Tumour implantation following laparoscopy using different insufflation gases

Background : Because of the possibility of intraperitoneal seeding and port‐site recurrences following laparoscopic surgery, the role of laparoscopy in cancer surgery remains controversial. Previous experimental studies have suggested that chemical, metabolic and immunological changes following carbon dioxide (CO₂) insufflation may be responsible for this phenomenon. Earlier experimental studies done by the University of Adelaide Department of Surgery have also shown that helium insufflation is associated with none of the adverse changes brought about by CO₂ insufflation. Helium insufflation is also associated with lower rates of intra‐abdominal tumour spread. The aim of this study was to determine whether these identified benefits apply to inert gases in general. Methods : Twenty‐four Dark Agouti rats were randomized to undergo laparoscopy with 40 min insufflation using one of the following four gases (six rats in each group); CO₂, helium, argon and nitrogen. A tumour cell suspension was injected into the abdominal cavity at the beginning of laparoscopy. The rats were killed 7 days after surgery, and the peritoneal cavity and port sites were examined for the presence of tumour. Results : Rats undergoing helium insufflation, had the least number of port‐site recurrences and the least amount of intraperitoneal tumour spread. Argon and nitrogen pneumoperitoneum were associated with a large number of port‐site recurrences and widespread tumour seeding. The effect of CO₂ insufflation was intermediate. Conclusion : The choice of insufflation gas influences the incidence of port‐site metastases and the degree of intraperitoneal tumour spread following laparoscopic cancer surgery. The reduced port‐site recurrences and intraperitoneal spread that followed helium pneumoperitoneum is likely to be a unique property of this gas rather than a property of inert gases in general.     

Influence of Gases on Intraperitoneal Immunity during Laparoscopy in Tumor-bearing Rats

Laparoscopy has been associated with metastases to abdominal wall wounds. In addition, many recent experimental studies suggest that laparoscopy is associated with increased tumor dissemination. It is possible that immune or metabolic disturbances due to the use of a pneumoperitoneum could contribute to this problem. To investigate this possibility, we studied the effect of two insufflation gases and gasless laparoscopy on in vivo peritoneal macrophage function and intraperitoneal pH in an experimental model. A carcinoma was implanted into the flank of 32 experimental rats that underwent laparoscopic surgery in one of four treatment groups: anesthesia alone, gasless laparoscopy, helium insufflation, and CO₂ insufflation. Intraperitoneal pH was monitored during surgery, and peritoneal macrophage function was determined 3 days after surgery by harvesting peritoneal macrophages and then examining their ability to produce tumour necrosis factor-α (TNF-α). CO₂ insufflation was associated with a consistent fall in intraperitoneal pH and a significant reduction in TNFα production. These findings did not occur in the other study groups. The results of this study demonstrate that CO₂ insufflation results in depressed intraperitoneal macrophage activity. It is possible that it is mediated by pH changes. In addition, it could be a contributing factor to the development of port-site metastases. Further studies are needed to determine whether the factors identified act during clinical surgery.     

Tumor implantation following laparoscopy using different insufflation gases

Background: Laparoscopic manipulation of malignancies is associated with an increased incidence of metastasis to port sites in experimental models. This study investigated the effect of different insufflation gases on the implantation of a tumor cell suspension following laparoscopic surgery in an established small animal model. Methods: Forty Dark Agouti rats underwent laparoscopy and the introduction into the peritoneal cavity of a tumor cell suspension. The insufflating gas used for each procedure was one of the following gases (10 rats in each group): carbon dioxide (CO₂), nitrous oxide (N₂O), helium, and air. The rats were killed 7 days after surgery, and the peritoneal cavity and port sites were examined for the presence of tumor. Results: Although no significant differences were seen between air, CO₂, and N₂O insufflation groups, tumor involvement of peritoneal surfaces was less likely following helium insufflation. Conclusion: The results of this study suggest that tumor metastasis to port sites following laparoscopic surgery may be influenced by the choice of insufflation gas. In this study, helium was associated with reduced tumor growth.     

