Problem: adhesion formation

During endoscopic surgery a pneumoperitoneum is needed to create a working space. For safety reasons, carbon dioxide (CO ₂ ) is used as an insufflation gas because it is highly soluble in water (1.45 mg/L), and it has a high exchange capacity in the lungs. This routine practice has been identified as a culprit in the development of postoperative adhesions, as a consequence of the associated mesothelial hypoxia and desiccation. The latter results from the flow rate, temperature, and relative humidity (RH) of the gas.

Trauma to the peritoneum followed by a local inflammatory reaction and mesothelial healing can lead to adhesions. The acute inflammation of the entire peritoneal cavity, however, is quantitatively the most important factor in adhesion formation. This acute inflammation results from the balance of bad factors such as mesothelial hypoxia associated with CO ₂ pneumoperitoneum, a mesothelial hyperoxia when the pO ₂ is >40 mm Hg, as occurs during open surgery (if air is roughly 20% oxygen, it has a pO ₂ of about 150 mm Hg), and desiccation of the mesothelium. The last, desiccation, has 2 opposing effects on adhesion formation–it directly damages cells by dehydrating them, but it also decreases the temperature of the affected area, and this is advantageous, since cells are more resistant to injury, such as hypoxia, at lower temperatures. For this reason, the damaging effect of desiccation has been difficult to isolate–and has been underestimated.

The degree of desiccation varies with flow rate, RH, and temperature of the gas used for the pneumoperitoneum, subsequently altering intraperitoneal and mesothelial temperature, mesothelial damage, peritoneal acute inflammation, and ultimately postoperative adhesion formation and pain. Over the last decade, humidification and temperature of the gas used during endoscopic surgery has received increasing attention. For example, it is clear that in a peritoneal cavity at 98.6°F (37°C) with a 100% RH, nonhumidified gas at 37°C will cause desiccation and some related cooling. Desiccation also obviously increases with the flow rate of the delivered gas. The relationship among desiccation, flow rate, and cooling, however, is more complex. First, the maximum amount of water a gas can hold increases linearly with temperature, and these maximum amounts are equivalent to 100% RH. At 25°C, 100% RH equals 25 mg/L whereas at 37°C this is 44 mg/L. Second, when flow rate increases desiccation increases, but when flow rate is too high, equilibration no longer occurs and the outgoing RH drops. Thirdly, when desiccation causes cooling this results in a cooling of the gas (thus the gas can hold less water) while simultaneously the cooling of tissues will slow down the rate of desiccation. Use of warm humidified gas has also been said to result in decreased postoperative pain, although this remains controversial.

To understand cooling, the relationship among humidification, temperature, enthalpy of a gas, and the energy requirements for evaporation of water must be considered. While heating of a humidified gas requires the amount of energy needed to heat the water contained in that gas–by definition, the energy to heat 1 mL of water by 1°C is 1 cal (4.1858 joules)–the energy required to heat 1 mL of dry gas by 1°C is only 0.00003 cal (0.0001 joules). In contrast, 577 cal (2415.2 joules) are needed to vaporize 1 mL of water at normal body temperature of 98.6°F (37°C). Therefore, practically, desiccation is the only important factor causing cooling, whereas cold humidified gas could cause some cooling, and the temperature of nonhumidified gas can almost be disregarded.

Desiccation and cooling are intrinsically related and have detrimental and favorable effects on adhesion formation, respectively. The quantitative effect of desiccation and peritoneal temperature on mesothelial damage during endoscopic surgery has not yet been investigated in detail. Indeed, the use of warm humidified gas has been suggested to be superior to dry and cold gas but it remains controversial whether it decreases postoperative pain, whereas there still is no evidence of decreased adhesion formation. The relationship between peritoneal damage caused by warm (37°C) and humidified gas and a high temperature and by cold and dry gas causing desiccation and cooling could be biphasic, with an optimum achieved with a little desiccation together with a little cooling. Experiments in mice, moreover, indicate that ideally, to reduce adhesions, prevention of desiccation should be combined with a slightly lower intraperitoneal temperature of 87.8-89.6°F (31-32°C), a temperature that achieves >80% of the cooling effect upon adhesion formation compared to gas at 25°C. So when an insufflation gas with close to 100% RH is used, a third means of cooling is required to achieve the total effect on adhesion formation of cooling.

