Regarding: Carbon Dioxide Pneumoperitoneum Prevents Postoperative Adhesion Formation in a Rat Cecal Abrasion Model

Dear Editor:

It is with great interest that we read the article on the prevention of postoperative adhesions by induction of a carbon dioxide pneumoperitoneum prior to a laparotomy. ¹ The mechanism by which adhesions were prevented in this model was difficult to explain. Moreover, there seems to be a contradiction with the observation that CO₂ pneumoperitoneum enhances adhesion formation and that this enhancement is pressure and duration dependent.

Traditionally, postoperative adhesion formation has been considered a local process between two injured surfaces. Following injury, exudation and fibrin deposition occur; simultaneously, repair mechanisms are started. If this fibrin is not removed within 2–3 days, the fibrin forms a scaffold for fibroblasts, activated by the repair mechanisms, to form adhesions.

We demonstrated over the last decade that this local phenomenon is essential for adhesion formation, but quantitatively not so important. Factors from the entire peritoneal cavity can stimulate this local process of adhesion formation up to some 20-fold. It was demonstrated that factors that damage the mesothelial cells lining the peritoneal cavity have this stimulating effect upon adhesion formation. ² Identified so far as stimulating factors are mesothelial hypoxia (e.g., by using CO₂ for pneumoperitoneum), mesothelial hyperoxia (e.g., by exposing the mesothelial cells to air with a pO₂ of 150 mm Hg), desiccation, and direct trauma.^3–5 These factors, alone or combined, result in an acute inflammation of the entire peritoneal cavity, as demonstrated by biopsies, and the severity of this acute inflammation determines the degree of adhesion formation enhancement (Corona et al. Submitted). At a lower peritoneal/mesothelial temperature than 37°C, this inflammatory reaction is decreased, that is, the mesothelial layer is more resistant to damage.

As manipulation of the bowels in the upper abdomen affects in a dose-dependent way, the acute inflammatory reaction in the entire cavity and simultaneously the adhesion formation between injured areas in the lower abdomen, it is clear that the effect is one involving the entire peritoneal cavity and not only a local effect on the injured areas. As all other factors obviously affect the entire peritoneal cavity and thus also the traumatized area, it could have been theoretically argued that the effect is localized only at the injured area and that the acute inflammation is an epiphenomenon. The manipulation experiments in the upper abdomen, enhancing adhesions at distance in the lower abdomen, and the acute inflammatory reaction as a common mechanism for all factors unequivocally demonstrate that the detrimental end beneficial effects upon adhesion formation are mediated through an effect upon the entire peritoneal cavity lining.

A possible mechanism by which it might be explained that CO₂ pneumoperitoneum decreases adhesion formation induced by laparotomy is the ischemic preconditioning. This has been studied over the last two decades in coronary occlusion models, wherein ischemia and reperfusion may activate a cascade of events leading to the death of myocardial cells. There is agreement that reactive oxygen species production by the mitochondria is an essential part in the protective mechanism of ischemic preconditioning. ⁶ Even brief ischemic preconditioning puts the cardiac cells in a protective phenotype for several hours, but this mechanism is not well understood today. This mechanism of protection is only exerted in the reperfusion phase, not in the ischemic phase. Indeed, we noted that reactive oxygen species (ROS) scavengers protected against adhesion formation in a laparoscopic mouse model exposed to a carbon dioxide pneumoperitoneum. ⁷

In conclusion, we suggest that the ischemic condition of a carbon dioxide pneumoperitoneum stimulates ROS production, which will have a protective effect in the reperfusion phase, which obviously occurs during laparotomy after laparoscopy.