Peritoneal and systemic pH during pneumoperitoneum with CO<Subscript>2</Subscript> and helium in a pig model

Background Local peritoneal effects of laparoscopic gases might be important in peritoneal biology during and after laparoscopic surgery. The most commonly used gas, CO₂, is known to be well tolerated, but also causes changes in acid-base balance. Helium is an alternative gas for laparoscopy. Although safe, it is not widely used. In this study a method for monitoring peritoneal pH during laparoscopy was evaluated and peritoneal pH during CO₂ and helium pneumoperitoneum was studied as well as its systemic reflection in arterial pH. Methods For these experiments 20 pigs were used, with ten exposed to pneumoperitoneum with CO₂, and ten to helium. Peritoneal and sub-peritoneal pH were continuously measured before and during gas insufflation, during a 30-minute period with a pneumoperitoneum and during a 30-minute recovery period. Arterial blood-gases were collected immediately before gas insufflation, at its completion, at 30 minutes of pneumoperitoneum and after the recovery period. Results Peritoneal pH before gas insufflation was in all animals 7.4. An immediate local drop in pH (6.6) occurred in the peritoneum with CO₂ insufflation. During pneumoperitoneum pH declined further, stabilising at 6.4, but was restored after the recovery period (7.3). With helium, tissue pH increased slightly (7.5) during insufflation, followed by a continuous decrease during pneumoperitoneum and recovery, reaching 7.2. Systemic pH decreased significantly with CO₂ insufflation, and increased slightly during helium insufflation. Systemic pH showed co-variation with intra-peritoneal pH at the the end of insufflation and after 30 minutes of pneumoperitoneum. Conclusions Insufflation of CO₂ into the peritoneal cavity seemed to result in an immediate decrease in peritoneal pH, a response that might influence biological events. This peritoneal effect also seems to influence systemic acid-base balance, probably due to trans-peritoneal absorption.     

Videoscopic surgery under local and regional anesthesia with helium abdominal insufflation

Background: High-risk patients may not be good candidates for laparoscopic surgery due to the metabolic consequences of transperitoneal absorption of insufflated CO₂ gas and the necessity of general anesthesia because CO₂ insufflation produces pain. Helium gas is metabolically inert and does not produce pain. Thus it permits an alternative approach to performing laparoscopic surgery in high-risk patients. Methods: Laparoscopic cholecystectomy, appendectomy, hernia repair, and peritoneal dialysis catheter procedures were performed under local or regional anesthesia in high-risk patients utilizing helium gas as the insufflation agent. Results: Twenty-one patients underwent laparoscopic procedures under local or regional anesthesia. None of the procedures initiated under local-regional anesthesia required abandonment of the laparoscopic approach or conversion to general anesthesia. There were no operative or perioperative mortalities. Two incidences of pneumothorax occurred with extraperitoneal hernia repair; one required a tube thoracostomy. Conclusions: Helium gas should be considered the agent of choice for intraperitoneal insufflation in high-risk patients not only because helium avoids the metabolic consequences of CO₂ insufflation but also because it permits selected procedures to be performed under local-regional anesthesia. Helium may be contraindicated for laparoscopic procedures involving extraperitoneal insufflation due to the increased risk for pneumothoraces. Received: 15 April 1998/Accepted: 25 August 1998     

The effect of laparoscopy on the movement of tumor cells and metastasis to surgical wounds

