Doctor of Philosophy
Graduate School of Medicine
Marshall, Jean Kathleen, A rat model to study the effects of gaseous exposure of the peritoneum during open abdominal surgery: tissue oxygenation and mesothelial damage, Doctor of Philosophy thesis, Graduate School of Medicine, University of Wollongong, 2015. http://ro.uow.edu.au/theses/4675
Background: Complications such as surgical site infection and post-operative adhesion formation following abdominal surgery are common and there has been a call for new approaches to reduce these complications. Insufflation of humidified-warm CO2 to protect the abdominal cavity during open abdominal surgery has been proposed as a promising new therapeutic invention; however mechanisms of action have not yet been fully investigated. After first setting out to develop a controlled animal model, this research has tested the hypotheses that humidified-warm CO2 can increase tissue oxygen partial pressure and that humidified-warm CO2 can reduce loss of peritoneal mesothelium that may be caused by exposure of the peritoneum to the dry operating room.
Methods: A systematic review was conducted to determine the current state of knowledge regarding the effect of gaseous exposure of the peritoneum during abdominal surgery on loss of peritoneal mesothelium. A rat model was then developed to allow the examination of gaseous exposure of the peritoneum during open abdominal surgery. Using that model, randomised cross-over trials were conducted to investigate the effect of humidified-warm CO2 on sub-peritoneal tissue oxygen partial pressure, and to elucidate the relative effect of dry versus humidified-warm CO2. Finally, a controlled trial was conducted to determine whether exposure of the peritoneum to the operating room environment during open abdominal surgery causes sufficient desiccation to result in loss of peritoneal mesothelium, and furthermore, whether any mesothelial loss can be reduced by the insufflation of humidified-warm CO2.
Findings: The systematic review of the literature revealed that the creation of pneumoperitoneum for laparoscopic surgery can cause loss of areas of the mesothelial layer of the peritoneum. The degree of disruption appears to be reduced at lower pneumoperitoneum pressures and by the reduction of desiccation via warming and humidification of the insufflation gas. However, the systematic review revealed a gap in current knowledge regarding understanding of the effect of gaseous exposure during open abdominal surgery, including whether desiccation of the peritoneum during open abdominal surgery is sufficient to damage the peritoneal mesothelium. Therefore, a controlled rat model was developed to investigate the effect of gaseous exposure during open abdominal surgery. Key properties of the model were: assurance of adequate exposure of the peritoneum; modelling of operating room air flow; creation of a CO2 environment within the constraints of the model; appropriate mechanical ventilation and anaesthetic/analgesic management protocol; measurement of tissue oxygen partial pressure; optimisation of protocols to ensure protection of the mesothelium during tissue fixation and processing. Results of investigations utilising the model showed firstly that insufflation of humidified-warm CO2 caused an immediate and clinically significant increase in tissue oxygen partial pressure. Two subsequent sets of randomised cross-over trials showed that exposure to CO2 and exposure to humidity/warmth individually increased PtO2 and that these effects were additive. Finally, the trial investigating mesothelial loss showed that simply exposing the peritoneum to standardised operating room airflow during open abdominal surgery led to significant loss of peritoneal mesothelium that was prevented by insufflation of humidified-warm CO2. Key methods that were utilised during this research were: design of a rat model and manipulation of conditions during experimental use; endotracheal intubation; blood gas measurement; filtering and displaying signals for monitoring of heart-rate, body temperature and pulse oximetry during general anaesthesia; measurement of tissue oxygen partial pressure; scanning electron microscopy; light microscopy; fluorescent microscopy; biochemical assay.
Conclusions: In a carefully designed rat model of open abdominal surgery, humidifiedwarm CO2 insufflation increased tissue oxygen partial pressure and prevented loss of peritoneal mesothelium. These are important mechanisms in the prevention of postoperative complications. Humidified-warm CO2 insufflation during abdominal surgery may have important clinical implications.