Results of the search

The electronic searches identified a total of 2392 citations. After removing duplicate studies, we reviewed 1850 titles or abstracts, and excluded trials that involved non‐abdominal procedures, uncommon laparoscopic procedures, non‐human subjects and those not using cold gas as a control. We also excluded duplicated studies and non‐randomised controlled trials. Finally, the review authors DB, NS and XS agreed that 22 trials met the inclusion criteria and included them in this review. See PRISMA diagram (Moher 2009) (Figure 1).

Figure 1

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Study flow diagram

Included studies

All 22 included studies were RCTs comparing heated CO₂ insufflation (with or without humidification) with standard cold CO₂ insufflation. All the included studies used CO₂ insufflation. We excluded from the review studies examining outcomes that were dissimilar to those relevant to this review and studies where we did not receive a response from the authors. Surgical procedures included in the studies were: gastric bypass (n = 168), gynaecologic surgery (n = 259), cholecystectomy (n = 500), Nissen fundoplication (n = 157), appendicectomy (n = 190), low anterior resection (n = 16), gastrectomy (n = 7), colonic surgery (n = 84), diagnostic laparoscopy (n = 40), hernioplasty (n = 4), myotomy (n = 2) and rectopexy (n = 1).

Primary outcome data were available for 1081 participants as three studies (Demco 2001; Klugsberger 2014; Slim 1999) did not report intraoperative changes in core temperature. Of these, 430 were in the heated, humidified gas group; 105 were in the heated‐only gas group; and 546 were in the cold gas group.

Five studies had relatively long operative times (more than 120 minutes) (Backlund 1998; Hamza 2005; Lee 2011; Ott 1991; Sammour 2010). Ten out of 22 studies used a warming blanket for simultaneous warming (Backlund 1998; Farley 2004; Hamza 2005; Lee 2011; Manwaring 2008; Nguyen 2002; Sammour 2010; Savel 2005; Wills 2001; Yu 2013). A heated insufflation company supported 11 of the 22 trials (Backlund 1998; Davis 2006; Farley 2004; Hamza 2005; Kissler 2004; Manwaring 2008; Mouton 1999; Nelskyla 1999; Ott 1998; Savel 2005; Wills 2001). Ten of the 22 studies demonstrated a benefit with the use of heated gas insufflation (Agaev 2013; Backlund 1998; Farley 2004; Hamza 2005; Klugsberger 2014; Lee 2011; Mouton 1999; Nelskyla 1999; Ott 1998; Puttick 1999). See Characteristics of included studies and Table 1; Table 2; Table 3 for full study details.

Agaev 2013: originally published in Russian, this study examined 150 laparoscopic operations (110 cholecystectomies and 40 fundoplications), participants with standard CO₂ vs. warmed, humidified CO₂ during the operations. Their conclusion was warmed, humidified CO₂ had advantages for maintaining a warmer intraoperative core temperature, having less postoperative pain and requiring fewer analgesic prescriptions.

Backlund 1998: examined the effect of 37 °C and room temperature‐insufflated CO₂ during and after prolonged laparoscopic surgery (more than 120 minutes). Twenty six participants undergoing fundoplication, hernioplasty, resection of the sigmoid colon and rectopexy were randomly assigned to warm or cold gas groups. Core temperature, cardiac index, urine output and recovery room opioid usage and pain scores were recorded.

Champion 2006: was a trial of heated, humidified versus cold dry CO₂ insufflation for laparoscopic gastric bypass, which examined 50 consecutive obese patients with homogeneous baseline characteristics (gender, age, preoperative weight, body mass index (BMI) and c‐reactive protein (CRP)) between groups. The ambient insufflation gas was at a temperature of 35 °C and 95% relative humidity. The sole difference identified in the heated group was a lower postoperative subjective shoulder pain score at 18 hours. There were no differences between groups in intraoperative core temperature, operating room temperature, litres of insufflation, operating time, number of lens cleanings, recovery room temperature, narcotic usage, length of hospitalisation, high‐sensitivity CRP at 24 hours or abdominal pain scores.

Davis 2006: with adequate allocation concealment, this study examined 44 laparoscopic Roux‐en‐Y gastric bypass patients in Ohio State University. There were four study groups with 11 participants in each and similar baseline characteristics across the groups. The groups included the following insufflation techniques: 1) cold dry, 2) cold humidified (97% relative humidity), 3) heated dry (37 °C) and 4) heated humidified (37 °C and 97% relative humidity) CO₂. There were no differences in patient core temperature, intra‐abdominal humidity, postoperative narcotic usage, pain scale scores, recovery room time, length of hospitalisation, lens fogging or macrophage activity between groups, though participants in the heated, humidified insufflation group demonstrated increased macrophage activity in biopsies.

