention Reviews. Cochrane, March 2020. Available from community.cochrane.org/mecir-manual.
Chen 2017
- Chen YQ, Xie YY, Wang B, Jin XJ.Effect of stellate ganglion block on hemodynamics and stress responses during CO(2)-pneumoperitoneum in elderly patients. Journal of Clinical Anesthesia 2017;37(1):149-53. [DOI] [PubMed] [Google Scholar]
Cheng 2012a
- Cheng Y, Xiong XZ, Wu SJ, Lin YX, Cheng NS.Laparoscopic vs. open cholecystectomy for cirrhotic patients: a systematic review and meta-analysis. Hepato-gastroenterology 2012;59(118):1727-34. [DOI] [PubMed] [Google Scholar]
Cheng 2012b
- Cheng Y, Xiong XZ, Wu SJ, Lu J, Lin YX, Cheng NS, et al.Carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography: a meta-analysis and systematic review. World Journal of Gastroenterology 2012;18(39):5622-31. [DOI] [PMC free article] [PubMed] [Google Scholar]
Clavien 2009
- Clavien PA, Barkun J, Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al.The Clavien-Dindo classification of surgical complications: five-year experience. Annals of Surgery 2009;250(2):187-96. [DOI] [PubMed] [Google Scholar]
Dasari 2011
- Dasari BV, McKay D, Gardiner K.Laparoscopic versus open surgery for small bowel Crohn's disease. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No: CD006956. [DOI: 10.1002/14651858.CD006956.pub2] [DOI] [PubMed] [Google Scholar]
Deeks 2021
- Deeks JJ, Higgins JP, Altman DG.Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.
Deng 2020
- Deng Y, He S, Cheng Y, Cheng N, Gong J, Gong J, et al.Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. Cochrane Database of Systematic Reviews 2020, Issue 3. Art. No: CD009621. [DOI: 10.1002/14651858.CD009621.pub4] [DOI] [PMC free article] [PubMed] [Google Scholar]
Eaton 2009
- Eaton S, McHoney M, Giacomello L, Pacilli M, Bishay M, De Coppi P, et al.Carbon dioxide absorption and elimination in breath during minimally invasive surgery. Journal of Breath Research 2009;3(4):047005. [DOI] [PubMed] [Google Scholar]
Gurusamy 2014
- Gurusamy KS, Vaughan J, Davidson BR.Low pressure versus standard pressure pneumoperitoneum in laparoscopic cholecystectomy. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No: CD006930. [DOI: 10.1002/14651858.CD006930.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Higgins 2017
- Higgins JP, Altman DG, Sterne JA.Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017), Cochrane, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Higgins 2021
- Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s).Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.
Ikechebelu 2005
- Ikechebelu JI, Obi RA, Udigwe GO, Joe-Ikechebelu NN.Comparison of carbon dioxide and room air pneumoperitoneum for day-case diagnostic laparoscopy. Journal of Obstetrics and Gynaecology 2005;25(2):172-3. [DOI] [PubMed] [Google Scholar]
Jaschinski 2018
- Jaschinski T, Mosch CG, Eikermann M, Neugebauer EA, Sauerland S.Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No: CD001546. [DOI: 10.1002/14651858.CD001546.pub4] [DOI] [PMC free article] [PubMed] [Google Scholar]
Kabakchiev 2020
- Kabakchiev C, Valverde A, Singh A, Beaufrère H.Cardiovascular and respiratory effects of carbon dioxide pneumoperitoneum in the domestic rabbit (Oryctolagus cuniculus). Canadian Journal of Veterinary Research 2020;84(2):108-14. [PMC free article] [PubMed] [Google Scholar]
Katz 2015
- Katz NP, Paillard FC, Ekman E.Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. Journal of Orthopaedic Surgery and Research 2015;10:24. [DOI] [PMC free article] [PubMed] [Google Scholar]
Keus 2006
- Keus F, Jong J, Gooszen HG, Laarhoven CJ.Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No: CD006231. [DOI: 10.1002/14651858.CD006231] [DOI] [PubMed] [Google Scholar]
Kuhry 2008
- Kuhry E, Schwenk W, Gaupset R, Romild U, Bonjer HJ.Long-term results of laparoscopic colorectal cancer resection. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No: CD003432. [DOI: 10.1002/14651858.CD003432.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]
la Chapelle 2015
- la Chapelle CF, Swank HA, Wessels ME, Mol BW, Rubinstein SM, Jansen FW.Trocar types in laparoscopy. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No: CD009814. [DOI: 10.1002/14651858.CD009814.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]
Lefebvre 2021
- Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al.Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.
Li 2018
- Li Z, Zhao L, Cheng Y, Cheng N, Deng Y.Abdominal drainage to prevent intra-peritoneal abscess after open appendectomy for complicated appendicitis. Cochrane Database of Systematic Reviews 2018, Issue 5. Art. No: CD010168. [DOI: 10.1002/14651858.CD010168.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Nabi 2016
- Nabi G, Cleves A, Shelley M.Surgical management of localised renal cell carcinoma. Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No: CD006579. [DOI: 10.1002/14651858.CD006579.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Neudecker 2002
- Neudecker J, Sauerland S, Neugebauer E, Bergamaschi R, Bonjer HJ, Cuschieri A, et al.The European Association for Endoscopic Surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surgical Endoscopy 2002;16(7):1121-43. [DOI] [PubMed] [Google Scholar]
Parker 2013
- Parker SL, Godil SS, Shau DN, Mendenhall SK, McGirt MJ.Assessment of the minimum clinically important difference in pain, disability, and quality of life after anterior cervical discectomy and fusion: clinical article. Journal of Neurosurgery. Spine 2013;18(2):154-60. [DOI] [PubMed] [Google Scholar]
Peng 2018
- Peng H, Zhang J, Cai C, Fang X, Wu J.The influence of carbon dioxide pneumoperitoneum on systemic inflammatory response syndrome and bacterial translocation in patients with bacterial peritonitis caused by acute appendicitis. Surgical Innovation 2018;25(1):7-15. [DOI] [PubMed] [Google Scholar]
Rao 2013
- Rao AM, Ahmed I.Laparoscopic versus open liver resection for benign and malignant hepatic lesions in adults. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No: CD010162. [DOI: 10.1002/14651858.CD010162.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]
Review Manager 2020 [Computer program]
- Nordic Cochrane Centre, The Cochrane Collaboration Review Manager (RevMan).Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020.
