Studies related to CO2

Experimetal and clinical consequences of using carbon dioxide

The effect of intra-abdominal pressure on the generation of 8-iso prostaglandin F(2alpha) during laparoscopy in rabbits.


De Souza AM, Wang CC, Chu CY, Lam PM, Rogers MS.


Department of Obstetrics & Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR.


BACKGROUND: Carbon dioxide pneumoperitoneum induces peritoneal oxidative stress. The aim of this study was to verify the effect of intra-abdominal pressure on oxidative stress in the peritoneum and on post-operative adhesion formation. METHODS: Forty-one rabbits underwent laparoscopic surgery: either gasless, or with CO2-pneumoperitoneum at pressures of 5, 10 or 15 mmHg. Serial parietal peritoneal biopsies were taken at various time-points: immediately after reaching the abdominal cavity, 30, 60, 90 and 120 min afterwards, and 15 min after abdominal desufflation. 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)), a marker of oxidative stresss, was assayed by enzyme immunoassay and adhesion formation was scored by second-look laparoscopy on day 14. RESULTS: The gasless group showed no significant changes in 8-iso PGF(2alpha). Conversely, significant changes occurred in CO2-pneumoperitoneum in a time- and pressure-dependent manner. Adhesions developed only in the CO2-pneumoperitoneum groups, and total adhesion score was correlated with the amount of CO2 insufflated and intra-abdominal pressure, but not with 8-iso PGF(2alpha), which was correlated with intra-abdominal pressure. CONCLUSION: Intra-abdominal pressure increased 8-iso PGF(2alpha) in the parietal peritoneum in a graded fashion, whilst gasless laparoscopy had no impact. It also influenced the frequency and severity of adhesion formation, but no causal link was found between 8-iso PGF(2alpha) and post-operative adhesion formation.


Hum Reprod. 2003 Oct;18(10):2181-8 



CO2 promotes plasminogen activator inhibitor type 1 expression in human mesothelial cells.


Bergstrom M, Falk P, Holmdahl L.


Department of Surgery, Sahlgrenska University Hospital/Ostra, Goteborg University, SE-41685 Goteborg, Sweden.


Background: Previous observations have indicated that CCO2 insufflation increases peritoneal plasminogen activator inhibitor type 1 (PAI-1) expression. Methods: Primarily cultured human peritoneal mesothelial cells were exposed to either flowing or pressurized CO2 for 90 min. Unexposed cultures served as controls. Samples of cell culture media were taken at 0, 5, and 24 h after exposure to measure media pH, PAI-1, and tissue-type plasminogen activator (t-PA) protein release. Simultaneous samples were taken to measure PAI-1 and t-PA mRNA expression. Results: Mesothelial cells exposed to flowing CO2 released more PAI-1 than those exposed to pressurized CO2 (p <0.001) and controls (p <0.001). Cells exposed to flowing CO2 had an increased PAI-1 mRNA expression at 5 h. Conclusions: CO2 increased mesothelial cell PAI-1 expression involving a transcriptional mechanism. These findings might provide a mechanism for adhesion formation and cancer progression following laparoscopic surgery.


Surg Endosc. 2003 Jun 17 



Adhesion formation in intubated rabbits increases with high insufflation pressure during endoscopic surgery. 


Yesildaglar N; Koninckx PR


The aim of the study was to test the hypothesis that the increase in adhesion formation by CO2 pneumoperitoneum is caused by mesothelial hypoxaemia. Therefore the effect of the intra-abdominal pressure together with the flow rate upon adhesion formation was evaluated in rabbits following laser and bipolar lesions during endoscopic surgery using humidified CO2 at 35 +/- 1 degrees C. The intra-abdominal pressure and flow rate were 5 mmHg and 1 l/min in group 1 (n = 5), 5 mmHg and 10 l/min in group 2 (n = 4), 20 mmHg and 1 l/min in group 3 (n = 5) and 20 mmHg and 10 l/min in group 4 (n = 4) respectively. A rapid and reliable intubation method for rabbits was developed to permit high insufflation pressure. By two-way analysis of variance, total adhesion scores following a laser lesion increased with flow rate (P = 0.0003) and insufflation pressure (P = 0.002). Total adhesion scores of bipolar lesions increased with pressure (P = 0.02) but not with flow rate (P = 0.1). The total adhesion scores of laser and bipolar lesions together increased with flow rate (P = 0.005) and with insufflation pressure (P = 0.004). There was no statistical interaction between flow rate and insufflation pressure. In conclusion, the insufflation pressure in endoscopic surgery with COpneumoperitoneum is a co-factor in adhesion formation, together with desiccation.