Demco 2001: 40 women undergoing diagnostic laparoscopy were randomised to heated, humidified insufflation or cold CO₂. Outcomes were shoulder pain, fentanyl use, percent requiring general anaesthetic, percent requiring intravenous sedation, amount of gas instilled before experiencing pain, operating time, recovery room time and time to recovery of shoulder pain. Outcomes were presented as percentages of participants in various groups (e.g. operative time more than 10 minutes, 10 to 20 minutes, etc.), which could not be included in meta‐analysis.

Farley 2004: with adequate allocation concealment, randomised 101 people undergoing laparoscopic cholecystectomy to either cold or heated and humidified CO₂ insufflation. The experimental group showed higher intraoperative core temperatures and decreased postoperative pain scores at day 14; the study authors questioned the clinical relevance of the latter outcome. They identified no differences in the rate of lens fogging, narcotic requirements, length of hospitalisation or time of return to baseline activity levels.

Hamza 2005: randomised 50 people undergoing laparoscopic Roux‐en‐Y gastric bypass surgery, with no information on allocation concealment, to cold or heated and humidified CO₂ insufflation. Six were excluded. Mean operative times for each group were greater than 120 min. The heated group showed a higher intraoperative core temperature, a reduction in time in the recovery room and narcotic requirements, and a higher quality of recovery at 48 hours postoperatively. There were no differences in postoperative tympanic membrane temperatures, pain scores, shivering, overall morphine usage, nausea scores, Aldrete recovery assessment scores, length of hospital stay or lens fogging.

Kissler 2004: recruited 90 consecutive women scheduled for gynaecologic laparoscopic surgery into this study with randomisation to heated humidified, heated non‐humidified and cold gas insufflation groups, each with 30 participants. The trial was stopped following enrolment of 53 participants due to a tendency for less pain and higher postoperative satisfaction in the cold insufflation control group.

Klugsberger 2014: randomised 148 people undergoing laparoscopic cholecystectomy to standard gas or warmed, humidified gas groups. Intraoperative core temperature was significantly higher with less six‐hour postoperative pain in the warmed, humidified gas group. Pain was not significantly different on the first day after operation.

Lee 2011: randomised 30 people undergoing laparoscopic low anterior resection, colectomy or gastrectomy to heated CO₂ or standard CO₂ groups. Mean operative times were greater than 200 minutes for each cohort. They recorded acid‐base parameters and core temperature. Heated CO₂ did not significantly change acid‐base parameters in participants but reduced the decrease in core body temperature 30 minutes after pneumoperitoneum.

Manwaring 2008: randomised 60 gynaecology patients to heated humidified or cold insufflation groups. Heated and humidified gas insufflation was not associated with any significant benefits as no difference was found in oesophageal temperature, pain scores or narcotic usage.

Mouton 1999): randomised 40 people undergoing cholecystectomy to heated, humidified insufflation or cold gas insufflation. Eight were excluded. Though they found no difference in core temperature during the relatively brief operations, there was significantly less pain compared to the experimental heated and humidified insufflation participants at six hours and on the first to third days postoperatively. Pain was also less on the 14th postoperative day.

Nelskyla 1999: randomised 40 women undergoing laparoscopic hysterectomy to heated or unheated gas insufflation groups. Three were excluded. Tympanic and nasopharyngeal intraoperative temperatures were not different between the groups.

Nguyen 2002: randomised 20 people undergoing laparoscopic Nissen fundoplication, without information on the allocation method, to heated and humidified or cold and dry gas insufflation groups. There were no differences in core temperature, pain scores, narcotic consumption, urine output or lens fogging.

Ott 1998: without stating the number of participants in each group, this study randomised 72 women undergoing laparoscopic gynaecologic surgery to heated and humidified or cold and dry gas insufflation. Most data was extracted from a systematic review (Sammour 2008) and was only available for 50 patients with no reason was given. The experimental heated group showed improved intraoperative normothermia and postoperative pain, and reduced recovery room stay.

Puttick 1999: randomised 30 people undergoing laparoscopic cholecystectomy to heated or cold gas insufflation. The study authors concluded that intraoperative cooling could be prevented by heating the insufflated gas.

Saad 2000: randomised 20 people undergoing laparoscopic cholecystectomy to heated or cold gas insufflation with no effects when comparing core temperature or postoperative pain. VAS pain scores were converted from a 0 to 100 scale to a standard 0 to 10 scale.