Background: A variety of mechanisms have been proposed to explain tumor growth in port sites following laparoscopic cancer surgery. We devised two experimental models to determine whether carbon dioxide (CO₂) insufflation during laparoscopic surgery influences the movement of tumor cells and leads to tumor implantation and growth in surgical wounds. Methods: Model 1: Viable adenocarcinoma cells were introduced into the upper abdomen of six syngeneic immune-competent rats during laparoscopy with CO₂ insufflation; the same procedure was followed for a further six rats during gasless laparoscopy. A length of plastic tubing introduced through the anterolateral aspect of the rats' left lower abdominal wall was used to vent the insufflation gas through the abdomen of a recipient rat for 30 min. After 21 days, the peritoneal cavity and surgical wounds of the recipient rat were examined for implanted tumor. Model 2: A suspension of radiolabeled adenocarcinoma cells was introduced into the upper abdomen of five rats during laparoscopy with CO₂ insufflation and an additional five rats during gasless laparoscopy. A length of plastic tubing introduced through the anterolateral aspect of the left lower abdominal flank was used to vent the insufflation gas through phosphate-buffered saline solution. After 30 min, the solution was counted for radioactivity. Results: Tumor growth occurred at the site of both the insufflation and venting ports in the second rat in five of the six rats from the group undergoing insufflation, but it was found in none of the gasless laparoscopy group (p= 0.015). In the second model, significant transfer of tumor cells to the vented gas occurred only in the rats undergoing laparoscopy with insufflation (median, 2.71% versus 0% of the introduced labeled cells; p= 0.008). Conclusions: Carbon dioxide insufflation results in tumor dissemination during laparoscopy, leading to port site metastasis. Gasless laparoscopy may prevent this problem. Received: 17 March 1997/Accepted: 6 June 1997     

Effects of carbon dioxide vs helium pneumoperitoneum on hepatic blood flow

Background: Elevated intraabdominal pressure due to gas insufflation for laparoscopic surgery may result in regional blood flow changes. Impairments of hepatic, splanchnic, and renal blood flow during peritoneal insufflation have been reported. Therefore we set out to investigate the effects of peritoneal insufflation with helium (He) and carbon dioxide (CO₂) on hepatic blood flow in a porcine model. Methods: Twelve pigs were anesthetized and mechanically ventilated with a fixed tidal volume after the stabilization period. Peritoneal cavity was insufflated with CO₂ (n= 6) or He (n= 6) to a maximum intraabdominal pressure of 15 mmHg. Hemodynamic parameters, gas exchange, and oxygen content were studied at baseline, 90 mm and 150 min after pneumoperitoneum, and 30 min after desufflation. Determination of hepatic blood flow with indocyanine green was made at all measured points by a one-compartment method using hepatic vein catheterization. Results: A similar decrease in cardiac output was observed during insufflation with both gases. Hepatic vein oxygen content decreased with respect to the baseline during He pneumoperitoneum (p < 0.05), but it did not change during CO₂ insufflation. Hepatic blood flow was significantly reduced in both the He and CO₂ pneumoperitoneums at 90 min following insufflation (63% and 24% decrease with respect to the baseline; p < 0.001 and p < 0.05, respectively) being this decrease marker in the He group (p= 0.02). Conclusions: These findings suggest that helium intraperitoneal insufflation results in a greater impairment on hepatic blood flow than CO₂ insufflation. Received: 27 March 1996/Accepted: 19 January 1997     

THE ROLE OF PERITONEAL IMMUNITY AND THE TUMOUR-BEARING STATE ON THE DEVELOPMENT OF WOUND AND PERITONEAL METASTASES AFTER LAPAROSCOPY

Background : The effect of the tumour-bearing state and alterations in peritoneal immune function on the incidence of port-site and peritoneal metastases was investigated after laparoscopy with and without CO₂ pneumoperitoneum. Methods : A suspension of viable adenocarcinoma cells was introduced into the left upper quadrant of the peritoneal cavity of syngeneic tumour-bearing rats at laparotomy, laparoscopy with CO₂, and gasless laparoscopy. Control rats did not have pre-existing tumours. A group of non-tumour-bearing rats were also injected intraperitoneally with endotoxin 4 h before intraperitoneal tumour cell injection. Six days later the peritoneal cavity and surgical wounds were examined for macroscopic evidence of implanted tumour. Peritoneal macrophages were obtained from tumour-bearing rats subjected to different laparoscopic procedures and the activation state measured following exposure to lipopolysaccharide in vitro. Results : In the control rats, tumour implantation in the surgical wounds and peritoneum was significantly greater in the rats that had undergone laparoscopy with CO₂. The presence of a pre-existing tumour was associated with increased tumour spread in all treatment groups and at most sites. Injection of endotoxin also resulted in increased tumour spread. Peritoneal macrophages from control and tumour-bearing rats who underwent laparoscopy with CO₂ produced significantly less TNF-αin vitro, compared to gasless laparoscopy or laparotomy. Conclusions : Carbon dioxide insufflation enhances tumour spread and implantation. The underlying immune or metabolic status of the host, as influenced by the tumour-bearing state or modification of the peritoneal environment, also has a marked independent effect on tumour spread and implantation. The immune and metabolic status of the peritoneum including the extent of macrophage activation is implicated in this effect.     