Richter 2012
- Richter S, Hückstädt T, Aksakal D, Klitscher D, Wowra T, Till H, et al.Embolism risk analysis – helium versus carbon dioxide. Journal of Laparoendoscopic and Advanced Surgical Techniques 2012;22(8):824-9. [DOI] [PubMed] [Google Scholar]
Riviere 2016
- Riviere D, Gurusamy KS, Kooby DA, Vollmer CM, Besselink MG, Davidson BR, et al.Laparoscopic versus open distal pancreatectomy for pancreatic cancer. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD011391. [DOI: 10.1002/14651858.CD011391.pub2] [DOI] [PMC free article] [PubMed] [Google Scholar]
Roberto Rodrigues Bicalho 2020
- Roberto Rodrigues Bicalho P, Magna Ribeiro F, Henrique Ferreira Marçal P, Gomes de Alvarenga D, Silva FS.Does helium pneumoperitoneum reduce the hyperinflammatory response in septic animals during laparoscopy? Surgery Research and Practice 2020;2020:5738236. [DOI] [PMC free article] [PubMed] [Google Scholar]
Sanabria 2013
- Sanabria A, Villegas MI, Morales Uribe CH.Laparoscopic repair for perforated peptic ulcer disease. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No: CD004778. [DOI: 10.1002/14651858.CD004778.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]
Schünemann 2009
- Schünemann H, Brozek J, Oxman A, editor(s).GRADE handbook for grading quality of evidence and strength of recommendations. Version 3.2 (updated March 2009). The GRADE Working Group, 2009. Available from www.cc-ims.net/gradepro.
Scott 2020
- Scott J, Singh A, Valverde A.Pneumoperitoneum in veterinary laparoscopy: a review. Veterinary Science 2020;7(2):64. [DOI] [PMC free article] [PubMed] [Google Scholar]
Shin 2019
- Shin RD, Lis R, Levergood NR, Brooks DC, Shoji BT, Tavakkoli A.Laparoscopic versus open splenectomy for splenomegaly: the verdict is unclear. Surgical Endoscopy 2019;33(4):1298-303. [DOI] [PubMed] [Google Scholar]
Sidler 2020
- Sidler M, Wong ZH, Eaton S, Ahmad N, Ong M, Morsi A, et al.Insufflation in minimally invasive surgery: is there any advantage in staying low? Journal of Pediatric Surgery. 2020;55(7):1356-62. [DOI] [PubMed] [Google Scholar]
Sterne 2017
- Sterne JA, Egger M, Moher D, Boutron I.Chapter 10: Addressing reporting biases. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from training.cochrane.org/handbook/archive/v5.2.
Todd 1996
- Todd KH, Funk JP.The minimum clinically important difference in physician-assigned visual analog pain scores. Academic Emergency Medicine 1996;3(2):142-6. [DOI] [PubMed] [Google Scholar]
TSA 2011 [Computer program]
- Copenhagen Trial Unit TSA – Trial Sequential Analysis.Copenhagen Trial Unit, Version 0.9.5.5 Beta. Copenhagen: Copenhagen Trial Unit, 2011.
Vilos 2017
- Vilos GA, Ternamian A, Dempster J, Laberge PY.No. 193 – laparoscopic entry: a review of techniques, technologies, and complications. Journal of Obstetrics and Gynaecology Canada 2017;39(7):e69-e84. [DOI] [PubMed] [Google Scholar]
Wetterslev 2008
- Wetterslev J, Thorlund K, Brok J, Gluud C.Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. Journal of Clinical Epidemiology 2008;61(1):64-75. [DOI] [PubMed] [Google Scholar]
Wetterslev 2009
- Wetterslev J, Thorlund K, Brok J, Gluud C.Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Medical Research Methodology 2009;9:86. [DOI] [PMC free article] [PubMed] [Google Scholar]
Ypsilantis 2016
- Ypsilantis P, Lambropoulou M, Tentes I, Chryssidou M, Georgantas T, Simopoulos C.Room air versus carbon dioxide pneumoperitoneum: effects on oxidative state, apoptosis and histology of splanchnic organs. Surgical Endoscopy 2016;30(4):1388-95. [DOI] [PubMed] [Google Scholar]
References to other published versions of this review
Cheng 2013
- Cheng Y, Lu J, Xiong X, Wu S, Lin Y, Wu T, et al.Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery. Cochrane Database of Systematic Reviews 2013, Issue 1. Art. No: CD009569. [DOI: 10.1002/14651858.CD009569.pub2] [DOI] [PubMed] [Google Scholar]
Lu 2012
- Lu J, Cheng Y, Xiong X, Wu S, Lin Y, Wu T, et al.Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No: CD009569. [DOI: 10.1002/14651858.CD009569] [DOI] [PubMed] [Google Scholar]
Yu 2017
- Yu T, Cheng Y, Wang X, Tu B, Cheng N, Gong J, et al.Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No: CD009569. [DOI: 10.1002/14651858.CD009569.pub3] [DOI] [PMC free article] [PubMed] [Google Scholar]