Sammour 2010: randomised 82 people undergoing laparoscopic colon surgery to heated, humidified or cold gas insufflation groups, each with 41 participants. Eight patients were excluded. They found no significant effects, including no effect on the early postoperative inflammatory cytokine response. Mean operative times were greater than 170 minutes for both cohorts.

Savel 2005: randomised 30 people undergoing laparoscopic Roux‐en‐Y gastric bypass to cold or heated and humidified gas insufflation groups. Length of hospitalisation and operative time were reduced in the experimental group but the study found no differences in pain sensation.

Slim 1999: enrolled 100 people undergoing laparoscopic cholecystectomy, fundoplication, or Heller's myotomy and randomised them to cold or heated insufflation. Shoulder and subcostal pain sensation was increased in the heated insufflation group and the study found no difference on core temperature or narcotic consumption.

Wills 2001: randomised 41 people to heated or cold gas insufflation during laparoscopic fundoplication. One was excluded. An increased core temperature was associated with the heated insufflation group, though the control group participants suffered less postoperative pain and required fewer narcotics. VAS pain scores were converted from a 0 to 100 scale to a standard 0 to 10 scale.

Yu 2013: randomised 195 children undergoing laparoscopic appendectomy to warm, humidified CO₂ or standard CO₂ groups. Five were excluded. The study assessed postoperative opioid usage, pain intensity, postoperative recovery and return to normal activities. Warm, humidified CO₂ insufflation had no short‐term clinical benefits on postoperative outcomes in children.

Excluded studies

We excluded Beste 2006 and Benavides 2009 from this review because they compared heated, humidified CO₂ with heated, non‐humidified CO₂, a comparison not intended for this review. However, they were included in two previously published systematic reviews (Sajid 2008; Sammour 2008). Herrmann 2015 we excluded because it assessed laparoscopic‐assisted vaginal hysterectomies which is not primarily an abdominal, laparoscopic surgery. We excluded the remaining studies because they were not RCTs. Excluded studies were excluded from both quantitative and qualitative analyses. See section on Characteristics of excluded studies for details.

Allocation

We rated 11 studies at unclear risk of bias, with nine of these studies (Backlund 1998; Demco 2001; Kissler 2004; Mouton 1999; Nelskyla 1999; Ott 1998; Puttick 1999; Saad 2000; Savel 2005) failing to report on the methodology for randomisation or allocation concealment. Agaev 2013 stated that randomisation was done with a computer model post‐anaesthetic, but comparative groups were very uneven with 84 in the heated group and 66 in non‐heated. Klugsberger 2014 was unclear about randomisation and also had uneven groups (67 in heated and 81 in non‐heated).

Blinding

We judged five studies (Backlund 1998; Mouton 1999; Ott 1998; Puttick 1999; Saad 2000) at unclear risk of bias because they had no description of blinding. The remaining studies were adequately blinded with only one or two operating‐room personnel unblinded to initiate the intervention.

Incomplete outcome data

We deemed three studies an unclear risk of attrition bias. Agaev 2013 did not state the number of participants included in their analysis. Kissler 2004 was stopped early because the control group had less pain and improved satisfaction. Nelskyla 1999 excluded three participants without clear reasoning. Ott 1998 reported data on only 55 of 72 participants and did not state a reason for this missing data. This was assessed a high risk of bias.

Selective reporting

Demco 2001 did not report any core temperatures which would be expected from a study on heated insufflation. Klugsberger 2014 and Slim 1999 reported mean core temperatures but did not report on intraoperative changes in core temperature. However, Slim 1999 only measured subdiaphragmatic core temperatures once during the operation so this is not due to selective reporting.

Other potential sources of bias

Agaev 2013, originally published in Russian, was translated voluntarily by a research scientist employed by a surgical humidification device company. We deemed this an unclear risk of bias due to a possible conflict of interest. Many studies (Agaev 2013; Backlund 1998; Champion 2006; Davis 2006; Hamza 2005; Kissler 2004; Lee 2011; Mouton 1999; Nguyen 2002; Ott 1998; Saad 2000; Savel 2005; Wills 2001) were also missing standard deviations and this potentially distorted the true effects and potentially increased the error.

Demco 2001 did not report any baseline demographics, while Ott 1998 did not separate demographics between groups and potential imbalances in participant characteristics could have contributed to bias.