Oncological effects of insufflation with different gases and a gasless procedure in rats

Background: The validity of using carbon dioxide (CO₂) pneumoperitoneum in laparoscopic tumor surgery has not been investigated thoroughly. The oncologic effects of a gasless procedure and insufflation with different gases were compared in rats. Methods: In all the experiments, Donryu rats were randomized to receive a gasless procedure; to receive insufflation with CO₂, helium, or air at 10 mmHg for 30 min, or to serve as control subjects without insufflation. In experiment 1, involving 60 rats, ascites hepatoma AH130 cells were inoculated intraperitoneally just before the procedures. The S-phase fraction of the intraperitoneal tumor cells was determined using a flow cytometry on day 7. In experiment 2, 60 rats injected intraperitoneally with latex particles received one of the procedures. At the end of the procedure, peritoneal macrophages were harvested to determine the number of phagocytosed particles. In experiment 3, 75 rats inoculated intraperitoneally with AH130 cells received one of the procedures for 5 consecutive days and were followed for survival analysis. Results: Experiment 1: The S-phase fraction was lower after insufflation with air or helium (p < 0.01) than with the anesthesia control condition. Insufflation with CO₂ showed a higher S-phase fraction than the gasless procedure or insufflation with air or helium ( p < 0.01). Experiment 2: The phagocytotic activity of peritoneal macrophages was increased by insufflation with helium and air, as compared with the control condition ( p < 0.01). Insufflation with CO₂ deteriorated the phagocytotic activity more than the gasless procedure ( p < 0.05) or insufflation with air or helium ( p < 0.001). Experiment 3: Insufflation with gases demonstrated shorter survival than the anesthesia control condition or the gasless procedure regardless of the gases used (p < 0.01). Conclusions: These results suggest that the choice of gases may affect the proliferation of tumor cells and the phagocytotic activity of peritoneal macrophages, insufflation itself may promote tumor spread regardless of the gases used, and the gasless procedure may be oncologically advantageous in this animal model.     

Alternative methods of exposure minimize cardiopulmonary risk in experimental animals during minimally invasive surgery

Background: Alternative methods of exposure are needed for minimally invasive surgery to avoid hypercarbia and acidosis associated with carbon dioxide (CO₂) abdominal insufflation. The goals of this study were to determine the pulmonary and hemodynamic effects of both helium (HE) abdominal insufflation and placement of a mechanical abdominal wall-lifting device (lifter) during laparoscopy. Methods: Sixteen adult domestic pigs under general endotracheal anesthesia underwent baseline measurements of pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and arterial blood gas. Six pigs underwent standard CO₂ abdominal insufflation, five pigs underwent abdominal insufflation with HE, and a lifter was used for exposure in five other animals. Sequential readings of PCWP, CO, and arterial blood gas were recorded at 20-min intervals for 60 min in all 16 animals. Results: No significant changes from baseline values were noted in arterial pCO₂ or pH in animals who underwent placement of the lifter at any time point. After undergoing HE insufflation, animals experienced modest but significant acidosis and little change in pCO₂. There was a significant rise in arterial pCO₂ and decrease in pH from baseline values at all time points in animals undergoing CO₂ insufflation. Conclusions: This study shows that neither HE abdominal insufflation or the lifter have significant deleterious pulmonary or hemodynamic effects on experimental animals during laparoscopy. Gasless laparoscopy or HE insufflation may provide a safer alternative method of exposure for minimally invasive surgery in patients with pre-existing pulmonary or cardiac dysfunction. By minimizing risk in these patients, costly invasive monitoring may be avoided.Presented at the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons (SAGES), Orlando, Florida, USA, 11–14 March 1995     