Hum Reprod – 01-MAR-2000; 15(3): 687-91



Hypoxaemia induced by CO2 or helium pneumoperitoneum is a co-factor in adhesion formation in rabbits.


Molinas CR; Koninckx PR


A prospective randomized trial in a rabbit model was performed to test the hypothesis that the increase in adhesion formation following prolonged pneumoperitoneum is mediated by peritoneal hypoxaemia. Laparoscopic standardized opposing lesions were performed in uterine horns and pelvic sidewalls by bipolar coagulation and CO2 laser in six groups of eight animals. Pure CO2 or helium pneumoperitoneum was used for 10 (groups I and IV) or 45 min (groups II and V) to confirm the effect of duration of pneumoperitoneum and 96% of CO2 or helium with 4% of oxygen (group III and VI) for 45 min to assess the effect of the addition of oxygen. After 7 days, adhesion formation was scored by laparoscopy. By two-way analysis of variance, total, extent, type and tenacity of adhesion scores increased (P = 0.0003, P = 0.0004, P = 0.0004 and P = 0.004) with increasing duration of pneumoperitoneum and decreased (P = 0.02, P = 0.03, P = 0.01 and P = 0.05) with the addition of oxygen. No differences were found between CO2 and helium. In conclusion these data confirm the effect of pneumoperitoneum upon adhesions and demonstrate its reduction by oxygen, strongly suggesting that the main cause of adhesion formation is the relatively superficial hypoxaemia produced by the pneumoperitoneum.


Hum Reprod – 01-AUG-2000; 15(8): 1758-63



Peritoneal response to pneumoperitoneum and laparoscopic surgery.


Bergström M; Ivarsson ML; Holmdahl L


BACKGROUND: It is generally believed that laparoscopic surgery inflicts less trauma to the peritoneum than open surgery. Local peritoneal fibrinolysis is a critical factor in adhesion development. The objective was to investigate fibrinolytic changes in the peritoneum during laparoscopic and open surgery. METHODS: At laparotomy (n = 10) peritoneal biopsies were taken at opening of the abdomen and just before closure. At laparoscopy (n = 12) opening peritoneal biopsies were taken after carbon dioxide insufflation, and closure biopsies just before exsufflation. Tissue concentrations of tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) and the resulting tPA activity were assayed. RESULTS: Concentrations of tPA in peritoneal tissue declined during operation in both groups, but significantly so only in the laparotomy group (- 53 per cent; P = 0.01). PAI-1 levels were higher in opening biopsies from the laparoscopy group (P = 0.004). There was an increase in PAI-1 concentration during laparotomy, but not during laparoscopy. At the end of the operation, there was no difference between the groups. The resulting tPA activity did not differ between groups at opening or closure. In both groups there was a significant decline during operation (laparotomy: – 59 per cent, P = 0.02; laparoscopy: – 63 per cent, P = 0.01). CONCLUSION: These findings indicate that the peritoneal response to open and laparoscopic surgery is similar. The initial rise in peritoneal PAI-1 concentration during laparoscopy suggests an adverse effect of carbon dioxide insufflation, which might affect peritoneal repair.


Br J Surg – 01-NOV-2002; 89(11): 1465-9



Role of the plasminogen system in basal adhesion formation and carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.