Industry supported eight trials by providing heated insufflation devices (Backlund 1998; Farley 2004; Kissler 2004; Manwaring 2008; Nelskyla 1999; Savel 2005; Wills 2001). Two trials received educational grants from industry (Davis 2006; Hamza 2005) and one trial reported industry assistance (Mouton 1999). We judged this a low risk of bias as there appeared to be no industry influence in the trials with industry support.

Primary outcome

Change in core temperature

(Analysis 1.1; Analysis 1.2; Analysis 1.3)

Nineteen studies reported change in intraoperative core temperatures. Overall, core temperature was slightly higher with heated CO₂ (MD 0.21 °C, 95% CI 0.06 to 0.36, P = 0.007) (Figure 4). Heterogeneity was substantial (I² = 86%), therefore subgroup analyses were performed for humidified and non‐humidified CO₂. Heated gas with humidification had a small, but positive effect on core temperature intraoperatively compared to cold CO₂ (MD 0.31 °C, 95% CI 0.09 to 0.53, P = 0.005) (Figure 4). When only studies with low risk of bias were assessed, this effect became statistically non‐significant (Figure 5). No apparent effect was found in the non‐humidified, heated‐gas group compared to cold gas, regardless of analysis based on all studies or only low‐risk studies. A subgroup analyses for operations lasting less and more than 120 minutes were also performed. There was no difference detected in temperature between heated and cold CO2 for operations lasting less than 120 minutes. However, for operations lasting over 120 minutes (Backlund 1998; Hamza 2005; Ott 1998; Sammour 2010), temperature was significantly higher with warming and humidification, but the studies exhibited significant statistical heterogeneity (I² = 91%) (Figure 6). When subgroup analyses of studies using external warming were conducted, core temperatures were significantly higher in the heated, humidified group (MD 0.29 °C, 95% CI 0.05 to 0.52) (Figure 7); but the studies were once again statistically heterogenous (I² = 84%). The only trial with a known low risk of bias (Savel 2005) showed no statistically significant difference between groups, however, with only 30 participants, such a small trial would unlikely be adequately powered to detect a difference between groups even if one was present (Figure 7). When only trials not using external warming were analysed, heated, humidified gas had no apparent effect on core temperature compared to cold gas. (Figure 8).

Figure 4

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Forest plot of comparison: 2 Core temperature, outcome: 2.1 Change in core temperature

Figure 5

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Forest plot of comparison: 2 Core temperature, outcome: 2.2 Change in core temperature for low risk of bias studies

Figure 6

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Forest plot of comparison: 1 Core temperature, outcome: 1.5 Change in core temperature in heated, humidified vs cold groups with OR > 120 Minutes

Figure 7

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Forest plot of comparison: 2 Core temperature, outcome: 2.3 Change in core temperature in heated, humidified vs cold groups with external warming

Figure 8

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Forest plot of comparison: 1 Core temperature, outcome: 1.4 Change in temperature in heated, humidified vs cold groups without external warming

Secondary outcomes

Pain scores

(Analysis 2.1; Analysis 2.2; Analysis 2.3; Analysis 2.4)

For pain scores (measured using a 0 to 10 visual analogue scale), there was no statistically significant difference detected between groups overall on day 1 (MD ‐0.04, 95% CI ‐0.42 to 0.34) or day 2 (MD ‐0.28, 95% CI ‐0.78 to 0.21). Subgroup analyses were performed for the effect of humidified CO₂ and non‐humidified CO₂, on shoulder and abdominal pain separately, and for heated only versus cold CO2 (not by location of pain).

Day 1

The effect of heated and humidified gas on postoperative day one showed no statistically significant difference compared to cold gas (abdominal pain MD ‐0.14, 95% CI ‐0.60 to 0.33, P = 0.57; shoulder pain MD ‐0.35, 95% CI ‐1.75 to 1.05, P = 0.62) (Figure 9). Given the significant heterogeneity across studies (abdominal P = 0.02, I² = 53%; shoulder P = 0.03, I² = 72%), sensitivity analyses were performed and only studies with a known low risk of bias were included. The pain scores were still apparently not different with respect to either abdominal or shoulder pain and the test of heterogeneity was no longer statistically significant (abdominal P = 0.32, I² = 15%; shoulder P = 0.22, I² = 35%) (Figure 10). When heated only gas was compared to cold gas, the day‐one pain scores were not statistically significantly different (Figure 9).