Increased transperitoneal bacterial translocation in laparoscopic surgery

Background: The indications for laparoscopic surgery have expanded to include diseases possibly associated with peritonitis such as appendicitis, perforated peptic ulcers, and diverticulitis. The safety of carbon dioxide (CO₂) pneumoperitoneum in the presence of peritonitis has not been proved. Our previous investigations demonstrated increased bacteremia associated with CO₂ insufflation. In effort to clarify the relative effects of intraabdominal pressure and type of gas, this study was designed to measure bacterial translocation with different gases at different pressures of pneumoperitoneum. Methods: For this study, 110 rats were given intraperitoneal bacterial innoculations with Escherichia coli and equally divided into five groups of 20 animals each. The study groups included a control group with no pneumoperitoneum administered (n = 30), insufflation at a commonly used pressure of 14 mmHg with helium (n = 20) and CO₂ (n = 20), and low insufflation at 3 mmHg with helium (n = 20) and CO₂ (n = 20) in an effort to minimize influences related to pressure. Blood cultures were checked at 15-min intervals for the first 45 min, then hourly thereafter for a total of 165 min after peritoneal inoculation with 2 × 10⁷ E. coli. Results: There is increased risk of bacterial translocation in comparing groups that underwent pneumoperitoneum with those that did not in the rat peritonitis model. Furthermore, these findings are dependent on the presence or absence of gas, but not necessarily on the type of gas used for insufflation. In the low-pressure groups of both gases (helium and CO₂), bacterial translocation was significantly increased, as compared with the control group. Low pressure also was associated with increased bacterial translocation, as compared with high pressure, but beyond 30 min of insufflation, no significant differences were apparent. Conclusions: The risk of bacterial translocation in the E. coli rat peritonitis model is increased with insufflation using CO₂ or helium, and this effect is more significant at lower pressures (3 mmHg) than at higher pressures (14 mmHg). However, no clinically applicable conclusions regarding the relative effects from type of gas or insufflation pressures could be confirmed.     

Peritoneal pH during laparoscopy is dependent on ambient gas environment: helium and nitrous oxide do not cause peritoneal acidosis

Background Little is know about the effects of different insufflation gases on peritoneal pH during laparoscopy. However, these changes may influence the intracellular signalling system, resulting in altered cell growth or adhesiveness. The aim of this study was to determine the effects of carbon dioxide (CO₂), nitrous oxide (N₂O), and helium (He) on parietal and visceral peritoneal pH. The effect of different intraabdominal pressures on parietal and visceral peritoneal pH was also examined.Methods We conducted both an ambient gas study and a pressure study. For the ambient gas study, 20 pigs were divided into the following four groups: (a) CO₂, (b) He, (c) N₂O, and (d) abdominal wall lift (Lift) laparoscopy. Parietal and visceral peritoneal pH were measured at 15 min intervals for 180 min. For the pressure study, 15 pigs were divided into the following three groups: (a) CO₂, (b) He, (c) N₂O laparoscopy. Baseline values were established for parietal and visceral peritoneal pH. Intraabdominal pressure was then increased stepwise at 1-mmHg intervals to 15 mmHg. After pressure was maintained for 15 min at each setting, parietal and visceral peritoneal pH were measured.Results Ambient gas environment was the major determinant of parietal peritoneal pH. Carbon dioxide caused parietal peritoneal acidosis. Helium, N₂O, and Lift caused alkalotic parietal peritoneal pH. Intraabdominal pressure had a minor effect on parietal peritoneal pH. At higher intraabdominal pressure (12–15 vs 5–8 mmHg), CO₂ caused a slight decrease in parietal peritoneal pH, whereas N₂O and He caused a slight increase in parietal peritoneal pH. Visceral peritoneal pH remained relatively unaffected during all studies.Conclusions Parietal peritoneal pH during laparoscopy was highly dependent on the ambient gas environment. The effect of intraabdominal pressure on parietal peritoneal pH was of minor significance. Carbon dioxide caused a slight worsening of parietal peritoneal acidosis at higher intraabdominal pressure, whereas, N₂O, He, and Lift did not cause parietal peritoneal acidosis.     