Our solution

We performed several studies in preparation for a randomized controlled trial (RCT) that will investigate the effects of flow rate, temperature (T), and RH of the insufflation gas combined with external cooling and thus desiccation and intraperitoneal temperature upon pain and adhesions in human beings. For all the studies we used the Thermoflator (Karl Storz GmbH & Co.KG, Tuttlingen, Germany) for insufflation. For humidification of the insufflation gas, the model 204320 33 humidifier (Karl Storz GmbH & Co.KG), the MR860 humidifier (Fisher and Paykel Healthcare Ltd, Auckland, New Zealand), and a modified humidifier (Fisher and Paykel Healthcare Ltd) were used.

The Storz humidifier blows gas over water warmed to 98.6°F (37°C) and uses a noninsulated tubing, 2.7 m in length and 7 mm in diameter (Kendall; Covidien, Mansfield, MA). Adequate humidification is provided at low flow rates but the tubing causes rapid cooling of the gas to ambient temperature. The standard F&P humidifier blows gas through a heated water chamber. To avoid condensation, the tubing that delivers the gas was heated to >104°F (40°C) with a heating wire. To permit higher flow rates than the device usually delivers, the luer lock was removed. In the modified F&P humidifier, modified by eSaturnus NV (Leuven, Belgium), the heating of the chamber and tubing was continuously adapted by an electronic feedback loop to maintain 100% RH at the end of the tubing, a preset temperature between 77-96.8°F (25-36°C) at flow rates between 0.5-30 L/min.

The flow rate, RH, and temperature of the gas at the end of the insufflation tubing and the gas flowing from the peritoneal cavity–or a box used to mimic the peritoneal cavity in the in vitro experiments–were measured twice a second; temperature and RH were captured with a digital sensor (SHT75; Sensirion AG, Zurich, Switzerland). This permitted calculation of water loss, a marker for desiccation, in real time. Cooling by a third means of the peritoneal cavity was accomplished by nebulizing 3 mL/min of water at room temperature or at 32°F (0°C) with a nozzle set at 2 bar entry pressure. This cooling/nebulization/humidification device had a diameter of <5 mm so that it could be used through a standard 5-mm trocar.

To validate the setup in vitro, the bottom and side walls of a closed polystyrene box were covered with plastic bags containing a total of 6 L of water at 98.6°F (37°C) ( Figure 1 ). It was assumed that temperature and RH coming out of the box would reflect temperature and RH inside the box. When the tubing was used for nonhumidified CO ₂ or for gas humidified with the Storz humidifier, the gas was permitted to cool to room temperature or was heated to 98.6°F (37°C) by putting the tubing inside a heated chamber.

In vitro system was used to validate accuracy of temperature and relative humidity (RH) measurements: heated chamber, maintained at 98.6°F (37°C), contained insufflator, humidifier, and tubing, while box with water bags at 98.6°F (37°C) served as model of peritoneal cavity. Protruding moistened towels, acting as “desiccation recipient,” were weighted before experiment and at its conclusion.

Corona. Intraperitoneal temperature and desiccation during endoscopic surgery. Am J Obstet Gynecol 2011.

First, the accuracy of the measurements of flow rate, RH, and temperature of the gas were validated. The exact water loss was measured by the difference in weight of the “desiccation recipient,” protruding moistened towels, before and after the experiment, and compared with the water loss calculated from the flow rate, RH, and temperature of the inflowing and outflowing gas with the following formula: humidity (g/m ³ ) = RH (%)/100 × (3.1243 10e-4 × T ³ + 8.1847 × 10e-3 × T ² + 0.32321 × T + 5.018). RHs and temperatures at inflow and outflow equilibrated within 2 minutes, so we used the mean values during the last 10 minutes of the experiment to calculate water loss. Since the accuracy of desiccation calculation was crucial for the in vivo experiments, the measurements were validated over a wide range of conditions and performed in triplicate.

The measurements of flow rate, RH, and temperature were accurate, as judged by the linear relationship between the calculated and measured water loss (MatLab software, MathWorks ™, Natick, Massachusetts, U.S.A.) ( Table 1 ). Measurements of temperature and RH, made twice a second, had a coefficient of variation of 0.8%, 0.9%, 0.5%, and 0.5%, and of 2.2%, 3%, 12.4%, and 22.9% at flow rates of 2.5, 5, 10, and 20 L/min, respectively. Therefore, mean values over 5 minutes were used for all further calculations.

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