Figure 9

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Forest plot of comparison: 1 Pain score, outcome: 1.1 Day 1 pain score

Figure 10

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Forest plot of comparison: 1 Pain score, outcome: 1.3 Day 1 pain score for low risk of bias study

Day 2

For pain on the second postoperative day, heated and humidified gas did not apparently improve abdominal or shoulder pain (abdominal MD ‐0.40, 95% CI ‐1.07 to 0.28, P = 0.25; shoulder MD ‐0.88, 95% CI ‐2.93 to 1.17, P = 0.40), but again, the studies were heterogenous (I² 62% and 92%, respectively) (Figure 11). When only low risk of bias studies were included, the conclusion remained unchanged (Figure 12) and I² decreased to 0%. With heated only gas, the postoperative day‐two pain score was similar to the cold gas control (MD 0.41, 95% CI ‐0.44 to 1.27, P = 0.34) with no statistically significant heterogeneity across trials (P = 0.23, I² = 33%).

Figure 11

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Forest plot of comparison: 1 Pain score, outcome: 1.2 Day 2 pain score

Figure 12

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Forest plot of comparison: 1 Pain score, outcome: 1.4 Day 2 pain score of low risk of bias studies

Morphine consumption

(Analysis 3.1; Analysis 3.2; Analysis 3.3)

Four studies comparing heated and humidified CO₂ with cold CO₂ insufflation reported no statistically significant difference in morphine consumption up to six hours post‐operatively between groups (MD 0.45 mg, 95% CI ‐1.19 to 2.08, P = 0.59) (Figure 13). Heterogeneity was not statistically significant across studies (I² = 0%). Morphine use on the first postoperative day was not significantly different either overall (MD ‐0.64 mg, 95% CI ‐4.48 to 3.20), or when CO₂ was heated and humidified (MD ‐1.66 mg, 95% CI ‐4.79 to 1.46, P = 0.30), but was higher when CO₂ was heated without humidification (MD 11.93 mg, 95% CI 0.92 to 22.94, P = 0.03) (Figure 14). A similar pattern was observed for the second postoperative day, where there was no difference overall or with humidification, but was higher with heated, non‐humidified CO₂ (MD 9.79 mg, 95% CI 1.58 to 18.00, P = 0.02) (Figure 15).

Figure 13

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Forest plot of comparison: 3 Morphine consumption, outcome: 3.1 Up to 6 hours

Figure 14

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Forest plot of comparison: 3 Morphine consumption, outcome: 3.2 Day 1 morphine

Figure 15

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Forest plot of comparison: 3 Morphine consumption, outcome: 3.3 Day 2 morphine

Hospital stay

(Analysis 4.1)

Length of stay in hospital was not different between the heated (with or without humidification) and cold gas insufflation groups (MD ‐0.06 days, 95% CI ‐0.31 to 0.19, P = 0.65) (Figure 16). There was no statistically significant heterogeneity across studies (I² = 28%).

Figure 16

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Forest plot of comparison: 4 Hospital stay, outcome: 4.1 Hospital stay

Recovery room stay

(Analysis 5.1; Analysis 5.2)

Recovery room time was documented in six studies and there was substantial heterogeneity among them (I² = 95%). Shorter recovery time (MD ‐26.79 minutes, 95% CI ‐51.34 to ‐2.25, P = 0.03) was found with heated insufflation (Figure 17). With exclusion of the only high risk study (Ott 1998), the studies were statistically homogenous (I² =12%) but the difference in recovery room stay was statistically not significant (MD ‐1.22 minutes, 95% CI ‐6.62 to 4.17, P = 0.44) (Figure 18).

Figure 17

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Forest plot of comparison: 7 Recovery room stay, outcome: 7.1 Recovery time

Figure 18

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Forest plot of comparison: 7 Recovery room stay, outcome: 7.2 Recovery time for low risk of bias studies

Lens fogging

(Analysis 6.1)

Evidence of substantial heterogeneity was present (I² = 78%) and no significant difference in the lens fogging scores was shown (MD 0.73, 95% CI ‐0.32 to 1.77, P = 0.17) (Figure 19).

Figure 19

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Forest plot of comparison: 5 Lens fogging, outcome: 5.1 Lens fogging

Operative time

(Analysis 7.1)

Twenty studies reported their mean operative time; no evidence of statistically significant heterogeneity was found (I² = 28%). The mean operative time was similar across groups (MD ‐0.44 minutes, 95% CI ‐3.91 to 3.04, P = 0.81) (Figure 20). Subgroup analyses on humidified and non‐humidified subgroups did not change the results.

Figure 20

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Forest plot of comparison: 6 Operative time, outcome: 6.1 Operative time

Adverse events

The majority of included studies did not report on adverse events (Table 3). There were a total of twelve major adverse events with six in the heated group and six in the cold group.