Gases for establishing pneumoperitoneum during laparoscopic abdominal surgery

Xudong Yang; Yao Cheng; Nansheng Cheng; Jianping Gong; Lian Bai; Longshuan Zhao; Yilei Deng

doi:10.1002/14651858.CD009569.pub4

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Figure 1

Study flow diagram.

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Figure 2

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

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Figure 3

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

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Figure 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.

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Figure 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.

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Figure 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.

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Figure 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.

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Analysis 1.1

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications

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Analysis 1.2

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Procedure‐related general complications

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Analysis 1.3

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)

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Analysis 1.4

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Analgesia requirements

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Analysis 1.5

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Cardiopulmonary changes

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Analysis 1.6

Comparison 1: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 6: Cardiopulmonary parameters

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Analysis 2.1

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications

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Analysis 2.2

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Pneumoperitoneum‐related serious adverse events

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Analysis 2.3

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)

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Analysis 2.4

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Analgesia requirements (morphine mg)

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Analysis 2.5

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Number of participants requiring analgesia

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Analysis 2.6

Comparison 2: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 6: Cardiopulmonary parameters

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Analysis 3.1

Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 1: Cardiopulmonary complications

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Analysis 3.2

Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 2: Pneumoperitoneum‐related serious adverse events

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Analysis 3.3

Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 3: Pain scores (cm) (first postoperative day)

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Analysis 3.4

Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 4: Hospital costs (CNY)

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Analysis 3.5

Comparison 3: Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum, Outcome 5: Cardiopulmonary parameters

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Analysis 4.1

Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 1: Cardiopulmonary complications

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Analysis 4.2

Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 2: Procedure‐related general complications

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Analysis 4.3

Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 3: Pneumoperitoneum‐related serious adverse events

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Analysis 4.4

Comparison 4: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 4: Mortality

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Analysis 5.1

Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 1: Cardiopulmonary complications

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Analysis 5.2

Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 2: Procedure‐related general complications

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Analysis 5.3

Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 3: Pneumoperitoneum‐related serious adverse events

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Analysis 5.4

Comparison 5: Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 4: Mortality

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Analysis 6.1

Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 1: Cardiopulmonary complications

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Analysis 6.2

Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 2: Procedure‐related general complications

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Analysis 6.3

Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 3: Pneumoperitoneum‐related serious adverse events

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Analysis 6.4

Comparison 6: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data), Outcome 4: Mortality

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Analysis 7.1

Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 1: Cardiopulmonary complications

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Analysis 7.2

Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 2: Procedure‐related general complications

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Analysis 7.3

Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 3: Pneumoperitoneum‐related serious adverse events

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Analysis 7.4

Comparison 7: Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data, Outcome 4: Mortality

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Summary of findings 1. Nitrous oxide versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with carbon dioxide pneumoperitoneum	Risk with nitrous oxide pneumoperitoneum	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
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 low^a,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 low^a,b	—
Pneumoperitoneum‐related serious adverse events Follow‐up: 0–1 month	See comment	See comment	Not estimable	260 (4 studies)	⊕⊝⊝⊝ Very low^b,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 low^b,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 low^c,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 low^c,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 1. Nitrous oxide versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

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Summary of findings 2. Helium versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with carbon dioxide pneumoperitoneum	Risk with helium pneumoperitoneum	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
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 low^a,b	—
Procedure‐related general complications (surgical morbidity) Follow‐up: 0–1 month	See comment	See comment	Not estimable	177 (5 studies)	⊕⊝⊝⊝ Very low^b,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 low^a,b	—
Mortality Follow‐up: 0–1 month	See comment	See comment	Not estimable	177 (5 studies)	⊕⊝⊝⊝ Very low^b,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)	⊕⊕⊝⊝ Low^d,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 low^d,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 2. Helium versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

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Summary of findings 3. Room air versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with carbon dioxide pneumoperitoneum	Risk with room air pneumoperitoneum	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
Cardiopulmonary complications Follow‐up: 1 month	See comment	See comment	Not estimable	146 (1 study)	⊕⊝⊝⊝ Very low^a,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 low^a,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 low^a,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 low^a,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 low^a,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).

