Methods: Electronic databases were accessed selecting only randomized controlled trials comparing insufflation with CO2 and ambient air in colonoscopy. The evaluated outcomes were pain, abdominal distension and flatulence, cecal intubation rate, cecal intubation and total procedure time, volume of gas, CO2 measurement, and need of sedation or analgesia, and polyp detection rate.
Results: Thirty randomized controlled trials were selected (4854 patients). Meta-analysis showed reduction in pain risk in the CO2 group immediately after the colonoscopy (Risk difference-RD 0.11[0.03, 0.19]), 1h (RD 0.29 [0.24, 0.34]), 3h (RD 0.22[0.11, 0.34]) and 6h (RD 0.21 [0.17, 0.26]) after colonoscopy. The reduction of flatulence risk 1h and 6h after the procedure was greater in CO2 group (RD 0.54 [0.43, 0.66] and RD 0.65[0.38,0.92], respectively). There were no significant differences between the two groups regarding pain during the procedure, pain and flatulence 24h after colonoscopy, abdominal bloating, request for medication, safety, gas volume, polyp detection rate, cecal intubation rate, time to cecum and total procedure time.
Conclusions: CO2 insufflation improves tolerance to colonoscopy, reducing pain and flatulence out to 6 hours following the procedure.
Keywords: Air; Carbon dioxide; Colonoscopy; Insufflations; Pain
However, because of the necessity of gas insufflation for the adequate visualization of the colonic mucosa, patients usually complain about pain and abdominal discomfort during and after the procedure associated mainly with the use of ambient air, which stays in the intestine for a longer period [4] due to the presence of nitrogen gas. To increase the tolerance and the disposition to repeat the examination, the insufflation of carbon dioxide (CO2) is increasingly utilized. CO2 is rapidly absorbed by the intestinal mucosa and subsequently eliminated by breath, which may lead to less pain, flatulence and distension related to the procedure [5-8]. Comparative analyses between the use of CO2 and ambient air in colonoscopy were shown in two meta-analyses published previously [9,10].
The objective of this systematic review and metaanalysis is to update this knowledge through new studies comparing which insufflation method is related to less unpleasant symptoms, faster and safer examinations, and to add outcomes that were not yet described in the literature.
1- Study design: RCT.
2- Population: patients subjected to colonoscopy.
3- Intervention: intestinal insufflation with CO2.
4- Comparison: intestinal insufflation with ambient air
5- Outcomes: the evaluated outcomes were pain, abdominal distension and flatulence related to colonoscopy, cecal intubation rate, cecal intubation time and total procedure time, volume of gas used, CO2 measurement at the end of the procedure, need of sedation or analgesia, and polyp detection rate.
Study |
Population (N) |
Co2 (N) |
Air (N) |
Follow Up |
Randomization |
Blinding |
Losses |
Power Calculation |
ITT |
Prognostic |
Outcomes |
Jadad Score |
Amato et al. 2013 [13 ] |
228 |
115 |
113 |
24 hours |
YES+ |
Only patient |
NO |
YES |
YES |
YES |
YES |
2 |
Bretthauer et al. 2002 [14 ] |
240 |
121 |
119 |
24 hours |
YES? |
Patient and endoscopists |
YES |
YES |
NO |
YES |
YES |
4 |
Bretthauer et al. 2003 [15 ] |
218 |
109 |
109 |
24 hours |
YES? |
Patient and endoscopists |
YES |
NO |
NO |
YES |
YES |
4 |
Bretthauer et al. 2005 [16 ] |
103 |
52 |
51 |
24 hours |
YES? |
Patient and endoscopists |
YES |
NO |
NO |
? |
YES |
4 |
Calderon et al. 2012 [4 ] |
214 |
132 |
82 |
2 hours |
Yes? |
Nurse |
NO |
NO |
NO |
YES |
YES |
1 |
Chao et al. 2010 [17 ] |
104 |
46 |
58 |
During colonoscopy |
Yes? |
Patient and anesthesiologist |
NO |
NO |
NO |
YES |
YES |
3 |
Chen et al. 2013 [18] |
193 |
96 |
97 |
24hours |
YES+ |
Patient, endoscopist, research staff |
YES |
YES |
YES |
YES |
YES |
5 |
Chen et al. 2014 [19 ] |
98 |
51 |
47 |
Until discharge |
YES+ |
Patient and endoscopists |
YES |
NO |
NO |
YES |
YES |
5 |
Chen et al. 2016 [20 ] |
125 |
63 |
62 |
24h |
YES+ |
Patient , endoscopists, anesthesiologist, study assistant |
YES |
YES |
YES |
YES |
YES |
5 |
Church et al. 2003 [21] |
247 |
123 |
124 |
1h |
Yes - |
Only patient |
NO |
NO |
NO |
YES |
YES |
1 |
Cleland et al. 2013 [22] |
205 |
108 |
97 |
1h |
Yes? |
Patient, endoscopist, nurse care |
NO |
YES |
NO |
YES |
YES |
3 |
Diez-Redondo et al. 2012 [23] |
270 |
129 |
141 |
24 hours |
Yes + |
Patient, endoscopist, nurse care |
YES |
YES |
NO |
YES |
YES |
4 |
Geyer et al. 2011 [24 ] |
219 |
110 |
109 |
24 hours |
Yes - |
Patient, endoscopist |
NO |
YES |
NO |
NO |
YES |
3 |
Hsu et al. 2012 [25] |
100 |
67 |
33 |
1 hour |
Yes ? |
Only patient |
YES |
NO |
NO |
YES |
YES |
2 |
Hsu et al. 2014 [26] |
120 |
60 |
60 |
2 hours |
Yes+ |
Patient, endoscopist, assistant nurses, nurses recovery room |
NO |
YES |
NO |
YES |
YES |
4 |
Imai et al. 2012 [27] |
37 |
19 |
18 |
24 hours |
Yes+ |
Patient, endoscopist |
YES |
YES |
NO |
YES |
YES |
5 |
Landaeta et al. 2014 [28] |
63 |
30 |
33 |
24h |
Yes? |
Not informed |
YES |
NO |
NO |
YES |
YES |
2 |
Liu et al.2009 [29] |
349 |
174 |