Mechanism of decreased in vitro murine macrophage cytokine release after exposure to carbon dioxide: relevance to laparoscopic surgery.

OBJECTIVE: The objective of this study was to determine the effect of carbon dioxide (CO2) on the function of peritoneal macrophages. SUMMARY BACKGROUND DATA: Laparoscopic surgery is associated with minimal pain, fever, and low levels of inflammatory cytokines. To understand the mechanisms involved, the authors investigated the effect of different gases on murine peritoneal macrophage intracellular pH and correlated these alterations with alterations in LPS-stimulated inflammatory cytokine release. METHODS: Peritoneal macrophages were incubated for 2 hours in air, helium, or CO2, and the effect of the test gas on immediate or next day lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 release compared. Cytosolic pH of macrophages exposed to test gases was measured using single-cell fluorescent imaging. The in vivo effects of test gases were determined in anesthetized rats during abdominal insufflation. RESULTS: Macrophages incubated in CO2 produced significantly less TNF and interleukin-1 in response to LPS compared to incubation in air or helium. Cytokine production returned to normal 24 hours later. Exposure to CO2, but not air or helium, caused a marked cytosolic acidification. Pharmacologic induction of intracellular acidification to similar levels reproduced the inhibitory effect. In vitro studies showed that CO2 insufflation lowered tissue pH and peritoneal macrophage LPS-stimulated TNF production. CONCLUSIONS: The authors propose that cellular acidification induced by peritoneal CO2 insufflation contributes to blunting of the local inflammatory response during laparoscopic surgery.     

Carbon dioxide pneumoperitoneum causes severe peritoneal acidosis,unaltered by heating,humidification, or bicarbonate in a porcine model

Background Carbon dioxide (CO₂) is the most common gas used for insufflation in laparoscopy, but its effects on peritoneal physiology are poorly understood. This study looks at the changes in peritoneal and bowel serosal pH during CO₂ pneumoperitoneum, and whether heating and humidification with or without bicarbonate alters the outcomes.Methods Twenty-one pigs divided into four groups as follows: (1) standard (STD) laparoscopy (n = 5); (2) heated and humidified (HH) laparoscopy (n = 6); (3) heated and humidified with bicarbonate (HHBI) laparoscopy (n = 5); and (4) laparotomy (n = 5). Peritoneal pH, bowel serosal pH, and arterial blood gas (ABG) were obtained at 15-min intervals for 3 h.Results Severe peritoneal acidosis (pH range 6.59–6.74) was observed in all laparoscopy groups, and this was unaltered by heating and humidification or the addition of bicarbonate. Bowel serosal acidosis was observed in all laparoscopy groups with onset of pneumoperitoneum, but it recovered after 45 minutes. No significant changes in peritoneal or bowel serosal pH were observed in the laparotomy group.Conclusion CO₂ pneumoperitoneum resulted in severe peritoneal acidosis that was unaltered by heating and humidification with or without bicarbonate. Alteration in peritoneal pH may conceivably be responsible for providing an environment favorable for tumor-cell implantation during laparoscopy.     

ADVERSE IMPACT OF PNEUMOPERITONEUM ON INTRAPERITONEAL IMPLANTATION AND GROWTH OF TUMOUR CELL SUSPENSION IN AN EXPERIMENTAL MODEL

Background : An investigation of the effect of laparoscopy and CO₂ pneumoperitoneum on the pattern of tumour implantation and growth in the peritoneal cavity was carried out. Methods : A suspension of viable adenocarcinoma cells was introduced into the left upper quadrant of the peritoneal cavity of 36 syngeneic immune-competent rats at laparotomy, laparoscopy with CO₂ insufflation, and gasless laparoscopy (12 rats in each group). Six days later the peritoneal cavity and surgical wounds were examined for macroscopic evidence of implanted tumour. The abdominal cavity was divided into sectors and macroscopic tumour implantation was determined for each sector and wound. This was confirmed by histological examination. Results : While tumour implantation occurred in the vicinity of the tumour suspension introduction site in the laparotomy and gasless laparoscopy groups, implantation occurred throughout the peritoneal cavity, including areas remote to the introduction site, in the laparoscopy with CO₂ insufflation group. Tumour growth was more likely in the port wounds of rats undergoing laparoscopy with insufflation than without. Conclusions : In this model, CO₂ insufflation during laparoscopy resulted in widespread tumour dissemination and implantation, when compared to laparotomy and gasless laparoscopy, supporting the postulate that wound metastasis and tumour spread may be more likely following laparoscopic cancer surgery in humans when CO₂ insufflation is used.     

