Humidification in Laparoscopic Colonic Surgery - A Double Blinded, Randomised Controlled Trial.

The key determinants of a return to normal activity after major colorectal surgery are pain and fatigue. Our research group has an interest in enhancing perioperative care to reduce postoperative fatigue.

We have investigated the effect of peritoneal inflammation and the local production of cytokines on fatigue. Our data indicate that there is an association between the development of postoperative fatigue and the concentration of peritoneal cytokines following colorectal surgery. (Paddison, Hill - manuscript in submission). It is known that following surgery, there are two possible modes of communication between the cytokines and the brain. One is a hormonal routine by which the cytokines produced at the site of surgery enter the blood and proceed through cell surface receptors to act directly on the brain. The second method is a neural route represented by paracrine action of cytokines on primary afferent neurons that innervate the body site where the injury has taken place. In the abdominal cavity, the vagus nerve plays an important role in the latter form of communication. Vagal sensory neurons express large numbers of receptors for immune derived mediators, including a number of cytokines involved in inflammation and it has been shown that a major function of vagus may involve signaling immune and inflammatory situations. The vagus is unique as it has termination at the nucleus tractus solitarius (NTS) in the brain. The NTS is intensely activated following peripheral immune challenges and is also by far the most sensitive area in the brain following immune stimulation. The NTS projects monosynaptically to many regions of the brain which mediate sickness responses. Pro-inflammatory cytokines have been found in the blood, the skin, and the central nervous system after surgery and injury, however following major abdominal surgery such as colectomy these cytokines are found in very high concentrations in the peritoneal cavity. This local production of cytokines is far in excess of the amounts found in the serum suggesting an important local role and potentially a significant role in metabolic changes associated with colonic surgery. Therefore, inflammation and the consequent production of large concentrations of cytokines at the site of the surgery may activate the rich neurosensory vagal afferents to stimulate regions of the brain which mediate "sickness" responses. Therefore, it is feasible to hypothesize that strategies which lead to a reduction of the concentration of pro-inflammatory cytokines will lead to a reduction in post-operative fatigue.

In laparoscopic surgery, insufflated CO2 is delivered as defined by the United States Pharmacopoeia and National Formulary, which requires impurity of less than 200 parts per million, including water vapor. It is delivered at room temperature (21°C) with a relative humidity approaching 0%. Heat is lost by the body in warming and humidifying the cold, dry gas 1, and animal models have demonstrated that this can induce hypothermia. Initial human investigations showed that by simply heating the insufflating gas, core temperature was maintained and pain scores were improved. Additional findings showed heating and humidification helped to maintain core temperature in a porcine model 4. There is clinical evidence suggesting that heating and humidification can increase intraoperative core body temperature and reduce post-operative use of analgesia and pain scores for up to 14 days postoperatively. This intervention has also been linked significantly to an earlier return to normal activity in patients undergoing cholecystectomy.

Experimental studies have also shown that humidified gas is associated with less peritoneal and systemic inflammation compared to unhumidified gas. Furthermore, it has been demonstrated that use of warm, humidified gas is associated with a reduction in the concentration of peritoneal IL-6. The magnitude of this change is even larger than the effect seen after administration of anti-inflammatory agents in a similar setting. Significant reduction in other inflammatory peritoneal cytokines (TNF, IL-1) have also been observed in patients undergoing laparoscopic cholecystectomy with warmed CO2 insufflation gas.

Currently, there are no studies which have examined the effect of humidification in patients undergoing laparoscopic colonic surgery. We hypothesize that use of warm, humidified insufflation gas will lead to a reduction in hypothermia and concentration of peritoneal cytokines, with consequently decreased post-operative pain and fatigue, and earlier return to normal bowel function and activity. Our aim is to design and execute a double-blinded randomised controlled trial to test this hypothesis.