175 |
24h |
Yes - |
Single blinded |
NO |
NO |
NO |
YES |
YES |
1 |
Lynch et al. 2015 [30] |
191 |
97 |
94 |
Until discharge |
Yes + |
Patient, endoscopist, nurse staff |
YES |
YES |
NO |
YES |
YES |
5 |
Mayr et al. 2012[31] |
156 |
77 |
79 |
24h |
Yes + |
Patient, endoscopist |
YES |
YES |
NO |
YES |
YES |
5 |
Murakami et al. 2016 [32] |
158 |
75 |
83 |
4h |
Yes - |
Only patient |
YES |
YES |
NO |
YES |
YES |
2 |
Riss et al. 2009 [33] |
300 |
157 |
143 |
12h |
Yes + |
Only patient |
YES |
YES |
YES |
YES |
YES |
3 |
Seo et al. 2013 [34] |
94 |
48 |
46 |
24h |
Yes + |
Patient, endoscopist, nurses recovery room |
YES |
YES |
YES |
YES |
YES |
5 |
Singh et al. 2012 [35] |
142 |
70 |
72 |
Until discharge(~3) |
Yes ? |
Patient, endoscopist, nurse |
NO |
NO |
NO |
NO |
YES |
3 |
Stevenson et al. 1992 [36] |
56 |
27 |
29 |
24h |
Yes + |
Patient, endoscopist |
NO |
NO |
NO |
? |
YES |
4 |
Sumanac et al. 2002 [37] |
97 |
46 |
51 |
24h |
Yes + |
Patient, endoscopist |
YES |
NO |
YES |
YES |
YES |
5 |
Szura et al.2015[38] |
200 |
100 |
100 |
1h |
Yes + |
Only patient |
YES |
YES |
YES |
YES |
YES |
3 |
Uraoka et al. 2009 [39] |
114 |
57 |
57 |
6h |
Yes + |
Patient, endoscopist |
YES |
YES |
YES |
YES |
YES |
5 |
Wong et al. 2008 [40] |
93 |
44 |
49 |
2h |
Yes ? |
Patient, endoscopist, assessor |
YES |
YES |
NO |
YES |
YES |
4 |
Yamano et al. 2010 [41] |
120 |
66 |
54 |
24h |
Yes ? |
Patient, endoscopist |
YES |
NO |
NO |
YES |
YES |
4 |
As for the pain score, there is no difference between the groups (MD -0.15[-2.56, 2.25]), but with heterogeneity of 100% [21,22,25,40].
Considering the calculation of the pain score, there was significant statistical difference, meaning that the CO2 group was associated with lower values of the numerical pain scale. (MD -0.71[-1.39, - 0.02]; I²=94%) [21,24,25,26,38].
In our systematic review, there was no difference between the CO2 insufflation group and the ambient air insufflation group in relation to pain reported during the examination. However, two meta-analysis [9,10] showed that the CO2 was associated to lower pain scores and lower pain risk during the procedure. This difference may be explained because we performed the sensibility analysis in cases of heterogeneity >50%, splitting the trials between the outcomes “pain during the colonoscopy” and “pain at the end of the colonoscopy”, which was not done in the two cited meta-analyses, in addition to the inclusion of new trials.
We demonstrated that the pain risk was lower with the use of CO2 in the analysis of 1h, 3h and 6h after the examination; no clear evidence was found between the groups in the outcome of 24h. Similar results were obtained in the studies cited above, except for the 3h analysis, which was not performed.
The CO2measurement after the procedure was compared between groups, with no significant statistical difference, which is also shown in the trials included in the systematic review by Wu et al [9]. It should be taken into account that the indirect measurements of CO2 through transcutaneous or end tidal monitoring may not be reliable. Arterial blood gases are more adequate, but not acceptable by the patients [42]. There was also no difference in relation to cecal intubation. Sajid et al [10] demonstrated that the cecum was reached faster using CO2, but our meta-analysis did not arrive at the same conclusion.
Among the strong points of our systematic review and meta-analysis, we can cite the addition of trials of high methodological quality (77% with Jadad>3), the number of involved patients and the outcomes that were not evaluated in the previous meta-analysis, such as abdominal distention, polyp detection rate, total procedure time, request for analgesia/ sedation during the examination.
Among the limitations of this study, we should punctuate that the high heterogeneity of some outcomes led to the execution of sensibility analysis, modifying some results, which is not possible especially in the outcomes that involve only two studies. Examinations performed in different periods (1992-2015) with particulate clinical practices, different employed methodologies and various forms of outcome measurements are some of the reasons. The presence of analgesia/sedation, type of preparation performed, exam time related to the endoscopist experience and the volume of gas used may relate more with pain, abdominal distention and flatulence than with the type of gas used during the examination.
The cost of a CO2 insufflator varies between 7,000 and 7,400 Euros. The cost of the CO2 gas per colonoscopy is less than 1 euro [43]. Yamano et al. state that the total cost of one endoscopy increases about 2.5% with the use of CO2 [41]. Thus, the costbenefit relationship between these two insufflation methods must be analyzed in other studies, considering the financial reality of dozens of developing countries.
Trials that evaluate the complications related to the colonoscopy and the evolution of those patients depending on the type of gas used are very important to consolidate the CO2 in the clinical practice.
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