Carbon dioxide pneumoperitoneum prevents mortality from sepsis

Background Carbon dioxide (CO₂) pneumoperitoneum has been shown to attenuate the inflammatory response after laparoscopy. This study tested the hypothesis that abdominal insufflation with CO₂ improves survival in an animal model of sepsis and investigated the associated mechanism. Methods The effect of CO₂, helium, and air pneumoperitoneum on mortality was studied by inducing sepsis in 143 rats via intravenous injection of lipopolysaccharide (LPS). To test the protective effect of CO₂ in the setting of a laparotomy, an additional 65 animals were subjected to CO₂ pneumoperitoneum, helium pneumoperitoneum, or the control condition after laparotomy and intraperitoneal LPS injection. The mechanism of CO₂ protection was investigated in another 84 animals. Statistical significance was determined via Kaplan– Meier analysis for survival and analysis of variance (ANOVA) for serum cytokines. Results Among rats with LPS-induced sepsis, CO₂ pneumoperitoneum increased survival to 78%, as compared with using helium pneumoperitoneum (52%; p < 0.05), air pneumoperitoneum (55%; p = 0.09), anesthesia control (50%; p < 0.05), and LPS-only control (42%; p < 0.01). Carbon dioxide insufflation also significantly increased survival over the control condition (85% vs 25%; p < 0.05) among laparotomized septic animals, whereas helium insufflation did not (65% survival). Carbon dioxide insufflation increased plasma interleukin-10 (IL-10) levels by 35% compared with helium pneumoperitoneum (p < 0.05), and by 34% compared with anesthesia control (p < 0.05) 90 min after LPS stimulation. Carbon dioxide pneumoperitoneum resulted in a threefold reduction in tumor necrosis factor-α (TNF-α) compared with helium pneumoperitoneum (p < 0.05), and a sixfold reduction with anesthesia control (p < 0.001). Conclusion Abdominal insufflation with CO₂, but not helium or air, significantly reduces mortality among animals with LPS-induced sepsis. Furthermore, CO₂ pneumoperitoneum rescues animals from abdominal sepsis after a laparotomy. Because IL-10 is known to downregulate TNF-α, the increase in IL-10 and the decrease in TNF-α found among the CO₂-insufflated animals in our study provide evidence for a mechanism whereby CO₂ pneumoperitoneum reduces mortality via IL-10-mediated downregulation of TNF-α. Supported by R01-GM062899-02, National Institutes of Health, Bethesda, MD. Presented at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), Ft. Lauderdale, Florida, 13–16 April 2005     

Abdominal insufflation with CO<Subscript>2</Subscript> causes peritoneal acidosis independent of systemic pH