Molinas CR; Elkelani O; Campo R; Luttun A; Carmeliet P; Koninckx PR


To evaluate the role of plasminogen activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in adhesion formation after laparoscopic surgery.Prospective, randomized study.Academic research center.Seventy female wild-type and transgenic knockout mice for PAI-1 (PAI-1(-/-)), uPA (uPA(-/-)) or tPA (tPA(-/-)).Standardized lesions to induce peritoneal adhesions were performed during laparoscopy. To evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, the pneumoperitoneum was maintained for 10 minutes or 60 minutes, respectively. Peritoneal biopsy samples were obtained during and after 60 minutes of carbon dioxide pneumoperitoneum.Adhesions were blindly scored after 7 days. Concentrations of PAI-1 and tPA were measured by using enzyme-linked immunosorbent assay.In PAI-1, uPA, and tPA wild-type mice, pneumoperitoneum enhanced adhesions. Compared with wild-type mice, basal adhesions were fewer in PAI-1(-/-) mice and more in uPA(-/-) and tPA(-/-) mice. Pneumoperitoneum did not enhance adhesions in these transgenic mice. PAI-1 concentration increased after 60 minutes of pneumoperitoneum whereas tPA concentration did not change.Impaired fibrinolysis increases basal adhesions. The absence of pneumoperitoneum-enhanced adhesions in PAI-1(-/-), uPA(-/-), and tPA(-/-) mice and the increase in PAI-1 expression indicate that PAI-1 up-regulation by carbon dioxide pneumoperitoneum is a mechanism of pneumoperitoneum-enhanced adhesion formation.


Fertil Steril – 01-JUL-2003; 80(1): 184-92



The impact of gas laparoscopy on abdominal plasminogen activator activity.


Nagelschmidt M; Gerbecks D; Minor T


BACKGROUND: The impairment of intestinal perfusion following induction of a pneumoperitoneum may lead to a reduction of peritoneal tissue plasminogen activator (tPA) activity and a concomitant increased risk of adhesion formation. METHODS: Pigs were laparotomized to take peritoneal biopsy specimens from the cecum, the ileum, and the abdominal wall. A 15 mmHg pneumoperitoneum was established for 3 h by the insufflation of carbon dioxide (group 2, n = 6) or helium (group 3, n = 6). Group 1 (n = 7) received no gas insufflation. After a 2-h recovery period, additional tissue samples were harvested. Specific tPA activity was then determined in the tissue extracts. RESULTS: During surgery, specific tPA activity decreased in all the samples. As compared with the control group (100%), this reduction was strongly aggravated in the cecum (-67.6%, p < 0.05) and the ileum (-70.8%) of the CO2 group but only slightly aggravated in the helium group. The parietal peritoneum was not specifically affected by gas insufflation. Conclusion: The use of a pneumoperitoneum with carbon dioxide significantly affects peritoneal tPA activity and thus may represent a stimulus for adhesion formation.

Surg Endosc – 01-JUN-2001; 15(6): 585-8 



De novo adhesions due to dry laparoscopy gas


R. Turner, D.Ott


The risk of adhesion formation at laparoscopy is dependent on circumstances that contribute to or minimize the likelihood of adhesion formation, just as it is during laparotomy. It has long been noted that one of the factors that causes peritoneal adhesion formation is tissue desiccation. The finding in this study of fewer adhesions with extraperitoneal surgery and more with intraperitoneal surgery validates this principle. The gas used to create a pneumoperitoneum has 0.0002% relative humidity and is delivered through trocars restricted with instruments creating a forceful jet streaming effect. This causes dramatic peritoneal cell vapor pressure changes resulting in rapid surface drying of the peritoneum and an increase in solute concentration and in peritoneal fluid viscosity. The "cold dry" gas alters peritoneal cell integrity and increases peritoneal cell trauma and death that can lead to adhesion formation. The maintenance of a normal physiologic intra-abdominal environment during laparoscopic surgery by heating and humidification ("warm and wet"), such as has been proven using the Insuflow (LEXION Medical, St Paul, Minn) device, reduces or eliminates cell desiccation, maintains peritoneal fluid integrity, allows for increased peritoneal cell survival, and improves clinical outcome.

By adhering to the principle of keeping peritoneal surfaces moist and euthermic throughout surgical procedures, there is a reduction in adhesion formation and peritoneal cell integrity is maintained. We propose that you add a third arm to your study to evaluate the use of the Insuflow device in laparoscopic transperitoneal lymphadenectomy to more appropriately compare lymphadenectomy by the transperitoneal with the extraperitoneal laparoscopic approach. It is our opinion that by maintaining a more normal physiologic intra-abdominal environment by heating and humidifying the gas stream there will be an improvement in outcome and reduction in de novo adhesion formation.


American Journal of Obstetrics and Gynecology, Volume 185 • Number 3 • September 2001