Summary of findings 3. Room air versus carbon dioxide for establishing pneumoperitoneum during laparoscopic abdominal surgery

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Table 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)
Outcomes	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).

Table 1. Sensitivity analysis by changing between worst‐case scenario analysis and best‐case scenario analysis for missing data

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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 Show forest plot	3	204	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.62 [0.78, 8.85]

1.2 Procedure‐related general complications Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.01 [0.14, 7.31]

1.3 Pain scores (cm) (first postoperative day) Show forest plot	1	64	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐2.10, 0.30]

1.4 Analgesia requirements Show forest plot	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 Show forest plot	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 Show forest plot	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 1. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum

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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 Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.66 [0.28, 9.72]

2.2 Pneumoperitoneum‐related serious adverse events Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	8.28 [0.86, 80.03]

2.3 Pain scores (cm) (first postoperative day) Show forest plot	2	108	Mean Difference (IV, Fixed, 95% CI)	0.49 [‐0.28, 1.26]

2.4 Analgesia requirements (morphine mg) Show forest plot	1	90	Mean Difference (IV, Fixed, 95% CI)	12.00 [4.44, 19.56]

2.5 Number of participants requiring analgesia Show forest plot	1	18	Risk Ratio (M‐H, Fixed, 95% CI)	0.42 [0.17, 1.04]

2.6 Cardiopulmonary parameters Show forest plot	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]

Comparison 2. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum

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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 Show forest plot	1	146	Risk Ratio (M‐H, Fixed, 95% CI)	Not estimable

3.2 Pneumoperitoneum‐related serious adverse events Show forest plot	1	146	Peto Odds Ratio (Peto, Fixed, 95% CI)	Not estimable

3.3 Pain scores (cm) (first postoperative day) Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	‐0.80 [‐1.15, ‐0.45]

3.4 Hospital costs (CNY) Show forest plot	1	146	Mean Difference (IV, Fixed, 95% CI)	‐2667.00 [‐3275.68, ‐2058.32]

3.5 Cardiopulmonary parameters Show forest plot	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]

Comparison 3. Room air pneumoperitoneum versus carbon dioxide pneumoperitoneum

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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 Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	3.16 [1.03, 9.69]

4.2 Procedure‐related general complications Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.01 [0.40, 10.20]

4.3 Pneumoperitoneum‐related serious adverse events Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.46 [0.47, 119.30]

4.4 Mortality Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	7.46 [0.47, 119.30]

Comparison 4. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data)

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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 Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.66 [0.54, 5.12]

5.2 Procedure‐related general complications Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.51 [0.10, 2.60]

5.3 Pneumoperitoneum‐related serious adverse events Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.14 [0.01, 2.19]

5.4 Mortality Show forest plot	3	207	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.14 [0.01, 2.19]

Comparison 5. Nitrous oxide pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data

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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 Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	4.66 [1.43, 15.15]

6.2 Procedure‐related general complications Show forest plot	4	144	Peto Odds Ratio (Peto, Fixed, 95% CI)	8.89 [1.94, 40.64]

6.3 Pneumoperitoneum‐related serious adverse events Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	9.19 [2.56, 33.01]

6.4 Mortality Show forest plot	4	144	Peto Odds Ratio (Peto, Fixed, 95% CI)	8.89 [1.94, 40.64]

Comparison 6. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (worst/best‐case scenario analysis for missing data)

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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 Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.66 [0.28, 9.72]

7.2 Procedure‐related general complications Show forest plot	4	144	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.12 [0.01, 2.07]

7.3 Pneumoperitoneum‐related serious adverse events Show forest plot	3	128	Peto Odds Ratio (Peto, Fixed, 95% CI)	8.28 [0.86, 80.03]

7.4 Mortality Show forest plot	4	144	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.12 [0.01, 2.07]

Comparison 7. Helium pneumoperitoneum versus carbon dioxide pneumoperitoneum (best/worst‐case scenario analysis for missing data

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