We have shown that the inflammation-attenuating effects of CO₂ pneumoperitoneum during laparoscopy are not due to changes in systemic pH. However, acidification of peritoneal macrophages in an in vitro CO₂ environment has been shown to reduce LPS-mediated cytokine release. We tested the hypothesis that the peritoneum is locally acidotic during abdominal insufflation with CO₂deven when systemic pH is corrected. Rats (n = 20) were anesthetized and randomized into two groups: continued spontaneous ventilation (SV) or intubation and mechanical ventilation (MV). All animals were then subjected to abdominal insufflation with CO₂. Mean arterial pH among SV rats decreased significantly from baseline after 15 and 30 minutes of CO₂ pneumoperitoneum (7.329→7.210→7.191, P < 0.05), while arterial pH among MV rats remained relatively constant (7.388→7.245→7.316, P = NS). In contrast, peritoneal pH dropped significantly from baseline and remained low for both groups during CO₂ abdominal insufflation (SV 6.74 → 6.41 → 6.40, P < 0.05; MV 6.94 → 6.45 → 6.45, P < 0.05). In a second experiment, rats (n = 10) were randomized to receive abdominal insufflation with either CO₂ or helium. Abdominal insufflation with helium did not significantly affect peritoneal pH (7.10 → 7.02 →6.95, P = NS), and the decrease in pH among CO₂-insufflated animals was significant compared with helium-insufflated animals (P < 0.05). Peritoneal pH returned to baseline levels in all groups within 15 minutes of desufflation in both experiments. A significant local peritoneal acidosis occurs during laparoscopy which is specifically attributable to the use of CO₂ and which is independent of systemic pH. These data provide additional evidence that localized peritoneal acidosis is central to the mechanism of CO₂-mediated attenuation of the inflammatory response following laparoscopic surgery. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Uniformed Services University, the Department of the Air Force, or the Department of Defense.     

Experimental study of peritoneal blood flow and insufflation pressure during laparoscopy

BACKGROUND: Port-site metastases after laparoscopic surgery may occur with greater frequency than would be expected following open resection of intra-abdominal malignancies, but the causal mechanism for this is incompletely understood. The possibility that insufflation may increase peritoneal blood flow producing a wound environment conducive to the formation of metastases was investigated.METHODS: The effects of insufflation gas type and pressure were studied in 30-kg female pigs. Pigs were divided into five groups, which were subjected to insufflation at 12 mmHg pressure with helium, insufflation at 12, 8 or 4 mmHg pressure with carbon dioxide, or laparotomy. A microsphere technique utilizing two distinct radiotracers, 99mTc-labelled macroaggregated albumin (MAA) and 51Cr-labelled MAA, was used to study blood flow to the peritoneum, liver and kidneys.RESULTS: Insufflation with carbon dioxide or helium gases had no effect on renal (P < 0.09) or hepatic blood flow (P = 0.54). However, insufflation significantly increased peritoneal blood flow when carbon dioxide (P < 0.05), but not when helium (P = 0.99), was used as the insufflating gas.CONCLUSION: These data suggest that blood flow within the peritoneum is influenced by insufflation with carbon dioxide. It is conceivable that such hyperaemia could increase the propensity for implanted tumour cells to metastasize in these sites following laparoscopy.     

IN VITRO INHIBITION OF TUMOUR GROWTH IN A HELIUM-RICH ENVIRONMENT: IMPLICATIONS FOR LAPAROSCOPIC SURGERY

Background : The recent results of several experimental studies have suggested that tumour implantation after laparoscopic surgery for intra-abdominal malignancy may be partly related to the chemical composition of the insufflation gas used during surgery. These studies have demonstrated that the use of helium as a laparoscopic insufflation agent for cancer surgery results in less tumour implantation and growth at port sites. To further investigate these findings, the present study was performed to compare the growth of cultured tumour cells after exposure to simulated laparoscopic environments, rich in helium, carbon dioxide (CO₂), or air. Methods : A rat mammary adenocarcinoma cell suspension was exposed to a simulated laparoscopic environment for 40 min in one of the following groups: (i) control (atmospheric air, equivalent to a ‘gasless’ laparoscopic environment); (ii) a CO₂-rich environment; and (iii) a helium-rich environment. Cells were then cultured for 18 h and optical density readings were used to assess the number of viable tumour cells at the end of this period. The experiment was performed twice using an identical protocol to ensure consistency in the results. In a further study, pH was continuously measured using an antimony probe during a 40 min insufflation period and for 10 min after insufflation. Results : Cell growth was significantly lower after incubation in the helium-rich environment compared to both the CO₂ and control groups (P < 0.001). There was a significant decrease in pH in the CO₂ group which was not observed during exposure to either air or helium. Conclusions : The inhibition of tumour growth in a helium-rich environment demonstrated by this study, and the reduced incidence of port–site metastases seen in other experimental studies, suggests that the clinical use of helium as an insufflation gas may have important advantages over CO₂.